AR-42_935881-37-1_DataSheet_MedChemExpress

Hirsch Teil1. What are chemical sensors?- Definition !!!2. Selectivity- Definition- Equilibrium based selectivity: free energy, dielectric constant and distance,- Kinetic based selectivity: steady-state regime3. Recognition Methods- Ion recognition: recognition-electric charge, selectivity-size,transduction-potentiometric, optical methodse.g. PH electrode ----> part 3- Recognition by affinity interactions: reversible, non-covalent bonds-ionic bonds, hydrogen bonds, van der Waals interaction => result in a molecular assiciation complex; also respect to shape and chemical reactivity; indicated by stability constant (very stable)- antibody - antigen interaction => immunochemical reactionantibody: glycoprotein produced by immune system to identify and neutralizepathogen microorganisms.antigen: the part of the pathogen that reactions with the antibody.use specific antibody receptor => identify pathogenuse antigen receptor => identify antibody (the detection of infection byparticular pathogen)- lectin proteins recognize caborhydrates (agglutinins, hemagglutinin)carbohydrate-binding modules link to the catalytic part of glycosidehydrolases => result in degradation of cell wall, storage of polysaccharide- A Molecularly Imprinted Polymer (MIP) is a polymer that has been processed usingthe molecular imprinting technique which leaves cavities in polymer matrix withaffinity to a chosen "template" molecule.In chemistry, molecular imprinting is a technique to create template-shaped cavities in polymer matrices with memory of the template molecules to be used in molecular recognition.-Nucleic acid aptamers are nucleic acid species that have been engineered throughrepeated rounds of in vitro selection to bind to various molecular targets such assmall molecules, proteins, nucleic acids, and even cells, tissues and organisms.Aptamers are useful in biotechnological and therapeutic a pplications as they offer molecular recognition properties that rival that of the commonly used bimolecular antibodies.- Recognition by nucleic acids: hydrogen bonds between two distinct pairs of nucleobases => two complementary nucleic acids form a double strand association complex => called hybridizationnucleic acid sensors: short single strand NA as receptor to recognize a particular NA sequence in the analyte NA => detection of genetic anomalies and pathogen mircoorganism- Recognition by enzyme: dynamic processEnzyme: protein compound that function as catalysts in chemical reaction occurring in living system.- Recognition by cells and tissues: advantages of enzyme incorporated in biological materials => in their natural environmentsee part 3, Wegener - Recognition by gases and vapors: based on sorption at solid material => surface-adsorption, inner-absorption; purely physical phenomenon or chemical reaction.4. Transduction MetohdosChemical transduction: monitoring the change of chemical composition of the sensing element in response to the recognition process. => change in concentration/amount is measured => detect primary product -> secondary product or coreagent -> labeling productLABEL can be a simple molecular species or nanoparticals that can be detected by available physiochemical methods => enzyme, fluorescent dyes, luminescent dyes, electroactive compoundsPhysical transduction: a specific physical property of the sensing element that is affected by its interaction with the analyte is monitored. => mass, reflective index, dielectric properties, electrical resistivity => LABEL-FREE- Thermometric transductionRecognition of the analyte leads to change in temperature => only catalytical processes generate sufficient heat to the measurement => application: combustible gases react with O2 at the surface of a catalyst.- Transduction based on mechanical effectsRecognition leads to change in mass of the sensing element => monitored by mass tranducer based on quartz crystal microbalance (QCM)----------------------------------------------------------------------------------------------------------------- QCM, correct name: Thickness shear modePiezoelectric effect:generation of electrical charges on the surface of a solid by strain, pressure or torsion (mechanical deformation of solid) =>electricity resulting from pressureI nverse piezoelectric effect:application of charges to surfaces of piezoelectricsolid generates mechanical deformation (elongation, contraction, torsion)QCM is based on Inverse piezoelectric effect!# AT cut => 35`15`=> minimum temperature coefficient at 50~70 CIt makes the AT-cut well suited to applications requiring high degree of frequency stability over wide temperature ranges.## Electrodes are applied on both sides, and AC voltage applied.DC cannot flow across the crystal because it consists of an insulator material;however the crystal somewhat behaves as capacitor and allow an AC current to f low along the left-hand loop.AC voltage applied => leads to shear oscillation of crystal => when the voltage frequency matches the intrinsic vibration frequency of the crystal => the vibration amplitude is at maximal => the resonant => resonant frequency (f0) => depend on crystal thickness (e.g. d q= 330 um, f0= 5MHZ), density and elasticity of piezoelectric material### AT-cut resonator: thickness: ~0.2 mm, diameter of the active area: 5~20 mm #### Deposition of a homogenous mass film (a rigid overlay)Sauerbrey equation:Cf indicate sensitivity of QCMcondition of this equation: rigid deposited mass; △m<2% of crystal mass;operated in vacuum or in gaseous atmopphereIn liquid: the liquid breaks the vibration by friction => lessen f0Thickness of the layer must be greater than the wave decay lengththat is of 250 nm of 5 MHz resonator at water. ----> part 2!!!##### QCM in practice => see p.41----------------------------------------------------------------------------------------------------------------- - Resistive and capacitive transductionRecognition leads to changes in the electrical property of this materialResistive transduction: gases interact with MOS => change in electrical resistivity Capactive transduction => dielectric constant- Electrochemical transductionsee part 2, Matysik - Optical transductionOptical transduction can be based on light emission or light absorption, also by physical quantity (reflective index) and light scattering.5. Sensor Configuration and Fabrication- Lateral flow assayA typical test strip consists of the following components:1. Sample pad – an absorbent pad onto which the test sample is applied2. Conjugate pad –this contains antibodies specific to the target analyte;conjugated to coloured particles (e.g. gold nanoparticles)3. Reaction membrane –typically a hydrophobic nitrocellulose or celluloseacetate membrane onto which anti-target analyte antibodies are immobilized in a line across the membrane as a capture zone or test line, and a control zonecontaining antibodies specific for the conjugate antibodies.4. Wicking pad –a further absorbent pad designed to draw the sample acrossthe reaction membrane by capillary action and collect it.Double antibody sandwich assays: the sample migrates from the sample pad through the conjugate pad where any target analyte present will bind to the c onjugate.=> The sample then continues to migrate across the membrane until it reaches the test line where the target or conjugate complex will bind to the immobilized antibodies producing a visible line on the membrane. => The sample then migrates further along the strip until it reaches the control line, where excess conjugate will bind and producea second visible line on the membrane.This control line indicates that the sample has migrated across the membrane as intended. Two clear lines on the membrane is a positive result. A single line in the control zone is a negative result. Double antibody sandwich assays are most suitable for larger analytes, such as bacterial pathogens and viruses, with multiple antigenic sites. 6. Methods and Material in Sensor Preparation- Immobilization at solid surface => integration of a transducer with the receptor Physical adsorption at a solid supportNon covalent immobilization at solid surface => hydrophobic interaction, hydrogen bonding, electrostatic attraction; monolayer; no restrict access; not stable; Langmuir isotherm -> equilibrium interactionSupport material: silica, cellulose acetate, PVCCovalent bonding to the solid supportCovalent conjugation => stable, covalent bond, time consuming, expensiveCommon reactive group: -OH, -NH2, -C=O, -SH- Carboxylic acid with DCC- Glutaraldehyde reacts with the a.a. of lysine in protein => widely used Support: porous material => high specific area, high density of immobilized compounds => hydrogel: immobilized by entrapment/covalent corsslink - Natural polymers: Cellulose, Dextran- Synthetic polymers: Polystyrene- Active polymers: Epoxide (without preliminary activation) -->DNA array !!!- Inactive Polymers: Vicinal hydroxyls actived by CNBr- Inorganic support: Silica, AL2O3, TiO2 => stable at extreme PH- Metal support: noble metals, thiols on golds --> self assembled monolayers!Affinity reaction: avidin-biotin !!!Thin molecular layers: one or several molecular layers in solid support - Self-assembly of amphiphilic compounds: preparation of liposome andmicelles; liposome can be used of entrapment of molecular- Bilipid layer membranes: Langmuir-Blodgett technique- Layer by Layer assembly- Sol-Gel chemistry methods: silica gel => -O-Si-O-- Hydrogels: Xerogel, aerogel- Conducting polymers: Polyacetylene, polyaniline --> gas senor based on CP (----> part 3 !!!); also as entrapment matrix for biological receptors- Mesoporous materials: porous materials with pore (diameter: 2-50 nm,close to protein) => enzyme immobilization by entrapment (crosslinking withglutaraldehyde)- Deposition of polymers onto solid surfaces: dip coating, drop coating, spin coating ----> part 2 !!!Perm-selective memberanes: Nafin ----> Clark oxygen electrode Support-free crosslinkingEntrapment in a polymer networkEncapsulation7. Microfabrication Methodes- Spot Arraying: Contact-based & Noncontact-based; DNA microarray !!!!!Pros & Cons- Thick-film Technology: screen-printing technique (5-50 um thick layer)- Thin-film Technology: Photolithography (2 um)- Softlithography ----> experiment !!!!- Microcontact printing ----> experiment !!!!8. Optical Sensors- Electromagnetic RadiationOptical sensor => interaction of electromagnetic radiation with sensor layer - frequency; wavelength; photon energy (definition)- Structure: integration with wavelength-selection (optical filters) device and light sources (lasers), light detectors (phototransistors)- Optical Waveguides- Optical FibersOptical fibers' structuretotal internal reflection => evanescent wave- Spectrochemical Transduction MethodsSpectrochemical method analysis => light absorption or emission by sample => optical label performs absorption or emission (organic dye or metal complexes) - Light absorption: absorbance => concentration; sensitivity => thickness, absorpyivity, absorptivity => wavelength- Diffuse reflectance spectrometry: refelctance => concentration; suitable forsolid in near IR- Luminescence: Fluorescence spectromerty => fluorophore (label, organic dye or metal complexes, luminescent nanparticle ); steady-statefluorescence measurement, Time-resolved fluormetry; fluorescencequenching; resonance energy transfer (FRET); chemical- andbioluminescence => luminol; electrochemicaluminescence; Ramanspetrometry- Surface Plasmon Resonance Spectroscopy (SPR)。

