PA-824_187235-37-6_DataSheet_MedChemExpress

The European Agency for the Evaluation of Medicinal ProductsHuman Medicines Evaluation UnitICH - Technical Coordination - R. Bass 7 Westferry Circus, Canary Wharf, London E14 4HB, UK ICH Topic S 2 BGenotoxicity: A Standard Battery forGenotoxicity Testing of PharmaceuticalsStep 4, Consensus guideline, 16 July 1997NOTE FOR GUIDANCE ON GENOTOXICITY:A STANDARD BATTERY FOR GENOTOXICITY TESTINGOF PHARMACEUTICALS(CPMP/ICH/174/95)TRANSMISSION TO CPMPOctober 1996TRANSMISSION TO INTERESTED PARTIESOctober 1996COMMENTS REQUESTED BEFOREApril 1997FINAL APPROVAL BY CPMPSeptember 1997DATE FOR COMING INTO OPERATION March 1998GENOTOXICITY: A STANDARD BATTERY FORGENOTOXICITY TESTING OF PHARMACEUTICALS[ICH Harmonised Tripartite Guideline]TABLE OF CONTENTS1.INTRODUCTION (2)2.GENERAL PURPOSE OF GENOTOXICITY TESTING (2)3.THE STANDARD TEST BATTERY FOR GENOTOXICITY (2)4.MODIFICATIONS OF THE 3-TEST BATTERY (4)4.1Limitations to the use of bacterial test organisms (4)4.2Compounds bearing structural alerts for genotoxic activity (4)4.3Limitations to the use of standard in vivo tests (4)4.4Additional genotoxicity testing in relation to the carcinogenicity bioassay (5)4.4.1 Evidence for tumour response (5)4.4.2 Structurally unique chemical classes (5)5.STANDARD PROCEDURES FOR IN VITRO TESTS (5)6.NOTES (6)7.GLOSSARY (8)1.INTRODUCTIONTwo fundamental areas in which harmonisation of genotoxicity testing for pharmaceuticals is considered necessary are the scope of this guideline: i) Identification of a standard set of tests to be conducted for registration. ii) The extent of confirmatory experimentation in in vitro genotoxicity tests in the standard battery. Further issues that were considered necessary for harmonisation can be found in the ICH guideline "Specific Aspects of Regulatory Genotoxicity Tests for Pharmaceuticals" (ICH topic S2A). The two ICH guidelines on genotoxicity complement each other and therefore should be used together as ICH guidance principles for testing of a pharmaceutical for potential genotoxicity.2.GENERAL PURPOSE OF GENOTOXICITY TESTINGGenotoxicity tests can be defined as in vitro and in vivo tests designed to detect compounds which induce genetic damage directly or indirectly by various mechanisms. These tests should enable a hazard identification with respect to damage to DNA and its fixation. Fixation of damage to DNA in the form of gene mutations, larger scale chromosomal damage, recombination and numerical chromosome changes is generally considered to be essential for heritable effects and in the multi-step process of malignancy, a complex process in which genetic changes may play only a part. Compounds which are positive in tests that detect such kinds of damage have the potential to be human carcinogens and/or mutagens, i.e. may induce cancer and/or heritable defects. Because the relationship between exposure to particular chemicals and carcinogenesis is established for man, whilst a similar relationship has been difficult to prove for heritable diseases, genotoxicity tests have been used mainly for the prediction of carcinogenicity. Nevertheless, because germ line mutations are clearly associated with human disease, the suspicion that a compound may induce heritable effects is considered to be just as serious as the suspicion that a compound may induce cancer. In addition, the outcome of such tests may be valuable for the interpretation of carcinogenicity studies.3.THE STANDARD TEST BATTERY FOR GENOTOXICITYRegistration of pharmaceuticals requires a comprehensive assessment of their genotoxic potential. It is clear that no single test is capable of detecting all relevant genotoxic agents. Therefore, the usual approach should be to carry out a battery of in vitro and in vivo tests for genotoxicity. Such tests are complementary rather than representing different levels of hierarchy.The general features of a standard test battery can be outlined as follows:i)It is appropriate to assess genotoxicity in a bacterial reverse mutation test. This test hasbeen shown to detect relevant genetic changes and the majority of genotoxic rodent carcinogens.ii)DNA damage considered to be relevant for mammalian cells and not adequately measured in bacteria should be evaluated in mammalian cells. Several mammalian cell systems are in use: systems that detect gross chromosomal damage (in vitro tests forstructural and numerical chromosomal aberrations), systems that detect primarily gene mutations (see Note 1), and a system that detects gene mutations and clastogenic effects (mouse lymphoma tk assay) (see Note 2). The information given in Notes 3 and4 demonstrate that with appropriate test protocols (see Section 5) the various in vitrotests for chromosomal damage and the mouse lymphoma tk assay yield results with a high level of congruence for compounds that are regarded as genotoxic but yield negative results in the bacterial reverse mutation assay. Therefore, these systems are currently considered interchangeable when used together with other genotoxicity tests in a standard battery for genotoxicity testing of pharmaceuticals, if these test protocols are used.iii)An in vivo test for genetic damage should usually be a part of the test battery to provide a test model in which additional relevant factors (absorption, distribution metabolism, excretion) that may influence the genotoxic activity of a compound are included. As a result, in vivo tests permit the detection of some additional genotoxic agents (see Note 5). An in vivo test for chromosomal damage in rodent hematopoietic cells fulfills this need. This in vivo test for chromosomal damage in rodents could be either an analysis of chromosomal aberrations in bone marrow cells or an analysis of micronuclei in bone marrow or peripheral blood erythrocytes.The following standard test battery is recommended based upon the considerations mentioned above:i) A test for gene mutation in bacteria.ii)An in vitro test with cytogenetic evaluation of chromosomal damage with mammalian cells or an in vitro mouse lymphoma tk assay.iii)An in vivo test for chromosomal damage using rodent hematopoietic cells.For compounds giving negative results, the completion of this 3-test battery, performed and evaluated in accordance with current recommendations, will usually provide a sufficient level of safety to demonstrate the absence of genotoxic activity (see Note 6). Compounds giving positive results in the standard test battery may, depending on their therapeutic use, need to be tested more extensively (see ICH Guideline “Specific Aspects of Regulatory Genotoxicity Tests for Pharmaceuticals”).The suggested standard set of tests does not imply that other genotoxicity tests are generally considered as inadequate or inappropriate (e.g. tests for measurement of DNA adducts, DNA strand breaks, DNA repair or recombination). Such tests serve as options in addition to the standard battery for further investigation of genotoxicity test results obtained in the standard battery. Furthermore, molecular techniques to study mechanisms of genotoxicity in the standard battery systems may be useful for risk assessment. Only under extreme conditions in which one or more tests comprising the standard battery cannot be employed for technical reasons, alternative validated tests can serve as substitutes. For this to occur, sufficient scientific justification should be provided to support the argument that a given standard battery test is not appropriate.The standard battery does not include an independent test designed specifically to test for aneuploidy. However, information on this type of damage may be derived from the tests for chromosomal damage in vitro and in vivo. Elements of the standard protocols that provide such information are elevations in the mitotic index, polyploidy induction and micronucleus evaluation. There is also limited experimental evidence that aneuploidy inducers can be detected in the mouse lymphoma tk assay (see Note 4). In such cases, further testing may be needed.4.MODIFICATIONS OF THE 3-TEST BATTERYThe following sections give situations where the standard 3-test battery may need modification.4.1Limitations to the use of bacterial test organismsThere are circumstances where the performance of the bacterial reverse mutation test does not provide appropriate or sufficient information for the assessment of genotoxicity. This may be the case for compounds that are excessively toxic to bacteria (e.g. some antibiotics) and compounds thought or known to interfere with the mammalian cell replication system (e.g. topoisomerase inhibitors, nucleoside analogues, or inhibitors of DNA metabolism). For these cases, usually two in vitro mammalian cell tests should be performed using two different cell types and of two different endpoints [gene mutation (see Note 1) and chromosomal damage]. Nevertheless, it is still important to perform the bacterial reverse mutation test (see Note 7); either a full test or a limited (range-finding) test (see Section 5) may be appropriate.4.2Compounds bearing structural alerts for genotoxic activityStructurally alerting compounds (see Note 8) are usually detectable in the standard 3-test battery. However, compounds bearing structural alerts that have given negative results in the standard 3-test battery may necessitate limited additional testing. The choice of additional test(s) or protocol modification(s) depend on the chemical nature, the known reactivity and metabolism data on the structurally alerting compound under question (see Note 9 and ICH “Guidance on Specific Aspects of Regulatory Genotoxicity Tests for Pharmaceuticals”).4.3Limitations to the use of standard in vivo testsThere are compounds for which standard in vivo tests do not provide additional useful information. This includes compounds for which data from studies on toxicokinetics or pharmacokinetics indicate that they are not systemically absorbed and therefore are not available for the target tissues in standard in vivo genotoxicity tests. Examples of such compounds are some radioimaging agents, aluminum based antacids, and some dermally applied pharmaceuticals. In cases where a modification of the route of administration does not provide sufficient target tissue exposure, it may be appropriate to base the evaluation only on in vitro testing.4.4Additional genotoxicity testing in relation to the carcinogenicity bioassay4.4.1Evidence for tumour responseAdditional genotoxicity testing in appropriate models may be conducted for compounds that were negative in the standard 3-test battery but which have shown effects in carcinogenicity bioassay(s) with no clear evidence for a non-genotoxic mechanism. To help understand the mechanism of action, additional testing can include modified conditions for metabolic activation in in vitro tests or can include in vivo tests measuring genetic damage in target organs of tumour induction (e.g. liver UDS test, 32P-postlabelling, mutation induction in transgenes, molecular characterisation of genetic changes in tumour-related genes).4.4.2Structurally unique chemical classesOn rare occasions, a completely novel compound in a unique structural chemical class will be introduced as a pharmaceutical. When such a compound will not be tested in chronic rodent carcinogenicity bioassays, further genotoxicity evaluation may be invoked.5.STANDARD PROCEDURES FOR IN VITRO TESTSReproducibility of experimental results is an essential component of research involving novel methods or unexpected findings; however, the routine testing of chemicals with standard, widely used genotoxicity tests need not always be completely replicated. These tests are sufficiently well characterised and have sufficient internal controls that repetition can usually be avoided if protocols with built-in confirmatory elements, such as those outlined below, are used.For both bacterial and mammalian cell gene mutation tests, the results of a range-finding test can be used to guide the selection of concentrations to be used in the definitive mutagenicity test. By these means, a range-finding test may supply sufficient data to provide reassurance that the reported result is the correct one. In bacterial mutagenicity tests, preliminary range-finding tests performed on all bacterial strains, with and without metabolic activation, with appropriate positive and negative controls, and with quantification of mutants, may be considered a sufficient replication of a subsequent complete test. Similarly, a range-finding test may also be a satisfactory substitute for a complete repeat of a test in gene mutation tests with mammalian cells other than the mouse lymphoma tk assay (see below) if the range-finding test is performed with and without metabolic activation, with appropriate positive and negative controls, and with quantification of mutants (see Note 10).For the cytogenetic evaluation of chromosomal damage in vitro, the test protocol includes the conduct of tests with and without metabolic activation, with appropriate positive and negative controls, where the exposure to the test articles is 3 to 6 hours and a sampling time of approximately 1.5 normal cell cycles from the beginning of the treatment. A continuous treatment without metabolic activation up to the sampling time of approximately 1.5 normal cell cycles is needed in case of a negative result for the short treatment period without metabolic activation. Certain chemicals may be more readily detected by longer treatment or delayed sampling times, e.g. some nucleoside analogues or some nitrosamines. Negative results in the presence of a metabolic activation system may need confirmation on a case by case basis (see Note 11). In any case information on the ploidy status should be obtained byrecording the incidence of polyploid cells as a percentage of the number of metaphase cells. An elevated mitotic index or an increased incidence of polyploid cells may give an indication of the potential of a compound to induce aneuploidy. In such cases, further testing may be needed.For the mouse lymphoma tk assay, the test protocol includes the conduct of tests with and without metabolic activation, with appropriate positive and negative controls, where the exposure to the test articles is 3 to 4 hours. A continuous treatment without metabolic activation for approximately 24 hours is needed in case of a negative result for the short treatment without metabolic activation (see Note 4). Negative results in the presence of a metabolic activation system may need confirmation on a case by case basis (see Note 11). In any case, an acceptable mouse lymphoma tk assay includes (i) the incorporation of positive controls which induces mainly small colonies, (ii) colony sizing for positive controls, solvent controls and at least one positive test compound dose (should any exist), including the culture that gave the greatest mutant frequency.Following such testing, further confirmatory testing in the case of clearly negative or positive test results is not usually needed.Ideally it should be possible to declare test results as clearly negative or clearly positive. However, test results sometimes do not fit the predetermined criteria for a positive or negative call and therefore are declared “equivocal”. The application of statistical methods aids in data interpretation, however, adequate biological interpretation is of critical importance. Nonetheless, further testing is usually indicated for equivocal results.6.NOTES1)Test approaches currently accepted for the assessment of mammalian cell genemutation involve the tk locus using mouse lymphoma L5178Y cells or human lymphoblastoid TK6 cells, the hprt locus using CHO cells, V79 cells, or L5178Y cells, or the gpt locus using AS52 cells.2)The molecular dissection of mutants induced at the tk locus shows a broad range ofgenetic events including point mutations, deletions, translocations, recombinations etc.Small colony mutants have been shown to predominantly lack the tk b allele as a consequence of structural or numerical alterations or recombinational events. There is some evidence that other loci, such as hprt or gpt are also sensitive to large deletion events. However, due to the X-chromosomal origin of the hprt gene which is probably flanked by essential genes, large scale deletionevents or numerical alterations often do not give rise to mutant colonies, thus limiting the sensitivity of this genetic locus relative to the tk locus for the detection of a wide range of genetic changes.3)With respect to the cytogenetic evaluation of chromosomal damage, it is notuncommon for the systems currently in use, i.e. several systems with permanent mammalian cells in culture and human lymphocytes either isolated or in whole blood, to give different results for the same test compound. However, there is evidence that some of the differences observed have been due to protocol differences. This may be minimised by using the procedures described in Section 5.For the great majority of presumptive genotoxic compounds that were negative in a bacterial reverse mutation assay, the data on chromosomal damage in vitro and mouse lymphoma tk results are in agreement. Several reliable studies indicate that the mouse lymphoma tk assay is able to detect compounds that induce structural and numerical chromosomal damage. For safety testing of pharmaceuticals, the mouse lymphoma tk assay is considered an acceptable alternative to the direct analysis of chromosomal damage in vitro. Although colony sizing is an essential element of the mouse lymphoma tk assay test protocol, it gives only limited information on the type of damage induced in mutant colonies. Further mechanistic investigations may be used to assess the nature of cytogenetic changes induced by clastogens and aneuploidy inducers in the mouse lymphoma tk assay. Such information could be provided by studies to demonstrate the loss of the tk gene or the loss of the chromosome carrying the tk gene.4)The detection of a number of different nucleoside analogues and base analogues isenhanced for the mouse lymphoma tk assay when the treatment protocol for both agar and microtitre methods include a 24 hour treatment regimen in the absence of an exogenous metabolic activation system. Similarly, the detection of aneuploidy inducers is enhanced if a 24 hour treatment regimen is used with the microtitre method. Currently, there is no evidence to support this conclusion for the soft agar method. The specificity of the test protocol, i.e. to obtain correct test results for presumptive non-genotoxic compounds, does not change significantly using a 24 hour treatment in the microtitre method. For the soft agar method there appears to be a reduction in specificity under the same treatment regimen. Based on this information, the microtitre method is recommended for use in the standard battery.5)There are a small but significant number of genotoxic carcinogens that are reliablydetected by the bone marrow tests for chromosomal damage that have yielded negative/weak/conflicting results in the pairs of in vitro tests outlined in the standard battery options e.g. bacterial reverse mutation plus one of a selection of possible tests with cytogenetic evaluation of chromosomal damage or bacterial mutation plus the mouse lymphoma tk assay. Carcinogens such as procarbazine, hydroquinone, urethane and benzene fall into this category.6)The continuing evolution of short-term tests and test methodologies will afford new,more sensitive, more practical, more expeditious, and more economical techniques for detection of genotoxic compounds. Some of these may ultimately replace the genotoxicity tests used for regulatory purposes. Among the more promising tests, the in vitro micronucleus test appears to offer potential for screening purposes.7)Some antibacterial agents, albeit highly toxic to the tester strains, are detected asgenotoxic at very low, sub-lethal concentrations in the bacterial reverse mutation test(e.g. nitrofuran antibiotics).8)Certain structurally alerting molecular entities are recognised as being causally relatedto the carcinogenic and/or mutagenic potential of chemicals. Examples of structural alerts include alkylating electrophilic centers, unstable epoxides, aromatic amines, azo-structures, N-nitroso-groups, aromatic nitro-groups.9)For some classes of compounds with specific structural alerts, it is established thatspecific protocol modifications/additional tests are necessary for optimum detection of genotoxicity (e.g. molecules containing an azo-group, glycosides, compounds such as nitroimidazoles requiring nitroreduction for activation, compounds such as phenacetin requiring another rodent S9 for metabolic activation). The additional testing needed when the chosen 3-test battery yields negative results for a structurally alerting test compound could consist of such modifications.10)The dose range-finding study should (i) give information on the shape of the toxicitydose-response curve if the test compound exhibits toxicity, (ii) include highly toxic concentrations, (iii) include quantification of mutants in the cytotoxic range. If a compound were not toxic, then mutants should nevertheless be quantified.11) A repetition of a test using the identical source and concentration of the metabolicactivation system is usually not necessary. A modification of the metabolic activation system may be indicated for certain chemical classes where knowledge is available on specific requirements of metabolism. This would usually invoke the use of an external metabolising system which is known to be competent for the metabolism/activation of the class of compound under test.7.GLOSSARYCytogenetic evaluation: chromosome structure analysis in mitosis or meiosis by light microscopyDNA adduct: (covalent) binding of chemicals to DNADNA repair: reconstitution of damaged DNA sequenceDNA strand breaks: single or double strand scissions in the DNANumerical chromosome changes: chromosome numbers different from the original haploid or diploid set of chromosomes; for cell lines, chromosome numbers different from the modal chromosome setRecombination: breakage and balanced or unbalanced rejoining of DNATransgene: an exogenous or foreign gene inserted into the host genome, either into somatic cells or germ lline cells。

