CN104628765A - Preparation method of diemodin oxovanadium complex having blood glucose reducing activity - Google Patents
Preparation method of diemodin oxovanadium complex having blood glucose reducing activity Download PDFInfo
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- CN104628765A CN104628765A CN201510018112.4A CN201510018112A CN104628765A CN 104628765 A CN104628765 A CN 104628765A CN 201510018112 A CN201510018112 A CN 201510018112A CN 104628765 A CN104628765 A CN 104628765A
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- schuttgelb
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- vanadyl
- diemodin
- diabetes
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Abstract
The invention discloses a preparation method of a diemodin oxovanadium complex having blood glucose reducing activity. The chemical formula of the diemodin oxovanadium complex is VO(L)2(L represents emodin, emodin ether, emodin n-propyl ether or emodin n-butyl ether); the emodin molecular or a derivative therefore is taken as an organic ligand, a vanadium source and an auxiliary are added to an organic solvent to react, and the obtained product is washed by use of hot ethanol and ice water and then dried in vacuum at a low temperature to obtain the diemodin oxovanadium complex. The diemodin oxovanadium complex has extremely excellent blood glucose reducing activity and is capable of obviously improving the glucose tolerance and the blood fat level; the diemodin oxovanadium complex can be prepared into a common preparation, a sustained-release preparation, a controlled-release preparation and a targeting preparation to serve as a drug for treating the diabetes, a drug for treating diabetic hyperglycemia and a health care product or a food additive for preventing the diabetes.
Description
Technical field
The invention belongs to field of medicine and chemical technology, relate to a kind of preparation method with the two Schuttgelb vanadyl title complex of hypoglycemic activity.
Research background
Diabetes insulin sensitivity are reduced to a kind of chronic metabolic derangements syndromes caused by the hyposecretion of Regular Insulin or target tissue.Control or the diabetes-alleviating state of an illness mainly through Long-term Oral medicine, insulin injection at present.Traditional orally-taken blood sugar reducing medicine has a lot of side effect, and such as, sulfonylurea drugs can cause hypoglycemia, appetite stimulator, ketoacidosis; Biguanides use is excessive has serious gastrointestinal reaction, and long-term taking easily causes lactic acidosis, increases liver kidney burden; Alpha-glucosidase inhibitor can produce stomachache, intestinal tympanites reaction etc.; And insulin injection very easily causes hypoglycemia.Therefore in the urgent need to the drug molecule with hypoglycemic activity of development of new.
In recent years, the hypoglycemic activity of vanadium compound has attracted to pay close attention to widely.Although inorganic vanadium compound has and good falls glycopenia activity, because the reasons such as fat-soluble difference, toxic side effect are large limit its application.Vanadyl organic coordination compound centered by Vanadyl is little with its toxicity, easily absorb, and the advantages such as hypoglycemic activity is strong illustrate good application prospect.The organic ligand that the vanadium complex of current report uses mainly comprises methyl ethyl diketone, voitol, nicotinic acid, amino acid, N1,N1-Dimethylbiguanide, phenformin etc.Utilize the rarely seen report of preparation method and application of the vanadyl title complex that Schuttgelb molecule (1,3,8-trihydroxy-6-methylanthraquinone) is organic ligand.Schuttgelb is the main active ingredient of Chinese herb rhubarb, has and improves the effects such as diabetes insulin opposing, reduction blood sugar and serum insulin level, reduction blood lipid level, anti-inflammatory protect the liver.For this reason, the present invention's a kind of new practical approach of proposition, use Schuttgelb molecule and derivative thereof to prepare vanadium complex for organic ligand, two Schuttgelb vanadyl complex molecules of preparation, falling hypoglycemic while, also can reduce the level of cholesterol and triglyceride level.
Summary of the invention
The invention provides the preparation method of a kind of pair of Schuttgelb vanadyl title complex with hypoglycemic activity.The structure of described two Schuttgelb vanadyl title complexs is as follows:
(R＝H,C
2H
5,C
3H
7,C
4H
9)
Technical scheme of the present invention be with Schuttgelb molecule or derivatives thereof for organic ligand, add vanadium source in organic solvent and auxiliary agent reacts, obtain two Schuttgelb vanadyl title complex; It is characterized in that the vanadium source category of use, organic ligand kind, solvent species, auxiliary agent kind, pH value of reaction system, temperature and time are as follows:
Any one is chosen in vanadium source in vanadylic sulfate and vanadyl acetylacetonate; Organic ligand is Schuttgelb (1,3,8-trihydroxy--6-tectoquinone), Schuttgelb ether (1,8-dihydroxyl-3-oxyethyl group-6-tectoquinone), Schuttgelb positive propyl ether (1,8-dihydroxyl-3-positive propoxy-6-tectoquinone), choose any one in Schuttgelb n-butyl ether (1,8-dihydroxyl-3-n-butoxy-6-tectoquinone); Solvent is choose any one in methyl alcohol, ethanol, n-propyl alcohol, propyl carbinol; Auxiliary agent is choose any one in ammoniacal liquor, sodium carbonate, sodium hydroxide, triethylamine, quadrol; PH value of reaction system is 6-12; Temperature of reaction is 60 DEG C-120 DEG C; Reaction times is 4-24 hour.
