CN1844137A - Preparation process of chromium glucosaminic acid and use thereof - Google Patents
Preparation process of chromium glucosaminic acid and use thereof Download PDFInfo
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- CN1844137A CN1844137A CN200610039938.XA CN200610039938A CN1844137A CN 1844137 A CN1844137 A CN 1844137A CN 200610039938 A CN200610039938 A CN 200610039938A CN 1844137 A CN1844137 A CN 1844137A
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- chromium
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- glucosaminic acid
- glucosaminicacid
- glucosaminic
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- 239000011651 chromium Substances 0.000 title claims abstract description 88
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 title claims abstract description 72
- 229910052804 chromium Inorganic materials 0.000 title claims abstract description 70
- UFYKDFXCZBTLOO-TXICZTDVSA-N 2-amino-2-deoxy-D-gluconic acid Chemical compound [O-]C(=O)[C@H]([NH3+])[C@@H](O)[C@H](O)[C@H](O)CO UFYKDFXCZBTLOO-TXICZTDVSA-N 0.000 title claims description 74
- 238000002360 preparation method Methods 0.000 title claims description 13
- 150000001875 compounds Chemical class 0.000 claims abstract description 14
- 238000006243 chemical reaction Methods 0.000 claims abstract description 11
- 238000000034 method Methods 0.000 claims abstract description 11
- GRWVQDDAKZFPFI-UHFFFAOYSA-H chromium(III) sulfate Chemical compound [Cr+3].[Cr+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O GRWVQDDAKZFPFI-UHFFFAOYSA-H 0.000 claims abstract description 9
- 206010012601 diabetes mellitus Diseases 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 11
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 9
- 229910052788 barium Inorganic materials 0.000 claims description 5
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 claims description 5
- 150000002500 ions Chemical class 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
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- 239000008103 glucose Substances 0.000 abstract description 5
- 239000011573 trace mineral Substances 0.000 abstract description 3
- 235000013619 trace mineral Nutrition 0.000 abstract description 3
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 abstract 1
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 abstract 1
- 229910001863 barium hydroxide Inorganic materials 0.000 abstract 1
- 229940055042 chromic sulfate Drugs 0.000 abstract 1
- 229910000356 chromium(III) sulfate Inorganic materials 0.000 abstract 1
- 235000015217 chromium(III) sulphate Nutrition 0.000 abstract 1
- 239000011696 chromium(III) sulphate Substances 0.000 abstract 1
- 229940050410 gluconate Drugs 0.000 abstract 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 36
- 238000001556 precipitation Methods 0.000 description 23
- 239000000243 solution Substances 0.000 description 23
- 150000001844 chromium Chemical class 0.000 description 18
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 18
- 230000000694 effects Effects 0.000 description 13
- 238000003756 stirring Methods 0.000 description 13
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- 241000699670 Mus sp. Species 0.000 description 9
- 229910001430 chromium ion Inorganic materials 0.000 description 9
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- 238000004458 analytical method Methods 0.000 description 8
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- 201000001421 hyperglycemia Diseases 0.000 description 8
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 6
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 6
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- 239000007864 aqueous solution Substances 0.000 description 5
- BFGKITSFLPAWGI-UHFFFAOYSA-N chromium(3+) Chemical compound [Cr+3] BFGKITSFLPAWGI-UHFFFAOYSA-N 0.000 description 5
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- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 3
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- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- NAOLWIGVYRIGTP-UHFFFAOYSA-N 1,3,5-trihydroxyanthracene-9,10-dione Chemical compound C1=CC(O)=C2C(=O)C3=CC(O)=CC(O)=C3C(=O)C2=C1 NAOLWIGVYRIGTP-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N Gluconic acid Natural products OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 238000000862 absorption spectrum Methods 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- HIMXGTXNXJYFGB-UHFFFAOYSA-N alloxan Chemical compound O=C1NC(=O)C(=O)C(=O)N1 HIMXGTXNXJYFGB-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229940046374 chromium picolinate Drugs 0.000 description 2
- QFSKIUZTIHBWFR-UHFFFAOYSA-N chromium;hydrate Chemical compound O.[Cr] QFSKIUZTIHBWFR-UHFFFAOYSA-N 0.000 description 2
- GJYSUGXFENSLOO-UHFFFAOYSA-N chromium;pyridine-2-carboxylic acid Chemical compound [Cr].OC(=O)C1=CC=CC=N1.OC(=O)C1=CC=CC=N1.OC(=O)C1=CC=CC=N1 GJYSUGXFENSLOO-UHFFFAOYSA-N 0.000 description 2