塑料添加剂(4):抗氧化剂(Antioxidants)标准品/对照品产品编号中文名称英文名称英文别名CAS NO. 浓度溶剂包装I05003-027 抗氧化剂THP-24bis(2,4-Di-tert-butylphenyl)pentaerythritol diphosphate andmagnesium aluminumhydroxy carbonate hydrateAlkanox® P2726741-53-7/50 mgI05003-028 抗氧化剂THP-24bis(2,4-Di-tert-butylphenyl)pentaerythritol diphosphate andmagnesium aluminumhydroxy carbonate hydrateAlkanox® P27 11097-59-9 1000 μg/mL己烷1mlI05003-029 三(壬基酚)亚磷酸酯Tris(mono-nonylphenyl)phosphite with up to 1%triisopropanol amineAlkanox TNPP 26523-78-4 50 mgI05003-030 三(壬基酚)亚磷酸酯Tris(mono-nonylphenyl)phosphite with up to 1%triisopropanol amineAlkanox TNPP 26523-78-4 1000 μg/mL己烷1mlI05003-031 橡胶防老剂MMBI2H-benzimidazole-2-thione,1,3-di-hydro-4(or 5)-methylAntioxidant 60 53988-10-6 50 mgI05003-032 橡胶防老剂MMBI2H-benzimidazole-2-thione,1,3-di-hydro-4(or 5)-methylAntioxidant 60 53988-10-6 1000 μg/mL甲醇1mlI05003-033 N-苯基苯胺与2,4,4-三甲基戊烯的反应产物Benzenamine, N-phenyl,reaction products with2,4,4-trimethylpenteneAntioxidant S 68411-46-1 50 mgI05003-034 N-苯基苯胺与2,4,4-三甲基戊烯的反应产物Benzenamine, N-phenyl,reaction products with2,4,4-trimethylpenteneAntioxidant S 68411-46-1 1000 μg/mL己烷1mlI05003-035 3-[[3-(十八烷氧基)-3-氧代丙基]硫代]-丙酸十八烷酯Lauryl stearylthiopropionate Cyanox® 1212 13103-52-1 50 mgI05003-036 3-[[3-(十八烷氧基)-3-氧代丙基]硫代]-丙酸十八烷酯Lauryl stearylthiopropionate Cyanox® 1212 13103-52-1 1000 μg/mL己烷1mlI05003-037 抗氧剂TH-1790 1,3,5-Tris(4-tert-butyl-3-hydroxy-2,6-dimethylbenzyl)-1,3,5-triazine-2,4,6-(1h,3h,5h)-trioneCyanox 1790 40601-76-1 50 mgI05003-038 抗氧剂TH-1790 1,3,5-Tris(4-tert-butyl-3-hydroxy-2,6-dimethylbenzyl)-1,3,5-triazine-2,4,6-(1h,Cyanox 1790 40601-76-1 1000 μg/mL己烷1ml3h,5h)-trioneI05003-039 抗氧剂2246 2,2'-Methylene-bis-(4-methyl-6-tert-butyl-phenol)Cyanox 2246 119-47-1 50 mgI05003-040 抗氧剂2246 2,2'-Methylene-bis-(4-methyl-6-tert-butyl-phenol)Cyanox 2246 119-47-1 1000 μg/mL己烷1mlI05003-041 2,2'-亚甲基双（4-乙基-6-叔丁基酚）2,2'-Methylene-bis-(4-ethyl-6-tert-butyl-phenol)Cyanox 425 88-24-4 50 mgI05003-042 2,2'-亚甲基双（4-乙基-6-叔丁基酚）2,2'-Methylene-bis-(4-ethyl-6-tert-butyl-phenol)Cyanox 425 88-24-4 1000 μg/mL己烷1mlI05003-043 硫代二丙酸二月桂酯Dilaurylthiopropionate Cyanox LTDP 123-28-4 50 mgI05003-044 硫代二丙酸二月桂酯Dilaurylthiopropionate Cyanox LTDP 123-28-4 1000 μg/mL己烷1mlI05003-045 硫代二丙酸二十八酯Distearylthiopropionate Cyanox STDP 693-36-7 50 mgI05003-046 硫代二丙酸二十八酯Distearylthiopropionate Cyanox STDP 693-36-7 1000 μg/mL己烷1mlI05003-047 抗氧剂1010 Pentaerythritol tetrakis(3-(3,5-di-t-butyl-4-hydroxyphenyl)propionateEthanox® 310 6683-19-8 50 mgI05003-048 抗氧剂1010 Pentaerythritol tetrakis(3-(3,5-di-t-butyl-4-hydroxyphenyl)propionateEthanox® 310 6683-19-8 1000 μg/mL己烷1mlI05003-049 暂缺Nonylphenol disulfideoligomerEthanox 323 50 mgI05003-050 暂缺Nonylphenol disulfideoligomerEthanox 323 1000 μg/mL己烷1mlI05003-051 抗氧剂330 1,3,5-Trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl)benzeneEthanox 330 1709-70-2 50 mgI05003-052 抗氧剂330 1,3,5-Trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl)benzeneEthanox 330 1709-70-2 1000 μg/mL己烷1mlI05003-053 抗氧剂1076 3,5-Di-tert-butyl-4-hydroxyhydrocinnamic acid,octadecylesterEthanox 376 2082-79-3 50 mgI05003-054 抗氧剂1076 3,5-Di-tert-butyl-4-hydroxyhydrocinnamic acid,octadecylesterEthanox 376 2082-79-3 1000 μg/mL己烷1mlI05003-055 抗氧剂702 4,4'-Methylenebis(2,6-di-tert-butylphenol)Ethanox 702 118-82-1 50 mgI05003-056 抗氧剂702 4,4'-Methylenebis(2,6-di-tert-butylphenol)Ethanox 702 118-82-1 1000 μg/mL己烷1mlI05003-057 三(2,4-二叔丁基苯基)亚磷酸酯Tris(2,4-di-tert-butylphenyl)phosphiteEthaphos®36831570-04-4 50 mgI05003-058 三(2,4-二叔丁基苯基)亚磷酸酯Tris(2,4-di-tert-butylphenyl)phosphiteEthaphos®36831570-04-4 1000 μg/mL己烷1mlI05003-059 二[3,5-二-(1,1-二甲基乙基)-4-羟基-]苯丙酸硫杂二甘醇酯Thiodiethylenebis(3,5-di-tert-butyl-4-hydroxyhydrocinnamate)Irganox® 1035 41484-35-9 50 mgI05003-060 二[3,5-二-(1,1-二甲基乙基)-4-羟基-]苯丙酸硫杂二甘醇酯Thiodiethylenebis(3,5-di-tert-butyl-4-hydroxyhydrocinnamate)Irganox® 1035 41484-35-9 1000 μg/mL己烷1mlI05003-061 抗氧剂LK-1081 6,6'-Di-tert-butyl-2,2’-thiodi-p-cresolIrganox 1081 90-66-4 50 mgI05003-062 抗氧剂LK-1081 6,6'-Di-tert-butyl-2,2’-thiodi-p-cresolIrganox 1081 90-66-4 1000 μg/mL己烷1mlI05003-063 N,N'-双-(3-(3,5-二叔丁基-4-羟基苯基)丙酰基)己二胺N,N'-1,6-Hexanediylbis[3,5-bis(1,1-dimethylethyl)-4-hydroxy-benzenepropanamide]Irganox 1098 * 23128-74-7 50 mgI05003-064 N,N'-双-(3-(3,5-二叔丁基-4-羟基苯基)丙酰基)己二胺N,N'-1,6-Hexanediylbis[3,5-bis(1,1-dimethylethyl)-4-hydroxy-benzenepropanamide]Irganox 1098 * 23128-74-7 1000 μg/mLHexane:Acetone1mlI05003-065 高密聚乙烯Ethyl3,5-di-tert-butyl-4-hydroxybenzylphosphonate calcium saltand polyethylene-wax mixtureIrganox 1425WL65140-91-2/9002-88-450 mgI05003-066 抗氧剂XH-245 Triethyleneglycolbis[3-(3'-tert-butyl-4'hydroxy-5'-methylphenol)propionateIrganox 245 36443-68-2 50 mgI05003-067 抗氧剂XH-245 Triethyleneglycolbis[3-(3'-tert-butyl-4'hydroxy-5'-methylphenol)propionateIrganox 245 36443-68-2 1000 μg/mL己烷1mlI05003-068 抗氧剂Irganox-259Hexamethylenebis(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate)Irganox 259 35074-77-2 50 mgI05003-069 抗氧剂Irganox-259Hexamethylenebis(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate)Irganox 259 35074-77-2 1000 μg/mL己烷1mlI05003-070 抗氧剂3114 1,3,5-Tris(3,5-di-tert-butyl-4-hydroxybenzyl)-1,3,5-triazine-2Irganox 3114FF27676-62-6 50 mg,4,6-(1H,3H,5H)-trioneI05003-071 抗氧剂3114 1,3,5-Tris(3,5-di-tert-butyl-4-hydroxybenzyl)-1,3,5-triazine-2,4,6-(1H,3H,5H)-trioneIrganox 3114FF27676-62-6 1000 μg/mL己烷1mlI05003-072 暂缺3,5-Di-tert-butyl-4-hydroxyhydrocinnamic ester with1,3,5-tris[2-hydroxyethyl]-s-triazine-2,4,6[1H,3H,5H]-trioneIrganox 3125 * 34137-09-2 50 mgI05003-073 暂缺3,5-Di-tert-butyl-4-hydroxyhydrocinnamic ester with1,3,5-tris[2-hydroxyethyl]-s-triazine-2,4,6[1H,3H,5H]-trioneIrganox 3125 * 34137-09-2 1000 μg/mLHexane:Acetone1mlI05003-074 暂缺2,4-bis(n-Octylthio)-6-(4-hydroxy-3,5-di-tert-butylanilino)-1,3,5-triazineIrganox 565 991-84-4 50 mgI05003-075 暂缺2,4-bis(n-Octylthio)-6-(4-hydroxy-3,5-di-tert-butylanilino)-1,3,5-triazineIrganox 565 991-84-4 1000 μg/mL己烷1mlI05003-076 维生素E alpha-Tocopherol Irganox E 201 10191-41-0 50 mg I05003-077 维生素E alpha-Tocopherol Irganox E 201 10191-41-0 1000 μg/mL己烷1mlI05003-078 N,N'-双[3-(3,5-二叔丁基-4-羟基苯基)丙酰]肼1,2-bis(3,5-Di-tert-butyl-4-hydroxyhydrocinnamoyl)hydrazideIrganox MD1024 *32687-78-8 50 mgI05003-079 N,N'-双[3-(3,5-二叔丁基-4-羟基苯基)丙酰]肼1,2-bis(3,5-Di-tert-butyl-4-hydroxyhydrocinnamoyl)hydrazideIrganox MD1024 *32687-78-8 1000 μg/mLHexane:Acetone1mlI05003-080 6-溴吲哚-3-甲醛2,6-Di-tert-butyl-4-sec-butylphenolIsonox® 132 17540-75-9 50 mgI05003-081 6-溴吲哚-3-甲醛2,6-Di-tert-butyl-4-sec-butylphenolIsonox® 132 17540-75-9 1000 μg/mL己烷1mlI05003-082 2,6-二-叔丁基-4-壬苯酚2,6-Di-tert-butyl-4-nonylphenolIsonox 232 4306-88-1 50 mgI05003-083 2,6-二-叔丁基-4-壬苯酚2,6-Di-tert-butyl-4-nonylphenolIsonox 232 4306-88-1 1000 μg/mL己烷1mlI05003-084 2,5-二叔戊基氢醌2,5-bis(1,1-Dimethylpropyl)-1,4-benzenediolLowinox AH25 79-74-3 50 mgI05003-085 2,5-二叔戊基氢醌2,5-bis(1,1-Dimethylpropyl)-1,4-benzenediolLowinox AH25 79-74-3 1000 μg/mL己烷1mlI05003-086 抗氧化剂TH-CPLPolymeric sterically hinderedphenolLowinox CPL 68610-51-5 50 mgI05003-087 抗氧化剂TH-CPLPolymeric sterically hinderedphenolLowinox CPL 68610-51-5 1000 μg/mL己烷1mlI05003-088 5-叔丁基-4-羟基-2-甲基苯硫醚4,4'-Thiobis(2-tert-butyl-5-methylphenol)LowinoxTBM-696-69-5 50 mgI05003-089 5-叔丁基-4-羟基-2-甲基苯硫醚4,4'-Thiobis(2-tert-butyl-5-methylphenol)LowinoxTBM-696-69-5 1000 μg/mL己烷1mlI05003-090 暂缺Polyglycol ester Markstat® 60 50 mg I05003-091 暂缺Polyglycol ester Markstat® 60 1000 μg/mL己烷1mlI05003-092 抗氧化剂PTLTP beta-Laurylthiopropionate Naugard®412S29598-76-3 50 mgI05003-093 抗氧化剂PTLTP beta-Laurylthiopropionate Naugard®412S29598-76-3 1000 μg/mL己烷1mlI05003-094 二[4-(1-甲基-1-苯乙基)苯]胺4,4'-bis(alpha,alpha-Dimethylbenzyl)diphenylamineNaugard 445 10081-67-1 50 mgI05003-095 二[4-(1-甲基-1-苯乙基)苯]胺4,4'-bis(alpha,alpha-Dimethylbenzyl)diphenylamineNaugard 445 10081-67-1 1000 μg/mL己烷1mlI05003-096 暂缺Proprietary blend of primaryand secondary antioxidantsNaugard 956 50 mgI05003-097 暂缺Proprietary blend of primaryand secondary antioxidantsNaugard 956 1000 μg/mL甲苯1mlI05003-098 二苯胺和2-丙酮的反应产物Acetone diphenylaminecondensation productsNaugard A * 68412-48-6 50 mgI05003-099 二苯胺和2-丙酮的反应产物Acetone diphenylaminecondensation productsNaugard A * 68412-48-6 1000 μg/mLHexane:Acetone1mlI05003-100 三(2,4-二叔丁基苯基)亚磷酸酯1:1 blend of Naugard® 10 andNaugard® 524Naugard B-25 6683-19-8 / 50 mgI05003-101 三(2,4-二叔丁基苯基)亚磷酸酯1:1 blend of Naugard® 10 andNaugard® 524Naugard B-25 31570-04-4 1000 μg/mL己烷1mlI05003-102 2，6-二叔丁基-4-甲基苯酚2,6-Di-tert-butyl-4-methylphenolNaugard BHT 128-37-0 50 mgI05003-103 2，6-二叔丁基-4-甲基苯酚2,6-Di-tert-butyl-4-methylphenolNaugard BHT 128-37-0 1000 μg/mL己烷1mlI05003-104 暂缺Blend of phenolic primary anddiphenylamine secondaryantioxidants (Naugards 76and 445)NaugardHM-2250 mgI05003-105 暂缺Blend of phenolic primary anddiphenylamine secondaryantioxidants (Naugards 76and 445)NaugardHM-221000 μg/mL己烷1mlI05003-106 N,N'-二苯基-1,4-N,N'-Diphenyl-p-phenylenedia Naugard J * 74-31-7 50 mg苯二胺mineI05003-107 N,N'-二苯基-1,4-苯二胺N,N'-Diphenyl-p-phenylenediamineNaugard J * 74-31-7 1000 μg/mLHexane:Acetone1mlI05003-108 防老剂NBC Nickel dibutyl dithiocarbamate Naugard NBC 13927-77-0 50 mg I05003-109 防老剂NBC Nickel dibutyl dithiocarbamate Naugard NBC 13927-77-0 1000 μg/mL己烷1mlI05003-110 N-苯基-1-萘胺N-Phenyl-1-naphthylamine NaugardPANA90-30-2 50 mgI05003-111 N-苯基-1-萘胺N-Phenyl-1-naphthylamine NaugardPANA90-30-2 1000 μg/mL己烷1mlI05003-112 三(壬基酚)亚磷酸酯Tris(mono-nonylphenyl)phosphite with up to 1%triisopropanol amineNaugard PHR 26523-78-4 50 mgI05003-113 三(壬基酚)亚磷酸酯Tris(mono-nonylphenyl)phosphite with up to 1%triisopropanol amineNaugard PHR 26523-78-4 1000 μg/mL己烷1mlI05003-114 N-苯基苯胺与2,4,4-三甲基戊烯的反应产物Benzenamine, N-phenyl,reaction products with2,4,4-trimethylpenteneNaugardPS-3068411-46-1 50 mgI05003-115 N-苯基苯胺与2,4,4-三甲基戊烯的反应产物Benzenamine, N-phenyl,reaction products with2,4,4-trimethylpenteneNaugardPS-3068411-46-1 1000 μg/mL己烷1mlI05003-116 暂缺Tris-nonyl phenyl phosphite NaugardPS-3550 mgI05003-117 暂缺Tris-nonyl phenyl phosphite NaugardPS-351000 μg/mL己烷1mlI05003-118 防老剂RD 1,2-Dihydro-2,2,4-trimethylquinoline (polymerized)Naugard QExtra26780-96-1 50 mgI05003-119 防老剂RD 1,2-Dihydro-2,2,4-trimethylquinoline (polymerized)Naugard QExtra26780-96-1 1000 μg/mL己烷1mlI05003-120 三(壬基酚)亚磷酸酯Tris(mono-nonylphenyl)phosphite,2,2'-methylene bis(4-methyl-6-nonyl phenol)NaugardRM-5126523-78-4 50 mgI05003-121 三(壬基酚)亚磷酸酯Tris(mono-nonylphenyl)phosphite,2,2'-methylene bis(4-methyl-6-nonyl phenol)NaugardRM-5126523-78-4 1000 μg/mL己烷1mlI05003-122 1,2-二氢化-2,2,4-三甲基喹啉1,2-Dihydro-2,2,4-trimethylquinoline (polymerized)Naugard SuperQ147-47-7 50 mgI05003-123 1,2-二氢化-2,2,4-三甲基喹啉1,2-Dihydro-2,2,4-trimethylquinoline (polymerized)Naugard SuperQ147-47-7 1000 μg/mL己烷1mlI05003-124 (3,5-二叔丁基-4-羟基苯基)丙酸草2,2'-Oxamidobis[ethyl-3-(3,5-di-tert-butyl-4-hydroxyphenyl)Naugard XL-1*70331-94-1 50 mg酰(二亚氨基-2,1亚乙基酯)propionate]I05003-125 (3,5-二叔丁基-4-羟基苯基)丙酸草酰(二亚氨基-2,1亚乙基酯)2,2'-Oxamidobis[ethyl-3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate]Naugard XL-1*70331-94-1 1000 μg/mL己烷1mlI05003-126 1,2-苯二甲酸-2,2-二甲基-1-(1-甲基乙基)-3-(异丁酰氧基)丙基苯甲酯Benzyl3-isobutyrloxy-1-isopropyl-2,2-dimethylpropyl phthalateSanticizer®27816883-83-3 50 mgI05003-127 1,2-苯二甲酸-2,2-二甲基-1-(1-甲基乙基)-3-(异丁酰氧基)丙基苯甲酯Benzyl3-isobutyrloxy-1-isopropyl-2,2-dimethylpropyl phthalateSanticizer®27816883-83-3 1000 μg/mL己烷1mlI05003-128 抗氧化剂THP-24bis(2,4-Di-tert-butylphenyl)pentaerythritol diphosphiteUltranox® 626 26741-53-7 50 mgI05003-129 抗氧化剂THP-24bis(2,4-Di-tert-butylphenyl)pentaerythritol diphosphiteUltranox® 626 26741-53-7 1000 μg/mL己烷1ml。