Preparation process is as follows:
Step 1: a certain amount of organic ligand is dissolved in a certain amount of solvent, reflux, and regulates pH;
Step 2: a certain amount of vanadium source is dissolved in solvent and makes solution;
Step 3: vanadium source solution is slowly added drop-wise in organic ligand solution, at a certain temperature heating reflux reaction a few hours; Suction filtration obtains solid while hot;
Step 4: by colourless to filtrate through hot ethanol, frozen water washing for the solid phase prod obtained, obtain two Schuttgelb vanadyl title complex after low-temperature vacuum drying.
Described two Schuttgelb vanadyl title complexs are for the preparation of the healthcare products for the treatment of diabetes and hyperlipidemia complications disease drug, prevent diabetes or dieletic foodstuff additive, two Schuttgelb vanadyl title complex, as activeconstituents, accounts for medicine or quality of food per-cent is 5%-99%.。
Effect of the present invention and benefit be, utilize Schuttgelb molecule or derivatives thereof to react two Schuttgelb vanadyl title complexs that can obtain having hypoglycemic activity for organic ligand and inorganic vanadium compound, preparation technology is simple in reaction; Two Schuttgelb vanadyl title complexs of preparation, falling hypoglycemic while, can also reduce the level of cholesterol and triglyceride level, can be used as healthcare products or the foodstuff additive for the treatment of diabetes medicament, diabetes and hyperlipidemia complications disease drug and prevent diabetes.
Accompanying drawing explanation
Fig. 1 Schuttgelb vanadyl is on the impact of blood glucose in diabetic mice level
Fig. 2 Schuttgelb vanadyl affects the sugar tolerance of diabetic mice
Embodiment
Following examples further illustrate of the present invention, is not limitation of the present invention.
Embodiment 1:
The structure of a kind of pair of Schuttgelb vanadyl title complex is as follows:
Preparation method and the process of described molecule are as follows:
0.270g (1mmol) Schuttgelb (1,3,8-trihydroxy-6-methylanthraquinone) is dissolved in 20mL dehydrated alcohol, reflux, utilizes ammoniacal liquor to regulate pH to be 7-8; By 0.125g (0.5mmol) VOSO
45H
2o is dissolved in wiring solution-forming in 5mL dehydrated alcohol and is slowly added drop-wise in the ethanolic soln of Schuttgelb, at 75-80 DEG C of temperature, continue reflux 4-5h; Suction filtration while hot, obtains red solid; Wash to filtrate colourless respectively with hot ethanol and frozen water, 40-50 DEG C of drying in vacuum drying oven, obtain pure red complex solid VO (C
15h
9o
5)
2.Ultimate analysis: theoretical value V 8.41%; Test value 8.43%.And the structure of title complex is determined by infrared spectra, UV spectrum, HNMR, thermogravimetric analysis etc.
The hypoglycemic performance of two Schuttgelb vanadyl title complex:
After all mouse adaptability feeds 3, feed 4 weeks with high-fat meal.Overnight fast 12 hours, freely intakes, and Streptomycin resistance is dissolved in citric acid and the sodium citrate buffer of pH=4.5, according to the dosage abdominal injection of 50mg/Kg b.w., inject after 7 days, timing is got blood from afterbody and is surveyed blood sugar, and blood sugar is greater than more than 11.1mmol/L, and person is defined as diabetes model.This model is close to type ii diabetes model.Getting the mouse of 10 non-modelings, is blank group.By model mice random packet, often organize 10, totally 5 groups, be respectively diabetic groups (DM), vanadylic sulfate group (VOSO
4), pioglitazone group (PIO), two Schuttgelb vanadyl group (BEOV), Schuttgelb group (Emodin).Once, blank group and DM group give placebo 5% Sudan Gum-arabic, VOSO to all group gastric infusions every day
4group and BEOV group are dissolved according to 10mgV/Kg b.w. dosed administration in 5% Sudan Gum-arabic, and PIO group and Emodin group are dissolved in 5% Sudan Gum-arabic according to 50mg/Kg b.w. dosed administration.Equal successive administration 21 days.
