Eastman Vitamin E TPGS NF
Applications and Properties
P h a r m a c e u t i c a l
I n g r e d i e n t s
Contents
Introduction1 Fundamental Properties 1 Oral Delivery Applications 2 Absorption/Bioavailability Enhancer 2 Solubilization of Poorly Water Soluble Compounds5 Vitamin E Bioavailability Enhancer 7 Controlled Delivery Applications 9 Other Applications 10 Non-Oral Delivery Applications11 Nasal/Pulmonary Delivery11 Ophthalmic Delivery11 Parenteral Delivery12 Dermal Delivery12 Formulating With TPGS13 Thermal Properties and Density 14 Solution Properties 15 Aqueous Solutions 15 Surface-Active and Critical Micelle Concentration 16 Chemical Stability in Aqueous Media16 Liquid Crystalline Phases 17 Wide Viscosity Range 18 Emulsifier 19 Safety Data 20 Regulatory Status20 Packaging 20 Safety Studies References 21
Introduction Eastman
Vitamin E TPGS NF, d-?-Tocopheryl polyethylene glycol 1000 succinate, is a surfactant
that can be used as an emulsifier, drug solubilizer, absorption enhancer, and as a vehicle for lipid-based drug-delivery formulations. Eastman Vitamin E TPGS (hereafter referred to as TPGS) was invented by Eastman in 1950 and has been continuously produced by Eastman for more than 30 years. Today Eastman continues to be a global producer of TPGS, meeting the needs of pharmaceutical and nutritional supplement companies worldwide.
TPGS has found wide utility in pharmaceutical formulations including the following:
?Improving drug bioavailability
–Surfactant properties enhance solubilization of
poorly water soluble drugs
–Stabilization of the amorphous drug form
–Enhances drug permeability by P-glycoprotein
efflux inhibition
?Emulsion vehicle
?Functional ingredient in self-emulsifying formulations ?Thermal binder in melt granulation/extrusion processing
?Reducing drug sensitivity on skin or tissues
?Carrier for wound care and treatment
?Water-soluble source of vitamin E
To provide formulation and application guidelines, this publication summarizes the physical and chemical properties of TPGS, methods of determination, and application examples.Fundamental Properties
TPGS is prepared by the esterification of the acid group of crystalline d-?-tocopheryl acid succinate by polyethylene glycol 1000. Figure 1 shows its chemical structure; Table 1 lists the product’s typical properties.
Eastman Vitamin E TPGS NF Applications and Properties
2
Oral Delivery Applications
bioavailability. Sokol et al. [1991,338:therapy to manage rejection of transplanted organs. This is a
crucial finding for organ transplant recipients. Due to the impaired absorption of cyclosporin, massive doses are required to achieve
mixing of hepatobiliary In Sokol’s study,was coadministered to seven clinical subjects taking a cyclosporin dose ranging from 29–136 mg/kg/day.As a consequence, the required cyclosporin daily dose was reduced to 12.5–40 mg/kg/day. Overall, there was a 40%–72% reduction in the cyclosporin dosage required to maintain therapeutic blood plasma concentrations of the drug. These results show that TPGS provides a substantial improvement of
cyclosporin absorption and a significant reduction of the high cost of immunosuppressive therapy. While Sokol originally suggested that the increased bioavailability was due to micelle formation
enhancing the solubility, others have since provided evidence supporting enhanced permeability due to P-glycoprotein (P-gp) inhibition [Dintaman, J. M. et al. 1999, Pharm. Res .16:1550–1556;Chang, T. et al. 1996, Clin. Pharmacol. Ther.59:1–7]. Figure 2 shows the increased bioavailability of cyclosporine when administered to rats using saline solution with TPGS and without TPGS [Wacher, V . et al. 2002, J. Pharm. Sci.91:77–90].
D ?D
Other examples of APIs that exhibit enhanced bioavailability with TPGS include amprenavir which showed no absorption in dog’s plasma without TPGS and 69% absorption in a 20% TPGS formulation [Yu, L. et al. 1999, Pharm. Res.16:1812–1817]. The dramatic effect of TPGS on the amprenavir absorption flux is shown in Figure 3.
Paclitaxel, an antimicrotubule anticancer drug, is very poorly absorbed on peroral administration because of both poor solubility and poor permeability. Thus, it is typically administered intravenously. The authors of a detailed in vitro, in vivo, and in situ paclitaxel and TPGS study conclude that the TPGS enhanced bioavailability of paclitaxel in the in vivo work is due to increased solubility and permeability.
They further conclude that the data suggest
“TPGS can serve to improve the
bioavailability not only of orally
administered paclitaxel but also of
other BCS [Biopharmaceutical
Classification System] class II–IV drugs,
which have either low solubility or limited permeability due to their efflux by P-gp
or both” [Varma, M.V. S. et al. 2005,
Eu. J. Pharm. Sci.25:4–5, 445–453].
While many of the examples of TPGS
use are for poorly water soluble drugs
there are also examples of using TPGS with poorly permeable drugs that are water soluble.
12.94 ?1.26 ?
al. 2003, Int. J. Pharm.250:
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0.8
0.7
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1
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6
Figure 3
Absorption Flux for Amprenavir
4
Many studies have been conducted to evaluate the mechanism by which TPGS affects bioavailability;however, there is still much to learn. TPGS’s action is likely attributable to its ability to improve solubility through micelle formation and/or through enhancing permeability across cell membranes by inhibition of the multi-drug efflux pump P-gp. While TPGS has been shown to rigidize cell membranes, this does not appear to be the primary mechanism for inhibition [Rege et al. 2002, Eur. J. Pharm. Sci.16:237–246]. A study sponsored by Eastman showed that TPGS containing polyethylene glycol 1000, the
commercial product, exhibits greater P-gp inhibition than analogs containing polyethylene glycol 200 to 6000 as shown in Figure 4 [Collnot et al. 2004, AAPS J.6:4Abstract T2234].
TPGS is a somewhat more effective P-gp inhibitor than many related excipients with surfactant properties as shown in Table 2; however, it is significantly less potent than other clinically-tested pharmacologically active compounds such as cyclosporine (IC 501?M), tariquidar (20–50 nM) and zosuquidar (50–60 nM) [Mistry, P . et al. 2001,Cancer Res.61:749–758; Dantzig, A. H. et al. 2001, Cur. Med. Chem.8:39–50].
Rege and others have found that TPGS is relatively selective in that it does not inhibit MRP2, hPeptT1 or MCT,nor does it have an effect on the membrane-bound metabolizing enzyme CYP3A [Bogman et al.2003, J. Pharm. Sci.92:1250–1261; Wacher et al. 2002, J. Pharm. Sci.91:77–90].
Solubilization of Poorly Water Soluble Compounds
It is estimated that over 40% of new drug entities (NDEs) are poorly water soluble as defined by BCS. There are many options for improving solubility and TPGS is a powerful tool for formulators to solubilize many of these NDEs. Some drug delivery systems that can utilize the solubilizing ability of TPGS are solid dispersions, self-emulsifying drug delivery systems (SEDDS), self-microemulsifying drug delivery systems (SMEDDS), spray drying, and others. Much work has been done to investigate the effect of TPGS on the aqueous solubility of poorly water soluble drugs as shown below.
One of the early discoveries on the solubilizing potential of TPGS is attributable to the work of Ismailos et al. who followed up on the discovery that TPGS can be co-administered with cyclosporine A(CyA) resulting in a dramatic decrease in the dosage required of this costly drug [Ismailos, G.
et al. 1994, Eu. J. Pharm. Sci.1:269–271]. The solubility in aqueous solutions at 5, 20, and 37°C increased from 2- to 16-fold with increasing TPGS concentration. Another commercial success story was documented in 1999 when it was found that TPGS improves the solubility of the poorly water soluble drug amprenavir, a potent HIV protease inhibitor [Yu, L. et al. 1999, Pharm. Res.16:1812–1817]. The solubility of amprenavir in pH 7 buffer solution is 20 times higher when 2% (w/v) TPGS is present
in the buffer and increases linearly from 0.02%
to 2%. Below the critical micelle concentration, there is no increase in solubility. As is discussed in the bioavailability section, TPGS also increases the permeability of amprenavir such that the amount
of amprenavir per dose was reduced by 48 fold.A more recent application involves taxoids which, while important for their chemotherapeutic action, are poorly water soluble and difficult to administer in oral formulations. There are several excipients in which taxoids are soluble and a few of which allow formulation of a semi-solid oral dosage form. TPGS is one of the best. It shows excellent solubilization properties for oral formulations containing paclitaxel and TPGS [Varma, M.V. S. et al. 2005, Eu. J. Pharm. Sci.25:4–5, 445–453].
Got Solubility Problems?
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6
Eastman has evaluated the effect of TPGS on several poorly water soluble APIs. Aqueous solutions of
alpha-lipoic acid containing 0.01 to 10% TPGS show a 7to 100% nearly linear increase in the solubility of alpha-lipoic acid. Griseofulvan, a poorly water soluble antifungal drug, has 185 times greater
solubility in a 2 wt % TPGS aqueous solution than it has in water. The solubility increases linearly with increasing TPGS concentration as shown in Figure 5.Like the APIs discussed above, nifedipine, phenytoin,carbamazepine, and erythromycin are very poorly water soluble APIs. Figure 6 shows the results graphically. The solubility for the four compounds in the graph increases from 130, 44, 1077, and 5
parts-per-million in water to about 1800, 1220, 2400,and 4500 ppm in 10 wt % TPGS aqueous solutions at room temperature, respectively. Diclofenac sodium,which is more soluble in water at 2 wt %, still shows a three-fold increase in a 10 wt % TPGS solution. Sulfadiazine, another poorly water soluble pharmaceutical, did not show an increase in solubility when exposed to aqueous TPGS solutions.
Researchers at the Taipei Medical University studied the effect of TPGS on the aqueous ethanol solubility and the percutaneous penetration of estradiol
[Sheu, M. T.et al. 2003, J. Contr.Rel. 88:355–368].A significant increase in estradiol solubility occurs in the aqueous solvent as well as in various concentrations of ethanol with increasing TPGS
concentration. The authors also observed an increase in the CMC with increasing alcohol content and an increase in estradiol solubility with increasing ethanol content. TPGS did not appear to increase the percutaneous penetration of estradiol.