Product Data SheetTrigonox BDi-tert-butyl peroxideTrigonox® B is a pure peroxide in liquid form.CAS number110-05-4EINECS/ELINCS No. 203-733-6TSCA statuslisted on inventory Molecular weight 146.2Active oxygen contentperoxide10.94%SpecificationsAppearance Clear liquidAssay≥ 99.0 %ApplicationsTrigonox® B (Di-tert-butyl peroxide) can be used for the market segments: polymer production, polymer crosslinking and acrylics production with their different applications/functions. For more information please check our website and/or contact us.Half-life dataThe reactivity of an organic peroxide is usually given by its half-life (t½) at various temperatures. For Trigonox® B in chlorobenzene half-life at other temperatures can be calculated by using the equations and constants mentioned below:0.1 hr at 164°C (327°F)1 hr at 141°C (286°F)10 hr at 121°C (250°F)Formula 1kd = A·e-Ea/RTFormula 2t½ = (ln2)/kdEa153.46 kJ/moleA 4.20E+15 s-1R8.3142 J/mole·KT(273.15+°C) KThermal stabilityOrganic peroxides are thermally unstable substances which may undergo self-accelerating decomposition. The lowest temperature at which self-accelerating decomposition may occur with a substance in the packaging as used for transport is the Self-Accelerating Decomposition Temperature (SADT). The SADT is determined on the basis of the Heat Accumulation Storage Test.SADT80°C (176°F)Method The Heat Accumulation Storage Test is a recognized test method for thedetermination of the SADT of organic peroxides (see Recommendations on theTransport of Dangerous Goods, Manual of Tests and Criteria - United Nations, NewYork and Geneva).StorageDue to the relatively unstable nature of organic peroxides, a loss of quality will occur over a period of time. To minimize the loss of quality, Nouryon recommends a maximum storage temperature (Ts max. ) for each organic peroxide product.Ts Max.40°C (104°F) andTs Min.-30°C (-22°F) to prevent crystallizationNote When stored according to these recommended storage conditions, Trigonox® Bwill remain within the Nouryon specifications for a period of at least 6 months afterdelivery.Packaging and transportIn North America Trigonox® B is packed in non-returnable, five gallon polyethylene containers of 30 lb net weight and steel drums of 100 or 340 lb net weight. In other regions the standard packaging is a 30-liter HDPE can (Nourytainer®) for 20 kg peroxide. Delivery in a 200 l steel drum for 150 kg peroxide is also possible in a number of countries. Both packaging and transport meet the international regulations. For the availability of other packed quantities consult your Nouryon representative. Trigonox® B is classified as Organic peroxide type E; liquid, Division 5. 2; UN 3107.Safety and handlingKeep containers tightly closed. Store and handle Trigonox® B in a dry well-ventilated place away from sources of heat or ignition and direct sunlight. Never weigh out in the storage room. Avoid contact with reducing agents (e. g. amines), acids, alkalis and heavy metal compounds (e. g. accelerators, driers and metal soaps). Please refer to the Safety Data Sheet (SDS) for detailed information on the safe storage, use and handling of Trigonox® B. This information should be thoroughly reviewed prior to acceptance of this product. The SDS is available at /sds-search.Major decomposition productsAcetone, Methane, tert-ButanolAll information concerning this product and/or suggestions for handling and use contained herein are offered in good faith and are believed to be reliable.Nouryon, however, makes no warranty as to accuracy and/or sufficiency of such information and/or suggestions, as to the product's merchantability or fitness for any particular purpose, or that any suggested use will not infringe any patent. Nouryon does not accept any liability whatsoever arising out of the use of or reliance on this information, or out of the use or the performance of the product. Nothing contained herein shall be construed as granting or extending any license under any patent. Customer must determine for himself, by preliminary tests or otherwise, the suitability of this product for his purposes.The information contained herein supersedes all previously issued information on the subject matter covered. The customer may forward, distribute, and/or photocopy this document only if unaltered and complete, including all of its headers and footers, and should refrain from any unauthorized use. Don’t copythis document to a website.Trigonox® and Nourytainer are registered trademarks of Nouryon Functional Chemicals B.V. or affiliates in one or more territories.Contact UsPolymer Specialties Americas************************Polymer Specialties Europe, Middle East, India and Africa*************************Polymer Specialties Asia Pacific************************2022-6-30© 2022Polymer crosslinking Trigonox B。

5.75.09Section:Prescription DrugsEffective Date: April 1, 2020 Subsection: Neuromuscular Drugs Original Policy Date: June 9, 2011 Subject:Hyaluronic Acid DerivativesPage:1 of 7Last Review Date:March 13, 2020Hyaluronic Acid DerivativesDescriptionDurolane, Euflexxa, GelSyn-3, GenVisc 850, Hyalgan , SodiumHyaluronate, Supartz , Synojoynt*, Triluron, TriVisc, Visco-3 (sodium hyaluronate)Gel-ONE , Hymovis, Monovisc, Orthovisc (hyaluronan)Synvisc, Synvisc-One (hylan G-F 20)Bolded medications are the preferred products*These medications are included in this policy but are not available in the market as of yetBackgroundOsteoarthritis of the knee is a disease in which the elastoviscous property of the synovial fluid in the knee joint becomes diminished, resulting in less protection and shock absorption. Durolane, Euflexxa, Gel-One, GelSyn-3, GenVisc 850, Hyalgan, Hymovis, Monovisc, Orthovisc, Sodium Hyaluronate, Synvisc, Synvisc-One, Supartz, Synojoynt, Triluron, TriVisc, Visco-3 are hyaluronan derivatives that are injected into the knee joints to increase the elastoviscous properties of arthritic joint fluid and slow its outflow from the joint . The goal of therapy is torestore the viscoelasticity in the affected joints, thereby decreasing pain, improving mobility, and restoring the natural protective functions (1).The American College of Rheumatology (ACR) updated its guidelines for the treatment of osteoarthritis (OA) of the knee in 2012. In mild symptomatic OA, treatment may be limited toFederal Employee Program® 1310 G Street, N.W.Washington, D.C. 20005 202.942.1000Fax 202.942.1125Section: Prescription Drugs Effective Date: April 1, 2020 Subsection: Neuromuscular Drugs Original Policy Date: June 9, 2011 Subject: Hyaluronic Acid Derivatives Page: 2 of 7patient education, physical and occupational therapy and other non-pharmacologic modalities. Nonpharmacologic modalities strongly recommended for the management of knee OA were aerobic, aquatic, and/or resistance exercises as well as weight loss for overweight patients. Nonpharmacologic modalities conditionally recommended for knee OA included medial wedge insoles for valgus knee OA, subtalar strapped lateral insoles for varus knee OA, medially directed patellar taping, manual therapy, walking aids, thermal agents, tai chi, self-management programs, and psychosocial interventions. Pharmacologic modalities conditionally recommended for the initial management of patients with knee OA included acetaminophen, oral and topical NSAIDs, tramadol, and intraarticular corticosteroid injections (1).Regulatory StatusFDA-approved indication: Hyaluronic acid derivatives are indicated for the treatment of pain in osteoarthritis (OA) of the knee in patients who have failed to respond adequately to conservative non-pharmacologic therapy, simple analgesics (e.g., acetaminophen), NSAIDs, tramadol, or intra-articular steroid injections (2-18).The hyaluronic acid derivatives are contraindicated for use in patients with known hypersensitivity to hyaluronan (sodium hyaluronate) preparations. Orthovisc lists hypersensitivity to gram positive bacterial proteins as an additional contraindication (4). Caution should be exercised when Gel-One, Hyalgan, Visco-3, Synvisc, Synvisc-One, Supartz, and Triluron are administered to patients with allergies to avian proteins, feathers, and egg products (3-8, 18).Hyaluronic acid derivatives are contraindicated to treat patients with knee joint infections, infections or skin diseases in the area of the injection site (2-17).A treatment cycle for most of the hyaluronan derivatives typically involves multiple weekly injections. Euflexxa, GelSyn-3, Sodium Hyaluronate, Synvisc, Triluron, TriVisc, and Visco-3 are given for a total of three injections. Orthovisc is given for three or four injections. GenVisc 850, Supartz and Hyalgan are given for a total of three or five injections. Durolane, Gel-One, Synojoynt, and Synvisc-One differ from the other hyaluronan derivatives in that it only requires one injection. Repeat courses of hyaluronan derivatives may be administered if symptoms return (2-18).Upon the basis of high quality supporting evidence, the American Academy of Orthopedic Surgeons cannot recommend using hyaluronic acid for patients with symptomatic osteoarthritis of the knee (19).Related policiesSection: Prescription Drugs Effective Date: April 1, 2020 Subsection: Neuromuscular Drugs Original Policy Date: June 9, 2011 Subject: Hyaluronic Acid Derivatives Page: 3 of 7Hyaluronate PowderPolicyThis policy statement applies to clinical review performed for pre-service (Prior Approval, Precertification, Advanced Benefit Determination, etc.) and/or post-service claims.Hyaluronic acid derivatives may be considered medically necessary for the treatment of osteoarthritis of the knee and if the conditions indicated below are met.Hyaluronic acid derivatives may be considered investigational for all other indications.Prior-Approval RequirementsAge18 years or older (22 or older for Synvisc, Synvisc-One, and TriVisc)DiagnosisPatient must have the following:Osteoarthritis of the kneeAND ALL of the following:1. Inadequate response to TWO or more of the following conservative non-pharmacologic therapy:a. Cardiovascular (aerobic) activity, such as: walking, biking, stationarybike, aquatic exerciseb. Resistance exercisec. Weight reduction (for persons who are overweight)d. Participation in self-management programse. Wear of medially directed patellar tapingf. Wear of wedged insolesg. Thermal agentsh. Walking aidsi. Physical therapyj. Occupational therapy2. Inadequate response, intolerance, or contraindication to TWO or more of thefollowing:Section: Prescription Drugs Effective Date: April 1, 2020 Subsection: Neuromuscular Drugs Original Policy Date: June 9, 2011 Subject: Hyaluronic Acid Derivatives Page: 4 of 7a. Acetaminophenb. Oral NSAIDsc. Topical NSAIDs3. Inadequate response, intolerance, or contraindication to intra-articularsteroid injections in which efficacy lasted less than 8 weeks4. Radiologic confirmation of Kellgren-Lawrence Scale score of grade 2 orgreater5. NO dual therapy with another hyaluronic acid injectable6. Non-preferred medications only: Patient MUST have tried at least TWO ofthe preferred products unless the patient has a valid medical exception (e.g.inadequate treatment response, intolerance, contraindication)Prior – Approval Renewal RequirementsAge18 years or older (22 or older for Synvisc, Synvisc-One, and TriVisc)DiagnosisPatient must have the following:Osteoarthritis of the kneeAND ALL of the following:1. Documentation of improvement in pain with previous course of treatment2. At least 12 months has elapsed since last injection of the prior treatmentcycle3. Documentation of reduction of dosing of NSAIDs or other analgesicsduring the 12 month period following the last injection of the prior treatmentcycle4. NO dual therapy with another hyaluronic acid injectable5. Non-preferred medications only: Patient MUST have tried at least TWOof the preferred products unless the patient has a valid medical exception(e.g. inadequate treatment response, intolerance, contraindication) Policy GuidelinesPre - PA AllowanceNoneSection: Prescription Drugs Effective Date: April 1, 2020 Subsection: Neuromuscular Drugs Original Policy Date: June 9, 2011 Subject: Hyaluronic Acid Derivatives Page: 5 of 7Prior - Approval LimitsDuration12 monthsQuantity One course of therapy for each kneePrior – Approval Renewal LimitsSame as aboveRationaleSummaryOsteoarthritis of the knee is a disease in which the elastoviscous property of the synovial fluid in the knee joint becomes diminished, resulting in less protection and shock absorption. Durolane, Euflexxa, Gel-One, GelSyn-3, GenVisc 850, Hyalgan, Hymovis, Monovisc, Orthovisc, Sodium Hyaluronate, Synvisc, Synvisc-One, Supartz, Synojoynt, Triluron, TriVisc, Visco-3 are hyaluronan derivatives that are injected into the knee joints to increase the elastoviscous properties of arthritic joint fluid and slow its outflow from the joint. The goal of therapy is to restore the viscoelasticity in the affected joints, thereby decreasing pain, improving mobility, and restoring the natural protective functions (1-18).Prior approval is required to ensure the safe, clinically appropriate and cost effective use of the hyaluronic acid derivatives while maintaining optimal therapeutic outcomes.References1. American College of Rheumatology, Subcommittee on Osteoarthritis Guidelines.Recommendations for the medical management of osteoarthritis of the hip and knee:2012 update. Arthritis Care & Research 2012; 64(4):465-474.2. Euflexxa [package insert]. Parsippany, NJ: Ferring Pharmaceuticals Inc.; July 2016.3. Hyalgan [package insert]. Parsippany, NJ: Fidia Pharma USA Inc.; May 2014.4. Orthovisc [package insert]. Woburn, MA: Anika Therapeutics; June 2005.5. Supartz [package insert]. Durham, NC: Bioventus LLC; April 2015.6. Synvisc [package insert]. Ridgefield, NJ: Genzyme Corp.; December 2014.7. Synvisc-One [package insert]. Ridgefield, NJ: Genzyme Corp.; September 2014;8. Gel-One [package insert]. Warsaw, IN: Zimmer Inc.; May 2011.9. Monovisc [package insert]. Bedford, MA: Anika Therapeutics; December 2013.10. Hymovis [package insert]. Parsippany, NJ: O Fidia Pharma USA Inc.; October 2015.Section: Prescription Drugs Effective Date: April 1, 2020 Subsection: Neuromuscular Drugs Original Policy Date: June 9, 2011 Subject: Hyaluronic Acid Derivatives Page: 6 of 711. GenVisc 850 [package insert]. Doylestown, PA: OrthogenRx Inc.; January 2015.12. GelSyn-3 [package insert]. Durham, NC: Bioventus LLC; January 2016.13. Durolane [package insert]. Durham, NC: Bioventus LLC; November 2017.14. Visco-3 [package insert]. Warsaw, IN: Zimmer, Inc.; May 2017.15. Sodium Hyaluronate [package insert]. North Wales, PA: Teva Pharmaceuticals USA,Inc.; March 2019.16. Synojoynt [package insert]. North Wales, PA: Teva Pharmaceuticals USA, Inc.;September 2019.17. TriVisc [package insert]. Doylestown, PA: OrthogenRx, Inc.; September 2018.18. Triluron [package insert]. Florham Park, NJ: Fidia Pharma USA Inc.; March 2019.19. American Academy of Orthopaedic Surgeons. Treatment of osteoarthritis of the knee.Evidence-based guideline 2nd edition. May 2013.Policy HistoryDate Action ReasonJanuary 2012 Added minimum age - only approved for adultsDecember 2012 Annual editorial review and reference updateDecember 2013 Annual editorial review and reference updateMarch 2014 Annual editorial reviewAddition of examples of non-pharmacological agents and agents of priorfailure medications.April 2014 Line-Addition of Monovisc to PAMarch 2015 Annual criteria review and reference updateMarch 2016 Change from one tried and failed to two tried and failed non-pharmacologic and pharmacologic therapies and addition of the tried and failed of intra-articular steroid and radiologic confirmation of Kellgren-Lawrence Scalescore of grade 2 or greaterAddition of HymovisPolicy # change from 5.11.04 to 5.75.09May 2016 Addition of GelSyn-3 and GenVisc 850December 2016 Annual editorial review and reference updateAdded: no dual therapy with another hyaluronic acid injectableMarch 2017 Bolded preferred products in the title pageJuly 2017 GelSyn-3 has been changed to preferredSeptember 2017 Annual reviewDecember 2017 Addition of Durolane and Visco-3March 2018 Annual editorial reviewRemoval of Tramadol from the T/F listSeptember 2019 Annual review and reference update. Addition of Sodium Hyaluronate,Synojoynt, and TriViscSection: Prescription Drugs Effective Date: April 1, 2020 Subsection: Neuromuscular Drugs Original Policy Date: June 9, 2011 Subject: Hyaluronic Acid Derivatives Page: 7 of 7December 2019 Annual review. Addition of requirement to trial preferred products January 2020 Addition of TriluronMarch 2020 Annual reviewKeywordsThis policy was approved by the FEP® Pharmacy and Medical Policy Committee on March 13, 2020 and is effective on April 1, 2020.。