安全技术说明书Insulcure 24 PT B产品标识产品名称Insulcure 24 PT B物质或混合物的推荐用途及限制用途推荐用途Casting compound供应商的详细情况供应商ITW Performance PolymersBay 150Shannon Industrial EstateCo. ClareIrelandV14 DF82353(61)771500353(61)471285应急电话应急电话+44(0)1235 239 670 (24h)物质或混合物的分类物理危险非此类健康危害急性毒性类别4 - H302 急性毒性类别4 - H312 皮肤刺激类别2 - H315 眼损伤类别1 - H318 皮肤致敏物类别1A - H317环境危害危害水生环境-长期危险类别2 - H411标签要素象形图警示词危险危险性说明H302+H312 吞咽或皮肤接触有害。

H315 造成皮肤刺激。

H317 可能造成皮肤过敏反应。

H318 造成严重眼损伤。

H411 对水生生物有毒并具有长期持续影响。

防范说明P261 避免吸入蒸气/ 喷雾。

P264 作业后彻底清洗沾染的皮肤。

P280 戴防护手套/ 穿防护服/ 戴防护眼罩/ 戴防护面具。

P302+P352 如皮肤沾染：用大量水清洗。

P305+P351+P338 如进入眼睛： 用水小心冲洗几分钟。

如戴隐形眼镜并可方便地取出，取出隐形眼镜。

继续冲洗。

P333+P313 如发生皮肤刺激或皮疹：求医/ 就诊。

含有POLYAMINOAMIDE, TRIETHYLENETETRAMINE所有危险性说明的全文会显示在第16部分。

急救措施说明吸入转移受影响的人员远离污染源。

将受影响的人员转移至新鲜空气处，并注意保暖和呼吸舒适的体位休息。

如果不适感持续，就医。

食入立即就医。

不要催吐。

漱口。

皮肤接触立即脱去污染的衣着，并用肥皂和水清洗皮肤。

连续用水冲洗至少15分钟。

浦北陈皮指纹图谱的建立及其黄酮类成分含量测定杨丽雯，陈旭煜*，何秋云，赖瑞英，张　卉（钦州市检验检测中心，广西钦州 535000）摘　要：目的：建立浦北陈皮甲醇提取物的HPLC指纹图谱，测定其橙皮苷、川陈皮素、橘皮素3种黄酮类成分，为浦北陈皮的质量控制及其品质鉴定提供科学的数据支撑。

方法：以浦北陈皮为研究对象，采用HPLC法，色谱柱为Thermo C18（250 mm×4.6 mm，5 μm），流动相为乙腈-水，梯度洗脱，流速为1.0 mL·min-1，柱温为35 ℃，检测波长为283 nm、330 nm，建立HPLC指纹图谱，以中药色谱指纹图谱相似度评价系统软件（2012.130723版）进行评价。

同时测定浦北陈皮中橙皮苷、川陈皮素、橘皮素3种黄酮类成分含量。

结果：建立的浦北陈皮指纹图谱相似度在0.910～0.995；测定的橙皮苷（以干燥品计）、川陈皮素（以干燥品计）、橘皮素（以干燥品计）含量分别为2.598%～5.266%、0.238 8%～0.586 8%、0.177 6%～0.435 8%。

结论：通过HPLC建立的浦北陈皮甲醇提取物指纹图谱的相似度较高，可为浦北陈皮质量控制提供依据。

同时，本次采集的浦北陈皮样品橙皮苷、川陈皮素、橘皮素3种黄酮类成分含量较高，其含量值都符合2020年版《中国药典》要求，可侧面表明浦北陈皮具有较高的利用价值。

关键词：浦北陈皮；指纹图谱；橙皮苷；川陈皮素；橘皮素；含量测定Establishment of Fingerprint of Pubei Chenpi andDetermination of Its Flavonoids ContentYANG Liwen, CHEN Xuyu*, HE Qiuyun, LAI Ruiying, ZHANG Hui(Qinzhou Inspection and Testing Center, Qinzhou 535000, China)Abstract: Objective: HPLC fingerprint of methanol extract of Pubei Chenpi was established and hesperidin, nobiletin and tangeretin were determined. It can provide scientific basis for quality control and identification of Pubei Chenpi. Method: Pubei Chenpi was studied by HPLC with Thermo C18 (250 mm× 4.6 mm, 5 μm), the mobile phase of acetonitrile-water and gradient elution at a flow rate of 1.0 mL·min-1, the column temperature of 35 ℃, and the detection wavelengths of 283 nm and 330 nm. HPLC fingerprint was established and evaluated by traditional Chinese medicine chromatographic fingerprint similarity evaluation system software (version 2012.130723). At the same time, the contents of hesperidin, nobiletin and tangerine in Pubei Chenpi were determined. Result: The similarity of the fingerprint of Pubei Chenpi was between 0.910 and 0.995, and the content of hesperidin (as dried product), nobiletin (as dried product) and tangerine (as dried product) were 2.598%～5.266%, 0.238 8%～0.586 8%, 0.177 6%～0.435 8%, respectively. Conclusion: The fingerprints of methanol extract of Pubei Chenpi established by HPLC showed high similarity, which can provide a basis for the quality control of Pubei Chenpi. At the same time, the contents of hesperidin, nobiletin and tangerine in Pubei Chenpi samples were higher, and their contents were in accordance with the requirements of Chinese Pharmacopoeia 2020 edition, which indicated that Pubei Chenpi had high utilization value.基金项目：广西食品安全科技项目（GSJKJZC2022-21）。

DULUX TRADE HI-CHEM EPOXY ENAMELTECHNICAL DATA SHEETVersion 3 – 2019 AUGUSTTHIS ISSUE SUPERSEDES ALL PREVIOUS PUBLICATIONSPRODUCT DESCRIPTIONSemi-gloss epoxy enamel for interior industrial and home use (e.g. garage floors, etc.)PRODUCT USES·Can be applied on walls, floors and suitably primed metal surfaces.FEATURES AND BENEFITS·Good resistance to a wide range of chemicals and most solvents.·Cures to a hard film with good adhesion and abrasion resistance.·Provides an economical alternative to tiling in bathrooms, showers, kitchens, toilets and low cost housing.·Suitable for surfaces that require frequent cleaning with solvents, detergents or alkaline cleaners.·The cured film is non-toxic. When properly applied and cured, the product is completely safe for direct or accidental food contact on floor and wall applications.PRODUCT INFORMATIONAppearance Semi- glossColour White, Light Grey, Dark Grey and Brilliant GreenBinder Type Polyamide cured EpoxyDensity at 23°C Approx. 1.30Solids Content By weight: Approx. 60%By volume: Approx. 44%Packaged Viscosity Viscosity at 23°C: Approx. 70 KUSpreading Rate at 35µm DFT Brush: Approx. 9 m² per litre, depending on surface porosity,profile and application methodRecommended DFT per coat Min. 50µm. Max. 60µm.Recommended WFT per coat Min. 110µm. Max. 140µm(Higher film build will increase resistance)Flash Point25ºCDULUX TRADE HI-CHEM EPOXY ENAMELAPPLICATION INFORMATIONMixing Stir the Base and Curing Agent separately untilhomogeneous with a flat paddle. Then add the Curing Agentto the Base and stirring until homogeneous with a flat paddle Mixing Ratio 4 parts Base to 1 part Curing Agent by volume.Application Surface conditions Surface Temperature between 10 - 35°C. Relative Humiditybetween 10 - 85 % OR 2ºC above dew point minimum. Application methods Dulux Trade Hichem Epoxy Enamel is packaged in twocomponents in the proper proportions which must be mixedtogether until homogenous before use. See MixingAirless Spray: Ready for use after induction period of 30minutes.Air Spray: After mixing, thin 10% by volume and allowinduction period of 30 minutes.Brush: Can be used on small areas where joining is not aproblem e.g. signs, pipes, colour bands, etc.Roller: Short nap roller may be used on tanks and silostaking precautions to pick up the wet edge to avoid “window-paning”.Self-Priming on porous masonry: The product can only beover coated with itself. If a primer is required,Dulux TradeHichem Epoxy Enamel thinned 10% by volume can beutilised as a primer coat.N.B. Mix the paint first, then stir in the thinners.Thinner Dulux Trade Heavy Duty Thinners for spraying tomaximum of 10% of product volume and should only beadded after mixing the Curing Agent with the Base andstirred homogeneous with a flat paddle.Induction Period30 minutes at 25°C (i.e. do not paint immediately aftermixing).Pot Life to gelation Approx. 8 hours at 25°CDrying Time Dry to handle: 24 hours at 25ºC.Recoating Time 6 hours minimum; up to 7 days maximum at 25°C. (Dryingtimes will be extended during cold, wet or humid conditions.)APPLICATION INFORMATIONCleaning of equipment After use, remove as much product as possible, and thenclean immediately with Dulux Trade Heavy Duty Thinners. Substrates Correctly prepared cement plaster, concrete and correctlyprepared and primed mild steel and ironDULUX TRADE HI-CHEM EPOXY ENAMELAPPLICATION INFORMATIONPrecautions:Do not apply during cold (below 10°C) or wet weather.Do not apply directly to bare metal surfaces.Recommended for interior surfaces only, as the film willchalk on exterior exposure.Cure is slow at low temperatures; below 15°C it takes somedays to reach handling and recoating hardness.The pot life is short above 35°C; shield pressure pots andfluid lines from direct sun.Equipment and brushes must be cleaned immediately.Heat resistant to + 120°C (continuous) although someyellowing occurs above 100°C.Not suitable for direct application to powdery or friablesurfaces whether previously painted or not.Coats Required Apply two to three finishing coats to new surfaces to achievea minimum continuous film of 70µm microns to produceclosed film and solid colour.For non-skid pedestrian areas, three full coats will berequired. See “SURFACE PREPARATION”.SURFACE PREPARATIONEnsure that surfaces are sound and free from dust, oil, grease, dirt, and debris. Surfaces must be thoroughly dry - no more than 12% moisture content.NEW SURFACESCement Plaster, Concrete (non-friable)·Freshly rendered concrete should have dried/cured for a minimum of 6 weeks, the moisture content of the concrete should be below 12% before any preparation andpainting is attempted.·It is recommended that fresh plaster should be allowed 1 week drying for every 5mm thickness; and longer in cold or damp weather.·Ensure the entire surface is sound and clean. Remove any plaster spills, and all loose debris from the surface, ensuring an even and clean surface.·Acid etch the surface with a solution of hydrochloric acid to remove laitance, uncured cement, etc. as follows: On steel or power floated concrete (very smooth), use onevolume hydrochloric acid to two volumes water. More than one application may benecessary to achieve a paintable surface. On wood floated concrete (rough), use one volume hydrochloric acid to four volumes water.N.B. Hydrochloric acid is corrosive -please wear protective clothing, gloves, masks and eye goggles against splashes.·Allow the acid solution to react for 15 minutes and then wash away all acid with copious amounts of clean water.·Remove excess water and allow thorough drying–no more than 12% moisture content.DULUX TRADE HI-CHEM EPOXY ENAMELSURFACE PREPARATIONNEW SURFACESFloors Concrete – NON-SKID Pedestrian areas (walkways and passages)·Follow the cleaning and etching instructions under surface preparation, new surfaces, Cement Plaster, Concrete (non-friable)·Coat 1 – Apply and, while it is still wet, sprinkle dry, silica sand over the surface. (The silica sand should be sifted through a 250µm sieve and retained on a 210µm sieve. A practical spreading rate is 500 grams of sand per square meter of painted floor.)·Coat 2 - The following day, sweep off any excess sand and apply a further coat to seal the surface. Allow overnight drying again·Coat 3 – Apply 3rd coat·Observe chemical curing times as stated in this technical data sheet.Mild Steel and Iron·Remove all shop-primer and corrosion products from the steel. Sand blast steel to achieve a bright metal condition, and a cleanliness standard of Sa2½ minimum.·Clean bare steel with a solvent wash (rags dipped in lacquer thinner). Change rags frequently.·Apply one or two coats Dulux Trade Corrocote 1 Metal Etch Primer, depending on the severity of the conditions. Two coats are preferred for coastal conditions. PREVIOUSLY PAINTED SURFACES·The existing coating system should be dry and free of contaminants such as oil, grease and loose paint.·Test that the surface will accept epoxy by allowing a cloth soaked with Dulux Trade Heavy Duty Thinners to rest on it for 15 minutes - it must not lift or wrinkle. If lifting or wrinkling occurs, the paint must be removed with paint stripper or any other suitable means.·Abrade damaged or failed areas back to a sound substrate and treat as new.·Aged or weathered epoxies or urethanes must be well sanded to a matt finish to providea profile for adhesion.DULUX TRADE HI-CHEM EPOXY ENAMELHEALTH AND SAFETY INFORMATIONSolvent based paints are flammable.This product contains no added lead. Avoid contact with skin or eyes. Keep out of reach of children. If accidently swallowed, seek medical advice immediately and show this container to the doctor. Dry sanding, flame cutting and/or welding of the dry paint film will give rise to dust and/or hazardous fumes. 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Please refer to colour cards for an accuraterepresentation of the colour.Among others, the following factors may affect final colourappearance: product sheen and texture, colour and lightreflections, application, surface texture and preparation.For best colour and sheen consistency, it is advisable to usecontainers of the same batch number, to mix differentbatches together in a large container, or to finish in a cornerbefore starting a new container.TDS STANDARD DISCLAIMERThe recommendations contained herein are given in good faith and meant to guide the specifier or user in accordance with good painting practices. They are gained from our tests and experiences and are believed to be accurate and reliable. No warranty/guarantee is implied by the recommendations contained herein since the conditions of use; application method, substrate and cleanliness of the substrate are beyond Dulux control.Important Note; Technology may change with time, necessitating changes to this Technical Data Sheet (TDS).It is the responsibility of the user to ensure that the latest TDS is being used for reference. Dulux Technical Data Sheets are available on our website www.duluxtrade.co.za or please contact: Dulux On-Line on 0860 330 111. Email*************************ICI Dulux (Pty) Ltd is part of AkzoNobel. ICI Dulux (Pty) Ltd Reg No.1946/020769/07。