Vitamin E Bioavailability Enhancer
As a water-soluble derivative of natural-source vitamin E, TPGS provides enhanced bioavailability of
vitamin E in animals and in some populations of humans. Several studies support the use of a water-soluble form of vitamin E, such as TPGS, to deliver vitamin E to human populations exhibiting fat malabsorption [Sokol, R. J. et al., Gastroenterology, 1987, 93:975–985; Sokol, R. J. et al., Gastroenterology, 1993, 104:1727–1733; Sokol, R. J. et al. 1997, J. Pediatr. Gastroenterol. Nutr.24:189–193; Traber et al. 1986, Am. J. Clin. Nutr.44:914–923; Weinberg, T. H. et al. 1958, Am. J. Pathol.34:55]. In those populations, none of the various forms of fat soluble vitamin E, including the naturally occurring and typically most active form—d-?-tocopherol, are bioavailable and the long-term result is a vitamin E deficiency. Populations at risk include those with cystic fibrosis, Crohn’s disease, pancreatic enzyme deficiency, cholestatic liver disease, short bowel disease, genetic defects in lipoprotein synthesis, and others [Physician’s Desk Reference Health,2005, http://www.phrhealth. com/drug_info/nmdrugprofiles/nutsupdrugs/vit_ 0266.shtml].
Traber [Traber et al. 1994, Am. J. Clin. Nutr.
59:1270–1274] investigated the use of TPGS
as an oral vitamin E supplement in a patient
with severe fat malabsorption and vitamin E deficiency secondary to short-bowel
syndrome. TPGS was absorbed and the
released ?-tocopherol was transported
normally in lipoproteins. The patient was
dosed with 10,360 mg of TPGS (4,000
IU/day) which resulted in normal blood
plasma levels of vitamin E and prevention
of further progression of neurological abnormalities. A clinical study using TPGS
as a vitamin E absorption enhancer was
performed by Sokol et al. [1993,
Gastroenterology 104:1727–1735]
at eight centers in the United
States. In that trial, Sokol et al.
dosed TPGS to 60 children with
chronic cholestasis, a lipid
malabsorption syndrome, who
were unresponsive to 70–212
IU/kg/day of other oral vitamin
E forms. These children suffered
from vitamin E deficiency
which had caused differing degrees of neurological degeneration. Under these conditions, painful intramuscular injections of vitamin E are required to maintain normalized vitamin E status. In the clinical trial, an oral 25
IU/kg/day dosage of TPGS was given to each child
for a mean duration of 2.5 years. The results showed that all children responded to TPGS with normalization of vitamin E status. Neurological function, which had deteriorated before entry in the trial, improved in 25 patients, stabilized in 27, and worsened in only 2 cases.
A similar trial was performed with an 8-year-old patient who had suffered neurologic hallmarks of vitamin E deficiency, including loss of muscle coordination [Traber et al. 1986, Am. J. Clin. Nutr. 44:914–923]. The vitamin E trial was performed using an emulsified form of tocopheryl acetate (emulsified with medium-chain triglycerides and polysorbate 80) known as MCT-E and TPGS. Results show the
concentrations of tocopherols detected in
plasma, erythrocytes, and
adipose tissues following
administration were
much higher with
TPGS. Obviously,
TPGS provided
better bioavailability
than the other
form.
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Additionally, the same authors performed a parallel study on rats, concluding that TPGS delivered
?-tocopherol to enterocytes in the absence of bile salts;?-or ?-tocopherols normally require the presence of bile salts to be absorbed. The authors proposed a hypothesis for the mechanism of enhanced
?-tocopherol absorption using TPGS. The proposed mechanism suggests that, because TPGS forms
micelles, it can cross from the intestinal lumen through the unstirred water layer to the enterocytes (intestinal cells). The mechanism for tocopherol to enter the enterocytes is not yet understood. TPGS may be
hydrolyzed to free the tocopherol in the proximity of the brush border, or a lipase on the surface of the
enterocyte may transfer tocopherol into the enterocyte,or the entire TPGS micelle could be taken up by the enterocyte.
Traber et al. [Traber, M. G. et al. 1988, Am. J. Clin.Nutr.48:605–611] reported on the uptake of Vitamin E TPGS by human cells in vitro and concludes that the cellular tocopherol content increases when human fibroblasts, erythrocytes or Caco-2 cells are incubated with radioactively labeled TPGS; however, most (80%)of the tocopherol is present in the form of TPGS and only 20% is present as free ?-tocopherol. Traber
tentatively concludes that the free tocopherol is released by esterification of TPGS after it enters the cells.Not only can TPGS improve the bioavailability of vitamin E, TPGS can also improve the bioavailability of other fat soluble vitamins. E. A. Argao et al.
reported that vitamin D absorption in seven children with severe cholestasis increased to within the normal range on administration with TPGS. In no case did the level increase above normal nor did the vitamin D levels which were normal in six patients and low in one rise above normal. [Ref: Abstract from the
American Association for the Study of Liver Diseases annual meeting, Chicago, Illinois, Nov. 3–6, 1990;Argao, E. A., Heubi, J. E., Hollis, B. W . 1992, Pediatr.Res.31:146–150].
What is the effect on vitamin E plasma levels of dosing TPGS to healthy humans? There is little work in this area with the exception of a Dimitrov study in which both fat and water soluble vitamin E were dosed to healthy humans [Dimitrov, N. V . et al. 1996, Am. J.Clin. Nutr .64:329–335]. The study looked at the effect of both single and multiple doses at 400, 800,and 1,200 IUs of both TPGS and RRR-?-tocopherol acetate. The increase in tocopherol plasma level
resulting from all dose levels of TPGS is minimal compared to that observed by dosing the fat soluble form of vitamin E. Additionally, there is no significant difference in the plasma levels for the three TPGS dose levels—400, 800, and 1,200 IU and the level is in all cases less than that observed for the 400 IU dose of tocopherol acetate and much less than for the 800 and 1,200 IU doses.
In addition to studying the use of of TPGS as a
source of vitamin E in humans, some effort has been expended studying it in animals. These results,
combined with the work of Dr. Sokol on children with cholestasis, have helped to develop an understanding of how TPGS is absorbed. The animal studies show that elephants and black rhinoceros absorb vitamin E when their feed is fortified with vitamin E TPGS but become deficient in vitamin E when their feed is fortified with oil-soluble forms of vitamin E
(natural or synthetic vitamin E or the acetate ester).Interestingly, the digestive systems of elephants and black rhinoceros (also West Indian manatee and
hyrax) contain bile devoid of all bile acids. It is likely that in the absence of bile acids, oil-soluble vitamin E does not form micelles and cannot be absorbed.
Horses have bile containing some bile acids and some bile alcohols—this is somewhere in between the bile of humans and the bile of elephants and rhinos. Indeed horses are able to absorb both water and oil-soluble forms of vitamin E as shown in Figure 7.
Controlled Delivery Applications
TPGS is useful in melt extrusion which can be used
in drug delivery to improve the dissolution rate and bioavailability by forming a solid dispersion or a solid solution; controlling or modifying the release of the drug; and/or masking the bitter taste of a drug. Use of TPGS to improve the bioavailability of drugs has been discussed at length. TPGS has been used in solid dispersions to improve the solubility and dissolution rate of the following drugs (not all incompassing): furosemide [Shin, S. C., Kim, J. 2003,Int. J. Pharm. 251:79–84], nifedipine [Rajebahadur, M. et al. 2004, The AAPS J.6: Abstract M1169], carbamazepine [Late, S. et al. 2004, The AAPS J.6:Abstract R6099 and R6101; Sethia, S. 2002, The AAPS J.4:Abstract W5086], lovastatin [Tsung, J. 2001, The AAPS J.
3:Abstract for poster session].
Polymeric nanoparticles, in which the active agent
is dissolved, entrapped, encapsulated, adsorbed, attached or chemically coupled, are an exciting
new area of research which can provide sustained, controlled, and targeted drug delivery. Co-polymerizing TPGS with a polymer such as polylactide (PLA), poly-d,l-lactide-coglycolide (PLGA) or polycaprolactone (PCL) can improve the emulsification efficiency, drug encapsulation efficiency and enhance the cellular uptake of the nanoparticles, thereby increasing the therapeutic effect. These beneficial actions by TPGS have been demonstrated on microencapsulated paclitaxel [Zhang, Z. and Feng, S. S. 2006, Biomaterials27: 2, 262–270; Mu, L. and Feng, S. S. 2003, J. Contr. Rel.86:33–48]. The 2005 paper indicates the paclitaxel encapsulation efficiency increased from 79.9% to 89.1% for PLGA and PLA/TPGS, respectively at 5 wt % drug loading and the in vitro drug release increased from 7 to 15% after one day, and from 19 to 51% after 31 days for the PLGA, and PLA/TPGS nanoparticles respectively. Not only can TPGS be used in the polymer for nanoparticles, it can also be used as an emulsifier. Mu and Feng conclude that “compared with traditional PVA, vitamin E TPGS could be a more effective and safer emulsifier with easier usage in fabrication and characterization of polymeric nanospheres for drug delivery” [Mu, L. and Feng, S. S. 2002, J. Contr. Rel.80:129–144].
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Other Applications
Kawata et al. used TPGS as a solubilizing adjuvant to formulate an emulsion for an oily composition of an antitumor drug that comprises at least one sparingly oil-soluble or water-soluble antitumor drug. For instance, effective emulsions for carmofur, fluorouracil, mitomycin C, acracinomycin A, and cyclocytidine antitumor drugs were formulated using TPGS [US Patent 4,578,391(1986)].