RNP 68K ANTIGEN (Sm-FREE)AROTEC_RNP_68K_Product_Info.pdf Version/Date: B/04.05.20 ATR04-02 RNP 68K antigen 0.20 mgATR04-10 RNP 68K antigen 1.0 mg_________________________________________________________________________________Description of the ProductPurified from bovine thymus. After coating onto ELISA plates the product will bind autoantibodies to RNP 68K antigen.Purity: The RNP 68K autoantigen is more than 90% pure, as assessed by SDS gel electrophoresis.Concentration: 0.1-1.0 mg protein/ml.Storage: The product is stabilised with 0.1% Micr-O-protect TM. Store at -20 o C or below (long term) or at +4o C (short term). Avoid repeated freezing and thawing. Mix thoroughly before use.Clinical and Biochemical DataAutoantibodies directed against the snRNP (small nuclear ribonucleoprotein) autoantigens referred to as RNP and Sm were originally detected in the sera of systemic lupus erythematosus (SLE) patients1,2. Anti-RNP antibodies were subsequently found in the sera of mixed connective tissue disease (MCTD) patients3, and it is now known that when these antibodies occur at high titre and in the absence of Sm, they are a good marker for MCTD3,4. Such autoantibodies are also known to occur in the sera of patients with a range of other rheumatic diseases including progressive systemic sclerosis, rheumatoid arthritis, discoid lupus erythematosus, Sjögren's syndrome and various overlapping conditions5-10.The snRNPs are a group of nuclear particles comprised of several polypeptides associated with a small nuclear RNA molecule11. The most abundant snRNPs are involved in pre-mRNA-splicing11. At least 13 different snRNAs have been identified in mammalian cells11. Whereas autoantibodies directed against Sm are able to precipitate a wide range of snRNAs, RNP autoantibodies are only able to precipitate one particular type, referred to as U1snRNA. Anti-RNP antibodies react with the U1 snRNP-specific polypeptides12 (68K, A and C antigens) whereas anti-Sm antibodies react with polypeptides associated with U1, U2, U5 and U4/U6 snRNAs (B,B', D, E, F and G antigens)12,13.Current ELISA methods for the detection of autoantibodies to RNP often require the simultaneous determination of reactivity to both RNP/Sm and Sm antigens. The reactivity with Sm is then subtracted from that with RNP/Sm, the difference being considered to be due to RNP-specific autoantibodies. The availability of RNP antigen in the absence of Sm would avoid the necessity for a dual assay to detect anti-RNP antibodies and assays have been reported using isolated U1-RNP specific subunits14,15. Since the 68K U1-RNP polypeptide constitutes the major MCTD RNP autoantigen16,17, efforts to produce a recombinant RNP antigen have focussed on this subunit18-20, and not the U1-RNP specific subunits A and C which are known to share sequence homology and cross-reactivity with the Sm antigen B/B’21.Native RNP 68K subunit (present as a 33/35K doublet) is the primary component of AroTec's RNP 68K antigen (Sm-free). Although the human RNP 68K sequence is known22, there is currently no data available for the bovine antigen. However the complete identity between human22 and mouse23 sequences would indicate that such antigens are highly conserved between mammalian species. MethodologyThe following is an ELISA procedure which can be used to detect anti-RNP 68K autoantibodies in human serum using the ATR04 purified antigen:1. Dilute the purified antigen to 0.5-1.0 μg/ml in PBS (10 mM Potassium phosphate, pH 7.4, 0.15 M NaCl).2. Coat ELISA plates with 100 μl of diluted antigen per well. Cover and incubate 24 hours at +4o C.3. Empty the plates and remove excess liquid by tapping on a paper towel.4. Block excess protein binding sites by adding 200 μl PBS containing 1% BSA per well. Cover and incubate at +4o C overnight.5. Empty plates and apply 100 μl of serum samples diluted 1:100 in PBS / 1% BSA / 1% casein / 0.1% Tween® 20. Incubate at room temperature for 1 hour.6. Empty plates and add 200 μl PBS / 0.1% Tween® 20 per well. Incubate 5 minutes then empty plates. Repeat this step twice.7. Apply 100 μl anti-human IgG-enzyme conjugate (horseradish peroxidase or alkaline phosphatase) diluted in PBS / 1% BSA / 1% casein / 0.1% Tween® 20 per well and incubate for 1 hour.8. Repeat step 6.9. Add enzyme substrate and stop the reaction when appropriate.10. Read absorbance in an ELISA spectrophotometer. References1. Tan, E.M. & Kunkel, H.G. (1966) J. Immunol. 96, 4642. Mattioli, M. & Reichlin, M. (1971) J. Immunol. 107, 12813. Sharp, G.C. et al. (1972) Am. J. Med. 52, 1484. Sharp, G.C. et al. (1976) New Engl. J. Med. 295, 11495. Notman, D.D. et al. (1975) Ann. Intern. Med. 83, 4646. Tan, E.M. et al. (1988) Clin. Immunol. Pathol. 47, 1217. Tan, E.M. (1989) Adv. Immunol. 44, 938. van Venrooij, W.J. & Pruijn, G.J.M. (1995) Curr. OpinionImmunol. 7, 8199. Guldner, H.H. (1986) Clin. Immunol. Immunopathol. 40, 53210. Williams, D.G. et al. (1988) J. Immunol. Meth. 113, 2511. Lührmann, R. et al. (1990) Biochim. Biophys. Acta 1087, 26512. Petersson, I. et al. (1984) J. Biol. Chem. 259, 590713. Reuter, R. et al. (1990) Eur. J. Immunol. 20, 43714. Takeda, Y. et al. (1989) Clin. Immunol. Immunopathol. 50, 21315. Williams, D.G. et al. (1988) J. Immunol. Meth. 113, 2516. Combe, B. et al. (1989) Clin. Exp. Immunol. 75, 1817. Francoeur, A.M. (1989) J. Clin. Immunol. 9, 25618. Nyman, U. et al. (1990) Clin. Exp. Immunol. 81, 5219. Ter-Borg, E.J. et al. (1991) J. Rheumatol. 18, 36320. Frorath, B. et al. (1991) BioTechniques 11, 36421. Habets, W.J. et al. (1989) Proc. Natl. Acad. Sci. USA 86, 467422. Theissen, H. et al. (1986) EMBO J. 5, 320923. Kawai, J. et al. (2001) Nature 409, 685Micr-O-protect TM is from Roche Diagnostics GmbH (Mannheim, Germany).Tween® 20 is a registered trademark of ICI Americas Inc. NOTE: No patented technology has been used by AroTecduring the preparation of this product.。