- HPCCGRCEBFBZQP-UHFFFAOYSA-N chromium;pyridine-3-carboxylic acid Chemical compound [Cr].OC(=O)C1=CC=CN=C1 HPCCGRCEBFBZQP-UHFFFAOYSA-N 0.000 description 2
- 238000002983 circular dichroism Methods 0.000 description 2
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- 206010022489 Insulin Resistance Diseases 0.000 description 1
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- 229930003427 Vitamin E Natural products 0.000 description 1
- OAJKSLKNPNSYKC-UHFFFAOYSA-N [H][Cl+][Cr++] Chemical compound [H][Cl+][Cr++] OAJKSLKNPNSYKC-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- LPQOADBMXVRBNX-UHFFFAOYSA-N ac1ldcw0 Chemical compound Cl.C1CN(C)CCN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN3CCSC1=C32 LPQOADBMXVRBNX-UHFFFAOYSA-N 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
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- 230000003712 anti-aging effect Effects 0.000 description 1
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- WDIHJSXYQDMJHN-UHFFFAOYSA-L barium chloride Chemical compound [Cl-].[Cl-].[Ba+2] WDIHJSXYQDMJHN-UHFFFAOYSA-L 0.000 description 1
- 229940045511 barium chloride Drugs 0.000 description 1
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- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention relates to chromium amino gluconate (III) having a molecular formula of Crn(C6H12NO6)3Ap, n=1 or 2, its preparing process and use, wherein the compound is obtained through the reaction between amino glucose acid, chromic sulfate and barium hydroxide in solution. The compound can be used as highly effective replenisher for trace elements in human body and for the treatment of high blood sugar.
Description
Technical field
The present invention relates to chromium glucosaminic acid and its production and use, the present invention especially refers to have the chromium glucosaminic acid of blood sugar reducing function.
Background technology
Nineteen fifty-nine, set up the theory that human body must replenish the trivalent chromium trace element at diet by Schwartz.Pyridine acid chromium salt (chromium picolinate or PicCr, U.S. Pat RE33988) is chromic a kind of organic compound, find that by U.S. Anderson doctor it has enhancing insulin sensitivity (Andersion, Clin.Psychol.Biochem.4:31-41,1986) effect, the acceptor of chromium pair cell also has effect, though not clear its mechanism of action, but the shortage of chromium can cause sugar, mixtinite, the obstacle of protein metabolism, also sick relevant with cardiovascular diseases with saccharic acid urine, chromium is the cofactor of Regular Insulin, the activity that chromium has been acknowledged as with Regular Insulin has very big relation (Boyle et al., Southern Med.i.70:1449-1453,1977).Pyridine acid chromium salt is absorbed in human body easily, and therefore, pyridine acid chromium salt is more effectively regulated the saccharic acid lipid metabolism than the chromium of other existence forms, and reduces body fat, strengthen muscle tissue.In addition, also can reduce postmenopausal women's urine calcium output, thus preventing osteoporosis.Experiment to animal finds that mending chromium can be anti-ageing, prolongs life.Trivalent chromium is safest in the micro elements needed by human, and chromium poisoning dosage is bigger at least 1000 times than safety intake every day of estimation.Close with it nicotinic acid chromium in addition has the report nicotinic acid chromium littler to the effect of paying of human body than pyridine acid chromium salt.Pyridine acid chromium salt is just becoming the vitamins C that continues in the U.S., one of four big single nutritive element supplement after vitamin-E and the calcium.The survey showed that to American public more than 18 years old in nineteen ninety-five in the whole America food council, and 2.9% American quantitatively takes pyridine acid chromium salt regularly.
Scientist has successfully carried out after the clinical study of pyridine acid chromium salt abroad, and China Beijing Hospital etc. and USDA human nutrition center have carried out clinical study to the diabetics jointly.The result shows that pyridine acid chromium salt cooperates hypoglycemic drug, can improve diabetic symptom, the lowering blood glucose blood fat.This studies show that, China's diabetic population exists and lacks the chromium element, replenishes pyridine acid chromium salt, and diabetes are had good assisting therapy effect, so delay senility to preventing and treating diabetes because trivalent chromium participates in the carbohydrate metabolism benefit chromium of human body, the research prospect that prolongs aspects such as human longevity is boundless.The further research of pyridine acid chromium salt can be referring to patents such as U.S. Pat 5948772, US5677461 with application.