TPGS can be used as a plasticizer in many types of films including hydroxypropylcellulose (HPC) [Repka, M. A. and McGinity, J. W. 2000, Int. J. Pharm. 202: 1–2, 63–70], and cellulose acetate and cellulose acetate butyrate [Bernard, B. 2004, The AAPS Journal6:4,Abstract W5089] to name a few. The mechanical and physical properties of the films were improved by the addition of TPGS. In addition, TPGS facilitated the film processing by lowering the barrel pressure, drive amps and torque of the extruder equipment. Improved processability also occurs when TPGS is used as a melt or thermal binder.TPGS can be used as a binder in formulating tablets. It works over a variety of concentrations to make tablets with good physical properties and its antioxidant properties are useful to stabilize readily oxidizable actives [Yuan, J. and Clipse, N. 2004,The AAPS Journal, 6:4,Abstract W5088]. Speaking of the antioxidant property of TPGS—it can be used to stabilize polyethylene oxide and polyethylene glycol containing coatings [Crowley, M. M. et al. 2001, AAPS Pharm. Sci.3:3; Zhang, F. and McGinity, J. W. 1999, The AAPS Journal Poster session abstract; Singleton, A. and Wu, S. H. W. 2000, AAPS Pharm. Sci.2:2, Abstract 255].
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Non-Oral Delivery Applications
Eastman actively promotes the use of TPGS in oral and topical drug formulations. The use of this material in novel drug delivery systems is still under investigation. TPGS has been, however, looked at by several pharmaceutical companies, drug delivery companies, and university researchers in non-oral applications. Although Eastman does not produce
a parenteral grade of TPGS, for the sake of completeness, parenteral uses are included in the overview of the non-oral drug delivery applications given below.
Nasal/Pulmonary Delivery
Use in nasal/pulmonary delivery formulations shows that TPGS increases the immune response toward diphtheria toxoid loaded poly(caprolactone) microparticles [Somavarapu, S. et al. 2005, Int. J. Pharm.298:344–347]. TPGS has also recently been found to be an adjuvant for nasally applied
anti-tetanus toxoid, anti-diphtheria toxoid
in mice [Alpar, H. O. et al. Intranasal vaccination against plague, tetanus and diphtheria [2001,
Adv. Drug Del. Rev.51:173–201].
Reichert used approximately 20 mg/L of TPGS in
a suspension formulation that was applied to the mucous membranes of the nose and pharynx to maintain proper moisture level and thus prevent snoring. In these applications, TPGS, which has good physiological compatibility with the mucous membrane surface, serves as a wetting agent to smooth the membrane surfaces, which in turn delimit the flow channels. In this formulation TPGS plays an important role not only as a surface-active agent but also as an emulsifier [US Patent 4,668,513 (1987)].Ophthalmic Delivery
A review of ophthalmic drug delivery systems,
while not mentioning TPGS, describes many drug delivery systems in which TPGS is compatible and has shown utility. These drug delivery systems include: bioadhesive hydrogels, liposomes, nanoparticles,
and the use of excipients with solubility enhancing properties [Bourlais, C. L. et al. 1997,Progress in Retinal and Eye Res. 17(1): 33–58].
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Parenteral Delivery
TPGS in a parenteral formulation has been used
in clinical trials and has been the subject of a pharmacokinetic study [Lissianskaya, A. et al. 2004, J.Clin. Oncol. 22:14S, 5047; Hanauske, A. R. et al. 2005,J. Clin. Oncol. 23:16S, 2045]. TPGS is included in the formulations of taxane analogues to improve their solubility. TPGS may also have some therapeutic value against cancer cells as it has been found to induce apoptosis and inhibit the growth of human lung carcinoma cells implanted in nude mice [Youk, H. 2005, J. Contr. Rel. 107: 2, 43–52].Dermal Delivery
Dermal applications can use TPGS’s surface active properties to improve the surface wetting of films with skin. Incorporating TPGS in hot-melt extruded hydroxypropylcellulose and polyethyleneoxide films resulted in nearly doubling the adhesive strength of the films [Repka, M. A. et al. 2001, J. Contr. Rel.70: 3, 341–351]. This result may indicate that TPGS could be an important additive in transdermal/ transmucosal or wound care systems. It may also serve as a human skin penetration enhancer as was shown for radiolabeled hydrocortisone [Trivedi, J. S. et al. 2000, Eu. J. Pharm. Sci.3:4, 241–243].
In addition, films made with TPGS can be used in dermal applications where the TPGS results in good bioadhesive properties [Repka, M. A. and McGinity, J. W. 2000, AAPS Pharm. Sci. 2:2, Abstract 750] or in film coatings for tablets.
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Formulating With TPGS
There are several ways to incorporate TPGS into a formulation. In some cases a simple melt dispersion can be formed in which the components are heated and mixed at a temperature above their melting points and then cooled to room temperature. In other cases it is better to dissolve the active drug into a solvent, mix with the TPGS and then evaporate off the solvent. TPGS can also be spray dried onto the active with or without other excipients and then compressed into tablets or filled in hard capsules. The particles may also be coated with enteric or sustained release coatings while in the particulate form or after tableting, if and as desired [Mu, L. et al. 2005, J. Contr. Rel.103:565–575].
TPGS is compatible with a wide variety of excipients such as propylene glycol, lactose, calcium carbonate, magnesium stearate, polysorbates, polyethylene glycols, polyvinylpyrrolidone, microcrystalline cellulose, glycerin, and other ingredients commonly used in drug formulations. TPGS is an ester, therefore mixing it with acids or bases, such as sodium lauryl sulfate, citric acid, or sodium bicarbonate in the presence of water can result in some hydrolysis of the ester functionalities.
Microcrystalline cellulose can be incorporated into
a molten TPGS/vitamin E acetate blend to make
free-flowing water-dispersible powder [Wu, S. H. W. 1993, US Patent 5,179,122]. Free flowing pure TPGS can be prepared by a number of ways such as spray drying, spray chilling, cryogenic grinding, etc. [Singleton, A. et al. 2005, Patent Application Docket No. 80219].An in-house study investigated the use of TPGS as a tableting aid for tableting ascorbic acid and its effect on the release profile and decomposition [Posters Sessions AAPS Salt Lake City, Utah, Oct. 26–30, 2003 and Baltimore, Maryland, Nov. 7–11, 2004]. Without TPGS, none of the formulations resulted
in satisfactory tablets (in terms of hardness and friability); however, incorporating 2–10 wt % TPGS in the formulation allows good tablets containing
52–70% ascorbic acid to be successfully made. In this case, TPGS served as both a melt binder and lubricant for tableting.
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14
Thermal Properties and Density
?Melt temperature: 38°–41°C (l00°–106°F)?Thermal degradation temperatures: 199°C, 212°C ?
Stable under heat sterilization conditions
Three calorimetry experiments were performed to examine the thermal properties of TPGS. The first experiment investigated the thermal stability of neat TPGS during repeated solid-liquid phase transitions using differential scanning calorimetry (DSC). Heating and cooling cycles were set between 0°and 85°C with a 10°C/min heating rate. Cooling was accomplished by liquid nitrogen purging. Figure 8 shows the thermograms generated. The melting point for the first heating cycle was approximately 41°C. Nineteen subsequent heating cycles show the melting point at about 38°C. The higher melting point exhibited for the first heating cycle demonstrates a solid TPGS with relatively high crystallinity. This crystalline state requires more thermal energy to melt than the lower-energy amorphous states that form during rapid cooling of the sample. These results show that TPGS is thermally stable during repeated solid-liquid phase transitions.
The second set of experiments determined the
oxidative and non-oxidative thermal degradation of TPGS. This study was also performed on a Mettler calorimeter using a 10°C/min heating rate from 0°to 300°C. Figure 9 shows the oxidative thermal degradation occurring at 199.9°C and the
non-oxidative thermal decomposition temperature at 212°C. The high degradation temperature indicates good thermal stability of TPGS under normal processing conditions used for pharmaceutical, cosmetics, or food applications.
The third experiment, an isothermal stability test,gave an indication of TPGS stability under heat sterilization conditions. There is no change in the
125°C thermogram over a 1 hour period. Thus, TPGS is thermally stable under these conditions. It has also been determined that TPGS is stable at 65°C for at least 5 days as shown in Figure 10.
The density of TPGS varies slightly with temperature.Figure 11 shows that the density decreases from 1.055at 60°C to 1.022 at 100°C.
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Solution Properties
Aqueous Solutions
TPGS is miscible with water and forms solutions with water at concentrations up to approximately 20wt %, beyond which liquid crystalline phases may form. A detailed description of TPGS/water phases as
1Melt the entire contents of a
container of TPGS to a molten state; stir to ensure homogeneity.Slowly pour the molten TPGS, with vigorous stirring, into water that has been heated to 60°–90°C. The TPGS will absorb a portion of the water immediately, forming high-viscosity gel particles; however,these particles will dissolve as
the solution is stirred.
2Stir at room temperature for
approximately 2 hours to ensure complete dissolution of the gel particles.
3A clear, fluid solution results from a
mixture containing up to 20% TPGS by weight.
a function of TPGS concentration is given on page 17.General guidelines for preparing an aqueous TPGS solution follow.
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Surface-Active and Critical Micelle Concentration
TPGS is an amphiphile, that is, it has a dual nature,part of the molecule exhibits hydrophilicity and the other lipophilicity. The exact portion of the molecule comprising the hydrophilic polar head or the lipophilic alkyl tail may not be elucidated from the molecular structure; however, a generally accepted view is that the polyethylene glycol portion serves as the polar head while the tocopherol succinate portion serves as the lipophilic tail. This amphiphilic characteristic leads to its self-association in water
when the concentration exceeds a threshold known as the critical micelle concentration (CMC). For
surfactant molecules, CMC value is a key parameter that characterizes their surface activity.
The CMC was determined by measuring surface tension as a function of the solute concentration.TPGS concentration was systematically increased from 0.0001 to 0.25 wt % with temperature
maintained at 37?0.1°C. This was achieved by first preparing a stock solution of 15 wt % TPGS,followed by dropwise addition to the surface-tension vessel containing 10 mL deionized water. Figure 12shows the results. A distinctive break can be
identified at approximately 0.02 wt % concentration,indicating the onset concentration (i.e., CMC) of
TPGS micellization. The measurement was performed for TPGS/water systems using a semiautomatic Kruss Model K-l0 tensiometer.