DOI:10.16605/ki.1007-7847.2021.06.0169抗菌肽LL-37抑制肝癌细胞恶性增殖的转录组分析吕继龙a,b,c ,李球棣a ,佘东阳a,b,c ,陈宁a,c,d ,丁晓慧a,c*(徐州医科大学a.病原生物学与免疫学教研室/江苏省免疫与代谢重点实验室;b.第二临床医学院;c.基础医学国家级实验教学示范中心;d.第一临床医学院,中国江苏徐州221004)摘要:抗菌肽LL-37与肿瘤的发生发展密切相关,课题组前期研究发现LL-37能够抑制肝癌细胞恶性增殖。

为了给其抑制肝癌发生发展的分子机制研究提供更多的生物学依据,本研究通过高通量RNA 测序技术以及生物信息学方法对LL-37作用前后肝癌细胞中的差异表达基因(differentially expressed gene,DEG)进行了分析,共筛选出753个DEG,其中上调的DEG 374个,下调的DEG 379个;进一步对筛选出的DEG 进行基因本体论(Gene Ontology,GO)及京都基因和基因组数据库(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析,并构建DEG 编码蛋白互作网络,筛选出10个可能参与LL-37抑制肝癌细胞恶性增殖的潜在关键基因。

经分析这些基因均表达下调,且对机体炎症的激活、转运以及肿瘤细胞的增殖、迁移至关重要。

以上结果为揭示LL-37在肝癌发生发展中的作用及机制提供了数据基础,为探索肝癌诊断和治疗手段提供了新的思路。

关键词:LL-37;肝细胞癌(HCC);转录组测序;差异表达基因(DEG);生物信息学分析中图分类号:Q51,Q811.4,R735.7文献标识码:A文章编号:1007-7847(2022)06-0528-10Transcriptomic Analysis of Malignant Proliferation of Hepatocellular Carcinoma Cells Inhibited by AntimicrobialPeptide LL-37L ÜJi-long a,b,c ,LI Qiu-di a ,SHE Dong-yang a,b,c ,CHEN Ning a,c,d ,DING Xiao-hui a,c*(a.Jiangsu Key Laboratory of Immunity and Metabolism/Department of Pathogenic Biology and Immunology ;b.The SecondClinical Medical College ;c.National Demonstration Center for Experimental Basic Medical Science Education ;d.The FirstClinical Medical College ,Xuzhou Medical University ,Xuzhou 221004,Jiangsu ,China )Abstract:Antimicrobial peptide LL-37is closely related to the occurrence and development of tumors.Our previous study found that LL-37can inhibit the malignant proliferation of hepatocellular carcinoma (HCC)cells.To provide more biological basis for the molecular mechanisms of LL-37inhibiting the occurrence and development of HCC,high-throughput RNA sequencing and bioinformatics methods were used to analyze the differentially expressed genes (DEGs)in HCC cells before and after LL-37treatment.A total of 753DEGs were screened out,among which 374genes were up-regulated and 379genes were down-regulated.The se-lected DEGs were further enriched by Gene Ontology (GO)and Kyoto Encyclopedia of Genes and Genomes (KEGG)pathway analyses,and the protein-protein interaction network encoded by DEGs was also construc-ted.Ten potential key genes that might be involved in inhibition of malignant proliferation of HCC cells by LL-37were screened out.It was found that these genes were all down-regulated and played an important role in the activation of inflammation as well as in the proliferation and migration of tumor cells.Taken to-gether,these results provide data foundation for revealing the role and mechanism of LL-37in the occur-rence and development of HCC,and provide new ideas for exploring the diagnosis and treatment of HCC.收稿日期:2021-06-10;修回日期:2021-09-11;网络首发日期:2022-03-09基金项目:江苏省高等学校大学生创新训练项目(202010313044Y);徐州医科大学优秀人才科研启动经费项目(D2019017);江苏省“双创博士”项目;基础医学国家级实验教学示范中心(徐州医科大学)资助项目作者简介:吕继龙(2000—),男,江苏宿迁人,学生;*通信作者:丁晓慧(1989—),女,河南商丘人,博士,讲师,主要从事肝癌致病机制相关研究,Tel:*************,E-mail:************************。

生物技术进展 2023 年 第 13 卷 第 4 期 596 ~ 603Current Biotechnology ISSN 2095‑2341研究论文Articles重组贻贝粘蛋白的表征及功效评价李敏 ， 魏文培 ， 乔莎 ， 郝东 ， 周浩 ， 赵硕文 ， 张立峰 ， 侯增淼 *西安德诺海思医疗科技有限公司，西安 710000摘要：为了推进重组贻贝粘蛋白在医疗、化妆品领域的应用，对大肠杆菌规模化发酵及纯化生产获得的重组贻贝粘蛋白进行了表征及功效评价。

经Edman 降解法、基质辅助激光解吸电离飞行时间质谱、PITC 法、非还原型SDS -聚丙烯酰胺凝胶电泳法、凝胶法、改良的Arnow 法对重组贻贝粘蛋白进行氨基酸N 端测序、相对分子量分析、氨基酸组成分析、蛋白纯度分析、内毒素含量测定、多巴含量测定；通过细胞迁移、斑马鱼尾鳍修复效果对重组贻贝粘蛋白进行功效评价。

结果显示，获得的重组贻贝粘蛋白与理论的一级结构一致，蛋白纯度达95%以上，内毒素<10 EU ·mg -1,多巴含量大于5%；重组贻贝粘蛋白浓度为60 μg ·mL -1时能够显著促进细胞增殖的活性（P <0.01）；斑马鱼尾鳍面积样品组与模型对照组相比极显著增加（P <0.001）。

研究结果表明，重组贻贝粘蛋白具有显著的促细胞迁移和修复愈合的功效，具备作为生物医学材料的潜质。

关键词：贻贝粘蛋白；基因重组；生物材料；表征；功效评价DOI ：10.19586/j.2095­2341.2023.0021 中图分类号：S985.3+1 文献标志码：ACharacterization and Efficacy Evaluation of Recombinant Mussel Adhesive ProteinLI Min ， WEI Wenpei ， QIAO Sha ， HAO Dong ， ZHOU Hao ， ZHAO Shuowen ， ZHANG Lifeng ，HOU Zengmiao *Xi'an DeNovo Hith Medical Technology Co.， Ltd ， Xi'an 710000， ChinaAbstract ：In order to promote the application of recombinant mussel adhesive protein in the medical and cosmetics field ， the recombi⁃nant mussel adhesive protein obtained from scale fermentation and purification of Escherichia coli was characterized and its efficacy was evaluated. Amino acid N -terminal sequencing ， relative molecular weight analysis ， amino acid composition analysis ， protein purityanalysis ， endotoxin content ， dihydroxyphenylalanine （DOPA ） content of recombinant mussel adhesive protein were determined by the following methods ： Edman degradation ， matrix -assisted laser desorption ionization time -of -flight mass spectrometry （MALDI -TOF -MS ）， phenyl -isothiocyanate （PITC ）， nonreductive SDS -polyacrylamide gel electrophoresis （SDS -PAGE ）， gel method ， modified Ar⁃now. The efficacy of recombinant mussel adhesive protein was evaluated by cell migration and repairing effect of zebrafish tail fin. Re⁃sults showed that the obtained recombinant mussel adhesive protein was confirmed to be consistent with the theoretical primary structure ， protein purity of more than 95%， endotoxin <10 EU ·mg -1， DOPA content above 5%. When the recombinant mussel adhesive protein concentration was 60 μg ·mL -1， the effect of promoting cell proliferation was the most obvious ， and it had very significant activity （P <0.01）. The caudal fin area of zebrafish in sample group was significantly increased compared with model control group （P <0.001）. The results indicated that recombinant mussel adhesive protein can promote cell migration and repair healing and has the potential to be used as biomedical materials.Key words ：mussel adhesive protein ； gene recombination ； biological materials ； representation ； efficacy evaluation贻贝粘蛋白（mussel adhesive protein ， MAP ）也称作贻贝足丝蛋白（mussel foot protein ，Mfps ），收稿日期：2023⁃02⁃24； 接受日期：2023⁃03⁃31联系方式：李敏 E -mail:*******************;*通信作者 侯增淼 E -mail:***********************.cn李敏，等：重组贻贝粘蛋白的表征及功效评价是海洋贝类——紫贻贝（Mytilus galloprovincalis）、厚壳贻贝（Mytilus coruscus）、翡翠贻贝（Perna viri⁃dis）等分泌的一种特殊的蛋白质，贻贝中含有多种贻贝粘蛋白，包括贻贝粘蛋白（Mfp 1～6）、前胶原蛋白（precollagens）和基质蛋白（matrix proteins）等［1］。

Inhibitors, Agonists, Screening LibrariesSafety Data Sheet Revision Date:May-24-2017Print Date:May-24-20171. PRODUCT AND COMPANY IDENTIFICATION1.1 Product identifierProduct name :AbacavirCatalog No. :HY-17423CAS No. :136470-78-51.2 Relevant identified uses of the substance or mixture and uses advised againstIdentified uses :Laboratory chemicals, manufacture of substances.1.3 Details of the supplier of the safety data sheetCompany:MedChemExpress USATel:609-228-6898Fax:609-228-5909E-mail:sales@1.4 Emergency telephone numberEmergency Phone #:609-228-68982. HAZARDS IDENTIFICATION2.1 Classification of the substance or mixtureGHS Classification in accordance with 29 CFR 1910 (OSHA HCS)Acute toxicity, Oral (Category 4),H302Acute aquatic toxicity (Category 1),H400Chronic aquatic toxicity (Category 1),H4102.2 GHS Label elements, including precautionary statementsPictogramSignal word WarningHazard statement(s)H302 Harmful if swallowed.H410 Very toxic to aquatic life with long lasting effects.Precautionary statement(s)P264 Wash skin thoroughly after handling.P270 Do not eat, drink or smoke when using this product.P273 Avoid release to the environment.P301 + P312 IF SWALLOWED: Call a POISON CENTER or doctor/ physician if you feel unwell.P330 Rinse mouth.P391 Collect spillage.P501 Dispose of contents/ container to an approved waste disposal plant.2.3 Other hazardsNone.3. COMPOSITION/INFORMATION ON INGREDIENTS3.1 SubstancesSynonyms:NoneFormula:C14H18N6OMolecular Weight:286.33CAS No. :136470-78-54. FIRST AID MEASURES4.1 Description of first aid measuresEye contactRemove any contact lenses, locate eye-wash station, and flush eyes immediately with large amounts of water. Separate eyelids with fingers to ensure adequate flushing. Promptly call a physician.Skin contactRinse skin thoroughly with large amounts of water. Remove contaminated clothing and shoes and call a physician.InhalationImmediately relocate self or casualty to fresh air. If breathing is difficult, give cardiopulmonary resuscitation (CPR). Avoid mouth-to-mouth resuscitation.IngestionWash out mouth with water; Do NOT induce vomiting; call a physician.4.2 Most important symptoms and effects, both acute and delayedThe most important known symptoms and effects are described in the labelling (see section 2.2).4.3 Indication of any immediate medical attention and special treatment neededTreat symptomatically.5. FIRE FIGHTING MEASURES5.1 Extinguishing mediaSuitable extinguishing mediaUse water spray, dry chemical, foam, and carbon dioxide fire extinguisher.5.2 Special hazards arising from the substance or mixtureDuring combustion, may emit irritant fumes.5.3 Advice for firefightersWear self-contained breathing apparatus and protective clothing.6. ACCIDENTAL RELEASE MEASURES6.1 Personal precautions, protective equipment and emergency proceduresUse full personal protective equipment. Avoid breathing vapors, mist, dust or gas. Ensure adequate ventilation. Evacuate personnel to safe areas.Refer to protective measures listed in sections 8.6.2 Environmental precautionsTry to prevent further leakage or spillage. Keep the product away from drains or water courses.6.3 Methods and materials for containment and cleaning upAbsorb solutions with finely-powdered liquid-binding material (diatomite, universal binders); Decontaminate surfaces and equipment by scrubbing with alcohol; Dispose of contaminated material according to Section 13.7. HANDLING AND STORAGE7.1 Precautions for safe handlingAvoid inhalation, contact with eyes and skin. Avoid dust and aerosol formation. Use only in areas with appropriate exhaust ventilation.7.2 Conditions for safe storage, including any incompatibilitiesKeep container tightly sealed in cool, well-ventilated area. Keep away from direct sunlight and sources of ignition.Recommended storage temperature:Powder-20°C 3 years4°C 2 yearsIn solvent-80°C 6 months-20°C 1 monthShipping at room temperature if less than 2 weeks.7.3 Specific end use(s)No data available.8. EXPOSURE CONTROLS/PERSONAL PROTECTION8.1 Control parametersComponents with workplace control parametersThis product contains no substances with occupational exposure limit values.8.2 Exposure controlsEngineering controlsEnsure adequate ventilation. Provide accessible safety shower and eye wash station.Personal protective equipmentEye protection Safety goggles with side-shields.Hand protection Protective gloves.Skin and body protection Impervious clothing.Respiratory protection Suitable respirator.Environmental exposure controls Keep the product away from drains, water courses or the soil. Cleanspillages in a safe way as soon as possible.9. PHYSICAL AND CHEMICAL PROPERTIES9.1 Information on basic physical and chemical propertiesAppearance White to off-white (Solid)Odor No data availableOdor threshold No data availablepH No data availableMelting/freezing point No data availableBoiling point/range No data availableFlash point No data availableEvaporation rate No data availableFlammability (solid, gas)No data availableUpper/lower flammability or explosive limits No data availableVapor pressure No data availableVapor density No data availableRelative density No data availableWater Solubility No data availablePartition coefficient No data availableAuto-ignition temperature No data availableDecomposition temperature No data availableViscosity No data availableExplosive properties No data availableOxidizing properties No data available9.2 Other safety informationNo data available.10. STABILITY AND REACTIVITY10.1 ReactivityNo data available.10.2 Chemical stabilityStable under recommended storage conditions.10.3 Possibility of hazardous reactionsNo data available.10.4 Conditions to avoidNo data available.10.5 Incompatible materialsStrong acids/alkalis, strong oxidising/reducing agents.10.6 Hazardous decomposition productsUnder fire conditions, may decompose and emit toxic fumes.Other decomposition products - no data available.11.TOXICOLOGICAL INFORMATION11.1 Information on toxicological effectsAcute toxicityClassified based on available data. For more details, see section 2Skin corrosion/irritationClassified based on available data. For more details, see section 2Serious eye damage/irritationClassified based on available data. For more details, see section 2Respiratory or skin sensitizationClassified based on available data. For more details, see section 2Germ cell mutagenicityClassified based on available data. For more details, see section 2CarcinogenicityIARC: No component of this product present at a level equal to or greater than 0.1% is identified as probable, possible or confirmed human carcinogen by IARC.ACGIH: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by ACGIH.NTP: No component of this product present at a level equal to or greater than 0.1% is identified as a anticipated or confirmed carcinogen by NTP.OSHA: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by OSHA.Reproductive toxicityClassified based on available data. For more details, see section 2Specific target organ toxicity - single exposureClassified based on available data. For more details, see section 2Specific target organ toxicity - repeated exposureClassified based on available data. For more details, see section 2Aspiration hazardClassified based on available data. For more details, see section 212. ECOLOGICAL INFORMATION12.1 ToxicityNo data available.12.2 Persistence and degradabilityNo data available.12.3 Bioaccumlative potentialNo data available.12.4 Mobility in soilNo data available.12.5 Results of PBT and vPvB assessmentPBT/vPvB assessment unavailable as chemical safety assessment not required or not conducted.12.6 Other adverse effectsNo data available.13. DISPOSAL CONSIDERATIONS13.1 Waste treatment methodsProductDispose substance in accordance with prevailing country, federal, state and local regulations.Contaminated packagingConduct recycling or disposal in accordance with prevailing country, federal, state and local regulations.14. TRANSPORT INFORMATIONDOT (US)This substance is considered to be non-hazardous for transport.IMDGUN number: 3077Class: 9Packing group: IIIEMS-No: F-A, S-FProper shipping name: ENVIRONMENTALLY HAZARDOUS SUBSTANCE, SOLID, N.O.S.Marine pollutant: Marine pollutant.IATAUN number: 3077Class: 9Packing group: IIIProper shipping name: Environmentally hazardous substance, solid, n.o.s.15. REGULATORY INFORMATIONSARA 302 Components:No chemicals in this material are subject to the reporting requirements of SARA Title III, Section 302.SARA 313 Components:This material does not contain any chemical components with known CAS numbers that exceed the threshold (De Minimis) reporting levels established by SARA Title III, Section 313.SARA 311/312 Hazards:No SARA Hazards.Massachusetts Right To Know Components:No components are subject to the Massachusetts Right to Know Act.Pennsylvania Right To Know Components:No components are subject to the Pennsylvania Right to Know Act.New Jersey Right To Know Components:No components are subject to the New Jersey Right to Know Act.California Prop. 65 Components:This product does not contain any chemicals known to State of California to cause cancer, birth defects, or anyother reproductive harm.16. OTHER INFORMATIONCopyright 2017 MedChemExpress. The above information is correct to the best of our present knowledge but does not purport to be all inclusive and should be used only as a guide. The product is for research use only and for experienced personnel. It must only be handled by suitably qualified experienced scientists in appropriately equipped and authorized facilities. The burden of safe use of this material rests entirely with the user. MedChemExpress disclaims all liability for any damage resulting from handling or from contact with this product.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。

Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:ARS–853 is a selective, covalent KRAS G12C inhibitor with IC 50 of 2.5 μM.IC50 & Target: IC50: 2.5 μM (KRAS G12C )[1]In Vitro: ARS853 is designed to bind KRAS G12C with high affinity. Treatment of KRAS G12C –mutant lung cancer cells with ARS853reduces the level of GTP–bound KRAS by more than 95% (10 μM). ARS853 inhibits proliferation with an inhibitory concentration 50% (IC 50) of 2.5 μM, which is similar to its IC 50 for target inhibition. ARS853 (10 μM) inhibits effector signaling and cellproliferation to varying degrees in six KRAS G12C mutant lung cancer cell lines, but not in non–KRAS G12C models. Similarly, it completely suppresses the effects of exogenous KRAS G12C expression on KRAS–GTP levels, KRAS–BRAF interaction, and ERKsignaling. ARS–853 treatment also induces apoptosis in four KRAS G12C mutant cell lines. ARS853 selectively reduces KRAS–GTP levels and RAS–effector signaling in KRAS G12C –mutant cells, while inhibiting their proliferation and inducing cell death [1].ARS–853 inhibits mutant KRAS–driven signaling by binding to the GDP–bound oncoprotein and preventing activation [2].PROTOCOL (Extracted from published papers and Only for reference)Kinase Assay:[1]Purified KRAS (1 μM) is incubated EDTA (10 mM) and GDP (1 mM) or GTPγS (1 mM) at room temperature for 1 h followed by addition of MgCl 2 (1 mM) to terminate the reaction. ARS853 (1 μM) is then added and the mixture is incubated for another hour at room temperature. HEK293 cells expressing various KRAS mutants are treated with ARS853. Proteins areextracted using a buffer containing 9M urea, 10 mM DTT and 50 mM ammonium bicarbonate, pH 8, heated to 65°C for 15 min and alkylated using 50 mM iodoacetamide at 37°C for 30 min. The samples are desalted by gel filtration in Zeba spin desalting plates followed by addition of sequencing–grade trypsin to a concentration of 10 μg/ml, and incubation for one hour at 37°C.Heavy isotopic standards (25 fmol) of the KRAS G12C target peptide and KRAS normalization peptide are added to the samples followed by desalting in Strata–X polymeric reverse phase plates. LC–MS/MS analysis is performed in a Q Exactive quadrupole orbitrap mass spectrometer under standard condition. The amount of KRAS G12C bound by the drug is determined by the ratio ofthe modified G12C peptide to that of the heavy isotopic standards [1].References:[1]. Lito P, et al. Allele–specific inhibitors inactivate mutant KRAS G12C by a trapping mechanism. Science. 2016 Feb 5;351(6273):604–8.[2]. Patricelli MP, et al. Selective Inhibition of Oncogenic KRAS Output with Small Molecules Targeting the Inactive State. Cancer Discov. 2016 Mar;6(3):316–29.Product Name:ARS–853Cat. No.:HY-19706CAS No.:1629268-00-3Molecular Formula:C 22H 29ClN 4O 3Molecular Weight:432.94Target:Ras Pathway:GPCR/G Protein Solubility:DMSO: ≥ 71 mg/mLCaution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。

ASTAspartate Aminotransferase IFCCMANUAL RX MONZAINTENDED USEFor the quantitative in vitro determination of AspartateAminotransferase (AST) in serum and plasma. This product is suitable for manual use and on the Rx Monza analyser.Cat. No. AS 1202 R1a. Buffer/Substrate 1 x 70 ml 20 x 2 ml R1b. Enzyme/Coenzyme/ 20 x 2 ml α-oxoglutarate GTIN: 05055273200416AS 1204 R1a. Buffer/Substrate 1 x 105 ml 10 x 10 ml R1b. Enzyme/Coenzyme/ 10 x 10 ml α-oxoglutarate GTIN: 05055273200423AS 1267 R1a. Buffer/Substrate 1 x 105 ml 5 x 20 ml R1b. Enzyme/Coenzyme/ 5 x 20 ml α-oxoglutarate GTIN: 05055273200430AS 2359 R1a. Buffer/Substrate 5 x 100 ml 5 x 100 ml R1b. Enzyme/Coenzyme/ 5 x 100 ml α-oxoglutarate GTIN: 05055273200454UV METHODThis is an optimised standard method according to the concentrations recommended by the IFCC.CLINICAL SIGNIFICANCE (1,2,3,4)The aminotransferases are a group of enzymes that catalyse the inter conversions of amino acids and α-oxoacids by transfer of amino groups. AST (aspartate aminotransferase or glutamate oxaloacetatetransaminase) has been found in the cytoplasm and the mitochondria of cells that have been studied. In cases of mild tissue damage, e.g. liver, the predominant form of serum AST is that from the cytoplasm, with a smaller amount coming from the mitochondria. Severe tissue damage will result in more mitochondrial enzyme being released. Elevated levels of AST can signal myocardial infarction, hepatic disease, muscular dystrophy and organ damage.Although heart muscle is found to have the most activity of the enzyme, significant activity has also been seen in the brain, liver, gastric mucosa, adipose tissue and kidneys of humans.The IFCC has now recommended (1980) standardised procedures for AST determinations including:-1. optimization of substrate concentrations.2. Employment of Tris buffers (instead of phosphate, which has beenshown to inhibit recombination of the apoenzyme with pyridoxal phosphate).3. Pre-incubation of combined buffer and serum to allow sidereactions with NADH to occur. 4. Substrate start (α-oxoglutarate)5. Optional pyridoxal phosphate activation.This is an optimised standard method according to the recommendations of the IFCC.PRINCIPLEα-oxoglutarate reacts with L-aspartate in the presence of AST to form L-glutamate plus oxaloacetate. The indicator reaction utilises the oxaloacetate for a kinetic determination of NADH consumption. AST -oxoglutarate + L-aspartate L-glutamate + oxaloacetate MDH oxaloacetate + NADH + H + L-malate + NAD +SPECIMEN COLLECTION AND PREPARATION (5) Serum:- Use serum free from haemolysis.Plasma:- EDTA or heparin can be used as the anticoagulant.Plasma should be separated from cells within one hour after collection.Specimens should be refrigerated if not used immediately:-Specimens stored longer than 3 days should be frozen at -20︒C.REAGENT COMPOSITIONContents Concentrations in the TestR1a. Buffer/Substrate Tris buffer 80 mmol/l, pH 7.5 L-aspartate 240 mmol/l R1b. Enzyme/Coenzyme/α-oxoglutarate α-oxoglutarate 12 mmol/l MDH ≥420 U/l LD ≥600 U/l NADH 0.18 mmol/lSAFETY PRECAUTIONS AND WARNINGS For in vitro diagnostic use only. Do not pipette by mouth.Exercise the normal precautions required for handling laboratory reagents.Solution R1a contains Sodium Azide. Avoid ingestion or contact with skin or mucous membranes. In case of skin contact, flush affected area with copious amounts of water. In case of contact with eyes or if ingested, seek immediate medical attention.Sodium Azide reacts with lead and copper plumbing, to form potentially explosive azides. When disposing of such reagents flush with large volumes of water to prevent azide build up. Exposed metal surfaces should be cleaned with 10% sodium hydroxide.Health and Safety data sheets available on request.The reagents must be used only for the purpose intended by suitably qualified laboratory personnel, under appropriate laboratory conditions.STABILITY AND PREPARATION OF REAGENTS R1a. Buffer/SubstrateContents ready for use. Stable up to the expiry date when stored at +2 to +8︒C.R1b. Enzyme/Coenzyme/α-oxoglutarate Reconstitute one vial of Enzyme/Coenzyme/α-oxoglutarate R1b with the appropriate volume of Buffer/Substrate R1a: 2 ml for the 20 x 2 ml kit (AS 1202) 10 ml for the 10 x 10 ml kit (AS 1204) 20 ml for the 5 x 20 ml kit (AS 1267) Stable for 14 days at +2 to +8︒C or 24 hours at +15 to +25︒C. Cat. AS 2359 5 x 100 mlReconstitute one vial of Enzyme/Coenzyme/α-oxoglutarate R1b with a portion of Buffer/Substrate R1a and then transfer the entire contents to bottle R1a rinsing bottle R1b several times. Stable for 14 days at +2 to +8︒C or 24 hours at +15 to +25︒C.MATERIALS PROVIDED Buffer/SubstrateEnzyme/Coenzyme/ -oxoglutarateMATERIALS REQUIRED BUT NOT PROVIDEDRandox Assayed Multisera Level 2 (Cat. No. HN 1530) and Level 3 (Cat. No. HE 1532)Randox Calibration Serum Level 3 (Cat. No. CAL 2351) RX series Saline (Cat. No. SA 3854)PROCEDUREAspirate fresh ddH 2O and perform a new Gain Calibration in flow cell mode. Select AST in the Run Test screen and carry out a water blank as instructed.Pipette into a test tube:Sample 0.05 ml Reagent 0.5 mlMix and aspirate into the Rx Monza.CALIBRATION FOR RX MONZAThe use of Saline and Randox Calibration Serum Level 3 isrecommended for calibration. Calibration is recommended with change of reagent lot or as indicated by quality control procedures.FOR MANUAL USEWavelength: 340 nm (Hg 334 nm or Hg 365 nm) Cuvette: 1 cm light path Temperature: 25/30/37︒C Measurement: against airPipette into cuvette: Macro MicroSample 0.2 ml 0.1 ml Enzyme/Coenzyme/ α-oxoglutarate R1 2.0 ml 1.0 mlMix, read initial absorbance after 1 minute. Read again after 1, 2 and 3 minutes. Note: If the absorbance change per minute is between 0.11 and 0.16 at 340/Hg 334 nm 0.06 and 0.08 at Hg 365 nmuse only the values for the first 2 minutes for the calculation.MANUAL CALCULATIONTo calculate the AST activity, use the following formulae:U/l = 1746 x A 340 nm/min U/l = 1780 x A Hg 334 nm/min U/l = 3235 x A Hg 365 nm/minSTANDARDISATIONRandox Calibration Serum Level 3 is traceable to AST reference material JSCC TS01.QUALITY CONTROLRandox Assayed Multisera, Level 2 and Level 3 are recommended for daily quality control. Two levels of controls should be assayed at least once a day. Values obtained should fall within a specified range. If these values fall outside the range and repetition excludes error the following steps should be taken:1. Check instrument settings and light source.2. Check cleanliness of all equipment in use.3. Check water. Contaminants, i.e. bacterial growth, maycontribute to inaccurate results. 4. Check reaction temperature.5. Check expiry date of kit and contents.6. Contact Randox Laboratories Customer Technical Services, Northern Ireland +44 (0) 28 9445 1070.SPECIFICITY/INTERFERENCE (6,7)Gross haemolysis will produce falsely elevated test results. The effects of various drugs on AST activity should be taken intoconsideration in the case of patients receiving large doses of drugs.The analytes below were tested up to the following levels and were found not to interfere: Haemoglobin 250 mg/dl Free Bilirubin 25 mg/dl Conjugate Bilirubin 25 mg/dl Triglycerides 1000 mg/dlIntralipid ® 200 mg/dlA list of substances and conditions known to effect AST activity in vivo is given by both Young et al and Friedman et al. Norepresentation is made by Randox Laboratories Ltd regarding the completeness of these lists and the accuracy of the information contained therein.NORMAL VALUES IN SERUM (8,9) +25︒C +30︒C +37︒C Men up to 18 U/l up to 25 U/l up to 37 U/l Women up to 15 U/l up to 21 U/l up to 31 U/lIt is recommended that each laboratory establish its own reference range to reflect the age, sex, diet and geographical location of the population.SPECIFIC PERFORMANCE CHARACTERISTICS The following performance data were obtained using an Rx Monza analyser running at +37o C.LINEARITYThis method is linear up to 562 U/l. If the sample concentration exceeds this value, dilute the sample 1+9 with 0.9% NaCl solution and re-assay. Multiply the result by 10.SENSITIVITYThe minimum detectable concentration of AST with an acceptable level of precision was determined as 9.3 U/l.PRECISIONIntra AssayLevel 2 Level 3Mean (U/l) 35.6 153SD 1.66 1.47CV(%) 4.65 0.96n 20 20Inter AssayLevel 2 Level 3Mean (U/l) 35.6 153SD 1.77 7.10CV(%) 4.96 4.63n 20 20CORRELATIONThis method (Y) was compared with another commerciallyavailable method (X) and the following linear regression equationobtained:Y = 1.07X + 4.9and a correlation coefficient of r = 0.997543 patient samples were analysed spanning the range 28 to 559U/l.REFERENCES1. Wroblewski F, La Due J.S: Ann Intern Med. 1956; 45: 801.2. Wroblewski F, La Due J.S: Proc Soc Exp Biol Med 1956;91: 569.3. Bergmeyer HU, Bowers GN Jr, et al: Clin Chem 1977; 23:887.4. Bergmeyer HU, Bowers GN Jr, et al: J.Clin Chem ClinBiochem 1980; 18: 521-534.5. Tietz N W: Fundamentals of Clinical Chemistry ed 3.Philadelphia, WB Saunders Co. 1987, pg 372.6. Young D S, et al: Clin Chem 1975, 21; No5.7. Friedman RB, et al: Clin Chem 1980, 26; No4.8. Wallnofer H, Schmidt.E, Schmidt FW, eds: Synopsis derLeberkrankheiten Stuttgart, Georg Thieme Verlag, 1974.9. Thefeld W, et al: Dtsch Med Wschr 1974; 99: 343.Revised 26 Apr 16 biRev. 003THIS PAGE IS INTENTIONALLY BLANK。