Table S5. Species, ODEs, and initial values for the anti-electrophilic gene regulatory network model.Species ODE Initialconcentration(nM) NoteATP 0 6105× Adenosine triphosphate. The reported physiologicalconcentration ranges between 1~7 mM [1-4]. Glu 0 61010×Glutamate. The reported physiologicalconcentration ranges between 4~30 mM [5-8]. Cys 0 6103.0×Cysteine. Since GCL-catalyzed GSH synthesis is sensitive to cysteine level, and the K m of cysteine in this reaction is 0.22 mM [9], we set the basal concentration at 0.3 mM so that cysteine is not completely saturating the reaction.γ-GC 5554f f − 61015.0× gamma-glutamylcysteine. In human fibroblast, the level of γ-GC was estimated to be 0.15 mM, given [GSH] is at 5mM [10].Gly0 6101× Glycine. The concentration was assumed. GSH575655f f f −−6105×Reduced glutathione. The reported intracellular GSH concentration ranges from 1 to 10 mM in various biological tissue and cells [11]. We used 5 mM.X576059f f f −+ 3101×Here X represent an active electrophile. A major endogenous electrophile is the lipid peroxidation product 4-hydroxnonenal, the concentration of which ranges from 0.1~3 uM [12,13]. We used 1 uM.GSX5857f f −200GSH conjugate of X. This basal concentration is set at about 25% of the Ki for inhibition of GST. Keap16531f f f f −−−20Kelch-like ECH-associated protein 1. Theintracellular concentration is unknown. The value here gives the desired control on Nrf2 half-live as specified in Table S4.Keap1o542f f f +− 0Oxidized or conjugated form of Keap1.Nrf2c 743V /f f f −−−15f 14f −+ 5.0Nuclear factor erythroid 2 related factor 2 in the cytosol. The intracellular concentration is unknown. Since transcription factors generally exist in low abundance (in the nanomolar range ), we implemented a basal level of 0.5 nM. Nrf2-Keap1 631f f f −+− 0 Complex of Nrf2 and Keap1. Nrf2-Keap1o642f f f ++− 0 Complex of Nrf2 and Keap1o .Nrf2n 98n 7f f V /f −−1 Nuclear Nrf2. As it appears that nuclear Nrf2 level is about twice that in the cytosol [14], we implemented a basal level of 1 nM.Maf 9f − 1Small maf protein. The intracellular concentration is unknown. A low concentration of 1 nM wasassumed since it is a transcription factor partner. Nrf2-Maf 2216109f 3f 3f f −−−463830f 2f 2f 2−−− 0Heterodimer of Nrf2 and Maf.EpRE gene, where ,Gclc ,2Nrf {gene ∈ }Mrp ,Gst ,Gs ,Gclmm f −, where }46,38,30,22,16,10{m ∈0167.0EpRE-containing promoter for Nrf2, Gclc , Gclm , Gs , Gst , and Mrp genes, respectively. The value of 0.0167 is equivalent to one copy of molecule in a nuclear volume of 100 um 3.Nrf2-Maf-EpRE gene ,where,Gclc ,2Nrf {gene ∈ }Mrp ,Gst ,Gs ,Gclm m f , where }46,38,30,22,16,10{m ∈Complex of Nrf2-Maf dimer and EpRE-containing promoter for Nrf2, Gclc , Gclm , Gs , Gst , and Mrp genes, respectively.Gene off , where ,Gclc ,2Nrf {gene ∈ }Mrp ,Gst ,Gs ,Gclm n f −, where }47,39,31,23,17,11{n ∈0167.0Inactive state of Nrf2, Gclc , Gclm , Gs , Gst , and Mrp genes, respectively. The value of 0.0167 isequivalent to one copy of gen in a nuclear volume of 100 um 3.Gene on , where ,Gclc ,2Nrf {gene ∈ }Mrp ,Gst ,Gs ,Gclm n f , where }47,39,31,23,17,11{n ∈Active state of Nrf2, Gclc , Gclm , Gs , Gst , and Mrp genes, respectively.Gene mRNA, where ,Gclc ,2Nrf {Gene ∈ }Mrp ,Gst ,Gs ,Gclmq c n p f V /V f −, where}48,40,32,24,18,12{p ∈}49,41,33,25,19,13{q ∈mRNA of Nrf2, Gclc , Gclm , Gs , Gst , and Mrp genes, respectively.GCLC 282120f f f −− 3107.1× Glutamate cysteine ligase catalytic subunit. See the GCLM and GCL entries in the same table.GCLM282726f f f −−31036.0×Glutamate cysteine ligase modifier subunit. At this concentration, the GCLC/GCL ratio is 3 at the basal condition, as specified in reaction 28 in Table S4. GCL2928f f − 3106.0×Glutamate cysteine ligase holoenzyme. Thisconcentration, together with that of GCLC, gives a basal GSH synthesis rate of 386 nM/s, which is close to 360 nM/s measured in B16M melanoma cells given a cell volume of 1000 um 3 [15] GS mono 363534f 2f f −− 0 Glutathione synthetase monomer. GST mono 444342f 2f f −− 0 Glutathione S-transferase monomer.MRP mono525150f 2f f −−Multidrug resistance-associated protein monomer. GS3736f f − 31096.0×Glutathione synthetase dimer. This concentration keeps γ-GC at 0.15 mM at the basal condition. See the γ-GC entry in the same table for the choice of 0.15 mM.GST 4544f f − 310185.0× Glutathione S-transferase dimer. This concentration keeps X at 1 uM at the basal condition. See the X entry in the same table for the choice of 1 uM. MRP5352f f −31022.7×Multidrug resistance-associated protein. This concentration keeps GSX at 0.2 uM at the basal condition.References1. Ko SH, Lee SK, Han YJ, Choe H, Kwak YG, et al. (1997) Blockade of myocardial ATP-sensitive potassium channels by ketamine. Anesthesiology 87: 68-74.2. Gribble FM, Loussouarn G, Tucker SJ, Zhao C, Nichols CG, et al. (2000) A novel method for measurement of submembrane ATP concentration. J Biol Chem 275: 30046-30049.3. Leist M, Single B, Castoldi AF, Kuhnle S, Nicotera P (1997) Intracellular adenosine triphosphate (ATP) concentration: a switch in the decision between apoptosis and necrosis. J Exp Med 185: 1481-1486.4. Marcussen M, Larsen PJ (1996) Cell cycle-dependent regulation of cellular ATP concentration, and depolymerization of the interphase microtubular network induced by elevated cellular ATP concentration in whole fibroblasts. Cell Motil Cytoskeleton 35: 94-99.5. Goldstein L (1966) Relation of glutamate to ammonia production in the rat kidney. Am J Physiol 210: 661-666.6. Geerts WJ, Jonker A, Boon L, Meijer AJ, Charles R, et al. (1997) In situ measurement of glutamateconcentrations in the periportal, intermediate, and pericentral zones of rat liver. J Histochem Cytochem 45: 1217-1229.7. Divino Filho JC, Hazel SJ, Furst P, Bergstrom J, Hall K (1998) Glutamate concentration in plasma,erythrocyte and muscle in relation to plasma levels of insulin-like growth factor (IGF)-I, IGF binding protein-1 and insulin in patients on haemodialysis. J Endocrinol 156: 519-527.8. Huang CS, Chang LS, Anderson ME, Meister A (1993) Catalytic and regulatory properties of the heavysubunit of rat kidney gamma-glutamylcysteine synthetase. J Biol Chem 268: 19675-19680.9. Chen Y, Shertzer HG, Schneider SN, Nebert DW, Dalton TP (2005) Glutamate cysteine ligase catalysis:Dependence on ATPand modifier subunit for regulation of tissue glutathione levels. J Biol Chem.10. Ristoff E, Hebert C, Njalsson R, Norgren S, Rooyackers O, et al. (2002) Glutathione synthetasedeficiency: is gamma-glutamylcysteine accumulation a way to cope with oxidative stress in cells with insufficient levels of glutathione? J Inherit Metab Dis 25: 577-584.11. Meister A, Anderson ME (1983) Glutathione. Annu Rev Biochem 52: 711-760.12. Esterbauer H, Zollner H (1989) Methods for determination of aldehydic lipid peroxidation products.Free Radic Biol Med 7: 197-203.13. Esterbauer H, Eckl P, Ortner A (1990) Possible mutagens derived from lipids and lipid precursors.Mutat Res 238: 223-233.14. Pi J, Qu W, Reece JM, Kumagai Y, Waalkes MP (2003) Transcription factor Nrf2 activation byinorganic arsenic in cultured keratinocytes: involvement of hydrogen peroxide. Exp Cell Res 290: 234-245.15. Benlloch M, Ortega A, Ferrer P, Segarra R, Obrador E, et al. (2005) Acceleration of glutathione effluxand inhibition of gamma-glutamyltranspeptidase sensitize metastatic B16 melanoma cells toendothelium-induced cytotoxicity. J Biol Chem 280: 6950-6959.。

CHEMISTRY ACP ALB ALP ALT AM 货号270010036008201110060180006051000503601850111018018001803601870111050018005003600930TEST ACP ALB ALP ALT AM SAMPLE VOL．20371025 DILUTION0101000 REAGENT VOL.1-STEP250300270290250 DILUTION00000 2-STEP50[N] DILUTION00000 WAVE-LENGTH-1410600410340340 WAVE-LENGTH-2450700480410700 METHOD RATE END RATE RATE END REACTION+++--FIRST-POINT-160439 LAST-POINT-1166161616 FIRST-POINT-2N/A N/A N/A N/A N/A LAST-POINT-2N/A N/A N/A N/A N/A NO LAG-TIME YES NO YES YES NO TURBIDITY NO NO NO NO NO PROZONE CHECK NO NO NO NO NO REAGENT OD L-0.5-0.5-0.5-0.5-0.5 H 2.5 2.5 2.5 2.5 2.5 SERUM BLANK L N/A N/A N/A N/A N/A REAGENT OD H N/A N/A N/A N/A N/A MIN-OD-0.5-0.5-0.5-0.5-0.5 MAX-OD 2.0 2.0 2.0 2.0 2.0 LINEARITYDYNAMIC RANGE L00000 H8060100010001180 UNIT U/L g/L U/L U/L umol/L CORRELATION FACTORA=11111 B=00000 COUNT11111 DILUTION VOLUME00000 CONDENSE VOLUME00000 MONITOR SPAN11111 AGC POINT00000 K.FACTOR1308.42628.260780上述参数仅供参考，详情请参阅试剂说明及仪器说明。

血清C肽、尿微量白蛋白与糖化血红蛋白应用于糖尿病肾病诊断中的效果分析陈丹，胡丽，王彬阶麻城市人民医院检验科，湖北麻城438300[摘要]目的探究血清C肽（C-PR）、尿微量白蛋白（mAlb）与糖化血红蛋白（HbA1c）应用于糖尿病肾病（dia‐betic nephropathy, DN）的诊断效果。

方法回顾性分析2021年4月—2022年4月麻城市人民医院检验科收治的95例糖尿病（diabetes mellitus, DM）患者的临床资料，依据是否合并肾病划分为DM组（50例）、DN组（45例），基于相同时期选取到本院接受健康体检的志愿者60名作为对照组，均接受C-PR、mAlb、HbA1c检测，分析联合检测效果。

结果DN组C-PR水平最低，对照组最高，DN组mAlb、HbA1c水平最高，对照组最低，差异有统计学意义（P<0.05）。

联合检测诊断灵敏度97.78%、特异度93.33%，均显著高于C-PR、mAlb或HbA1c单一检测结果，差异有统计学意义（P<0.05）。

结论在DN患者中实施C-PR、mAlb、HbA1c联合检测具有较高的诊断价值，便于患者尽早得到有效治疗。

[关键词] 血清C肽；尿微量白蛋白；糖化血红蛋白；糖尿病肾病；糖尿病[中图分类号] R587.2；R692.9 [文献标识码] A [文章编号] 1672-4062（2023）06（b）-0181-04 Analysis of the Effect of Serum C Peptide, Urine Microalbumin and Gly⁃cated Hemoglobin Applied to the Diagnosis of Diabetic NephropathyCHEN Dan, HU Li, WANG BinjieDepartment of Laboratory, Macheng People′s Hospital, Macheng, Hubei Province, 438300 China[Abstract] Objective To explore the diagnostic effect of serum C-peptide (C-PR), urinary microalbumin (mAlb) and glycated hemoglobin in diabetes nephropathy (DN). Methods Retrospective analysis was made on the clinical data of 95 patients with diabetes mellitus (DM) admitted to the Laboratory Department of Macheng People′s Hospital from April 2021 to April 2022. They were divided into DM group (50 cases) and DN group (45 cases) according to whether they were complicated with kidney disease or not. Based on the same period, 60 volunteers who received physical ex‐amination in our hospital were selected as the control group, all of whom received C-PR, mAlb, and HbA1c tests, and the effect of the joint test was analyzed. Results The C-PR level in the DN group was the lowest, while the control group was the highest, the levels of mAlb and HbA1c in the DN group were the highest, while the control group was the lowest, the difference was statistically significant (P<0.05). The diagnostic sensitivity and specificity of the com‐bined test were 97.78% and 93.33%, which were significantly higher than those of the single test results of C-PR, mA1b, or HbA1c, and the difference was statistically significant (P<0.05). Conclusion The implementation of com‐bined C-PR, mAlb, and HbA1c assay in DN patients has high diagnostic value and facilitate patients to get effective treatment as early as possible.[Key words] Serum C peptide; Urine microalbumin; Glycated hemoglobin; Diabetic nephropathy; Diabetes mellitus糖尿病（diabetes mellitus, DM）作为我国较为常见的一种慢性代谢性疾病，据流行病学调查显示，我国每11个人里面就有1例糖尿病，患病率高达30.2%，且近年来随着人们生活方式及饮食习惯的改变，患病率呈现出逐年递增趋势，引起了社会各界的广泛重视。