Chemical Stability in Aqueous Media
For applications requiring the use of TPGS in aqueous media, hydrolytic stability becomes an important issue. Because TPGS is an ester it can be expected to undergo hydrolysis of the ester linkage on exposure to acidic or alkaline aqueous conditions. As shown in Figure 13, hydrolysis is fairly slow at pH 4.0, 6.8, and 8.1, faster at pH 10 and very rapid at pH 1.2. Millipore water was used both for the pure water aqueous solution and for the buffer solutions.
Liquid Crystalline Phases
TPGS forms micelles at 0.02 wt % and continues
to form relatively low-viscosity solutions with water until a concentration of approximately 20 wt %
is obtained. When TPGS concentration is above
20 wt %, higher-viscosity liquid crystalline phases start to form.
As the TPGS concentration is increased, the structure of the TPGS/water liquid crystalline phase evolves gradually from isotropic globular micellar to isotropic cylindrical micellar, mixed isotropic cylindrical micellar and hexagonal, mixed hexagonal and reversed hexagonal, reversed globular micellar, and finally to the lamellar phase. Figure14 summarizes these phase transitions. Recently, it was found that over a narrow concentration range a cubic phase forms with ringing gel properties.
At both ends of the concentration range where either micelles or reverse micelles exist, the phase exhibits liquid-like behavior. Between about 20
and 90 wt % TPGS, the mixtures have gel-like characteristics.
From a thermodynamic point of view, each phase has a unique crystalline structure and dynamic characteristics. Systems exhibiting multiple phases, such as TPGS/H2O blends, have potential for broad applications. Additionally, TPGS does not need
to be mixed with surfactants to form other liquid crystalline phases. Furthermore, TPGS can be
used as a surface-active agent or an emulsifier in a multi-component formulation. Examples are given in the Other Applications section on page 10.
Figure 14
Liquid Crystalline Phases of TPGS/Water Systems at 37°C
17
18
Wide Viscosity Range
The viscosity measurements for TPGS/water systems were performed in Eastman’s research laboratory using a Brookfield low-shear viscometer with a
cylindrical cell. The working range of the instrument was from 0 to 100 cP with a standard error of ?1%.Figure 15 shows a 3-D viscosity plot using TPGS concentration, temperature, and viscosity as the axes.The curves were obtained by combining the
experimental data and the calculated values from an expert system for experimental design. The viscosity appears to be constant and low within the triangular area defined by (20 wt %, 45°C), (10 wt %, 20°C),and (10 wt %, 45°C). The underlying reason for this viscosity stability likely arises from the intermicellar repulsive interaction that stabilizes the system from rapid micellar growth, flocculation, or coagulation.This compositional range (shaded area on the concentration-temperature plane) provides a wide range for low-viscosity applications.
For some applications, high viscosity is desirable. In those cases, one can easily increase the TPGS/water viscosity by adjusting the concentration to above 10% (see Figure 16). Above 20 wt % TPGS the viscosity continues to rise very rapidly as shown in Figure 16.
The melt viscosity of neat TPGS decreases from about 600 centipoise at its melting point to about 50 centipoise at 100°C as shown in Figure 17.
反相高效液相色谱法测定食品中水溶性维 生素的含量 分析洲第16卷第3期1997.525 FENXICKSHIXUEB&O(Jota'naloflnstmmel~talAzasis, 反相高效液相色谱法测定食品中 水溶性维生素的含量 李来生张江华功午 (南昌大学应用化学研究所南昌330047j 摘要采坍反相色l蒋时洲宜传?溶性维生求(vtir_]c,,Bl,B2剜Bt2的古培.PC8一IO/S2504【4.0 25010)牡.0】I..艘铵一l_盹蒲漩(pH:45,青04%己胺)+甲醇(75+25)为流曲丰日.流速1 nalJminuY2_54呲I】l12…l1_j瑚r岛好汁离.己酰苯胺为内标物.苹果及强化奶粉中维生索平均收率井别为 925f)%一I(∞%干Ⅱ9500%～】∞80%.该法拇怍简便,迅谜可靠,测试费用低一 业= 水溶性堆生素是维持凡体正常生理代谢的一类重要化台物.有关其测定方j击较多,其中有}硼Lc法小1 报道但个别检测为主,食品中系列测定方法偏少,现在普遍栗用的离子对色谱法需耗鞍贵的己烷磺酸盐等 离子对试剂,且对色谱柱和高压泵甫…定的腐蚀作用, 本文采用选扦性较高的c8吲定棚,价格便宜的甲醇一水为流动栩.通过改变pH值等色谱条件,短时间内实 现了上述6种维生素的分离浚法平衡时间短,测定迅速,实用性强. 1实验材料与方法 11主要仪器与试剂
日本岛津I￡一6A液相色谱仪,酸度计等 甲醇(AR)用前重蒸次:维生素对照品均符中国药典(1990版)规定;淀粉酶(杭l州大学生物制品厂 产):其它试剂均为分析纯 果蔬及强化奶粉样品购于集贸市场. 1.2色谱条件 色谱拄:PC8—10/s25O4(40『¨mx2501111"131,日本岛津产;流动相:0.1mol/L甲酸铵一甲酸(DH=4.5,舍o.4% 二己胺)+甲醇(75+25),1tv,]g'mJn;柱温3【);【254nm:【)04AUFS. 1.3标准液配镧c避光操作) 准确称取下靖(mg)的标准品:VitaminC13帅,Vitamin12.25,Vitanfin20.15,VitaminBL8.65 Vha~nB211.15,Vitamin111,20,己酰苯胺6 用0.1mol/LHCI溶解并定容至 50ml-作储备被,VitaminC改用 3%偏磷酸溶解:依次等鼙移取 各组分储备ji蔓5,10,20,1'00,500, 10(30于10mL棕色餐瓶中,用 水定容(每个容量瓶预先分别加 内标储备液1'00l正),得六组标准 液,分别进样测定标准品及强 化奶粉样品色谱圈见图1和圈 2c 1.4样品前处理 05l00, nt~dtt 圉j标样色谱圈圈2强化奶粉色谱图 1~tattmaC;2,VilaminB5;3Vilam/n;4.viIBj; 5Vitatn~n;6内杯;7.~PaminB12.