Product Information Presentation, Storage and StabilityThe Incucyte® Fabfluor-pH Antibody Labeling Reagents for antibody internalization are supplied as lyophilized solids in sufficient quantity to label 50 μg of test antibody, when used at the suggested molar ratio (1:3 of test antibody to labeling Fab). The lyophilized solid can be stored at 2-8° C for one year. Once re-hydrated, any unused reagent should be aliquoted and stored at -80° C for up to one year. Avoid repeated freeze-thaw cycles.Incucyte® Fabfluor-pH Antibody Labeling ReagentsFor Antibody Internalization AssaysAntibody Labeling Reagent Rehydrated: -80° C *Excitation and Emission maxima were determined at a pH of 4.5.Fabfluor_quick_guideBackgroundIncucyte ® Fabfluor-pH Antibody Labeling Reagents are designed for quick, easy labeling of Fc-containing test antibodies with a Fab fragment-conjugated pH-sensitive fluorophore. The pH-sensitive dye based system exploits the acidic environment of the lysosomes to quantify in-ternalization of the labeled antibody. As Fabfluor labeled antibodies reside in the neutral extracellular solution (pH 7.4), they interact with cell surface specific antigens and are internalized. Once in the lysosomes, they enter an acidic environment (pH 4.5–5.5) and a substantial in-crease in fluorescence is observed. In the absence of ex-pression of the specific antigen, no internalization occurs and the fluorescence intensity of the labeled antibodies remains low. With the Incucyte ® integrated analysis soft-ware, background fluorescence is minimized. These reagents have been validated for use with a number of different antibodies in a range of cell types. The Incucyte ® Live-Cell Analysis System enables real-time, kinetic eval -uation of antibody internalization.Recommended UseWe recommend that the Incucyte ® Fabfluor-pH Antibody Labeling Reagents are prepared at a stock concentration of 0.5 mg/mL by the addition of 100 μL of sterile water and triturated (centrifuge if solution not clear). The reagent may then be diluted directly into the labeling mixture with test antibody. Do NOT sonicate the solution.Additional InformationThe Fab antibody was purified from antisera by a combination of papain digestion and immunoaffinity chromatography using antigens coupled to agarose beads. Fc fragments and whole IgG molecules have been removed.Human Red (Cat. No. 4722) or Human Orange (Cat. No. 4812)—Based on immunoelectrophoresis and/ or ELISA, the antibody reacts with the Fc portion of human IgG heavy chain but not the Fab portion of human IgG. No antibody was detected against human IgM, IgA or against non-immunoglobulin serum proteins. The anti-body may cross-react with other immunoglobulins from other species.Mouse IgG1 (Cat. No. 4723), IgG2a (Cat. No. 4750) or IgG2b (Cat. No. 4751)—Based on antigen-binding assay and/or ELISA, the antibody reacts with the Fc portion of mouse IgG, IgG2a or IgG2b, respectively, but not the Fab portion of mouse immunoglobulins. No antibody was detected against mouse IgM or against non–immunoglobulin serum proteins. The antibody may cross-react with other mouse IgG subclasses or with immunoglobulins from other species.Rat (Cat. No. 4737)—Based on immunoelectrophoresis and/or ELISA, the antibody reacts with the Fc portion of rat IgG heavy chain but not the Fab portion of rat IgG. No antibody was detected against rat IgM, IgA or against non-immunoglobulin serum proteins. The antibody may cross-react with other immunoglobulins from other species.A.B.C.D.R e d O b j e c t A r e a (x 105 μm 2 p e r w e l l )Time (hours)A U C x 106 (0–12 h )log [α–CD71] (g/mL)Example DataFigure 1: Concentration-dependent increase in antibody internalization of Incucyte ® Fabfluor labeled-α-CD71 in HT1080 cells. α-CD71 and mouse IgG1 isotype control were labeled with Incucyte ® Mouse IgG1 Fabfluor-pH Red Antibody Labeling Reagent. HT1080 cells were treated with either Fabfluor-α-CD71 or Fabfluor-IgG1 (4 μg/mL); HD phase and red fluorescence images were captured every 30 minutes over 12 hours using a 10X magnification. (A) Images of cells treated with Fabfluor-α-CD71 display red fluorescence in the cytoplasm (images shown at 6 h). (B) Cells treated with labeled isotype control display no cellular fluorescence. (C) Time-course of Fabfluor-α-CD71 internalization with increasing concentrations of Fabfluor-α-CD71 (progressively darker symbols). Internalization has been quantified as the red object area for each time-point. (D) Concentration response curve to Fabfluor-α-CD71. Area under the curve (AUC) values have been determined from the time-course shown in panel C (0-12 hours) and are presented as the mean ± SEM, n=3 wells.CD71-FabfluorIgG-FabfluorProtocols and ProceduresMaterialsIncucyte® Fabfluor-pH Antibody Labeling ReagentTest antibody of interest containing human, mouse, or rat IgG Fc region (at known concentration)Target cells of interestTarget cell growth mediaSterile distilled water96-well flat bottom microplate (e.g. Corning Cat. No. 3595) for imaging96-well round black round bottom ULA plate (e.g. Corning Cat. No. 45913799) or amber microtube (e.g. Cole Parmer Cat. No. MCT-150-X, autoclaved) for conjugation step0.01% Poly-L-Ornithine (PLO) solution (e.g. Sigma Cat. No. P4957), optional for non-adherent cells Recommended control antibodiesIt is strongly recommended that a positive and negative control is run alongside test antibodies and cell lines. For example, CD71, which is a mouse anti-human antibody, is recommended as a positive control for the mouse Fab.Anti-CD71, clone MEM-189, IgG1 e.g. Sigma Cat. No. SAB4700520-100UGAnti-CD71, clone CYG4, IgG2a e.g. BioLegend Cat. No. 334102Isotype controls, depending on isotype being studied—Mouse IgG1, e.g. BioLegend Cat. No. 400124, Mouse IgG2a e.g. BioLegend Cat. No. 401501Preparation of Incucyte® Antibody Internalization Assay 1. Seed target cells of interest1.1 Harvest cells of interest and determine cell concentra-tion (e.g. trypan blue + hemocytometer).1.2 Prepare cell seeding stock in target cell growth mediawith a cell density to achieve 40–50% confluence be-fore the addition of labeled antibodies. The suggested starting range is 5,000–30,000 cells/well, although the seeding density will need to be optimized for each cell type.Note: For non-adherent cell types, a well coating may be required to maintain even cell distribution in the well. For a 96-well flat bottom plate, we recommend coating with 50 μL of either 0.01% Poly-L-Or-nithine (PLO) solution or 5 μg/mL fibronectin diluted in 0.1% BSA.Coat plates for 1 hour at ambient temperature, remove solution from wells and then allow the plates to dry for 30-60 minutes prior to cell addition.1.3 Using a multi-channel pipette, seed cells (50 µL perwell) into a 96-well flat bottom microplate. Lightly tapplate side to ensure even liquid distribution in well. Toensure uniform distribution of cells in each well, allowthe covered plate sit on a level surface undisturbed at room temperature in the tissue culture hood for 30minutes. After cells are settled, place the plate insidethe Incucyte® Live-Cell Analysis System to monitor cell confluence.Note: Depending on cell type, plates can be used in assay once cells have adhered to plastic and achieved normal cell morphology e.g.2-3 hours for HT1080 or 1-2 hours for non-adherent cell types. Some cell types may require overnight incubation.2. Label Test Antibody2.1 Rehydrate the Incucyte® Fabfluor-pH Antibody Label-ing Reagent with 100 µL sterile water to result in a final concentration of 0.5 mg/mL. Triturate to mix (centrifuge if solution is not clear).Note: The reagent is light sensitive and should be protected fromlight. Rehydrated reagent can be aliquoted into amber or foilwrapped tubes and stored at -80° C for up to 1 year (avoid freezing and thawing).2.2 Mix test antibody with rehydrated Incucyte® Fabfluor–pH Antibody Labeling Reagent and target cell growth media in a black round bottom microplate or ambertube to protect from light (50 µL/well).a. Add test antibody and Incucyte® Fabfluor–pH Anti-body Labeling Reagent at 2X the final concentration.We suggest optimizing the assay by starting with afinal concentration of 4 µg/mL of test antibody or theFabfluor-pH Antibody Labeling Reagent (i.e. 2Xworking concentration = 8 µg/mL).Note: A 1:3 molar ratio of test antibody to Incucyte® Fabfluor-pHAntibody Labeling Reagent is recommended. The labeling re-agent is a third of the size of a standard antibody (50 and 150KDa, respectively). Therefore, labeling equal quantities will pro-duce a 1:3 molar ratio of test antibody to labeling Fab.b. Make sufficient volume of 2X labeling solution for50 µL/well for each sample. Triturate to mix.c. Incubate at 37° C for 15 minutes protected from light.Note: If performing a range of concentrations of test antibody,e.g. concentration response-curve, it is recommended to createthe dilution series post the conjugation step to ensure consistentmolar ratio. We strongly recommend the use of both a negativeand positive control antibody in the same plate.3. Add labeled antibody to cells3.1 Remove cell plate from incubator.3.2 Using a multi-channel pipette, add 50 µL of 2X labeledantibody and control solutions to designated wells.Remove any bubbles and immediately place plate in the Incucyte® Live-Cell Analysis System and start scanning.Note: To reduce the risk of condensation formation on the lid priorto first image acquisition, maintain all reagents at 37° C prior toplate addition.4. Acquire images and analyze4.1 In the Incucyte® Software, schedule to image every15-30 minutes, depending on the speed of the specific antibody internalization.a Scan on schedule, standard. If the Incucyte® Cell-by-Cell Analysis Software Module (Cat. No. 9600-0031)is available, adherent cell-by-cell or non-adherentcell-by-cell scan types can be selected.b Channel selection: select “phase” and “red” or“phase” and "orange” (depending on reagent used).c Objective: 10X or 20X depending on cell types used,generally 10X is recommended for adherent cells,and 20X for non-adherent or smaller cells.NOTE: The optional Incucyte® Cell-by-Cell Analysis SoftwareModule enables the classification of cells into sub-populationsbased on properties including fluorescence intensity, size andshape. For further details on this analysis module and its appli-cation, please see: /cell-by-cell.4.2 To generate the metrics, user must create an AnalysisDefinition suited to the cell type, assay conditions andmagnification selected.4.3 Select images from a well containing a positiveinternalization signal and an isotype control well(negative signal) at a time point where internalizationis visible.4.4 In the Analysis Definition:Basic Analyzer:a. Set up the mask for the phase confluence measurewith fluorescence channel turned off.b. Once the phase mask is determined, turn the fluores-cence channel on: Exclude background fluorescencefrom the mask using the background subtractionfeature. The feature “Top-Hat” will subtract localbackground from brightly fluorescent objects withina given radius; this is a useful tool for analyzing ob-jects which change in fluorescence intensity overtime.i The radius chosen should reflect the size of thefluorescent object but contain enough backgroundto reliably estimate background fluorescence inthe image; 20-30 μm is often a useful startingpoint.ii The threshold chosen will ensure that objectsbelow a fluorescence threshold will not bemasked.iii Choose a threshold in which red or orange objectsare masked in the positive response image but lownumbers in the isotype control, negative responsewell. For a very sensitive measurement, for example,if interested in early responses, we suggest athreshold of 0.2.NOTE: The Adaptive feature can be used for analysis but maynot be as sensitive and may miss early responses. If interestedin rate of response, Top-Hat may be preferable.Cell-by-Cell (if available):a. Create a Cell-by-Cell mask following the softwaremanual.b. There is no need to separate phase and fluorescencemasks. The default setting of Top-Hat No Mask forthe fluorescence channel will enable backgroundsubtraction without generation of a mask. Ensurethat the Top-Hat radius is set to a value higher thanthe radius of the larger clusters to avoid excess back-ground subtraction.c. The threshold of fluorescence can be determined inCell-by-Cell Classification.Specifications subject to change without notice.© 2020. All rights reserved. Incucyte, Essen BioScience, and all names of Essen BioScience prod -ucts are registered trademarks and the property of Essen BioScience unless otherwise specified. Essen BioScience is a Sartorius Company. Publication No.: 8000-0728-A00Version 1 | 2020 | 04Sales and Service ContactsFor further contacts, visit Essen BioScience, A Sartorius Company /incucyte Sartorius Lab Instruments GmbH & Co. KGOtto-Brenner-Strasse 20 37079 Goettingen, Germany Phone +49 551 308 0North AmericaEssen BioScience Inc. 300 West Morgan Road Ann Arbor, Michigan, 48108USATelephone +1 734 769 1600E-Mail:***************************EuropeEssen BioScience Ltd.Units 2 & 3 The Quadrant Newark CloseRoyston Hertfordshire SG8 5HLUnited KingdomTelephone +44 (0) 1763 227400E-Mail:***************************APACEssen BioScience K.K.4th floor Daiwa Shinagawa North Bldg.1-8-11 Kita-Shinagawa Shinagawa-ku, Tokyo 140-0001 JapanTelephone: +81 3 6478 5202E-Mail:*************************5. Analysis GuidelinesAs the labeled antibody is internalized into the acidic environment of the lysosome, the area of fluorescence intensity inside the cells increases.This can be reported in two ways:Ways to Report Basic AnalyzerCell-by-Cell Analysis* To correct for cell proliferation, it is advisable to normalize the fluorescence area to the total cell area using User Defined Metrics.For Research Use Only. Not For Therapeutic or Diagnostic Use.LicensesFor non-commercial research use only. Not for therapeutic or in vivo applications. Other license needs contact Essen BioS cience.Fabfluor-pH Red Antibody Labeling Reagent: This product or portions thereof is manufactured under license from Carnegie Mellon University and U.S. patent numbers 7615646 and 8044203 and related patents. This product is licensed for sale only for research. It is not licensed for any other use. There is no implied license hereunder for any commercial use.Fabfluor-pH Orange Antibody Labeling Reagent: This product or portions thereof is manufactured under a license from Tokyo University and is covered by issued patents EP2098529B1, JP5636080B2, US8258171, and US9784732 and related patent applications. This product and related products are trademarks of Goryo Chemical. Any application of above mentioned technology for commercial purpose requires a separate li -cense from: Goryo Chemical, EAREE Bldg., SF Kita 8 Nishi 18-35-100, Chuo-Ku, Sapporo, 060-0008 Japan.SupportA complete suite of cell health applications is available to fit your experimental needs. Find more information at /incucyte Foradditionalproductortechnicalinformation,************************************************************/incucyte。

2023年第3期品牌与标准化Prepared Radix Rehmanniae Research Progressin Chemical Composition Changes and Pharmacological EffectsGENG Xiaotong（Xinyang Agricultural and Forestry University 〔School of Pharmaceutical Engineering 〕，Xinyang 464000，China ）Abstract ：In this paper ，the processing methods of Radix Rehmanniae Preparata and the representative research results of the changes of its chemical components before and after are reviewed.Its main changes include iridoid and its glycosides ，phenylethanolamine glycosides and 5-HMF ，carbohydrates and others.Its main effects include improving the immune system ，blood system ，inhibiting tumor growth ，etc.Key words ：rehmanniae radix praeparata ；processing method ；chemical composition ；pharmacological action熟地黄炮制过程中的化学成分变化和药理作用研究进展耿晓桐（信阳农林学院〔制药工程学院〕，河南信阳464000）【摘要】本文对熟地黄的炮制方法和化学成分前后变化的代表性研究成果进行综述，其主要变化成分包括环烯醚萜及其苷类、苯乙醇苷类和5-HMF ，糖类以及其他，主要功效包括改善免疫系统、血液系统、抑制肿瘤生长等。