Although the effect of pyridine acid chromium salt is generally acknowledged, but whether pyridine acid chromium salt has side effect or detrimentally affect still inquiring into to human body: the influencing in the literary composition of the tem analysis pyridine acid chromium salt pair cell microstructure that Manygoats KY etc. delivers, think that pyridine acid chromium salt can make cell become crude (Ultrastructual Damage in chromiumpicolinate-treated cell:a TEM study, J of Bio Inorganic chemistry, 7:791-798 sep2002).
The application of chitosan chromium aspect hypoglycemic has effect preferably, can eliminate the effect of paying or harm (referring to the inventor's patent z103112734.7 " chitosan chromium and its production and use ") that pyridine acid chromium salt etc. may bring to human body.Chitosan is considered to the 6th key element that necessary for human will replenish.But the molecular weight of chitosan is bigger, be difficult to directly be absorbed by the body, and glucosamine has better effect undoubtedly as the monose of chitosan.The inventor uses glucosamine or glucosamine and high valence chrome or chromic salt reaction, all obtained having the chromium glucosaminic acid (inventor's patent z103112734.7, " chromic compound of glucosaminicacid and derivative thereof and its production and use ") of hypoglycemic activity.But its product obtains by redox reaction, and it is complicated to obtain operation such as single purified product.The inventor has found reactions such as use glucosaminicacid and chromic salts and barium sulfate through research with keen determination, obtains single product easily, and through the model mice test, effect is identical with the effect of z103112734.7.
Summary of the invention
The objective of the invention is: provide structure clear and definite and existence form can hold, and be easy to be absorbed by organism, can effectively replenish the required trivalent chromium of body, has good hypoglycemic activity, useful chromium of organic acid compound and its esters on preparation prevention and treatment health-care product for curing diabetes and medicine.The preparation method and the application thereof of this compound are provided simultaneously.
Trivalent chromium compound of the present invention is a chromium glucosaminic acid, and its molecular formula is:
Cr
n(C
6H
12NO
6)
3A
p (1)
N=1 or 2 in the formula (1); During n=1, p gets 0; During n=2, A is a negatively charged ion, and the p value makes charge balance.
In the formula (1), when n=1, three glucosaminicacid and chromium ion coordination are arranged, generate triamino glucose and close chromium, total charge is zero.When n=2, be that two chromium ions are arranged in the molecule, the triamino gluconic acid that generates double-cores with three glucosaminicacid coordinations closes the positive trivalent ion of two chromium, according to the anionic difference of using chromic salts and difference, or carries out the salt that ion-exchange obtains different negatively charged ion A.
The present invention also provides a kind of preparation process of chromium glucosaminic acid of the present invention, and this method comprises the steps:
Glucosaminicacid and hydrated barta reaction are obtained glucosaminicacid barium; With glucosaminicacid barium and chromium sulphate reaction, obtain chromium glucosaminic acid; By the control glucosaminicacid, hydrated barta obtains n=1 or 2 multi-form chromium glucosaminic acid products with sulfuric acid chromic salts and pH value.
Another kind of preparation method's method also is provided, and this method comprises the steps: that this method comprises the steps:
Glucosaminicacid is mixed with chromium sulfate solution, with the hydrated barta reaction, obtain chromium glucosaminic acid again; By the control glucosaminicacid, hydrated barta obtains n=1 or 2 multi-form chromium glucosaminic acid products with sulfuric acid chromic salts and pH value.
More than two kinds of methods, utilizing sulfate radical and barium ion generation insoluble neobalgin to be beneficial in essence separates, utilize in the hydrated barta and glucosaminicacid acquisition glucosamine acid group, the characteristics that easy and chromium ion generates coordination compound prepare the compound shown in the formula of the present invention (1).According to the characteristics of title complex, the pH value of the usage quantity regulator solution by changing hydrated barta obtains two kinds of title complexs shown in the present.