维生素总结 一、脂溶性维生素 1、维生素A 名称:类视黄素、抗干眼病维生素、A1:视黄醇、A2:3-脱氢视黄醇 活性形式:视黄醇、视黄醛、视黄酸 功能:1、视黄醛与视蛋白结合发挥视觉功能2、调控细胞的生长与分化、抗癌3、抗氧化 缺乏时病症:夜盲症、干眼病 发病机理或治病原理:感受弱光的视杆细胞内,全反式视黄醇被异构成11-顺视黄醇,氧化成11-顺视黄醛。此物作为光敏感视蛋白的辅基与之结合生成视紫红质。视紫红质感光时,异构为全反式视黄醛,并引起视蛋白变构。进而视蛋白通过一系列反应产生视觉冲动。视紫红质分解,全反式视黄醛与视蛋白分离,构成视循环。维生素A缺乏,视循环关键物质11-顺视黄醛不足,视紫红质少,对弱光敏感性降低,暗适应延长。 过量的影响:中毒,组织损伤。症状:头痛、恶心、肝细胞损伤、高血脂、软组织钙化、高钙血症、皮肤干燥、脱屑、脱发 2.维生素D 名称:抗佝偻病维生素(本质就是类固醇衍生物) 活性形式:1,25-二羟维生素D3 功能:1、调节血钙水平,促进小肠对钙、磷的吸收、影响骨组织钙代谢,维持血钙、磷的正常水平2、影响细胞的分化 (免疫细胞、胰岛B细胞、肿瘤细胞) 缺乏时病症:儿童:佝偻病成人:软骨病自身免疫性疾病 过量的影响:中毒。表现:高钙血症、高钙尿症、高血压、软组织钙化 备注:在体内可合成:皮下储有维生素D3原,紫外线照射下可变成维生素D3 3.维生素E 名称:生育酚类化合物(生育酚、生育三烯酚) 活性形式:生育酚 功能:1、抗氧化剂、自由基清除剂、保护细胞膜,维持其流动性2、调节基因表达(抗炎、维持正常免疫功能、抑制细胞增殖,降低血浆低密度脂蛋白的浓度。预防治疗冠状动脉粥样硬化性心脏病、肿瘤与延缓衰老有一定作用)3、提高血红素合成关键酶活性,促进血红素合成。缺乏时病症:新生儿:轻度溶血性贫血一般不易缺乏。重度损伤导致红细胞数量减少,脆性增加等溶血性贫血。动物缺乏,生殖器发育受损,甚至不育 备注:临床常用维生素E治疗先兆流产与习惯性流产 4.维生素K 名称:凝血维生素 活性形式:2-甲基1,4-萘醌 功能:1、维生素K具有促进凝血的作用, 就是许多γ-谷氨酰羧化酶的辅酶2、对骨代谢有重要作用,对减少动脉钙化有重要作用,大剂量可降低动脉硬化的危险性。 缺乏时病症:维生素K缺乏引起出血。 备注:长期应用抗生素及肠道灭菌有引起维生素K缺乏的可能性。引发脂类吸收障碍的疾病,可引起维生素K缺乏。新生儿易缺乏(不能通过胎盘) 二、水溶性维生素
维生素C 中国居民膳食营养素参考摄入量（2013版）摘录 维生素C又名抗坏血酸，是人体内重要的水溶性抗氧化营养素之一。维生素C缺乏导致的坏血病是最早被发现的维生素缺乏病之一，早在公元前1550年就有坏血病的记载。公元前450年，希腊的医学资料记在了坏血病的症状。15~16世纪，坏血病曾波及整个欧洲，并导致多起远航海员死亡事件。1747年英国的一名海军军医首次发现柑橘和柠檬能治疗坏血病。1928年剑桥大学的学者从牛肾上腺、柑橘和甘蓝叶中分离出了抗坏血酸。到20世纪30年代，科学家们以阐明了维生素C的结构，并成功地合成了维生素C。 近年来，营养学界对人类维生素C的摄入量与慢性病的预防进行了多项研究，取得了许多重要研究进展。本书根据有关研究资料，就修订了我国维生素C的DRIs提出建议。 一、消化吸收与代谢 （一）吸收 食物中的维生素C在小肠上段吸收，吸收方式是通过一种转运蛋白以主动转运为主，经被动扩散吸收量较少。维生素C的吸收率与摄入量有关，其吸收率随摄入量的增加而减少。维生素C的摄入量较低时几乎完全被吸收；摄入量30~200mg/d，吸收率为80%~100%；摄入量达500mg时，吸收率下降至75%左右；摄入量达1250mg/d时，吸收率下降至50%左右。 （二）分布 维生素C被吸收后迅速进入血压循环，分布在体内不同组织器官中。人体组织中，维生素C浓度以脑下垂体最高，其次是肾上腺、肾脏、脾脏和肝脏，胰腺和胸腺也存在一定量的维生素C，血浆和唾液中含量最低。当组织中的维生素C达到饱和后，多余的维生素C将从组织中排出。 维生素C能逆浓度梯度被转运至细胞内储存。人体内可有少量维生素C储存，健康人体代谢池内维生素C的含量一般在1200~2000mg，最多可达3000mg，总转换率是45~60mg/d。体内储存的维生素C大部分在细胞内，不同细胞的维生素C通常要比血浆高很多。体内维生素C的储存量随摄入量变化，但不成线性关系，在不连续摄入维生素C时，其在体内储存较少。 （三）排泄 维生素C及其代谢产物主要随尿排出，其次由汗和粪便排出。正常情况下，大部分维生素C在体内经代谢分解为草酸、2,3-二酮古洛糖酸或与硫酸结合生成抗坏血酸-2-硫酸有尿排出；一部分可直接有尿排出。尿中排除量受摄入量、体内储存量及肾功能影响。人体处于稳态时，维生素C摄入量在60~100mg/d，可以在尿中检测出维生素C的排出。摄入量＜60mg/d 时，尿中无维生素C排出。静脉注射高剂量维生素C500mg/d和1250mg/d时，绝大部分维生素C经尿排出（Levine et al.,2001）。 二、生理功能 （一）羟化作用
第十八章维生素 复习测试 （一）名词解释 1．维生素 2．维生素需要量 3．脂溶性维生素 4．水溶性维生素5．辅酶Ⅰ 6．辅酶Ⅱ 7．辅酶A 8．黄素酶 （二）选择题 A型题： 1．下列关于维生素的叙述正确的是： A．维生素是一类高分子有机化合物 B．维生素每天需要量约数克 C．B族维生素的主要作用是构成辅酶或辅基 D．维生素参与机体组织细胞的构成 E．维生素主要在机体合成 2．关于水溶性维生素的叙述错误的是： A．在人体内只有少量储存 B．易随尿排出体外 C，每日必须通过膳食提供足够的数量 D．当膳食供给不足时，易导致人体出现相应的缺乏症 E．在人体内主要储存于脂肪组织 3．关于脂溶性维生素的叙述错误的是： A．溶于脂肪和脂溶剂 B．不溶于水 C．在肠道中与脂肪共同吸收 D．长期摄入量过多可引起相应的中毒症 E．可随尿排除体外
4．有关维生素A的叙述错误的是：A．维生素A缺乏可引起夜盲症。B．维生素A是水溶性维生素 C．维生素A可由β-胡萝卜素转变而来 D．维生素A有两种形式，即A 1和A 2 E．维生素A参与视紫红质的形成 5．胡萝卜素类物质转为维生素A的转变率最高的是： A．α-胡萝卜素 B．β-胡萝卜素 C．γ-胡萝卜素 D．玉米黄素 E．新玉米黄素 6．关于维生素D的叙述错误的是： A．在酵母和植物油中的麦角固醇可以转化为维生素D 2 B．皮肤的7-脱氢胆固醇可转化为维生素D 3 C．维生素D 3的生理活性型是25-（OH）D 3 D．化学性质稳定，光照下不被破坏 E．儿童缺乏维生素D可引起佝偻病 7．下面关于维生素E的叙述正确的是： A．是6-羟苯骈二氢吡喃衍生物，极易被氧化B．易溶于水 C．具有抗生育和抗氧化作用 D．缺乏维生素E，可产生癞皮病
第6章维生素与辅酶单元自测题 (一) 名词解释 1．维生素, 2．抗维生素, 3．维生素缺乏症, 4．维生素中毒症, 5．脂溶性维生素 6．水溶性维生素, 7．维生素原, 8．内源因子 (二) 填空 1．维生素是维持机体正常代谢和健康所必需的一类化合物，该物质主要来自，其中，两种维生素可以在体内由和转变生成。 2．维生素A在体内的活性形式包括、和。 3．自然界黄红色植物中含β—胡萝卜素、它在小肠粘膜催化下生成两分子，所以通常将β—胡萝卜素称为。 4．维生素D是属于衍生物，储存于皮下的经紫外线照射转变为维生素D3，必须在肝、肾羟化生成是D3型。 5．维生素E对极敏感，且易自身，因而能保护其它物质免遭氧化，所以具有作用。 6．维生素K的生化作用是促进肝合成的前体分子中谷氨酸残基羧化生成转变为活性型。催化这一反应的为酶，维生素K是该酶的，因此具有促凝血作用。 7．维生素B1 因含有硫和氨基又名，其在体内活性形式为，它是体内酶和的辅酶，参与糖代谢。 8．维生素B l缺乏时，神经组织不足，并伴有和等物质堆积，可引起。 9．维生素B2是和的缩合物，因其结晶呈桔黄色又称。 10．维生素B2在体内黄素激酶和焦磷化酶的催化下转变成活性型的和，是黄素酶的辅基，参与氧化还原反应。 11．维生素PP包括和两种，都是的衍生物，在体内可由转变生成。 12．维生素PP在体内的活性形式是和是多种不需氧脱氢酶的辅酶，分子中的尼可酰胺部分具有可逆的及特性。 13．维生素B6在体内经磷酸化转变为活性型的和，它们是及的辅酶。 14．临床上常用维生素B6治疗小儿惊厥和呕吐，其机理是维生素B6是的辅酶，能催化脱羧生成，该产物是一种抑制性神经递质。 15．泛酸与及3′磷酸腺苷5′焦磷酸结合组成，后者是酶的辅酶。 16．因为生物素具有转移、携带和固定的作用，所以是体内酶的辅酶，参与多种物质的反应。 17．叶酸在体内叶酸还原酶的催化下转变为活性型的，是体内酶的辅酶，携带参与多种物质的合成。 18．维生素B12在消化道与胃粘膜分泌的结合才能在小肠被吸收。维生素B12体内的活性型为。 19．维生素B12是的辅基，参与同型半胱氨酸转变成的反应。当维生素B12缺乏时导致核酸合成障碍，影响细胞分裂结果产生。 20．维生素C参与体内多种物质的反应，因此具有促进合成的作用。维生素C还可作为一种，参与体内多种氧化还原反应。 (三) 选择题 1．下列辅酶中的哪个不是来自于维生素? A CoA B CoQ C PLP D FH2 2．肠道细菌可以合成下列哪种维生素? A 维生素K B 维生素 C C 维生素 D D 维生素E 3．下列叙述哪一种是正确的? A 所有的辅酶都包含维生素组分。 B 所有的维生素都可以作为辅酶或辅基的组分。 C 所有的B族维生素都可以作为辅酶或辅基的组分。 D 只有B族维生素可以作为辅酶或辅基的组分。 4．下列化合物中除哪个外都是环戊烷多氢菲的衍生物。 A 维生素D B 胆汁酸 C 促肾上腺皮质激素 D 肾上腺皮质激素 5．下列化合物中，除哪个外都是异戊二烯的衍生物。 A 视黄醇 B 生育酚 C 鲨烯 D 核黄醇 6．多食糖类需补充 A 维生素B1 B 维生素B2 C 维生素B5 D 维生素B6 7．多食肉类，需补充