注射用泮托拉唑钠中依地酸二钠含量分析方法的建立雷小平杨明亮姚吉勰陈青连（杭州澳亚生物技术股份有限公司杭州 310018）摘要目的：建立高效液相色谱法测定注射用泮托拉唑钠中依地酸二钠的含量。

方法：采用十八烷基硅烷键合硅胶为填充剂的C18色谱柱（4.6 mm×250 mm，5 m m），以磷酸盐缓冲液-乙腈（90∶10）、乙腈进行梯度洗脱，流速为1.0 mL/min，检测波长为254 nm，柱温为35 ℃，进样体积为20 m L。

结果：依地酸二钠的检测不受其他成分干扰，不同浓度依地酸二钠的回收率均在98.0%~102.0%之间，回收率RSD为0.39%，浓度在27.52~64.20 m g/mL范围内线性良好（r=1.000 0）。

结论：本方法简便、迅速、专属性及重现性好，可用于注射用泮托拉唑钠中依地酸二钠含量的测定。

关键词依地酸二钠注射用泮托拉唑钠含量高效液相色谱法中图分类号：O657.72; R975.2 文献标志码：A 文章编号：1006-1533(2022)05-0077-04引用本文雷小平, 杨明亮, 姚吉勰, 等. 注射用泮托拉唑钠中依地酸二钠含量分析方法的建立[J]. 上海医药, 2022, 43(5): 77-80.Establishment of method for disodium edetate in pantoprazole sodium for injectionLEI Xiaoping, YANG Mingliang, YAO Jixie, CHEN Qinglian(Hangzhou Ausia Biological Tech. Co., Ltd., Hangzhou 310018, China)ABSTRACT Objective: To establish a high performance liquid chromatography (HPLC) method for the determination of disodium edetate in pantoprazole sodium for injection. Methods: HPLC was performed using C18 column (4.6 mm×250 mm, 5 μm) with gradient elution containing phosphate buffer-acetonitrile (90:10) (A) and acetonitrile (B) at a flow rate of 1.0 mL/min, detection wavelength 254 nm, column temperature 35 ℃ and sample volume 20 m L. Results: The determination of disodium edetate was not interfered by other components in the injection. The recovery rates of different concentrations of disodium edetate were between 98.0%-102.0% with RSD 0.39%. Standard curve of disodium edetate showed good linearity over the range of27.52-64.20 m g/mL with r=1.000 0. Conclusion: This method is simple, rapid, specific and reproduceable and can be used for thedetermination of disodium edetate in pantoprazole sodium for injection.KEy WORDS disodium edetate; pantoprazole sodium for injection; assay; HPLC依地酸和依地酸盐在药物制剂、化妆品和食品中被用作螯合剂，它们与碱土金属和重金属离子形成稳定的水溶性络合物（螯合剂）。

碧云天生物技术/Beyotime Biotechnology 订货热线：400-1683301或800-8283301 订货e-mail ：******************技术咨询：*****************网址：碧云天网站 微信公众号细胞膜远红外荧光染色试剂盒(DiD)产品编号 产品名称包装 C1995S细胞膜远红外荧光染色试剂盒(DiD)200-1000次产品简介：细胞膜远红外荧光染色试剂盒(DiD)，Cell Plasma Membrane Staining Kit with DiD (Far-red Fluorescence)是一种以DiD 为荧光探针，并提供了染色增强剂、能快速灵敏地对细胞膜进行远红外荧光染色标记的试剂盒。

DiD 即DiIC 18(5)，也称为DiD' solid ，全称为1,1'-Dioctadecyl-3,3,3',3'-Tetramethylindodicarbocyanine,4-Chlorobenzenesulfonate Salt ，分子式为C 67H 103ClN 2O 3S ，分子量为1052.08。