As synthetic n=1, promptly during the monokaryon chromium glucosaminic acid, the amount of using hydrated barta is corresponding with the amount of the amount of glucosaminicacid and chromium sulphate, i.e. acid neutralizes with the alkali equivalent, and makes sulfate radical and barium just in time form neobalgin to be precipitated as better.
As synthetic n=2, when being the double-core chromium glucosaminic acid, use hydrated barta to equate with the amount of glucosaminicacid that as alkali neutralization gets final product, consider to replenish other barium salts again, for example barium ion molar weight that make to use of bariumchloride equates with the chromium sulphate equimolar amount for well, makes sulfate radical with barium ion formation barium sulfate precipitate and separate.The chromium sulphate amount of using makes chromium ion and glucosaminicacid be beneficial to the formation dinuclear complex and gets final product that the mol ratio of chromium ion and glucosaminicacid remains on 1.2～2 more than 1: 3: 3 is better, and 1.4～1.7: 3 is better.
The concentration of reactant in water needn't special stipulation, usually can determine according to the solubleness of reactant, particularly forming the barium sulfate crystallite is beneficial to aftertreatment and is separated into according to being determined by experiment, can make used glucosamine acid concentration 0.1～5 volumetric molar concentration of reaction better, 0.2～1 volumetric molar concentration is better.
Glucosaminicacid can be buied from reagent merchant (Sigma), also can obtain glucosaminicacid from glucosamine with method oxidation chemistry or biochemical fermentation by literature method.Used sulfuric acid chromic salts needs only and be easy to dissolving in reaction medium, for example, and anhydrous slufuric acid chromium Cr
2(SO
4)
3, six water chromium sulphate Cr
2(SO
4)
36H
2O, common six water chromium sulphates are more conducive to use.
Temperature of reaction is as long as keep reaction smoothly, and general 30～60 ℃, 35～55 ℃ for well, and 40～50 ℃ of actually operatings better.
Chromium glucosaminic acid provided by the invention can the liquid or solid form as a supplement the foodstuff additive of organic trace element chromium (III) use; Can also use as the prevention of diabetes, the functional component of healthcare products; Also can on various pharmaceutical preparations such as tablet, capsule and other drug, can accept to use in the composition forms; Can in the ofhypoglycemic medicine of preparation treatment diabetes, use;
Chromium glucosaminic acid provided by the invention and composition thereof are mainly taked oral method.
The medicament purpose that can be used on of the present invention, be mainly used in the effect that reaches lowering blood glucose, can make any pharmaceutical dosage form, tablet for example, capsule, solution, suspension agent, emulsion, gelifying agent, ointment, lyophilisate, pill, film, lipid topic etc.Use as foodstuff additive, add beverage to the liquid or solid powder type, in the food such as cheese, bread, flour.
Chromium glucosaminic acid of the present invention (III) is made prevention, Halth-care composition or the pharmaceutical composition that is used for hypoglycemic, comprises chromium glucosaminic acid and other component nuclear pharmaceuticals carrier or auxiliary material.It is one of to select preferably that chitosan adds as other components.
In chromium glucosaminic acid of the present invention (III) composition, functional component is a chromium glucosaminic acid.According to pharmacy and preparation needs, carrier in the composition or auxiliary material can the time medicine acceptable any.It is one of to select preferably that chitosan adds as other components.
The pharmaceutical composition that is used for the Halth-care composition of hypoglycemic or is used for the treatment of diabetes of the present invention can be formulations such as tablet, injection, capsule, injection liquid or oral liquid.
The usage quantity of chromium glucosaminic acid of the present invention can be determined the needs of different preparations according to pharmacy.