A 只作供氢体 B 只作受氢体 C 既作供氢体又作受氢体 D 是呼吸链中的递氢体 E 是呼吸链中的递电子体 维生素 一级要求 多选题 1 哪种维生素的前身由绿色植物合成？ A 维生素 A B 生物素 C 尼克酸 D 维生素D E 维生素B 12 A 2 构成视紫红质的维生素 A 活性形式是: A 9-顺视黄醛 B 11-顺视黄醛 C 13-顺视黄醛 D 15-顺视黄醛 E 17-顺视黄醛 B 3 维生素 K 与下列哪种凝血因子合成有关? A 因子 XII B 因子 XI C 因子 II D 因子 VIII E 因子 V C 4 维生素B 2是下列哪种酶辅基的组成成分? A NAD + B NADP + C 吡哆醛 D TPP E FAD E 5 维生素 PP 是下列哪种酶辅酶的组成成分? A 乙酰辅酶A B FMN C NAD + D TPP E 吡哆醛 E 6 泛酸是下列那种酶辅酶的组成成分: A FMN B NAD + C NADP + D TPP E CoASH E 7 CoASH 的生化作用是: A 递氢体 B 递电子体 C 转移酮基 D 转移酰基 E 脱硫 D 8 生物素的生化作用是: A 转移酰基 B 转移CO 2 C 转移CO D 转移氨基 E 转移巯基 B 9 维生素 C 的生化作用是: C 10 人类缺乏维生素 C 时可引起: A 坏血病 B 佝偻病 C 脚气病 D 癞皮病 E 贫血症 A 11 维生素 C 的化学本质是一种: A 含有二个羧基的有机酸 B 含有一个羧基的有机酸 C 含有六碳原子的、二个烯醇式羟基的化合物 D 含有六个碳原子及一个羟基的化合物 E 含 8 个碳的有机酸 C 12 日光或紫外线照射可使: A 7-脱氢胆固醇转变成维生素D 3 B A 1生成 C 7-脱氢胆固醇转变成维生素 D 2 D A 2生成 E 维生素 E 活化 A 13 维生素 D 的活性形式是: A 1,24-(OH) 2-D 3 B 1-(OH)-D 3 C 1,25-(OH) 2-D 3 D 1,26-(OH) 2-D 3 E 24-(OH)-D 3 C 14 维生素 K 是下列那种酶的辅酶: A 丙酮酸羧化酶 B 草酰乙酸脱羧酶 C 谷氨酸γ-羧化酶 D 天冬氨酸γ-羧化酶
xx 1哪种xx的前身由绿色植物合成？ A 维生素A B 生物素 C 尼克酸 D 维生素D E 维生素B 12 A 2构成视紫红质的维生素A活性形式是: A 9-顺视黄醛 B 11-顺视黄醛 C 13-顺视黄醛 D 15-顺视黄醛 E 17-顺视黄醛 B 3维生素K与下列哪种凝血因子合成有关? A 因子XII B 因子XI C 因子II D 因子VIII E 因子V C 4维生素B 2是下列哪种酶辅基的组成成分? A NAD+ B NADP+ C 吡哆醛 D TPP E FAD E 5维生素PP是下列哪种酶辅酶的组成成分? A 乙酰辅酶A B FMN C NAD+ D TPP E 吡哆醛 E 6泛酸是下列那种酶辅酶的组成成分: A FMN B NAD+ C NADP+ D TPP E CoASH E 7 CoASH的生化作用是: A 递氢体 B 递电子体 C 转移酮基
D 转移酰基 E 脱硫 D 8生物素的生化作用是: A 转移酰基 B 转移CO 2C 转移CO D 转移氨基 E 转移巯基 B 9维生素C的生化作用是: A 只作供氢体 B 只作受氢体 C 既作供氢体又作受氢体 D 是呼吸链中的递氢体 E 是呼吸链中的递电子体 C 10人类缺乏维生素C时可引起: A 坏血病 B 佝偻病 C 脚气病 D 癞皮病 E 贫血症 A 11维生素C的化学本质是一种: A 含有二个羧基的有机酸 B 含有一个羧基的有机酸 C 含有六碳原子的、二个烯醇式羟基的化合物 D 含有六个碳原子及一个羟基的化合物 E 含8个碳的有机酸 C 12日光或紫外线照射可使: A 7-脱氢胆固醇转变成xxD 3 B A 1生成 C 7-脱氢胆固醇转变成xxD
第十一章微生素 1.单项选择题 1)下面关于维生素A的叙述哪一个是错误的 A.维生素A异构体中,活性最高的是全反式结构。 B.维生素A醋酸酯的化学稳定性比维生素A高。 C.维生素A对光照稳定,但加热或重金属离子可促进氧化。 D.维生素A在食物中对热有一定稳定性。 E.维生素A及维生素A醋酸酯临床用于防止维生素A缺乏症。 C 2)目前发现的维生素A的几何异构体有 A.2个 B.4个 C.6个 D.8个 E.10个 C 3)下面关于核黄素的叙述哪项是错误的 A.化学名为7,8-二甲基-10-(D-核糖型-2,3,4,5-四羟基戊基)异咯嗪。 B.本品干燥时性质稳定,耐热性好,对大多数氧化剂稳定,但可被铬酸和高锰酸钾氧化。 C.本品是碱性化合物,溶于酸不溶于碱。 D.本品母核中N1和N5间有共轭双键,连二亚硫酸钠等强还原剂可生成不具荧光的二氢核黄素。 E.本品用于治疗维生素B2缺乏造成的唇炎、舌炎、脂溢性皮炎等。 C 4)维生素C的异构体有 A.2个 B.3个 C.4个 D.5个 E.6个 C 5)下列哪一项是VitB1的适应症 A.硫胺缺乏症 B.妊娠呕吐 C.放射病呕吐 D.异烟肼中毒 E.糙皮病 A 2.配比选择题
1) A.Vit B6 B.Vit D2 C.Vit E D.Vit B2 F.Vit C 1.又名:生育酚 2.又名:抗坏血酸 3.又名:核黄素 4.又名:骨化醇 5.又名:吡多辛 1.C 2.E 3.D 4.B 5.A 2) 下列维生素类药物的化学结构分别是 A. B. C. D. E. 1.维生素A1醋酸酯 2.维生素B1 3.维生素B6 4.维生素D2 5.维生素D3 1.A 2.D 3.E 4.C 5.B 3) A.维生素D2 B.维生素D3 C.维生素C D.维生素B1 E.维生素B2 1. 氯化-3-[(2-甲基-4-氨基-5-嘧啶基)甲基]-5-(2-羟基乙基)-4-甲基噻唑盐酸盐 2. L(+)-苏阿糖-2,3,4,5,6-五羟基-2-己烯酸-4-内酯 3. 7,8-二甲基-10-(D-核糖型-2,3,4,5-四羟基戊基)异咯嗪 4. 3β,5Z、7E-9,10-开链胆甾-5,7,10(19)-三烯 -3-醇 5. 3β、5Z、7E、22E、9,10-开链麦角甾-5,7,10(19),22-四烯-3-醇
脂溶性维生素 一、维生素A 维生素A又称抗干眼醇，有A1、A2两种，A1是视黄醇，A2是3-脱氢视黄醇，活性是前者的一半。肝脏是储存维生素A的场所。 植物中的类胡萝卜素是VA前体，一分子β胡萝卜素在一个氧化酶催化下加两分子水，断裂生成两分子VA1。这个过程在小肠粘膜内进行。类胡萝卜素还包括α、γ胡萝卜素、隐黄质、番茄红素、叶黄素等，前三种加水生成一分子VA1，后两种不生成VA1。 维生素A与暗视觉有关。维生素A在醇脱氢酶作用下转化为视黄醛，11-顺视黄醛与视蛋白上赖氨酸氨基结合构成视紫红质，视紫红质在光中分解成全反式视黄醛和视蛋白，在暗中再合成，形成一个视循环。维生素A缺乏可导致暗视觉障碍，即夜盲症。食用肝脏及绿色蔬菜可治疗。全反式视黄醛主要在肝脏中转变成11-顺视黄醛，所以中医认为“肝与目相通”。 二、维生素D 又称钙化醇，是类固醇衍生物，含环戊烷多氢菲结构。可直接摄取，也可由维生素D原经紫外线照射转化。植物油和酵母中的麦角固醇转化为D2（麦角钙化醇），动物皮下的7-脱氢胆固醇转化为D3（胆钙化醇）。 维生素D与动物骨骼钙化有关。钙化需要足够的钙和磷，其比例应在1：1到2：1之间，还要有维生素D的存在。 三、维生素E
又称生育酚，含有一个6-羟色环和一个16烷侧链，共有8种其色环的取代基不同。α生育酚的活性最高。 存在于蔬菜、麦胚、植物油的非皂化部分，对动物的生育是必需的。缺乏时还会发生肌肉退化。生育酚极易氧化，是良好的脂溶性抗氧化剂。可清除自由基，保护不饱和脂肪酸和生物大分子，维持生物膜完好，延缓衰老。 维生素E很少缺乏，毒性也较低。早产儿缺乏会产生溶血性贫血，成人回导致红细胞寿命短，但不致贫血。 四、维生素K 天然维生素K有K1、K2两种，都由2-甲基-1,4-萘醌和萜类侧链构成。人工合成的K3无侧链。K1存在于绿叶蔬菜及动物肝脏中，K2由人体肠道细菌合成。 维生素K参与蛋白质谷氨酸残基的γ-羧化。凝血因子Ⅱ、Ⅶ、Ⅸ、Ⅹ肽链中的谷氨酸残基在翻译后加工过程中，由蛋白羧化酶催化，成为γ-羧基谷氨酸(Gla)。这两个羧基可络合钙离子，对钙的输送和调节有重要意义。有关凝血因子与钙结合，并通过钙与磷脂结合形成复合物，发挥凝血功能。这些凝血因子称为维生素K依赖性凝血因子。 缺乏维生素K时常有出血倾向。新生儿、长期服用抗生素或吸收障碍可引起缺乏。 水溶性维生素 一、硫胺素(VB1)