DiD 是DiI 的类似物，但具有更长的激发和发射波长，为远红外荧光，在一些细胞和组织染色中更有优势，特别适合用于进行多种荧光的同时染色。

DiD 是一种亲脂性羰花青(carbocyanine)染料，具有很长的亲脂性烃链，进入细胞膜后可以侧向扩散逐渐使整个细胞的细胞膜被染色，染色后非常稳定。

DiD 可被633nm 的氦-氖(He-Ne)激光所激发，DiD 在进入细胞膜之前荧光非常弱，仅当进入到细胞膜后才可以被激发出很强的荧光。

DiD 被激发后可以发出远红外的荧光，DiD 和磷酯双层膜结合后的激发光谱和发射光谱参考图1。

其中，最大激发波长为644nm ，最大发射波长为665nm 。

图1. DiD 和磷酯双层膜结合后的激发光谱和发射光谱。

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:************************。

ElisaRSR TM AQP4 Ab Version 2 Aquaporin-4 (AQP4) AutoantibodyELISA Version 2 Kit –Instructions for useRSR LimitedParc Ty Glas, Llanishen, CardiffCF14 5DU United KingdomTel.: +44 29 2068 9299 Fax: +44 29 2075 7770 Email: Website: EC REP Advena Ltd. Tower Business Centre, 2nd Flr., Tower Street, Swatar, BKR 4013 Malta.INTENDED USEThe RSR AQP4 Autoantibody ELISA Version 2 kit is intended for use by professional persons only, for the quantitative determination of AQP4 autoantibodies (AQP4 Ab) in human serum. Neuromyelitis optica (NMO), also known as Devic’s syndrome, is an immune-mediated neurologic disease that involves the spinal cord and optic nerves. It can be considered to be a disorder distinct from multiple sclerosis (MS). A serum immunoglobulin G autoantibody (NMO-IgG) has been shown to be a specific marker for NMO and the water channel aquaporin 4 (AQP4) has been identified as the antigen for NMO IgG. Measurement of AQP4 Ab can be of considerable value in distinguishing NMO from MS when full clinical features may not be apparent and early intervention may prevent or delay disability. REFERENCESV. A. Lennon et al.A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis.Lancet 2004 364(9451): 2106 - 2112V. A. Lennon et al.IgG marker of optic-spinal multiple sclerosis bindsto the aquaporin-4 water channel.The Journal of Experimental Medicine 2005 202: 473 - 477B. G. Weinshenker et al.Neuromyelitis optica IgG predicts relapse after longitudinally extensive transverse myelitis.Annals of Neurology 2006 59: 566 - 569N. Isobe et al.Quantitative assays for anti-aquaporin-4 antibody with subclass analysis in neuromyelitis optica. Multiple Sclerosis Journal 2012 18: 1541 – 155S. Jarius et al.Testing for antibodies to human aquaporin-4 by ELISA: Sensitivity, specificity and direct comparison with immunohistochemistry.Journal of the Neurological Sciences 2012 320:32 - 37PATENTSThe following patents apply:European patent EP 1 700 120 B1, US patents US 7,101,679 B2, US 7,947,254 B2 and US 8,889,102 B2, Chinese patent ZL200480040851.3 and Japanese patent 4538464. ASSAY PRINCIPLEIn RSR’s AQP4 Ab ELISA Version 2 kit, AQP4 Ab in patient s’ sera, calibrators and controls are allowed to interact with AQP4 coated onto ELISA plate wells and liquid phase biotinylated AQP4 (AQP4-Biotin). After incubation at room temperature for 2 hours with shaking, the well contents are discarded. AQP4 Ab bound to the AQP4 coated on the well will also interact with AQP4-Biotin through the ability of AQP4 Ab in the samples to act divalently leaving AQP4-Biotin bound to the well via an AQP4 Ab bridge. The amount of AQP4-Biotin bound is then determined in a second incubation step involving addition of streptavidin peroxidase (SA-POD), which binds specifically to biotin. Excess, unbound streptavidin peroxidase is then washed away and addition of the peroxidase substrate, 3,3’,5,5’-tetramethlybenzidine (TMB), results in formation of a blue colour. This reaction is stopped by the addition of a stop solution, causing the well contents to turn yellow. The absorbance of the yellow reaction mixture at 450nm and 405nm is then read using an ELISA plate reader. A higher absorbance indicates the presence of AQP4 autoantibody in the test sample. Reading at 405nm allows quantitation of high absorbances. It is recommended that values below 10 u/mL should be measured at 450nm. If it is possible to read at only one wavelength 405nm may be used. The measuring interval is 3.0 –80 u/mL (arbitrary RSR units).STORAGE AND PREPARATION OF SERUM SAMPLESSera to be analysed should be assayed soon after separation or stored, preferably in aliquots, at or below –20o C. 100 μL is sufficient for one assay (duplicate 50 μL determinations). Repeated freeze thawing or increases in storage temperature should be avoided. Do not use lipaemic or haemolysed samples. Studies in which EDTA, citrate and heparin plasma samples were spiked with AQP4 Ab positive sera showed minor changes in signal compared with spiked serum from the same donor. In particular OD450values with spiked EDTA, citrate and heparin plasmas were 79% - 128% of spiked serum (15 samples with serum concentrations ranging from 2.6 u/mL – 30 u/mL) or 87% - 130% in terms of u/mL. When required, thaw test sera at room temperature and mix gently to ensure homogeneity. Centrifuge serum prior to assay (preferably for 5 min at 10-15,000 rpm in a microfuge) to remove particulate matter. Please do not omit this centrifugation step if sera are cloudy or contain particulates.SYMBOLSSymbol MeaningEC Declaration of Conformity IVD In Vitro Diagnostic DeviceREF Catalogue NumberLOT Lot NumberConsult InstructionsManufactured bySufficient forExpiry DateStoreNegative ControlPositive ControlMATERIALS REQUIRED AND NOT SUPPLIED Pipettes capable of dispensing 25 μL, 50 μL and 100 μL.Means of measuring various volumes to reconstitute or dilute reagents supplied.Pure water.ELISA Plate reader suitable for 96 well formats and capable of measuring at 450nm and 405nm.ELISA Plate shaker, capable of 500 shakes/min (not an orbital shaker).ELISA Plate cover.PREPARATION OF REAGENTS SUPPLIEDStore unopened kit and all kit components at 2-8o C.A AQP4 Coated Wells12 breakapart strips of 8 wells (96 in total) in a frame and sealed in foil bag. Allow foil bag to stand at room temperature (20-25o C) for 30 minutes before opening.Ensure wells are firmly fitted in the frame provided. After opening return any unused wells to the original foil bag and seal with adhesive tape. Then place foil bag in the self-seal plastic bag with desiccant provided and store at 2-8o C for up to4 months.B1-5 Calibrators1.5, 5, 20, 40, 80 u/mL (arbitrary RSR units)5 x 0.7 mLReady for useC1-2 Positive Controls I & II(see label for concentration range) 2 x 0.7 mLReady for useD Negative Control0.7 mLReady for useEAQP4–Biotin3 vialsLyophilisedImmediately before use, reconstitute withreconstitution buffer for AQP4-Biotin (F),1.5 mL per vial. When more than one vialis to be used, pool the contents of thevials and mix gently.FReconstitution Buffer for AQP4-Biotin10 mLReady for useGStreptavidin Peroxidase (SA-POD)0.8 mLConcentratedDilute 1 in 20 with diluent for diluting SA-POD (H). For example, 0.5 mL (G) + 9.5mL (H). Store for up to 16 weeks at 2-8o Cafter dilution.HDiluent for SA-POD15 mLReady for useIPeroxidase Substrate (TMB)15 mLReady for useJConcentrated Wash Solution120 mLConcentratedDilute 1 in 10 with pure water before use.Store at 2-8o C up to kit expiry date.KStop Solution14 mLReady for useASSAY PROCEDUREAllow all reagents to stand at room temperature (20-25o C) for at least 30 minutes prior to use. Do notreconstitute AQP4-Biotin until step 2 below. AnEppendorf type repeating pipette is recommended forsteps 2, 5, 8, and 9.1. Pipette 50 μL(in duplicate) of patientsera, calibrators (B1-5) and controls (C1-2 and D) into respective wells. Leave onewell empty for blank.2. Reconstitute AQP4-Biotin and pipette25μL into each well (except blank).3. Cover the frame and shake the wells for2 hours at room temperature on an ELISAplate shaker (500 shakes per min).4. Use an ELISA plate washer to aspirateand wash the wells three times withdiluted wash solution (J). If a platewasher is not available, discard the wellcontents by briskly inverting the frame ofwells over a suitable receptacle, washthree times manually and tap the invertedwells gently on a clean dry absorbentsurface to remove excess wash.RESULT ANALYSISA calibration curve can be established by plotting calibrator concentration on the x-axis (log scale) against the absorbance of the calibrators on the y-axis (linear scale). The AQP4 Ab concentrations in patient sera can then be read off the calibration curve [plotted at RSR as a spline log/lin curve (smoothing factor = 0)]. Other data reduction systems can be used. The negative control can be assigned a value of 0.15 u/mL to assist in computer processing of assay results. Samples with AQP4 Ab concentrations above 80 u/mL can be diluted (e.g.10 x and/or 100 x) in AQP4 Ab negative serum. Some sera will not dilute in a linear way. TYPICAL RESULTS (Example only; not forAbsorbance readings at 405nm can be converted to 450nm absorbances by multiplying by the appropriate factor (3.4 in the case of equipment used at RSR).This cut off has been validated at RSR. However each laboratory should establish its own normal and pathological reference ranges for AQP4 Ab levels. Also it is recommended that each laboratory include its own panel of control samples in the assay. CLINICAL EVALUATION(The information below is derived from 450nm data) Clinical SpecificitySera from 358 individual healthy blood donors were tested in the AQP4 Ab ELISA Version 2 kit. 356 (99%) sera were identified as being negative for AQP4 Ab.Clinical SensitivityOf 62 sera from patients with NMO or NMO spectrum disorder (NMOSD) 48 (77%) were positive for AQP4 Ab.Lower Detection LimitThe negative control was assayed 20 times and the mean and standard deviation calculated. The lower detection limit at 2 standard deviations was0.17 u/mL.Clinical AccuracyAnalysis of 205 sera from patients with autoimmune diseases other than neuromyelitis optica spectrum disorders (NMOSD) indicated no interference from autoantibodies to the TSH receptor (n=110), glutamic acid decarboxylase (n=26), 21-hydroxylase (n=12), the acetylcholine receptor (n=10), thyroid peroxidase (n=15), thyroglobulin (n=10), IA-2 (n=7) or from rheumatoid factor (n=15) in the RSR AQP4 Ab ELISA Version 2. InterferenceNo interference was observed when samples were spiked with the following materials; bilirubin at 20 mg/dL or intralipid up to 3000 mg/dL. Interference was seen from haemoglobin at 500 mg/dL. SAFETY CONSIDERATIONSStreptavidin Peroxidase (SA-POD)Signal word: WarningHazard statement(s)H317: May cause an allergic skin reaction Precautionary statement(s)P280: Wear protective gloves/protective clothing/ eye protection/face protectionP302 + P352: IF ON SKIN: Wash with plenty of soap and waterP333 + P313: If skin irritation or rash occurs: Get medical advice/attentionP362 + P364: Take off contaminated clothing and wash it before reusePeroxidase Substrate (TMB)Signal word: DangerHazard statement(s)H360: May damage fertility or the unborn child Precautionary statement(s)P280: Wear protective gloves/protective clothing/eye protection/face protectionP308 + P313: IF exposed or concerned: Get medical advice/attentionThis kit is intended for use by professional persons only. Follow the instructions carefully. Observe expiry dates stated on the labels and the specified stability for reconstituted reagents. Refer to Safety Data Sheet for more detailed safety information. Avoid all actions likely to lead to ingestion. Avoid contact with skin and clothing. Wear protective clothing. Material of human origin used in the preparation of the kit has been tested and found non-reactive for HIV1 and 2 and HCV antibodies and HBsAg but should, none-the-less, be handled as potentially infectious. Wash hands thoroughly if contamination has occurred and before leaving the laboratory. Sterilise all potentially contaminated waste, including test specimens before disposal. Material of animal origin used in the preparation of the kit has been obtained from animals certified as healthy but these materials should be handled as potentially infectious. Some components contain small quantities of sodium azide as preservative. With all kit components, avoid ingestion, inhalation, injection or contact with skin, eyes or clothing. Avoid formation of heavy metal azides in the drainage system by flushing any kit component away with copious amounts of water.ASSAY PLANAllow all reagents and samples to reach room temperature (20-25 o C) before usePipette: 50 μL Calibrators, controls and patient seraPipette: 25 μL AQP4-Biotin (reconstituted) into each well (except blank)Incubate: 2 Hours at room temperature on an ELISA plate shaker at 500 shakes/min Aspirate/Decant: PlateWash: Plate three times and tap dry on absorbent material1Pipette: 100 μL SA-POD (diluted 1:20) into each well (except blank)Incubate: 20 Minutes at room temperature on a ELISA plate shaker at 500 shakes/min Aspirate/Decant: PlateWash: Plate three times and tap dry on absorbent material1, 2Pipette: 100 μL TMB into each well (including blank)Incubate: 20 Minutes at room temperature in the dark without shakingPipette: 100 μL Stop solution into each well (including blank) and shake for 5 seconds Read absorbance at 450nm and 405nm within 10 minutes of adding stop solution31It is not necessary to tap the plates dry after washing when an automatic plate washer is used2Use pure water for the final wash when washing manually3If it is possible to read at only one wavelength, 405nm may be used。

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］。

食品与药品Food and Drug2021年第23卷第1期17加速溶剂萃取-超高效液相色谱-串联质谱法测定大枣中3种五环三祜酸张萍，何婷，王颖，胡克特，顾丁，陈荣祥**(遵义医科大学基础医学院，贵州遵义563000)摘要：目的建立加速溶剂萃取-超高效液相色谱-串联质谱法(ASE-UPLC-MS/MS)同时测定大枣中桦木酸、齐墩果酸和熊果酸的方法。

方法样品釆用ASE提取，优化提取条件，并与超声辅助提取法进行比较。

优化 后的提取条件为：以80%甲醇为提取溶剂，提取温度100-C,静态萃取时间15min,萃取1次。

提取液釆用Waters ACQUITY BEH C18色谱柱分离，以乙ffi-15mmol/L乙酸钱(pH9.3)为流动相，梯度洗脱，经UPLC-MSZMS仪，釆用电喷雾电离源，负离子模式下多反应监测模式检测。

结果桦木酸、齐墩果酸、熊果酸在0.5~10 mg/L范围内，浓度与峰面积线性关系良好，相关系数大于0.9900。

不同浓度3种化合物的加标回收率93.6%〜101.7%,相对标准偏差在1.18%~6.83%之间。

结论此法简单快速、准确稳定、重复性好，可用于大枣中桦木酸、齐墩果酸、熊果酸的含量测定。

关键词：加速溶剂萃取；超高效液相色谱；串联质谱法；大枣中图分类号：R284.1文献标识码：A文章编号：1672-979X(2021)01-0017-06DOI：10.3969/j.issn.l672-979X.2021.01.004Simultaneous Determination of Three Pentacyclic Triterpenic Acids in Jujubae Fructus byAccelerated Solvent Extraction-UPLC-MS/MSZHANG Ping,HE Ting,WANG Ying,HU Ke-te,GU Ding,CHEN Rong-xiang(School of B asic Medical Sciences,Zunyi Medical University,Zu^yi563000,China)Abstract:Objective To establish a method for the simultaneous determination of betulinic acid,oleanolic acid and ursolic acid in Jujubae fructus by ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)with accelerated solvent extraction(ASE).Methods The extract parameters of A SE were optimized and the efficiency was compared with the ultrasound-assisted extraction method.The optimum extraction conditions were as follows:80%methanol was selected as extraction solvent,oven temperature was100°C,the static extraction time was 15min and one extraction cycle was adopted.A waters ACQUITY BEH C18(2.1mmx]00mn,1.7“m)column was used as the stationary phase,acetonitrile and ammonium acetate solution(15mmol/L,pH9.3)was used as the mobile phase.Mass detection was conducted by electrospray ionization in negative ion multiple reaction monitoring mode. Results The calibration curves were linear over a concentration range of0.5-10mg/L for betulinic acid,oleanolic acid and ursolic acid.The correlation coefficients were greater than0.9900.The recoveries of different spiked levels were between93.6%and101.7%,with RSDs between1.18%and6.83%.Conclusion The method is simple,rapid,收稿日期：2020-09-04基金项目：国家自然科学基金(31660131,81760652)；贵州省联合基金(黔科合J字LKZ[2013]17号)；遵义医学院博士启动基金(F-568)作者简介：张萍，硕士研究生，研究方向：药用植物开发与利用E-mail:******************通讯作者：陈荣祥，教授，博士，研究方向：药用植物开发与利用E-mail:*************************18食品与药品Food and Drug2021年第23卷第1期accurate,stable and reproducible.It can be used for the determination of betulinic acid,oleanolic acid and ursolic acid in Jujubae f ructus.Key Words:accelerated solvent extraction;ultra-high performance liquid chromatography;tandem mass spectrometry; Jujubae f ructus.大枣为鼠李科植物枣树（Ziziphus jujuba Mill.）的干燥成熟果实，不仅作为食物，还是传统中医药中的常用药材。