Chromium glucosaminic acid of the present invention, can determine the content of component and chromium with common ultimate analysis and ICP, the complex structure that forms can be used infrared spectra (accompanying drawing 1,2), visible absorption spectra (accompanying drawing 3,4) characterizes the formation of coordinate bond, use circular dichroism spectrum (accompanying drawing 5,6), characterize the chirality that has kept glucosaminicacid in the chromium glucosaminic acid title complex.The valence state that characterizes chromium in the coordination compound with powder electron paramagnetic resonance spectrum (accompanying drawing 7,8) is positive trivalent.。
Description of drawings
Fig. 1. the chromium glucosaminic acid title complex infrared spectrogram of embodiment 1
Fig. 2. the chromium glucosaminic acid title complex infrared spectrogram of embodiment 3
Fig. 3. the ultraviolet-visible spectrogram of the chromium glucosaminic acid title complex of embodiment 1 in water
Fig. 4. the ultraviolet-visible spectrogram of the chromium glucosaminic acid title complex of embodiment 3 in water
Fig. 5. the circular dichroism spectrogram of the chromium glucosaminic acid title complex of embodiment 1 in water
Fig. 6. the circular dichroism spectrogram of the chromium glucosaminic acid title complex of embodiment 3 in water
Fig. 7. the powder electron paramagnetic resonance spectrum of the chromium glucosaminic acid title complex of embodiment 1 when temperature is 110K
Fig. 8. the powder electron paramagnetic resonance spectrum of the chromium glucosaminic acid title complex of embodiment 3 when temperature is 110K
Embodiment
In order to be illustrated more clearly in content of the present invention, be described as follows with specific embodiment, specific embodiment does not limit context of the present invention.
Embodiment 1 triamino gluconic acid closes the synthetic of chromium (III)
Glucosaminicacid 1.17 grams (6 mmole) are dissolved in 12 ml waters, add 6 milliliters and contain 0.5 gram Cr
2(SO
4)
36H
2The aqueous solution of O (1 mmole), stirring heating solution to 45 ℃.At 1.5 hours, slowly add 30 milliliters and contain 0.514 gram Ba (OH)
2The solution of (3 mmole).Generate precipitation at once, solution colour becomes purple by green.After continuing to stir half an hour, the elimination precipitation, solution continued to stir 3 hours again.Concentrated solution adds methyl alcohol and separates out precipitation to 2/3 of original volume.Leach precipitation, with methyl alcohol and ether washing precipitation.With minimum water dissolution, the methyl alcohol that adds quintuple again carries out recrystallization.Precipitation leaches, and puts the phosphorus pentoxide desiccator drying.Productive rate 60%. ultimate analyses, Cr (C
6H
12NO
6)
3H
2O theoretical value: C 33.13 H 5.87N 6.44 Cr 7.96%. trial value: C 33.31 H, 6.08 N, 6.40 Cr, 8.20% infrared spectras (KBr, accompanying drawing 1): 3300cm
-1(wide), 2964cm
-1, 1622cm
-1(wide), 1489cm
-1, 1453cm
-1, 1405cm
-1, 1347cm
-1, 1203cm
-1, 1112cm
-1, 1084cm
-1, 1034cm
-1, 963cm
-1, 934cm
-1, 885cm
-1, 814cm
-1, 748cm
-1, 652cm
-1, 612cm
-1, 573cm
-1, 499cm
-1, 457cm
-1, 414cm
-1. visible absorption spectra (H
2O, accompanying drawing 3): maximum absorption position λ max=404nm (More's uptake factor ε=29M
-1Cm
-1), 550nm (23M
-1Cm
-1). garden dichroscope spectrum (accompanying drawing 5) shows in the title complex based on the three-dimensional chirality around the chromium ion.Powder electron paramagnetic resonance spectrum (accompanying drawing 7) shows that the chromium ion valence state is positive trivalent.
Use amount of reagent identical with embodiment 1, interpolation is adjusted in proper order: earlier with glucosaminicacid and hydrated barta Ba (OH)
2Solution adds chromium sulphate Cr after 45 ℃ of stirrings
2(SO
4)
36H
2The O aqueous solution.Subsequent disposal is carried out with embodiment 1.Close spectroscopic analysis through ultimate analysis, identical with embodiment 1 product.