第二章食品样品的采集与处理 一、选择题 3．可用“四分法”制备平均样品的是（ 1 ）。 （1）稻谷（2）蜂蜜（3）鲜乳（4）苹果 4．湿法消化方法通常采用的消化剂是（ 3 ）。 （1）强还原剂（2）强萃取剂（3）强氧化剂（4）强吸附剂8．用溶剂浸泡固体样品，抽提其中的溶质，习惯上称为（ 1 ）。 (1)浸提 (2)抽提 (3)萃取 (4)抽取 二、填空题 2．对于液体样品，正确采样的方法是。从样品的上、中、下分别取样混合均匀 3．样品预处理的目的、和。消除干扰因素、使被测组分浓缩、完整保留被测组分 5．样品预处理的常用方法有：、、、和。有机物破坏法、蒸馏法、溶剂提取法、色层分离法、化学分离法、浓缩法 6．按照样品采集的过程，依次得到、和等三类。检样、原始样品、平均样品 四、简答题 1．简述采样必须遵循的原则。 答：（1）采集的样品具有代表性； ⑵采样方法必须与分析目的保持一致； ⑶采样及样品制备过程中高潮保持原有理化指标，避免预测组分发生化学变化或丢失； ⑷要防止和避免预测组分的玷污； ⑸样品的处理过程尽可能简单易行。 6．为什么要对样品进行预处理？选择预处理方法的原则是什么? 答：在食品分析中，由于食品或食品原料种类繁多，组分复杂，而组分之间往往又以复杂的结合形式存在，常对直接分析带来干扰，这就需要在正式测定之前，对样品进行适当的处理，使被测组分同其他组分分离，或者将干扰物除去。有的被测组分由于浓度太低或含量太少，直接测有困难，这就需要对被测组分进行浓缩，这些过程称为样品的预处理。而且，食品中有些预测组分常有较大的不稳定性，需要经过样品的预处理才能获得可靠的测定结果。 样品预处理的原则是：（1）消除干扰因素；（2）完整保留被测组分；（3）使被测组分浓缩。 第四章食品的物理检测法 一、选择题 6．下列说法正确的是（ 1 ）。 （1）全脂牛乳相对密度为1.028—1.032（20/20℃） （2）不饱和脂肪酸的折射率比饱和脂肪酸的折射率小得多 （3）锤度计专用于测定糖液浓度，是以蔗糖溶液的密度百分含量为刻度，以°Bx 表示 （4）蜂蜡的折射率在1.4410～1.4430（25℃） 7．水色度的常用测定方法是（2 ）
米糠多糖的提取研究及米糠中水溶性维生素的测定 （江南大学化学与材料工程学院，江苏无锡214122） 摘要：微波浸提法研究了米糠多糖的提取，HPLC法同时测定了米糠中4种水溶性维生素。料液比为1：8在50％微波火力条件下浸提30min，三氯乙酸去蛋白，两步去淀粉，30％醇沉，米糠多糖得率达1.41%。以体积比为88:12的0.1％磷酸水溶液-甲醇为流动相，以0.6 mL/min流速等度洗脱，在266nm波长下检测。各组分在8min能基线分离。米糠中VB1、VB6、烟酸和烟酰胺的含量分别为7.7×10-6 g/g、1.3×10-6g/g、14.9×10-6 g/g、16.2×10-6 g/g。关键词：米糠；多糖；微波浸提；水溶性维生素；高效液相色谱 Study on Microwave Assistant Extraction of Rice Bran Polysaccharides and Determination of W ater-Soluble Vitamins in Rice Bran Abstract: Microwave assistant extraction has been applied for polysaccharides in rice bran samples. The best technology were that the material-water ratio was 1:8, the time of microwave assistant extraction was 30 min under 50% firepower. It was proved that α-amylase could wipe off amylum effectively by two steps, and trichloroacetic acid method was the best way to wipe off albuminoid. And the ethanol concentration was 30%, the extraction rate of the water-soluble polysaccharides of rice bran was 1.41%.High performance liquid chromatography (HPLC) has been applied for the simultaneous determination of four kinds of water-soluble vitamins including vitamin B1, vitamin B6,nicotinic acid, and nicotinamide in rice bran. The separation was performed on a Hypersil C18 column (250cm×4.6mm i.d., 5.0 μm) with a mobile phase of 0.1% H3PO4- methanol (88:12, V/V) at flow rate of 0.6 mL /min, and detection wavelength was 266 nm.. Baseline separation of four vitamins can be achieved within 8 minutes.The content of 7.7×10-6 g/g、1.3×10-6g/g、14.9×10-6 g/g、16.2×10-6 g/g for vitamin B1,nicotinic acid ,vitamin B6 and nicotinamide. Key words: rice bran; polysaccharides; microwave assistant extraction; water-soluble vitamins; high performance liquid chromatography 米糠是一类具有广泛开发潜力的高附加值资源，含有稻米的64％营养物质及90％人体所需要的各种营养元素[1]，包括维生素、米糠多糖、氨基酸、脂肪酸、矿物质，还有二十八碳烷醇、神经酰胺等生理功能卓越的活性物质[2]。米糠多糖（Rice Brain polysaccharide，RBP）
注射用水溶性维生素说明书 【药品名称】 通用名：注射用水溶性维生素 商品名：V佳林 英文名：Water-soluble vitamin for injection 汉语拼音：：Zhusheyong Shuirongxing Weishengsu 【成份】 1. 本品为复方制剂，每瓶中组分为：硝酸硫胺3.1mg ,核黄素磷酸钠4.9 m g,烟酰胺40mg,盐酸吡哆辛 4.9mg,泛酸钠16.5mg,维生素C钠113mg,生物素60μg,叶酸0.4mg,维生素B12 5.0μg,甘氨酸300mg,对羟基苯甲酸甲酯0.5mg,乙二胺四醋酸二钠0.5mg。 2. 辅料：盐酸半胱氨酸、甘氨酸、对羟基苯甲酸甲酯、乙二胺四醋酸二钠。 【性状】本品为淡黄色的疏松块状物或粉末。 【适应症】用于水溶性维生素缺乏的预防和治疗。 【规格】复方 【用法用量】 临用前，加灭菌注射用水适量使溶解，加入0.9%氯化钠注射液或5%或10%葡萄糖注射液中静脉滴注。成人以及体重10kg 以上小儿，一次量为1瓶；体重低于10kg 的儿童常用剂量为每公斤体重1/10瓶。 【不良反应】对本品中任何一种成分过敏的患者，对本品均可能发生过敏反应。 【禁忌症】对本品中任一成分有过敏的患者禁用。 【注意事项】 某些高危病人可发生过敏反应；本品加入葡萄糖注射液中进行输注时，应注意避光。【孕妇及哺乳期妇女用药】尚不明确。 【儿童用药】新生儿及体重不满10kg 的儿童，需按体重计算给药剂量。 【老年患者用药】尚不明确。 【药物相互作用】 1、本品所含维生素B6能降低左旋多巴的作用； 2、本品所含叶酸可降低苯妥英钠的血浆浓度和掩盖恶性贫血的临床表现； 3、维生素B12对大剂量羟钴胺治疗某些神经疾病有不利影响。 【药物过量】尚不明确。 【药理毒理】 本品是静脉营养的一部分，用以补充每日各种水溶性维生素的生理需要， 使机体各有关生化反应能正常进行。 【药代动力学】尚不明确。 【贮藏】遮光，严封，在15℃以下保存。 【包装】低硼硅玻璃管制注射剂瓶，注射用无菌粉末用卤化丁基橡胶塞；10瓶/盒。 【有效期】30个月。
要想维持人体正常生理活动，还需要维生素。 维生素是人体代谢中必不可少的有机化合物。人体有如一座极为复杂的化工厂，不断地进行着各种生化反应。其反应与酶的催化作用有密切关系。酶要产生活性，必须有辅酶参加。已知许多维生素是酶的辅酶或者是辅酶的组成分子。因此，维生素是维持和调节机体正常代谢的重要物质。可以认为，维生素是以“生物活性物质”的形式，存在于人体组织中。 维生素大部分不能在人体内合成，或者合成量不足，不能满足人体的需要。因而，必须从食物中摄取。 食物中维生素的含量较少，人体的需要量也不多，但却是绝不可少的物质。膳食中如缺乏维生素，就会引起人体代谢紊乱，以致发生维生素缺乏症。如缺乏维生素A会出现夜盲症、干眼病和皮肤干燥；缺乏维生素D可患佝偻病；缺乏维生素B1可得脚气病；缺乏维生素B2可患唇炎、口角炎、舌炎和阴囊炎；缺乏PP可患癞皮病；缺乏维生素B12可患恶性贫血；缺乏维生素C可患坏血病。 维生素是个庞大的家族，就目前所知的维生素就有几十种，大致可分为脂溶性和水溶性两大类。前者包括维生素A、D、E、K，后一类包括维生素B族和维生素C，以及许多“类维生素”。 现在医学上发现的维生素主要有： 脂溶性维生素 1.维生素A。维持正常视力，预防夜盲症；维持上皮细胞组织健康；促进生长发育；增加对传染病 的抵抗力；预防和治疗干眼病。 2.维生素D。调节人体内钙和磷的代谢，促进吸收利用，促进骨骼成长。 3.维生素E。维持正常的生殖能力和肌肉正常代谢；维持中枢神经和血管系统的完整。 4.维生素K。止血。它不但是凝血酶原的主要成分，而且还能促使肝脏制造凝血酶原。小儿维生素K 缺乏症 水溶性维生素 1.维生素B1。保持循环、消化、神经和肌内正常功能；调整胃肠道的功能；构成脱羧酶的辅酶，参 加糖的代谢；能预防脚气病。 2.维生素B2。又叫核黄素。核典素是体内许多重要辅酶类的组成成分，这些酶能在体内物质代谢过 程中传递氢，它还是蛋白质、糖、脂肪酸代谢和能量利用与组成所必需的物质。能促进生长发育，保护眼睛、皮肤的健康。 3.泛酸(维生素B5)。抗应激、抗寒冷、抗感染、防止某些抗生素的毒性，消除术后腹胀。 4.维生素B6。在蛋白质代谢中起重要作用。治疗神经衰弱、眩晕、动脉粥样硬化等。 5.维生素B12。抗脂肪肝，促进维生素A在肝中的贮存；促进细胞发育成熟和机体代谢；治疗恶性 贫血。 6.维生素B13（乳酸清）。 7.维生素B15（潘氨酸）。主要用于抗脂肪肝，提高组织的氧气代谢率。有时用来治疗冠心病和慢 性酒精中毒。 8.维生素B17。剧毒。有人认为有控制及预防癌症的作用。 9.对氨基苯甲酸。在维生素B族中属于最新发现的维生素之一。在人体内可合成。 10.肌醇。维生素B族中的一种，和胆碱一样是亲脂肪性的维生素。 11.维生素C。连接骨骼、牙齿、结缔组织结构；对毛细血管壁的各个细胞间有粘合功能；增加抗体， 增强抵抗力；促进红细胞成熟。 12.维生素P。 13.维生素PP(烟酸)。在细胞生理氧化过程中起传递氢作用，具有防治癞皮病的功效。 14.叶酸(维生素M)。抗贫血；维护细胞的正常生长和免疫系统的功能。