ICH领域专业术语表（质量、安全性）序号英文中文1"relevant" viruses and "model" viruses“相关”病毒和“模型”病毒225-fold AUC radio25倍的AUC比值3 a single 2 generation study单项包括两代（生殖毒性）的研究4abbreviated or abridged application简略申请5abnormal karyology异常核形6abortions流产7absorbed moisture吸附水8absorption吸收9acceptable daily intake可接受的日摄入量10acceptable test加速试验11acceptance criteia认可标准12accuracy准确性13accuracy准确度14acelerated/stress stability studies加速/强力破坏稳定性研究15acentric fragment无着丝点片段16acetylation 乙酰化作用17achiral assay非手性测定18achlorhydric eldderly老年性胃酸缺乏症19acridine orange吖啶橙20action limits内控限值21active components/compound/moiety活性成分22active ingredient活性组分23active metabolite活性代谢产物24adaption to specific culture conditions特定培养条件的适应25additional test 附加实验26additions添加剂27adduct加合物28adequate exposure充分暴露29adjuvant 佐剂30ADME吸收、分布、代谢、排泄31administration period给药期32adventitious agents外源性因子33adventitious contaminants外来污染物34adventitious viral or mycoplasma contamination外源性病毒或支原体污染35adventitious viruses外源病毒36advers effect不良反应37adverse reaction不良反应38aerobic microorganisms需氧微生物39affinity亲和力40affinity chromatography亲和层析41affinity column亲和柱42against humanised proteins serum antibodies抗人源蛋白血清抗体　43agar and broth琼脂和肉汤44aggregates 聚合体45aggregation聚集46aginal smear阴道涂片　47air ighting reflex空中翻正反射48alkylating electrophilic center烷化亲电子中心49allele基因突变产生的遗传因子50allergenic/allergic extracts过敏原抽提物51allergic reactions过敏性反应（变应性反应）52altenative validated test有效替代试验53altered conjugated forms改变的结合物形式54altered growth 生长改变55ambient condition自然条件56amino acid composition氨基酸组成57amino acid sequence氨基酸顺序58amino acids氨基酸59amino sugars氨基糖60amino-terminal amino acids氨基端氨基酸61ammonia production Rates产氨率62ammoniun sulphide staining of the uterus子宫硫化胺染色　63analogue类似物（同系物）64analogue series of substances同系物65analyte 被测物66analytical method 分析方法67analytical procedure分析方法68anaphase分裂后期69aneuploidy非整倍体70aneuploidy inducer非整倍体诱导剂71animal cell lines动物细胞系72animal tissues or organs动物组织或器官73antennary profile 触角形状74antibiotic resistance genes抗生素耐药基因75antibiotics抗生素76antibody抗体77antibody production tests抗体产生试验78antigenic specificity抗原特异性79antisera抗血清80apoptosis凋亡81applicant申报者82art and ethical standards技术和伦理标准83ascites腹水84assay含量测定85assay procedure定量方法86assessment of genotoxicity遗传毒性评价87attainment of full sexual function达到性成熟　88AUC曲线下面积89auditory startle relex惊愕反射（听觉惊跳反射）90autoimmune自身免疫91autoradiographic assessment放射自显影评价92autoradiography放射自显影93avian鸟类94avidity亲和性95background 背景96bacteria细菌97bacterial mutagenicity test细菌致变突试验98bacterial reverse mutation test细菌回复突变试验99bacterial strains菌株100bacterial test organisms微生物试验菌101base pairs碱基对102base set of strains基本菌株103base substitution碱基置换104batches批次105batch-to-batch逐批106between-assay variation试验间变异107binary fission双数分裂108binding assays结合试验109bioanalytical method生物学分析方法110bioavaiability生物利用度111bioburden生长量/生物负荷112biochemical methods生化方法113bioequivalency生物等效性114biohazard enformation生物有害信息115biological activity生物活性116biological products生物制品117biological relevance生物学意义118bioreactor生物反应器119biotechnological products生物技术产品120biotechnological/biological products生物技术/生物制品121biotechnology-derived pharmaceuticals生物技术药物122biphasic curve双相曲线123birth出生124blood plasma factors血浆因子125body burden机体负担126body fluids体液127bone marrow cell骨髓细胞128bouin's fixation包氏液固定129bovine牛130bovine spongiform encephalopathy(BSE)疯牛病131bracketing括号法132breakage of chromatid染色单体断裂133breakage of chromosome染色体断裂134breeding conditions饲养条件135bridging character桥梁作用136by-products副产物137C(time)一定剂量、某一时间的浓度138calibrate标化139canine犬140cap liner瓶帽内垫141capillary electrophoresis毛细管电泳142carbohydrate碳水化合物143carboxy-terminal amino acids羧基端氨基酸144carcinogen致癌物质145carcinogenesis致癌性146carcinogenic hazard致癌性危害147carcinogenicity bioassay致癌性生物检测148carcinogenicity potential of chemical化合物的潜在致癌性149carcinoginicity(oncogenicity)致癌（致瘤）150cardiovascular心血管151carrier载体/担体152case-by-case个例153catalysts催化剂154cell bank 细胞库155cell bank system细胞库系统156cell banking procedures细胞建库过程157cell banking system细胞库系统158cell culture-derived impurities来源于细胞培养基的杂质159cell cultures 细胞培养物160cell cultures 细胞培养161cell expansion细胞扩增162cell fusion细胞融合163cell line细胞系164cell lines 细胞系165cell membrane lipid细胞膜脂质层166cell metabolites细胞代谢物167cell pooling细胞混合168cell proliferation细胞增植169cell replication system细胞复制系统170cell substrate-derived impurities 来源于细胞基质的杂质171cell substrates细胞基质172cell suspension细胞悬液173cell viability细胞活力174cell-derived biological products细胞来源的生物制品175cell-mediated immunity细胞介导的免疫176cellular blood components血细胞成分177cellular therapy细胞治疗178cemadsorbing viruses红细胞吸附病毒179central nervous systems中枢神经系统180cerbral spinal fluid脑脊液181characterization and testing of cell banks细胞库鉴定及检测182charcoal活性炭183charge电荷184chemical actionmertric system化学光化线强度系统185chemical nature化学性质186chemical reactivity 化学反应性187chemical syntheses化学合成188chemically inert化学惰性189chewable tablets咀嚼片190childbeering potential生育可能性191chinese hamster V79 cell中国仓鼠V79细胞192chiral impurities手性杂质193CHL cell中国仓鼠肺细胞194CHO cell中国仓鼠卵巢细胞195chromatide染色单体196chromatograms色谱图197chromatographic behavior色谱行为198chromatographic procedures色谱方法199chromatography columns色谱分离柱200chromosomal aberration染色体畸变201chromosomal damage染色体损伤202chromosomal integrity染色体完整性203chronic toxicity testing 慢性毒性试验204circular dichroism圆二色性205classfical biotransformation studies经典的生物转化试验206clastogen染色体断裂剂207clastogenic致染色体断裂的208clearance studies清除研究209cleavage of the balanopreputial gland 龟头包皮腺裂开210climatic zones气候带211clinical indication临床适应证212clinical research临床研究213clinical trial application 临床试验申请214clisure闭塞物215cloning 克隆216cloning efficiency克隆形成率217closure of hard palate硬腭闭合218C max峰浓度219coat growth毛发生长220code number编号221coding sequence编码序列222coefficient of variance变异系数223collaborative studies协作实验研究224colony isolation菌落分离225colony sizing集落大小226colony-stimulating factors集落刺激因子227combination product复方制剂228comparative trial对比试验229complement binding补体结合230completely novel compound全新化合物231components成分232compound bearing stuctural alerts结构可疑化合物233concentration threshold阈浓度234conception受孕235concomitant toxicokinetics相伴毒代动力学236confidence interval置信区间237confidence limits可信限238confirmatory studies确认研究239conformance to specifcations符合规范240conformation构型241conjugated product连接产物242conjugation连接243consistency一致性244container容器245container/closure容器/闭塞物246container/closure integrity testing 容器/密封完整性试验247contaminants污染物248contaminated cell substrate污染的细胞基质249content uniformity含量均匀度250continuous treatment 连续接触251control methodology控制方法学252controlled released product控释制剂253conventional live virus vaccines传统的活病毒疫苗254conventional vaccines传统疫苗255cool white fluorescent冷白荧光灯256corpora lutea黄体257corpora lutea count黄体数258correction factor校正因子259correlation coefficient相关系数260covalent or noncovalent共价或非共价261creams霜剂262cross-contamination交叉污染263cross-linking agent交联剂264cross-reactivity交叉反应265cryopreservation冷冻保存266cryoprotectants防冻剂267crystals晶体268culture components 培养基成分269culture condiction培养条件270culture confluency培养克隆率271culture confluenty培养融合272culture media/medium培养基273culture medium培养基274cyanogen bromide溴化氰275cytogenetic细胞遗传学的276cytogenetic change细胞遗传学改变277cytogenetic evaluation细胞遗传学评价278cytokines细胞因子279cytopathic细胞病的280cytoplasmic A-and R-type particles细胞浆a型和r型颗粒281cytotoxicity细胞毒282dark control暗度控制283dead offspring at birth 出生时死亡的子代284deamidation去氨基285deaminated去酰胺化的286deamination脱氨基287decision flow chart/tree判断图288definable and measurable biological activity明确和可测定的生物学活性289degradant降解产物290degradation降解291degradation pathway降解途径292degradation product降解产物293degradation profile降解概况294degree of aggregation 凝集度295degree of scatter离散程度296delay of parturition分娩延迟297delayed-release延迟释放298deleterious有害的299deletion缺失300delivery systems给药体系301derivatives衍生物302description 性状303descriptive statistics描述性统计304detection limit检测限度305detection of bacterial mutagen细菌诱变剂检测306detection of clastogen染色体断裂剂检测307determination of metabolites测定代谢产物308development of the offspring 子代发育309developmental toxicity发育毒性310dilivery systems释放系统311dilution ratio释放倍数312dimers二聚体313diminution of the background lawn背景减少314diode array二极管阵列315diploid cells二倍体细胞316direct genetic damage 直接遗传损伤317dissociation解离318dissolution testing溶出试验319dissolution time溶出时间320distribution分布321DNA adduct DNA加合物322DNA damage DNA损伤323DNA repair DNA修复324DNA strand breaks DNA链断裂325dosage form剂型326dose dependence剂量依赖关系327dose escalation剂量递增328dose level剂量水平329dose -liming toxicity剂量限制性毒性330dose-ranging studies剂量范围研究331dose-related剂量相关　332dose-relatived cytotoxicity剂量相关性细胞毒性333dose-relatived genotoxic activity剂量相关性遗传毒性334dose-relatived mutagenicity剂量相关性诱变性335dose-response curve剂量－反应曲线336dosing route给药途径337downstream purification下游纯化338drug product制剂339drug product components制剂组方340drug substances原料药341duration周期342duration of pregnancy妊娠周期343eaning断奶344earlier physical malformation早期身体畸形345early embryonic development早期胚胎发育346early embryonic development to implantation着床早期的胚胎发育347ectromelia virus脱脚病病毒348elastomeric closures橡皮塞349electro ejaculation电射精350electron microscopy(EM)电镜351electrophoresis电泳352electrophoretic pattern电泳图谱353elimination消除354elution profile洗脱方案355embryofetal deaths胚胎和胎仔死亡356embryo-fetal development 胚胎－胎仔发育357embryo-fetal toxicity胚胎－胎仔毒性358embryonated eggs鸡胚359embryonic death胚胎死亡360embryonic development胚胎发育361embryonic period胚胎期362embryos胚胎　363embryotoxicity胚胎毒性364enantiomer对映体365enantiomer对映异构体366enantiomeric镜像异构体367enantioselective对映体选择性368encephalomyocarditis virus(EMC)脑心肌炎病毒369end of pregnancy怀孕终止370endocytic 内吞噬（胞饮）371endocytic activity内吞噬活性372endogenous agents内源性因子373endogenous components内源性物质374endogenous gene内源性基因375endogenous proteins内源性蛋白376endogenous retrovirus内源性逆转录病毒377endonuclease核酸内切酶378endonuclease release form lysosomes溶酶体释放核酸内切酶379endotoxins内毒素380end-point终点381end-product sterility test-ing最终产品的无菌试验382enhancers增强子383enveloped RNA viruses包膜RNA病毒384environmental factors环境因素385enzymatic reaction rates酶反应速率386enzyme酶387epididymal sperm maturation附睾精子成熟性388epitope表位389epitope抗原决定部位390Epstein-Barr virus (EBV)EB病毒391equine马392error prone repair易错性修复393erythropoietins促红细胞生成素394escalation递增395escherichia coli starn大肠杆菌菌株396esscherichia coli 大肠杆菌397ethnic origin种族起源398eukaryotic cell真核细胞399evaluation of test result试验结果评价400ex vivo体外401exaggerated pharmacological response超常增强的药理作用402excipient赋形剂403excipient specifications赋形剂规范404excretion排泄(消除)405expiration date/dating失效日期406exposure assessment 接触剂量评价407exposure level暴露程度408exposure period光照时间409exposure period接触期410expression constract表达构建体411expression system表达系统412expression vector表达载体413extended-release延时释放414extent of the virus test病毒测试的程度415external metabolising system体外代谢系统416extinction coefficient消光系数417extrachromosomal染色体外418extraneous contaminants外源性污染物419extrapolation 外推法420F1-animals子一代动物421false negative result假阴性结果422false positive result假阳性结果423fecundity多产424feed-back反馈425fermentation发酵426fermentation products发酵产品427fertilisation受精428fertility生育力429fertility studies生育力研究430fetal abnormalities胎仔异常431fetal and neonatal parameters胎仔和仔鼠的生长发育参数432fetal development and growth胎仔发育和生长433fetal period 胎仔期434fetotoxicity胎仔毒性435fill volume装量436filter aids 过滤介质437final manufacturing最终生产438finished product成品439first pass testing 一期试验440flanking region侧翼区441fluorescence in situ hybridisation (FISH)原位荧光分子杂文442foetuses胎仔443forced degradation testing强制降解试验444foreign matter异质性物质445formal labeling正式标签446formal stability studies正式的稳定性研究447formulation 处方/配方448formulation 制剂449fragmentation片段化450frameshift mutation移码突变451frameshift point mutation移码点突变452free-standing独立453freeze-dried product冻干产品454fresh dissection technique新鲜切片技术455friability脆碎度456functional deficits功能试验457functional test功能性指标458funetional indices融合蛋白459fungi真菌460fusion partners融合伴侣461fusion protein融合蛋白462fusion proteins配子463gametes动物性别464gel filtration 凝胶过滤465gender of animals性别专一性药物466gender-specific drug基因剔除467gene amplification基因扩增468gene knockout基因治疗469gene mutation基因突变470gene therapy基因疗法471generation of the cell substrate细胞基质的产生472genetic遗传473genetic change 遗传学改变474genetic damage遗传学损伤475genetic endpoint遗传终点476genetic manipulation基因操作477genetic toxicity遗传毒性478genomic dinucleotide repeats基因组双核苷酸重复数479genomic DNA基因组DNA480genomic polymorphism pattern基因组形态类型481genotoxic activity遗传毒性作用482genotoxic carcinogen遗传毒性致癌剂483genotoxic effect 遗传毒性效应484genotoxic hazard遗传毒性危害485genotoxic potential潜在遗传毒性486genotoxic rodent carcinogen啮齿类动物遗传毒性致癌剂487genotoxicity 遗传毒性488genotoxicity evaluation遗传毒性评价489genotoxicity test遗传毒性试验490genotoxicity test battery遗传毒性试验组合491genotypic 基因型492germ cell mutagen生殖细胞诱变剂493germ line mutation生殖系统突变494GLP临床前研究质量管理规范495glucose consumption rates耗糖率496glycoforms糖化形式497glycosylation糖基化498goegrapgical origin 地理起源499gross chromosomal damage 染色体大损伤500gross evaluation of placenta 胎盘的大体评价501growth factors生长因子502growth hormones 生长激素503guanidine胍504haematoxylin staining苏木素染色505half-life半衰期506hamster antibody production(HAP) test仓鼠抗体产生实验507Hantaan