Embodiment 3 triamino gluconic acids close two chromium (III) hydrochloride
Glucosaminicacid 1.960 grams (10 mmole) are dissolved in 20 ml waters, add 15 milliliters and contain 1.251 gram Cr
2(SO
4)
36H
2The aqueous solution of O (2.5 mmole), stirring heating solution to 45 ℃.At 1.5 hours, slowly add 50 milliliters and contain 0.857 gram Ba (OH)
2(5 mmole) and 0.611 gram BaCl
2The solution of (2.5 mmole).Generate precipitation at once, solution colour becomes purple by green.After continuing to stir half an hour, the elimination precipitation, solution continued to stir 3 hours again.Concentrated solution adds methyl alcohol and separates out precipitation to 2/3 of original volume.Leach precipitation, with methyl alcohol and ether washing precipitation.With minimum water dissolution, the methyl alcohol that adds quintuple again carries out recrystallization.Productive rate: 35%. ultimate analyses: Cr
2(C
6Hi
2NO
6)
3Cl
3Theoretical value: C 27.27 H 4.58 N5.30 Cr 13.12% trial value: C 27.41 H, 5.08 N, 5.48 Cr, 12.98% infrared spectras (KBr, accompanying drawing 2): 3383cm
-1(wide), 2940cm
-1, 2940cm
-1, 1632cm
-1(wide), 1500cm
-1, 1444cm
-1, 1399cm
-1, 1347cm
-1, 1077cm
-1, 1036cm
-1, 881cm
-1, 815cm
-1, 605cm
-1. visible absorbance (H
2O, accompanying drawing 4): maximum absorption position λ max=406nm (molar absorption coefficient ε=30M
-1Cm
-1), 558nm (20M
-1Cm
-1). garden dichroscope spectrum (accompanying drawing 6) shows in the title complex based on the three-dimensional chirality around the chromium ion.Powder electron paramagnetic resonance spectrum (accompanying drawing 8) shows that the chromium ion valence state is positive trivalent.
Embodiment 4 triamino gluconic acids close the synthetic of chromium (III)
Glucosaminicacid 2.35 grams (12 mmole) are dissolved in 17 ml waters, add 6 milliliters and contain 1.0 gram Cr
2(SO
4)
36H
2The aqueous solution of O (2 mmole), stirring heating solution to 45 ℃.At 1.5 hours, slowly add 25 milliliters and contain 1.03 gram Ba (OH)
2The solution of (6 mmole).Generate precipitation at once, solution colour becomes purple by green.After continuing to stir half an hour, the elimination precipitation, solution continued to stir 3 hours again.Concentrated solution adds methyl alcohol and separates out precipitation to 2/3 of original volume.Leach precipitation, with methyl alcohol and ether washing precipitation.With minimum water dissolution, the methyl alcohol that adds quintuple again carries out recrystallization.Precipitation leaches, and puts the phosphorus pentoxide desiccator drying.Productive rate 70%. is through ultimate analysis, and is identical with embodiment 1 product.
Glucosaminicacid 0.59 gram (3 mmole) is dissolved in 36 ml waters, adds 18 milliliters and contains 0.25 gram Cr
2(SO)
36H
2The aqueous solution of O (0.5 mmole), stirring heating solution to 45 ℃.At 1.5 hours, slowly add 90 milliliters and contain 0.26 gram Ba (OH)
2The solution of (1.5 mmole).Generate precipitation at once, solution colour becomes purple by green.After continuing to stir half an hour, the elimination precipitation, solution continued to stir 3 hours again.Concentrated solution adds methyl alcohol and separates out precipitation to 2/3 of original volume.Leach precipitation, with methyl alcohol and ether washing precipitation.With minimum water dissolution, the methyl alcohol that adds quintuple again carries out recrystallization.Precipitation leaches, and puts the phosphorus pentoxide desiccator drying.Productive rate 40%. is through ultimate analysis, and infrared measurement is identical with embodiment 1 product.
Embodiment 6: the hypoglycemic test of hyperglycemia model mouse
Use aseptic 8 all male mices, body weight 35.0 ± 3.2 grams, 5 in every cage, on 12 hour daytime, at 12 hour night, 23 ± 2 ℃, 60% relative humidity is cultivated.The use deionized water is fed.Insulin-dependent diabetes (hyperglycemia) model mice uses model induced by alloxan.2 week back blood sugar reach＞and the mouse of 11.2mmol/L is used for test.
Test mice is divided into 10 every group group at random, and blood sugar mouse normal and hyperglycemia is fed product and the pyridine acid chromium salt (buying from the commercial channel) of embodiment 1,3 respectively, continues 30 days.The eye socket blood sampling carries out analysis of blood sugar.Test-results is listed in table 1-4.Wherein the A group is the chromium glucosaminic acid title complex administration group of embodiment 1, B is the chromium glucosaminic acid title complex administration group of embodiment 3, C is made into the administration group that contains chromium 99.96 μ g (Cr)/g samples for chromium glucosaminic acid title complex and the chitosan compatibility of embodiment 1, D is made into the administration group that contains chromium 99.96 μ g (Cr)/g samples for chromium glucosaminic acid title complex and the chitosan compatibility of embodiment 3, control group E is a pyridine acid chromium salt, and control group F is that pyridine acid chromium salt and chitosan compatibility are made into the administration group that contains chromium 99.96 μ g (Cr)/g control samples.Group is represented to represent in the unquote, and to be conversion be the chromium amount (μ g) with respect to the administration of test mice body weight (Kg).