第五章维生素与辅酶 3学时 定义：维持生物正常生命过程必需的一类小分子有机化合物，它在生物体内含量极少，大多数由食物供给，人体自身不能合成它们。 脂溶性：A、D、E、K，单独具有生理功能。 水溶性：B1、B2、B6、B12、C等，辅酶。 第一节脂溶性维生素 一、维生素A和胡萝卜素P360 1、结构 化学名称：视黄醇，包括两种：A1、A2 2、维生素A的来源 β-胡萝卜素、α-胡萝卜素、γ-胡萝卜素、黄玉米色素在肝脏、肠粘膜内转化成A。 β-胡萝卜素转化成二个维生素A（一切有色蔬菜） α-胡萝卜素 γ-胡萝卜素转化成一个维生素A 黄玉米色素 3、功能 与视觉有关。 缺乏症：夜盲症。 活性形式：11-顺式视黄醛 P361 视循环 视紫红质为弱光感受物，当弱光射到视网膜上时，视紫红质分解，并刺激视神经而发生光觉。 11-顺式视黄醛，在暗光下经视网膜圆柱细胞作用后，与视蛋白结合成视紫红质，形成一个视循环。 当全反视黄醛变成11-顺式视黄醛时，部分全反视黄醛被分解为无用物质，故必需随时补充维生素A，每日补充量1 mg。 二、维生素D（D1、D3，还有D4、D5） P361 有两种：D3（又名胆钙化醇），D2（又名麦角钙化固醇）。 植物体内不含维生素D（但有维生素D原） 1、来源
鱼肝油、蛋黄、牛奶、肝、肾、皮肤组织等富含维生素D。 酵母、真菌、植物中：麦角固醇（D2原） 动物体内：7一脱氢胆固醇（D3原） 2、结构P362反应式： 麦角固醇→维生素D2 （麦角钙化固醇） 7-脱氢胆固醇（皮肤）→维生素D3 （胆钙化固醇） 3、功能 调节钙磷代谢，维持血中钙磷正常水平，促进骨骼正常生长。 缺乏症：佝偻症等。 活性形式：1，25一二羟基胆钙固醇。 维生素D3 （胆钙化固醇）→25-羟基胆钙固醇（肝脏）→1，25一二羟基胆钙固醇（肾脏）→小肠（促进Ca2+ 的吸收、运输）及骨骼（促进Ca2+的沉积）中，参与调节钙磷代谢。 三、维生素E P363 化学名称：生育酚，共有8种，直接具有活性。 1、结构 P363 结构式：α-生育酚 2、来源 动、植物油、麦胚油、玉米油、花生油、棉子油、蛋黄、牛奶、水果等。 3、功能（抗氧剂—油脂氧化） 生理功能：抗生殖不育、肌肉委缩、贫血、血细胞形态异常 机理：有抗氧化活性，能防止不饱和脂肪酸自动氧化，保护细胞膜，延长细胞寿命，还可保护巯基酶的活性。 四、维生素K（K1、K2、K3）P364 1、结构 2、来源 食物和肠道微生物合成；绿色蔬菜、动物肝脏、牛奶、大豆，大肠杆菌、乳酸菌 3、功能 促进凝血。 缺乏症：肌肉出血、凝血时间延长。 凝血过程中，许多凝血因子的生成与维生K有关。 ①凝血酶原，即因子II ②转变加速因子前体，因子VII ③血浆凝血酶激酶因子IX ④司徒氏因子因子X 第二节水溶性维生素与辅酶 主要是B族维生素，绝大多数都是辅酶。 一、维生B1与焦磷酸硫胺素（TPP）P367 化学名称：硫胺素， 活性形式：焦磷酸硫胺素（TPP） 1、结构
水乐维他(注射用水溶性维生素) 【药品名称】 商品名称：水乐维他 通用名称：注射用水溶性维生素 英文名称：Verapamil Hydrochloride T ablets 【成份】 本品主要成分为多种维生素，每1000瓶中组分为：硝酸硫胺3.1g ,核黄素磷酸钠4.9g,烟酰胺40g,盐酸吡哆辛4.9g,泛酸钠16.5g,维生素C钠113g,生物素60mg,叶酸0.4g,维生素B12 5.0mg,甘氨酸300g,乙二胺四醋酸二钠0.5g,对羟基苯甲酸甲酯0.5g。【适应症】 本品系肠外营养不可少的组成部分之一，用以满足成人和儿童每日对水溶性维生素的生理需要。 【用法用量】 大多数成人和体重在10公斤以上的儿童每日需要1瓶，体重不满10公斤的儿童，每日每公斤需要1/10瓶。本品可用10ml脂肪乳剂、注射用水或5%～50%葡萄糖液溶解，加入脂肪乳剂或%～50%葡萄糖液中静脉滴注。 【不良反应】 对本品中任何一种成分过敏的患者，对本品均可能发生过敏反应。 【禁忌】 对本品中任一成分有过敏的患者禁用。 【注意事项】 某些高敏病人可发生过敏反应。本品加入葡萄糖注射液中进行输注时，应注意避光。新生儿
及体重不满10kg的儿童，需按体重计算给药剂量。 【特殊人群用药】 儿童注意事项： 新生儿及体重不满10kg的儿童，需按体重计算给药剂量。 妊娠与哺乳期注意事项： 尚不明确。 老人注意事项： 未进行该项实验且无可靠参考文献。 【药物相互作用】 1 本品所含维生素B6能降低左旋多巴的作用。 2 本品所含叶酸可能降低苯妥英钠的血浆浓度和掩盖恶性贫血的临床表现。 3 维生素B12对剂量羟钴胺治疗某些神经疾病有不利影响。 【药理作用】 本品是静脉营养的一部分，用以补充每日各种水溶性维生素的生理需要，使机体各有关生化反应能正常进行。 【贮藏】 15°C以下避光保存。有效期2年半。 【有效期】 30个月 【批准文号】 国药准字H32023002 【说明书修订日期】
第七章维生素 一、填空 1、维生素D的缺乏症有、骨质软化症、和。 2、水溶性维生素包括和。 3、烟酸缺乏引起的“3D”症状包括、和。 4、谷类是膳食中族维生素的重要来源。 5、与胎儿“神经管畸形”形成密切相关的维生素是。 6、硫胺素缺乏引起的脚气病主要有、、急性暴发性脚气病三种类型。 7、硫胺素在条件下易被氧化失活，缺乏它易引。 8、当出现口角炎、口腔黏膜溃疡时，很可能与水溶性维生素缺乏有关。 9、维生素B2的化学名称为。 10、人体暗适应能力下降与缺乏相关。 11、维生素D缺乏症在成人表现为，在婴幼儿表现为。 二、选择 1、具有激素性质的维生素是。 A.维生素B1 B. 维生素B2 C. 维生素D D. 维生素PP 2、维生素B2缺乏体征之一是。 A.脂溢性皮炎 B.周围神经炎 C.“3D”症状 D.牙龈疼痛出血 3、含维生素C最多的蔬菜是。 A.大白菜 B.油菜 C.柿子椒 D.大萝卜 4、野果的营养特点是。 A.富含维生素C和胡萝卜素 B. 富含维生素B1 C. 富含维生素A和D D. 富含维生素E 5、豆芽中富含。 A.维生素E B.叶酸 C.维生素B D.维生素C 6、几乎不能通过乳腺，故母乳中的含量很低。 A.维生素A B.维生素B C.维生素C D.维生素D 7、婴幼儿佝偻病主要是由缺乏引起的。 A.维生素A B.维生素C C.维生素D D.硫胺素
8、增加维生素能作为亚硝酸化合物的阻断剂。 A.维生素A B.维生素B C.维生素C D.维生素D 9、下列哪种维生素具有抗氧化功能? A.维生素A B.维生素B2 C.维生素C D.维生素D 10、以下属于脂溶性维生素的选项是。 A.维生素B1、维生素B2 B.维生素A、维生素D C.维生素B1、维生素C D. 维生素E、维生素C 三、名词解释 1、维生素 2、食品添加剂 四、简答 (一)简述维生素的特点。 (二)简述维生素B1的生理功能 (三)简述维生素B2的生理功能 (四)简述维生素PP的生理功能。 (五)简述维生素B12的生理功能。 (六)简述如何预防维生素缺乏。
水溶性维生素检测分析的研究进展 摘要：维生素是维持生命活动必不可少的一类有机化合物，摄入不足或过量均可导致机体功能障碍，因其易在烹调、加工过程中损失，因此分析和评价食品和营养保健品中的维生素含量将对指导人群科学摄取维生素具有重要参考价值。水溶性维生素多为强极性化合物，其检测难度较大，因此系统介绍了微生物法、分光光度法、高效液相色谱法等水溶性维生素的检测方法，并针对多种水溶性维生素联合检测的高效液相色谱法，从同时提取、分离以及检测等方面进行综述，以期为今后开展水溶性维生素的高通量快速分析提供借鉴和参考。 关键词：水溶性维生素；联合检测；高效液相色谱法 维生素是一类人体不能合成或合成量不足、必须直接或间接从食品中摄取的化合物，广泛存在于谷类、果蔬、肉禽及蛋类等动植物细胞中。根据其溶解性差异，分为水溶性维生素（Water-soluble vitamins，WSVs）和脂溶性维生素（Fat-soluble vitamins，FSVs）。WSVs通常指极性较大，易溶于水的一类维生素，包括B族维生素、生物素（H）和抗坏血酸（VC）等。现已知WSVs具备多种生理生化功能。例如：B族维生素是多种辅酶的组成成分，参与有机体中的糖、脂肪、蛋白质及核苷酸的合成代谢；VC作为强氧化剂参与了氨基酸羟化反应和去除自由基等过程。目前已建立了单一WSV的检测方法[1-3]，现行分析方法（国标、欧盟指令条例和AOAC标准等）多数为微生物法、分光光度法，但这类方法耗时、费力，已难以满足当前分析要求和发展趋势。基于色谱技术的分析方法准确、快速、重现性好等特点，目前已在WSVs上得到了应用，高通量WSVs 检测方法已有报道，但由于WSVs结构各异，理化性质差异大，导致建立高通量的维生素前处理和检测方法难度较大，本研究将围绕相关进展进行评述，以期为开展相关工作提供参考。 1 微生物法 1889年Beijerinck首次发现酵母菌的生长与其生长环境中的某些营养成分存在对应关系，由Williams首次提出微生物测定维生素的构想，随后B族维生素的微生物法相继建立，并于20世纪50年代广泛地应用于食物、药剂和饲料等各类样品的分析[4-6]。尽管早期微生物法是分析WSVs的标准方法，但是该方法检测时间长、操作复杂，检测结果的相对不确定度达到±20%，而且还存在培养污染、菌株个体差异、样品基质影响菌株生长等[7]不确定性因素，导致方法重现性较差。基于上述原因，目前微生物法在常规WSVs分析中已基本淘汰。 2 光度法 光度法（Spectrophotometry）是继微生物法之后开发的一类方法，包括紫外分光光度法和分子荧光法等。这类方法一般是测定维生素或其衍生物在特定波长或激发光下的吸光度或发射光强度从而进行定性定量分析的一类方法。紫外分光