virus汉坦病毒508hardness硬度509heavy metals重金属510hematopoietic cells造血细胞511heparins肝素512heptachlor七氯化合物513herbal products草药514heritable遗传515heritable defect遗传缺陷516heritable disease遗传性疾病517heritable effect 遗传效应518herpes virus 疱疹病毒519heterogeneities异质性520heterohybrid cell lines异种杂交细胞系521high concentration高浓度522high-resolution chromatography高分辨色谱523histologic appearance of reproductive organ生殖器官的组织学表现524histopathological chang组织病理学改变525homogeneity均一性526homologous proteins同系蛋白527homologous series同系528host cell 宿主细胞529host cell banks宿主细胞库530host cell DNA宿主细胞DNA531host cell proteins宿主细胞蛋白质532hot-stage microscopy热价显微镜533human carcinogen人类致癌剂534human cell lines人细胞系535human diploid fibroblasts人二倍体成纤维细胞536human lymphoblastoid TK6 cell 人成淋巴TK6细胞537human mutagen人类致突变剂538human polio virus人脊髓灰质炎病毒539human subjects人体540human tropism人向性541humidity湿度542humidity-protecting containers防湿容器543humoral immunity 体液免疫544hybridization techniques杂交技术545hybridoma cell杂交瘤细胞546hybridomas杂交瘤547hydrolysates水解物548hydrolytic enzymes水解酶549hydrophobicity疏水性550hygroscopic吸湿性551identification/identity鉴别552immature erythrocyte未成熟红细胞553immediate and latent effect速发和迟发效应554immediate container/closure直接接触的容器/密闭物555immediate pack内包装556immediate release立即释放557immortalization激活558immune spleen cells免疫脾细胞559immunoassay免疫检测560immunochemical methods免疫化学方法561immunochemical properties免疫化学性质562immunoelectrophoresis免疫电泳563immunogenicity免疫原性564immunological interations免疫相互作用565immunopathological effects免疫病理反应566immunoreactivity免疫反应性567immunotoxicity免疫毒性568implantation着床569implantation sites着床部位570impurity profile杂质概况571in vitro体外572in vitro and in vivo inoculation tests体内和体外接种试验573in vitro assay体外检测574in vitro cell age体外细胞传代期575in vitro lifespan体外生命周期576in vitro test体外试验577in vitro tests体外试验578in vitro/in vivo correlation体内体外相关性579in vivo体内580in vivo assays体内检测581in vivo test体内试验582inactivated vaccine 灭活疫苗583incidence of polyploid cell 多倍体细胞发生率584incisor eruption门齿萌出585independent test独立试验586indicator cell指示细胞587indicator organisms指示菌588individual fetal body weight单个胎仔体重589indoor indirect daylight室内间接日光590induced and spontaneous models of disease诱发或自发的疾病模型591inducer of micronuclei微核诱导剂592inducers 诱导剂593inedntification test鉴别试验594infectious agents感染性因子595influenza virus流感病毒596inhalation吸入597inhalation dosage forms 吸入剂型598inhibitor of DNA metabolism DNA代谢抑制剂599in-house内部的600in-house criterea内控标准601in-house primary reference material内部一级参比物质602in-house reference materials内部参比物质603in-house working reference material内部工作参比物质604initial filing原始文件605initial submission最初申报606initial text最初文本607inoculation接种608inorganic impurities无机杂质609inorganic mineral无机矿物质610inorganic salts无机盐611in-process acceptance criteia生产过程认可标准612in-process controls生产过程中控制613in-process testing生产过程中检测614insect昆虫615insulins胰岛素616intact animals完整动物（整体动物）617intake摄入618intended effect预期效果619intended storage period 预期的贮藏期620intentional degradation人为降解621interactions相互作用622interferon干扰素623interleukins白细胞介素624intermediate中间体625intermediate precision中间精密度626intermediates半成品627internal control内对照628international reference standards国际参比标准品629interphase muclei分裂间期细胞核630intra-and inter-individual个体与个体间631intra-assay precision间隙含量精密度632intracytoplasmic细胞浆内633introduction of virus病毒介入634inverted or horizontal position倒立或水平位置635ion-exchange离子交换636ionic content离子含量637isoelectric focusing/isoelectrofocusing等电聚焦638isoenzyme analysis同工酶分析639isoform pattern异构体类型640isolated organs离体器官641isomerized 异构化的642Jp/Ph.Eur./Usp.日本药局方/欧洲药典/美国药典643juvenile animal studies未成年动物研究644K virus K病毒645karyology胞核学646Kinetic profile动力学特点647Kinetics 动力学648laboratory scale实验室规模649lactate production rates乳糖产生速率650Lactating授乳、哺乳651lactic dehydrogenase virus (LDM)乳酸脱氢酶病毒652Large deletion event大缺失事件653Late embryo loss后期胚胎丢失654leachables沥出物655Level of safety安全水平656Libido性欲657Life threatering危及生命658ligand 配位体/配体659light光照660light resistant packaging避光包装661limit for in vitro cell age 细胞体外传代限度662limit of acceptance可接受的限度663limit of in vitro cell age 体外细胞代次664limit test限度试验665limulus amoebocyte lysate鲎试剂666linear relation ship 线性关系667linearity线性668Lipophilic compound亲脂性化合物669liquid nitrogen 液氮670liquid oral dosage forms 液体口服制剂671Litter size每窝胎仔数目672Live and dead conceptuese活胎和死胎673Live offspring at birth出生时存活的子代674live vaccine 活疫苗675living cells活细胞676Local toxicity局部毒性677Lockl tolerance studies 局部耐受性研究678Locu位点679logarithmic scale:对数级680long term test长期试验681Long-term carcinogenicity study长期致癌性试验682long-time and accelerated stability长期和加速稳定性试验683Loss of the tk gene tk 基因丢失684losses of activity活性丧失685lot release 批签发686low molecular weight subsances低分子量物质687lower-observed effect level (LOEL)能观察到反应的最低量688lymphocytic choriomeningitis virus (LCM)淋巴细胞性脉络丛脑膜炎病毒689lyophilised cakes冻干粉饼690lysate of cells 细胞溶解物691Major organ fomeation主要器官形成692Male fertility雄性生育力693Male fertility assessment雄性生育力评价694mammalian哺乳类695Mammalian cell mutation test哺乳动物细胞致突变试验696Mammalian cells哺乳动物细胞697Mammalian species哺乳类动物698manufacturing scale生产规模699marieting pack 上市包装700marker chromosome 标志染色体701marketing approval批准上市702Marketing approval上市许可703mass 重量704mass balance质量平衡705mass spectrometry质谱706master cell bank (MCB)主细胞库707Matemal animal亲代动物708material balance物质平衡709Mating behaviour交配行为710Mating period交配期711Mating ratio交配比例712Matrices基质713matrix基质、矩阵714matrix system矩阵化设计715matrixing每日最大剂量716maximum daily dose平均动力学温度717Maximum tolerated dese(MTD)最大耐受剂量718mean kinetic temperature后生动物细胞培养719Mechanism of genotoxicity遗传毒性机制720Mechanistic activation代谢活化721Mechanistic activation pathway代谢活化途径722Mechanistic activation system代谢活化系统723Mechanistic investigation机制研究724Metabolism代谢725Metabolites profile代谢物的概况726Metaphase中期727Metaphase analysis分裂中期相分析728Metaphase cell分裂中期细胞729metazoan cell culture微生物细胞培养730microbial cells微生物细胞731microbial contamunation 微生物污染732microbial expression system微生物表达系统733microbial limits微生物限度734microbial metabolites微生物代谢物735microbial proteases微生物蛋白酶736microbial vaccine antigens微生物疫苗抗原737microbiological testing 微生物学试验738Micronucleus微核739Micronucleus formation微核形成740Microtitre微滴定741Microtitre method微滴定法742Mimicking模拟743minimum exposure time最低作用时间744minimum of pilot plant试产规模745minute virus of mice小鼠小病毒746mirror image 镜像747mismached S-S linked错连的S-S键748Mitotic index有丝分裂指数749modified-/modifying release修饰释放750modifying factor修正因子751moisture level水分752molar absorptivity克分子吸收753Molecular characterisation分子特性754molecular characteristics分子特性755molecular confirmation分子构型756molecular entities/entity分子实体757molecular size分子大小758Molecular technique分子技术759Monitor监测760Monoclonal antibodies单克隆抗体761monoclonal antibody单克隆抗体762mork run空白对照试验763morphological analysis形态学分析764mouse antibody production (MAP) test小鼠抗体产生试验765mouse cytomegalovirus (MCMV)小鼠巨细胞病毒766mouse encephalomyelitis virus (GDVII)小鼠脑脊髓炎病毒767mouse hepatitis virus (MHV)小鼠肝炎病毒768Mouse lymphoma tk assay小鼠淋巴瘤tk检测769Mouse lymphoma L5178Y cell小鼠淋巴瘤L5178Y细胞770mouse rotavirus (EDIM)小鼠小轮状病毒771MuLV murine leukemia virus鼠白血病病毒772murine hybridoma cell lines鼠杂交瘤细胞系773Mutagen诱变原774Mutagen carcinogen诱变性致癌剂775Mutagen potential of chemical化合物的潜在致突变性776Mutant colony突变体集落777Mutation突变778Mutation induction in transgenes转基因诱导突变779mutations 突变780mycoplasma支原体781myeloma cell line骨髓瘤细胞系782Naked eye肉眼783national or international reference material国家或国际参比物质784national reference standards国家参比标准品785near ultraviolet lamp近紫外灯786Necropsy(macroscopic examination)解剖（大体检查）787Negative control阴性对照788Negative result阴性结果789Neonate adaptation to extrautenrine life新生仔宫外生活的适应性790neural sugars中性糖791new chemical entity新化学体792new dosage form新剂型793new drug products/produce新药制剂794new drug substance新原料药795new molecular entities新分子体796Newbom新生仔797Newcleated有核798no effect level不产生反应的量799Non rodent非啮齿类800Non-clinical非临床801noncovalent/convalent forces非共价/共价键802non-enveloped viruses非包膜病毒803Non-genotoxic carcinogen非遗传毒性致癌剂804Non-genotoxic mechanism非遗传毒性机制805Non-human primate非人灵长类806Non-linear非线性807non-mammalian animal cell lines非哺乳动物细胞系808non-recombinant cell-cul-ture expression systems非重组细胞培养表达系统809non-recombinant products/vaccines非重组制品/疫苗810non-specific model virus非特异模型病毒811Non-toxic compound无毒化合物812Non-toxic-effect dose level无毒性反应剂量水平813no-observed effect level不能观察到反应的量814N-terminal sequencing N端测序815nuclear magnetic resonance 核磁共振816Nucleated bone marrow cell有核骨髓细胞817nucleic acid核酸818Nucleoside analogue核苷酸同系物819nucleotide sequences 核苷酸序列820Number of live and dead implantation宫内活胎和死胎数821Numerical chromosmal aberration染色体数目畸变822Numerical chromosome changes染色体数目改变823Oestrous cycle动情周期824official procedure正式方法825ointments软膏826oligonucleotide低聚核苷酸827Oligonucleotide grugs寡核苷酸药物828oligosaccharide pattern寡糖类型829One,two,three generation studies一、二、三子代研究830opacity浊度831Organ development器官发育832organic impurities有机杂质833origins of replication复制起点834osmolality摩尔渗透压浓度835outdoor daylight室外日光836Ovulation rate排卵率837oxidation氧化838oxygen consumption rates耗氧量839package包装840Paraffine embedding石蜡包埋841parainfluenza virus副流感病毒842parallel control assays 平行对照分析843Parameter参数844Parent compound母体化合物845parent stability Guideline稳定性试验总指导原则846parental cell line母细胞系847Parenteral非肠道848parenterals非肠道制剂849particle size粒度850Particulate material颗粒物851particulate matter微粒852Parturition分娩延迟853parvoviruses细小病毒854passage history of the cell line细胞系的传代史855pathogenic agents致病因子856pathogenicity致病性857patterns of degradation降解方式858Pediatric populations小儿人群859peptide肽860peptide map 肽图861percent recovery回收率862periodic/skip testing定期检验/抽验863Peripheral blood erythrocyte外周血红细胞864permitted daily exposure允许的日接触量865Perpoductive competence生殖能力866phage typing噬菌体分型867pharcodynamic studies药效学研究868Pharmacodinetic药代动力学869Pharmacodynamic effects药效作用870Pharmacodynamics药效学（药效动力学）871pharmacopoeial药典872pharmacopoeial pharmacoppeial specifications药典规范873pharmacopoeial standards药典标准874phenotypic 表型875Phenylene diamine苯二胺876phosphorylation磷酸化作用877photostability testing光稳定性试验878Physical development身体发育879physicochemical changes理化改变880physicochemical methods物理化学方法881physico-chemical properties物理化学特性882Physiological stress生理应激883Pilot studies 前期研究884pilot-plant scale试生产规模/中试规模885Pinna unfolding耳廓张开886piston release force活塞释放力887piston travel force活塞移动力888pivotal stability studies关键的稳定性研究889plaque assays菌斑测定890plasmid质粒891Plasmid质粒892plasmid banks质粒库893plasminogen activators纤溶酶原激活素894Plasminogen activators纤维蛋白溶解酶原激活因子895Ploidy整倍体896pneumonia virus of mice小鼠肺炎病毒897Point mutation点突变898poisson distribution泊松分布899Polychromatic erythrocyte嗜多染红细胞900polyclonal antibody多克隆抗体901Polycyclic hydrocarbon多环芳烃902Polymer聚合物903polymerase chain reaction (PCR)聚合酶链式反应904polymorphic form多晶性型905polymorphs多晶型906polyoma virus多瘤病毒907polypeptides多肽908Polyploid cell多倍体细胞909Polyploidy多倍体910Polyploidy induction多倍体诱导911pooled havest集中回收912Poorly soluble compound难溶化合物913population doubling细胞数倍增/群体倍增914porcine猪915Positive control阳性对照916Positive result阳性结果917Post meiotic stages减数分裂后期918Post-approval批准后919Postcoital time frame交配后日期920Postimplantation deaths着床后死亡921Postnatal deaths出生后死亡922post-translational modifications批准后923post-translationally modified forms翻译后修饰924Postweaning development and growth断奶后发育和生长925potency效价926potent功效927Potential 潜在性928potential adverse consequences潜在的不良后果929potential excipients准赋形剂930Potential immunogenecity潜在免疫原性931potential impurity潜在杂质932potential new drug products准新药制剂933potential new drug substances准新药原料934Potentialtarget organs for toxicity潜在毒性靶器官935potentiometric titrimetry电位滴定936powders粉剂937power outages and human error断电和人为错误938preamble引言939Pre-and post-natal development study围产期的发育研究940Pre-and postweaning survival and growth断奶前后的存活和生长941pre-approval or pre-liscense stage批准前或发证前阶段942Precipitate沉淀物943precision精密度944preclinical and clinical studies临床前和临床研究945Preclinical safety evaluation临床前安全性评价946precursors前体947Predetermined criteria预定标准948Prediction of carcinogenicity致癌性预测949Pregnant怀孕950Pregnant and lactating animals怀孕与哺乳期动物951Preimplantation development着床前发育952Preimplantation stages of the embryo胚胎着床前期953preliminary assessment初步评估954preliminary cell bank初级细胞库955Preliminary studies预试验956Premating交配前957Premating treatment交配前给药958preparation制剂959Pre-screening预筛选960preservative防腐剂961Prevalence of abnormalities异常情况的普遍程度962Preweaning断奶前963Primary active entity主要活性实体964primary cells原代细胞965primary stability data主要稳定性数据966primary stability study/formal study/formal stability study主要稳定性研究/正式研究/正式稳定性研究967primary structure一级结构968primer引物969priming regimen接种方案970Priority selection优先选择971probability概率972process characterisation studies工艺鉴定研究973process controls工艺控制974process optimisation工艺优化975process parameters工艺参数976process validation工艺确证977process-related impurities工艺相关杂质978Pro-drug前体药物979product-related imputies产品相关杂质980progenitor祖细胞981prokaryotic cell原核细胞982Prolongation of parturition产程延长983promoters启动子984proposed commercial process模拟上市985protected samples避光样品。