收稿日期:20201027基金项目:江苏省大型科学仪器设备共享服务平台资助(BZ201403)作者简介:马雨璇(1996 ),女,硕士,研究方向:药物晶型,E-mail:1209232209@;通讯联系人:李钢(1959 ),男,教授,研究方向:药物晶型,E-mail:40010@㊂doi :10．16597/j．cnki．issn．1002154x．2020．12．001新冠肺炎药物盐酸阿比多尔的结构分析和稳定性考察马雨璇㊀王㊀娜㊀王㊀冰㊀李㊀钢(南京师范大学食品与制药工程学院分析测试中心,江苏南京210023)摘㊀要㊀本文利用多种现代分析手段对新型冠状病毒肺炎的推荐用药盐酸阿比多尔进行了结构分析,结果表明:质谱分析(MS )测得样品分子量为477.9,傅里叶变换红外光谱(FTIR )分析出样品骨架苯并吡咯及主要官能团与盐酸阿比多尔化学结构一致;热分析(DSC 和TGA )测得盐酸阿比多尔熔点为154.06ħ,在90.02ħ和188.51ħ发生两步失重分解;X -射线粉末衍射(PXRD )测得其八条特征峰2θ分别为4.80ʎ㊁7.63ʎ㊁9.29ʎ㊁11.74ʎ㊁19.09ʎ㊁21.14ʎ㊁22.98ʎ㊁28.81ʎ;扫描电子显微镜(SEM )观察到盐酸阿比多尔呈长条状㊂此外,高湿㊁高温㊁研磨实验表明,盐酸阿比多尔在高湿和高温环境下晶型稳定,研磨会减小晶型的择优取向,影响衍射峰的强度,随着研磨时间的增加盐酸阿比多尔由结晶态向非晶态转化㊂关键词㊀盐酸阿比多尔㊀结构分析㊀稳定性分析㊀X 射线粉末衍射Structural Analysis and Stability of Arbidol Hydrochloride ,a Treatment Drug for COVID -19Ma Yuxuan㊀Wang Na㊀Wang Bing㊀Li Gang(School of Food Science and Pharmaceutical Engineering,Test &Analysis Center,Nanjing Normal University,Jiangsu Nanjing 210023)Abstract ㊀In this paper,a variety of modern analytical methods were used to analyze the structure andmorphology of Abidor hydrochloride a recommended drug for COVID -19.The results are as follows,the molecular weight of the sample was 477.9measured by mass spectrometry (MS),and the skeleton of the sample and its main functional groups were analyzed by fourier transform infrared spectroscopy (FTIR ).The results of FTIR were consistent with the chemical structure of Abidor hydrochloride.The DSC thermogram of it showed a desolvation peak starting at 154.06ħ.The TGA curve showed that two-step weight-loss decomposition occurred at 90.02ħand 188.51ħ.The PXRD patterns of it indicated peaks at 2θ=4.80ʎ,7.63ʎ,9.29ʎ,11.74ʎ,19.09ʎ,21.14ʎ,22.98ʎ,28.81ʎ.It is seams that a few unique peaks and can be used for the identification.The SEM examination indicates that the morphological of it possess a long strip.In addition,the experiments of high humidity,high temperature and grinding showed that the crystal shape of Abidor hydrochloride was stable under high humidity and high temperature,and grinding would reduce the preferred orientation of the crystal shape and affect the strength of the diffraction peak.㊀2020.Vol.34,No.12㊀科技进展‘Advances in Science&Technology“With the increase of grinding time,Abidor hydrochloride transformed from crystal state to amorphous state.Keywords㊀Arbidol hydrochloride㊀structure analysis㊀stability analysis㊀X-ray powder diffraction㊀㊀2019年12月,新型冠状病毒肺炎(corona virus disease-19,COVID-19)爆发,是继严重急性呼吸综合征(SARS)和中东呼吸综合征(MERS)后,严重危害人类健康的全球突发公共卫生事件之一[1]㊂国际病毒分类委员会将该病毒命名为严重急性呼吸系统综合征冠状病毒2(SARS-CoV-2)㊂从2012年开始,冠状病毒被分为α㊁β㊁γ㊁δ这4种类型,SARS-CoV-2为β属,是单股正链RNA病毒,颗粒呈圆形或椭圆形,有包膜,常为多形性,直径60~140nm,具有很强的传染性且传播方式多样,人群普遍易感[2~3]㊂它主要作用于呼吸道,所以临床多以发热㊁乏力为主,少数伴有鼻塞㊁流涕㊁咽痛腹泻等症状[2]㊂发病一周后重症患者可能出现低氧血症和呼吸困难,并伴有休克等症状,严重影响患者生命安全[4~6]㊂‘新型冠状病毒肺炎诊疗方案(试行第六版)“由国家卫健委员会在2月18日发布,其中明确指出阿比多尔治疗SARS-CoV-2效果确切,可广泛应用于临床㊂阿比多尔是非核苷类广谱抗病毒药,由前苏联研发,在俄罗斯和中国获批上市[7~9]㊂它是一种高选择性血凝素抑制剂,通过激活2,5-寡聚腺苷酸合成酶来特异性抑制病毒囊膜和宿主细胞膜的融合,从而抑制病毒的DNA和RNA合成[1,1013],并且阿比多尔还能促进细胞自身释放干扰素,从而发挥抗病毒作用,能有效缓解COVID-19患者的症状[1416]㊂李兰娟院士团队通过初步体外细胞实验证实阿比多尔在较低浓度时可以有效抑制SARS-CoV-2[17,18]㊂还有报道指出患者在感染早期服用阿比多尔可显著减少临床抗菌药物的使用和SARS-CoV-2并发症的发生且可以缩短病程㊁减轻症状,是一个治疗指数和安全性双高的药物[19]㊂作为新型冠状病毒肺炎的推荐用药,盐酸阿比多尔在疫情期间具有极大的临床价值㊂对盐酸阿比多尔的X-射线粉末衍射法(PXRD)㊁差示扫描量热分析法(DSC)㊁扫描电子显微镜法(SEM)研究,在相关文献中未见报道㊂盐酸阿比多尔(ArbidolHydrochloride,AH)的化学名称为6-溴-4-(二甲胺基甲基)-5-羟基-1-甲基-2-(苯硫甲基)-1H-吲哚-3-羧酸乙酯盐酸盐-水合物,分子式为C22H25BrN2O3S㊃HCI㊃H2O (如图1所示),分子量是531.89㊂为了增加药物的稳定性将其制备成盐酸盐,药用为一水合物[20]㊂本文使用质谱分析(MS)㊁傅里叶变换红外光谱(FTIR)确证样品化学结构,检测结果与盐酸阿比多尔化学结构一致,再利用热分析(DSC和TGA)㊁X -射线粉末衍射(PXRD)以及扫描电子显微镜(SEM)等仪器测定盐酸阿比多尔的熔点㊁分解温度㊁晶型结构以及微观形貌㊂此外,对盐酸阿比多尔样品进行高湿㊁高温和研磨对晶型的稳定性考察,结果显示盐酸阿比多尔样品晶型在高湿和高温条件下十分稳定没有发生变化,不同研磨时间会影响样品的择优取向㊂图1㊀盐酸阿比多尔的化学结构(分子量为531.89) Fig.1㊀Structure ofArbidol Hydrochloride(Mr531.89)1㊀盐酸阿比多尔样品的结构确证1.1㊀仪器与材料仪器:日本理学公司的D/max2500VL/PC型阳极转靶X射线衍射仪;日本电子公司的JSM-5610型扫描电子显微镜;美国Perkin Elmer公司的Analysis Diamond差示扫描量热仪和Analysis Pyrisl 热重分析仪;美国瓦里安公司的Varian2200质谱仪;德国布鲁克公司的VERTEX70型傅里叶变换红外光谱仪㊂材料:盐酸阿比多尔样品由重庆某公司提供㊂1.2㊀质谱分析以甲醇为溶剂,+ESI源为检测条件,用Varian2200质谱仪检测样品㊂1.3㊀傅里叶变换红外光谱分析采用KBr压片法检测样品,扫描范围4000~ 400cm-1,分辨率4cm-1,扫描次数32次,用聚苯乙烯膜校正㊂㊀马雨璇等.新冠肺炎药物盐酸阿比多尔的结构分析和稳定性考察㊀2020.Vol.34,No.121.4㊀热分析差示扫描量热法分析:称取样品约2.5mg放入铝坩埚中密封,将坩埚放入DSC中进行测试,以氮气为保护气,升温速率为10K㊃min-1,升温范围为25~200ħ,进行DSC分析㊂热重分析:称取样品约2.5mg放入坩埚,将坩埚放入TGA中进行测试,以氮气为保护气,升温速率为10K㊃min-1,升温范围为25~400ħ,进行TGA 分析㊂1.5㊀X-射线粉末衍射法分析测定条件为管压:40kV,管流:100mA,Cu-Kα辐射,石墨弯晶单色器,发射狭缝(DS)=防散射狭缝(SS)=1ʎ,接收狭缝(RS)=0.15mm㊂扫描速度: 10ʎ㊃min-1,步宽:0.02ʎ㊂1.6㊀扫描电子显微镜法分析取样品粘结在样品座上,镀膜处理后置于扫描电子显微镜下观察形态结构㊂测定条件:加速电压10kV,加大倍率6000,样品台直径30mm㊂2㊀稳定性考察2.1㊀高湿的影响为了确保该制剂的有效性和安全性,按照中国药典2015版第四部 原料药物与药物制剂稳定性试验指导原则 ,我们考察了盐酸阿比多尔在25ħ避光,相对湿度为92.5%条件下放置的外观性状㊁晶型及吸湿增重等重要指标随时间变化的情况㊂2.2㊀高温的影响为考察温度对药物原材料晶型的影响,按照中国药典2015版第四部 原料药物与药物制剂稳定性试验指导原则 ,将盐酸阿比多尔于60ħ下恒温放置10天,于第五天和第十天取样进行检测,观察其晶型随时间变化的情况㊂2.3㊀研磨的影响室内环境下,取适量盐酸阿比多尔样品置于玛瑙研钵中,分别研磨5min㊁10min和30min,然后置于载样架上,制样,进行PXRD检测,观察研磨不同时间对样品晶型的影响㊂3㊀结果分析3.1㊀质谱分析对盐酸阿比多尔样品进行质谱检测㊂盐酸阿比多尔的分子量为477.4,质谱检测结果质荷比为477.9㊂通过质谱分析可证明样品的分子量与盐酸阿比多尔的分子量一致㊂3.2㊀傅里叶变换红外光谱法分析图2为盐酸阿比多尔的红外图谱,图中3128cm-1㊁1577cm-1㊁1502cm-1㊁1255cm-1㊁741cm-1㊁和958cm-1是样品苯并吡咯骨架的吸收峰;1680cm-1㊁1186cm-1和1087cm-1是酯基的吸收峰;1231cm-1㊁1326cm-1和3341cm-1是酚羟基的吸收峰;1380cm-1㊁1475cm-1和2968cm-1是甲基的吸收峰;1417cm-1和2902cm-1是亚甲基的吸收峰;1131cm-1是脂肪胺的吸收峰;2588cm-1是盐酸盐的伸缩振动;3341cm-1也是样品结晶水的吸收峰;690cm-1是C-S键的吸收峰;484cm-1是苯环上溴的吸收峰;3128cm-1㊁1502cm-1和782cm-1也是苯环的吸收峰㊂图2㊀盐酸阿比多尔的红外图谱Fig.2㊀FT-IR of Arbidol Hydrochloride3.3㊀热分析差示扫描量热仪分析:图3是盐酸阿比多尔的DSC曲线㊂由图3可知,盐酸阿比多尔在120.15ħ有一个吸热峰,起始温度为90.78ħ,此时测得的热晗为93.94J/g,推测为样品脱去结晶水导致㊂在161.35ħ有一个热晗为34.04J/g的吸热峰,起始温度为154.06ħ,为样品熔融所致,由此可知在这种测试条件下盐酸阿比多尔的熔点为154.06ħ㊂热重分析:图4是盐酸阿比多尔的TGA曲线㊂由图4可知,样品在90.02ħ发生第一个分解失重,失去一个结晶水,失重为3.21%,在188.51ħ时发生第二个分解失重,为样品分解所导致㊂㊀2020.Vol.34,No.12㊀科技进展‘Advances in Science &Technology“图3㊀盐酸阿比多尔的DSC 曲线Fig.3㊀DSC curve of Arbidol Hydrochloride图4㊀盐酸阿比多尔的TGA 曲线Fig.4㊀TGA curve of Arbidol Hydrochloride3.4㊀X -射线粉末衍射法分析用PXRD 检测盐酸阿比多尔样品,衍射图谱呈现出尖锐的衍射峰,表明该样品以结晶形式存在,且结晶度较高㊂经由计算机软件分析图谱,先采取平滑处理㊁背景扣除㊁剥离Kα2峰,再进行全谱拟合,得到该样品的衍射角度(2θ/ʎ)分别为4.80㊁7．63㊁9.29㊁9．55㊁11.74㊁15.70㊁16.74㊁19.09㊁21．14㊁21.76㊁22．98㊁23.32㊁23.71㊁25.29㊁28.79,晶面间距d (nm)分别为1.84㊁1.15㊁0.95㊁0.93㊁0．75㊁0.56㊁0.53㊁0．46㊁0.42㊁0.41㊁0.39㊁0.38㊁0．38㊁0.35㊁0.31,相对丰度/%)分别为100.0㊁21．4㊁20.2㊁7.4㊁12.4㊁7.1㊁3.6㊁32.8㊁8.3㊁7.0㊁7．3㊁19.(I/I 03㊁14.0㊁16.5㊁19.5,平均晶粒尺寸为100.7nm,其衍射图谱见图5㊂图5㊀盐酸阿比多尔的PXRD 图谱Fig.5㊀PXRD image of Arbidol Hydrochloride3.5㊀扫描电子显微镜法分析盐酸阿比多尔的扫描电镜图如图6所示㊂由图6可知,盐酸阿比多尔样品外观形貌呈长条状,宽度大约为1μm 左右㊂图6㊀盐酸阿比多尔的SEM 图谱Fig.6㊀SEM image of Arbidol Hydrochloride3.6㊀高湿稳定性影响取盐酸阿比多尔样品分成A㊁B 两份敞口放置在以饱和硝酸钾溶液营造相对湿度为92.5%的密闭容器中,避光放置10天,在第五天和第十天分别对A 样品进行外观性状观察和称重,对B 样品取出部分进行PXRD 检测㊂结果如图7和表1所示,盐酸阿比多尔样品在高湿环境下稳定,晶型的2θ㊁d 值和I /I 0基本没有变化,在高湿环境下样品颜色一直呈白色,没有发生改变,吸重在5%以下㊂综合判断盐酸阿比多尔在高湿(RH =92.5%)环境下稳定㊂根据药典无须进行RH =75%环境下的湿度稳定性考察㊂㊀马雨璇等.新冠肺炎药物盐酸阿比多尔的结构分析和稳定性考察㊀2020.Vol.34,No.12图7㊀不同天数的高湿PXRD 图谱Fig.7㊀High-humidity PXRD image of different days表1㊀盐酸阿比多尔的高湿数据Tab.1㊀high humidity data of Arbidol Hydrochloride试验条件时间/d 性状重量/g 吸湿量/(%)25ħ,RH =92.5%0白色0.36925ħ,RH =92.5%5白色0.379 2.7125ħ,RH =92.5%10白色0.3874.883.7㊀高温稳定性影响取盐酸阿比多尔样品敞口放置在恒温烘箱内,温度设置为60ħ,避光放置10天,在第五天和第十天分别取样进行PXRD 检测㊂结果如图8所示,盐酸阿比多尔样品在高温环境下稳定,晶型的2θ㊁d 值和I/I 0基本没有变化㊂根据药典无须进行40ħ环境下的温度稳定性考察㊂图8㊀不同天数的高温PXRD 图谱Fig.8㊀High-temperature PXRD image of different days3.8㊀研磨稳定性影响图9是盐酸阿比多尔样品用玛瑙研钵研磨5min㊁10min 和30min 的PXRD 图谱㊂从图中可以看出,衍射图谱随着研磨时间的增加发生了改变㊂样品经过研磨后,减少了择优取向,部分强峰变弱,弱峰变强,尤其是2θ为4.8ʎ的峰(最强峰)强度降低最明显,其他峰强度与之相比(I /I 0),比值增加㊂在标记①②③④⑤处可明显看出随研磨时间增长,部分小峰消失,衍射峰峰型变宽,这是由于研磨导致晶粒变小,晶型药物出现向非晶态转化的趋势㊂因此在制剂过程中要注意研磨对盐酸阿比多尔晶型的影响,以免晶型变化影响生物利用度㊂图9㊀研磨不同时间的PXRD 图谱Fig.9㊀PXRD patterns of grinding at different times4㊀讨论在对药物药理作用研究前必须建立一系列系统的表征方法,以确保该生产药物是目标药物㊂对药物晶型进行结构表征是临床用药的前提,也是药物稳定性考察的基础和依据㊂本文通过质谱分析(MS)㊁傅里叶变换红外光谱分析(FT-IR)㊁差示扫描量热分析(DSC)㊁热重分析(TGA)㊁X 射线粉末衍射分析(PXRD)和扫描电子显微分析(SEM)等现代分析手段对样品进行表征,为药物的生产制备㊁储存鉴定以及定量分析提供参考依据㊂参考文献[1]王璐,徐艳娇,郭洁茹,李伟杰,张程亮,刘东.重症新型冠状病毒肺炎患者抗病毒治疗的药物利用评价:阿比多尔[J].医药导报,2020,39(07):922925.[2]国家中医药管理局办公室,国卫办医函[2020]145号,关于印发新型冠状病毒肺炎诊疗方案(试行第六版)的通知[EB].[20200218].㊀2020.Vol.34,No.12㊀科技进展‘Advances in Science&Technology“[3]任秀华,祁星星,左琴,汤杰,刘东.方舱医院813例新型冠状病毒肺炎患者治疗用药分析[J].医药导报,2020, 39(07):926930.[4]Zhu N,Zhang D Y,Wang W L,et al.A novel coronavirusfrom patients with pneumonia in China,2019[J].New England Journal of Medicine,2020,382(8). [5]马亦林.冠状病毒的特性及其致病性研究进展[J].中华临床感染病杂志,2018,11(4):305315. [6]Xu X,Chen P,Wang J,et al.Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission[J].Sci China Life Sci,2020,63(3):457460.[7]吕睿冰,王文菊,李欣.连花清瘟颗粒联合西药常规疗法法治疗新型冠状病毒肺炎疑似病例63例临床观察[J].中医杂志,2020,61(08):655659.[8]余平,李叶子,万少兵,王瑛.连花清瘟颗粒联合阿比多尔治疗轻度新型冠状病毒肺炎的疗效观察[J].中国药学杂志,2020,55(12):10421045.[9]曹瑜.盐酸阿比多尔片在治疗急性呼吸道病毒感染中的安全性与有效性观察[J].中国现代药物应用,2018,12(17):101103.[10]Brooks M J,Burtseva E I,Ellery P J,et al.Antiviralactivity ofarbidol,a broad-spectrum drug for use againstrespiratory viruses,varies according to test conditions[J].Med Virol,2012,84(1):170181.[11]王孟昭,蔡柏蔷,李龙芸,等.阿比朵尔治疗流行性感冒的随机㊁双盲㊁安慰剂对照㊁多中心临床研究[J].中国医学科学院学报,2004,26(3):289293. [12]Shi L,Xiong H,He J,et al.Antiviral activity ofarbidolagainst influenza A virus,respiratory syncytial virus, rhinovirus,coxsackie virus,and adenovirus in vitro and in vivo[J].Arch Virol,2007,152(8):144755. [13]李洋,赵立.盐酸阿比多尔抗呼吸道病毒的药理作用与体外和体内疗效研究现状[J].中国临床药理学杂志, 2019,35(17):19641968.[14]Perfetto B,Filosa R,De Gregorio V,etal.In vitro antiviraland immunomodulatory activity of arbidol and structurally related derivatives in herpes simplex virus type1-infected human keratinocytes(HaCat)[J].J Med Microbiol, 2014,63(11):14741483.[15]Wang Y,Ding Y,Yang C,et al.Inhibition of theinfectivity and inflammatory response of influenza virus by arbidol hydrochloride in vitro and in vivo[J].Biomed Pharmacother,2017,91:393401.[16]Han W Z,Quan B,Guo Y,et al.The course of clinicaldiagnosis and treatment of a case infected with coronavirus disease2019[J].Med Virol,2020.[17]苏广胜,谷秀.新型冠状病毒肺炎的抗病毒药物治疗进展[J].疑难病杂志.2020,19(06):548551. [18]李洋,赵立.阿比多尔抗呼吸道病毒的药理作用与体外和体内疗效研究现状[J].中国临床药理学杂志,2019, 35(17):19641968.[19]Huang C,Wang Y,Li X,et al.Clinical features ofpatients infected with2019novel coronavirus in Wuhan, China[J].The Lancet,2020,395(10223). [20]王俊菊,袁改玲.抗流感药物盐酸阿比朵尔的研究进展[J].中国兽药杂志,2011,45(04):5255.ʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏʏ液化空气(中国)投资有限公司与四川中核国兴科技有限公司签署全面合作协议2020年12月3日,液化空气(中国)投资有限公司与四川中核国兴科技有限公司在成都签署全面合作协议,进一步推进在西南地区的氢能产业链部署,尤其是可再生氢能产业的发展㊂在此协议下,两家公司的合作将贯穿整个氢能产业链㊂双方将发挥各自优势,在四川省雅安市成立合资企业,携手打造 氢能产业集群 项目,高品质建设水电解制氢㊁氢气液化及空分系统工厂,稳步推进可再生氢的生产及储运㊂液化空气还将与中核国兴在加氢站项目领域开展合作,同时进行氢能技术与装备制造领域的研发工作㊂对于城市地区可持续交通和局部污染带来的挑战,氢可提供切实有效的应对方式㊂50年来,液化空气积累了独特的专有技术,掌握了从生产㊁储存㊁运输㊁到最终用户应用开发的整个氢供应链,从而促进了氢作为清洁能源,尤其是交通领域的应用㊂四川中核国兴科技有限公司是一家隶属于中国核工业集团公司㊁专注于氢能㊁光伏和地热等新能源开发和应用的公司㊂。