Table 1, contain Chroma-Pak to the influence of normal mouse blood sugar and sugar tolerance (x ± s)
| Group | Number of mice (only) | Blood sugar (mmol/L) | |||
| Before the medicine | 0h behind the medicine | 0.5h behind the medicine | 2h behind the medicine | ||
| Normal mouse A (20 μ g/Kg) A (40 μ g/Kg) B (20 μ g/Kg) B (40 μ g/Kg) C (40 μ g/Kg) D (40 μ g/Kg) control group E (40 μ g/Kg) control group F (40 μ g/Kg) | 10 10 10 10 10 10 10 10 10 | 5.82±0.73 6.13±0.39 5.91±0.56 5.73±0.53 6.01±0.49 5.94±0.61 5.90±0.83 6.00±0.52 5.83±0.70 | 6.03±0.82 5.96±1.01 5.87±0.94 5.90±1.13 6.12±0.59 5.59±0.86 6.00±0.73 6.25±1.11 5.34±0.76 | 9.29±0.91 8.62±1.31 8.34±0.83 * 8.99±1.01 8.39±1.02 * 8.30±0.89 * 8.06±1.37 * 8.33±0.85 * 8.50±0.67 * | 6.96±0.77 6.51±0.83 6.14±1.06 6.30±1.22 6.34±0.68 6.20±0.90 6.34±0.76 6.21±1.34 5.99±0.57 |
*P＜0.05 vs normal mouse group
Table 2, contain Chroma-Pak to the influence of tetraoxypyrimidine inductive diabetic mice fasting plasma glucose (x ± s)
| Group | Number of mice (only) | Blood sugar (mmol/L) before the medicine | Blood sugar behind the medicine (mmol/L) |
| Hyperglycemia model mouse A (20 μ g/Kg) A (40 μ g/Kg) B (20 μ g/Kg) B (40 μ g/Kg) C (40 μ g/Kg) D (40 μ g/Kg) control group E (40 μ g/Kg) control group F (40 μ g/Kg) | 10 10 10 10 10 10 10 10 10 | 17.64±3.05 18.02±2.87 16.92±2.15 16.43±3.24 17.13±3.52 16.83±2.56 17.15±2.57 16.24±3.11 17.36±2.55 | 21.54±3.27 19.16±2.56 17.13±3.93 ▲ 20.05±4.12 17.74±2.71 ▲ 18.53±1.94 ▲ 17.36±3.75 ▲ 18.26±2.31 ▲ 18.30±2.43 ▲ |
▲P＜0.05, vs hyperglycemia model mouse group
Table 3, contain Chroma-Pak to the influence of tetraoxypyrimidine inductive diabetic mice postprandial blood sugar (x ± s)
| Group | Number of mice (only) | Blood sugar (mmol/L) | ||
| 0h | 0.5h | 2h | ||
| Hyperglycemia model mouse A (20 μ g/Kg) A (40 μ g/Kg) B (20 μ g/Kg) B (40 μ g/Kg) C (40 μ g/Kg) D (40 μ g/Kg) control group E (40 μ g/Kg) control group F (40 μ g/Kg) | 10 10 10 10 10 10 10 10 10 | 21.54±3.27 19.16±2.56 17.13±3.93 ▲20.05±4.12 17.74±2.71 ▲18.53±1.94 ▲17.36±3.75 ▲18.26±2.31 ▲18.30±2.43 ▲ | 27.62±2.05 26.85±2.11 24.53±1.98 ▲25.94±3.72 25.11±2.19 ▲24.81±2.36 ▲25.26±1.69 ▲25.46±1.72 ▲25.77±2.73 | 23.35±2.36 23.11±1.96 20.65±2.45 ▲21.55±3.11 20.69±2.54 ▲20.35±2.48 ▲20.59±2.67 ▲21.86±2.11 22.73±1.51 |
▲P＜0.05 vs hyperglycemia model mouse group
Table 4, contain Chroma-Pak to the influence of tetraoxypyrimidine inductive diabetic mice sugar tolerance (x ± s)
| Group | Number of animals (only) | Blood sugar (mmol/L) | |
| 0.5-1h | 0.5-2h | ||
| Hyperglycemia model mouse A (20 μ g/Kg) A (40 μ g/Kg) B (20 μ g/Kg) B (40 μ g/Kg) C (40 μ g/Kg) D (40 μ g/Kg) control group E (40 μ g/Kg) control group F (40 μ g/Kg) | 10 10 10 10 10 10 10 10 10 | 6.09±2.91 7.70±2.40 7.38±2.36 5.87±3.89 7.88±2.34 6.26±2.09 7.90±2.77 7.19±2.17 7.45±2.50 | 4.26±2.21 3.70±1.98 3.89±2.33 4.40±3.48 4.41±2.30 4.45±2.39 4.68±2.26 3.60±1.97 3.05±2.31 |
Claims (9)
1, the chromium glucosaminic acid of following formula (III) compound:
Cr
n(C
6H
12NO
6)
3A
p
N=1 or 2 in the formula; During n=1, p gets 0; During n=2, A is a negatively charged ion, and the p value makes charge balance.