Certificate（证书）PREDNISONE TABLETS（泼尼松片）USP Catalog No.: 1559505USP Lot No。

: R031Y1（10 mg nominal prednisone content per tablet）（每片含泼尼松10mg）FOR DISSOLUTION PERFORMANCE VERIFICATION TEST （PVT）用于溶出性能确认实验Period of validity: This certificate of USP Prednisone Tablets Lot R031Y1 is valid through June 30th, 2017。

有效期：USP泼尼松片批号R031Y1的证书有效期到2017年6月30日The USP Prednisone Tablets RS is provided for use in the Performance Verification Test for USP Apparatus 1 and 2 with 1 liter vessels in the USP General Test Chapter on DISSOLUTION <711〉and DRUG RELEASE <724〉，APPARATUS SUITABILITY。

Store in a dry place. Store the tablets at controlled room temperature not exceeding 25°.USP泼尼松标准片用于采取USP中方法1和方法2对1升溶出杯，进行USP通用测试部分溶出（711）和释放（724)项目的性能能确认实验，药品贮藏在干燥,温度低于25℃环境中。

Dissolution Medium: We recommend preparing the medium as follows:Heat a suitable amount of water, while stirring gently, to about 41-45°. Filter under vacuum through a 0.45—μm-porosity filter into a suitable filtering flask equipped with a stirring device。