2, the chromium glucosaminic acid of claim 1 (III) compound, wherein n=2.
3, the chromium glucosaminic acid of claim 2 (III) compound, wherein A is Cl
-, p=3.
4, the preparation method of the described compound of one of claim 1 to 3, this method comprises the steps:
1) glucosaminicacid and hydrated barta are obtained glucosaminicacid barium;
2) with glucosaminicacid barium and chromium sulphate reaction, obtain chromium glucosaminic acid;
3) by the control glucosaminicacid, hydrated barta obtains n=1 or 2 multi-form chromium glucosaminic acid products with sulfuric acid chromic salts and pH value.
5, the preparation method of the described compound of one of claim 1 to 3, this method comprises the steps:
1) glucosaminicacid is mixed with chromium sulfate solution;
2) 1) react with hydrated barta, obtain chromium glucosaminic acid;
3) by the control glucosaminicacid, hydrated barta obtains n=1 or 2 multi-form chromium glucosaminic acid products with sulfuric acid chromic salts and pH value.
6, a kind of Halth-care composition of prevent diabetes, said composition comprise on the chromium glucosaminic acid of one of claim 1 to 3 and the medicine can accept carrier or auxiliary material.
7, a kind of pharmaceutical composition for the treatment of diabetes, said composition comprise on the chromium glucosaminic acid of one of claim 1 to 3 and the medicine can accept carrier or auxiliary material.
8, the application of the chromium glucosaminic acid of one of claim 1 to 3 (III) compound in preparation prevent diabetes healthcare products.
9, the application of the chromium glucosaminic acid of one of claim 1 to 3 (III) compound in preparation treatment diabetes medicament.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102659844A (en) * | 2012-05-21 | 2012-09-12 | 山西大学 | Cr (III) chelate, and preparation method and application thereof |
| CN103224532A (en) * | 2013-04-17 | 2013-07-31 | 山西大学 | Cr(III) compound, and preparation method and application thereof |
| CN104513279A (en) * | 2015-01-15 | 2015-04-15 | 山西大学 | Cr (III) chelate compound as well as preparation method and application thereof |
| CN116237532A (en) * | 2022-12-22 | 2023-06-09 | 江南大学 | Synthesis method of glycosyl ligand analogue induced chiral cobalt-based ultra-small nano particles |
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2006
- 2006-04-27 CN CN200610039938.XA patent/CN1844137A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102659844A (en) * | 2012-05-21 | 2012-09-12 | 山西大学 | Cr (III) chelate, and preparation method and application thereof |
| CN103224532A (en) * | 2013-04-17 | 2013-07-31 | 山西大学 | Cr(III) compound, and preparation method and application thereof |
| CN104513279A (en) * | 2015-01-15 | 2015-04-15 | 山西大学 | Cr (III) chelate compound as well as preparation method and application thereof |
| CN104513279B (en) * | 2015-01-15 | 2017-04-26 | 山西大学 | Cr (III) chelate compound as well as preparation method and application thereof |
| CN116237532A (en) * | 2022-12-22 | 2023-06-09 | 江南大学 | Synthesis method of glycosyl ligand analogue induced chiral cobalt-based ultra-small nano particles |
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