As shown in Figure 1, the blood sugar of diabetic groups mouse still maintained higher level after 21 days, illustrated that model is more stable.Namely the blood sugar of two Schuttgelb vanadyl title complex group mouse obviously reduced at the 7th day, and maintained euglycemia about 7.3 by the 21st day, effect is better than commercially available medicine pioglitazone group as a control group.Vanadylic sulfate group mouse as a control group also can make normalizing plasma glucose; but toxic side effect is obvious; wherein have 2 mouse dead in the process for the treatment of, after dissecting, find that enteron aisle blackening is rotten to the corn, not dead 8 be condemned to death after also find that there is 3 enteron aisles and have inflammation in various degree.And the mouse intestinal of two Schuttgelb vanadyl title complex group does not all have considerable change.As shown in accompanying drawing 2 figure, the trend of the sugar tolerance of each group mouse is substantially identical, and within 30 minutes, blood sugar reaches maximum value, and 60 points and 120 points decline gradually, meet the model of type ii diabetes.Wherein the sugar tolerance of two Schuttgelb vanadyl group mouse is best, and 120 points of blood sugar have recovered normal, and lower than the blood sugar of 0 minute.And the vanadylic sulfate group mouse blood sugar of 0 minute is similar with BEOV, but the blood sugar of 120 points is a lot of apparently higher than BEOV.Illustrate that the provide protection of BEOV to mice pancreatic is better than vanadylic sulfate, more effectively can improve the opposing of body to Regular Insulin.Lipid determination experiment shows.After treatment, with the contrast of diabetic groups mouse after two Schuttgelb vanadyl title complex group mouse treatment, total cholesterol and triglyceride level obviously reduce, and have returned within normal range.Liver starch determination experiment shows, compares with normal mice, and the liver starch of diabetic mice reduces obviously, two Schuttgelb vanadyl title complex group Mouse Liver glycogen is compared with diabetic mice, slightly increases, close with normal mice, illustrate that title complex can affect metabolism of fat, glycogen is converted into fat and glycolysis.
Experimental result shows, two Schuttgelb vanadyl title complexs of synthesis have good hypoglycemic activity, and obviously can reduce the content of total cholesterol and triglyceride level, significantly improve the sugar tolerance of diabetic mice.The sharpest edges of this compound are, do not affect normal mice blood sugar, namely can not produce hypoglycemic reaction.Two Schuttgelb vanadyl title complex can make ordinary preparation, sustained release preparation, controlled release preparation and targeting preparation, can as the healthcare products for the treatment of diabetes medicament, diabetes and hyperlipidemia complications disease drug and prevent diabetes or foodstuff additive.
Claims (3)
1. have a preparation method for the two Schuttgelb vanadyl title complex of hypoglycemic activity, it is characterized in that, described pair of Schuttgelb vanadyl complex structure is as follows:
Wherein R=H, C
2h
5, C
3h
7, C
4h
9;
Preparation process is as follows:
Step 1: organic ligand is dissolved in organic solvent, reflux, and regulates pH; Described organic ligand is Schuttgelb (1,3,8-trihydroxy--6-tectoquinone), Schuttgelb ether (1,8-dihydroxyl-3-oxyethyl group-6-tectoquinone), Schuttgelb propyl ether (1,8-dihydroxyl-3-positive propyl ether-6-tectoquinone), choose one in Schuttgelb n-butyl ether (1,8-dihydroxyl-3-n-butyl ether-6-tectoquinone); Organic solvent is choose one in methyl alcohol, ethanol, n-propyl alcohol, propyl carbinol;
Step 2: vanadium source is dissolved in solvent and makes solution;
Step 3: vanadium source solution is slowly added drop-wise in organic ligand solution, heating reflux reaction a few hours; Suction filtration obtains solid while hot; Described vanadium source is vanadylic sulfate or vanadyl acetylacetonate;
Step 4: by colourless to filtrate through hot ethanol, frozen water washing for the solid phase prod obtained, obtain two Schuttgelb vanadyl title complex after low-temperature vacuum drying; PH value of reaction system is 6-12, and temperature of reaction is 60 DEG C-120 DEG C, and the reaction times is 4-24 hour.
2. preparation method according to claim 1, is characterized in that, auxiliary agent is choose one in ammoniacal liquor, sodium carbonate, sodium hydroxide, triethylamine, quadrol.
3. the two Schuttgelb vanadyl title complexs described in claim 1 or 2 are for the preparation for the treatment of diabetes medicament or food, it is characterized in that, two Schuttgelb vanadyl title complex is for the preparation of the healthcare products for the treatment of diabetes and hyperlipidemia complications disease drug, prevent diabetes or dieletic foodstuff additive, two Schuttgelb vanadyl title complex, as activeconstituents, accounts for medicine or quality of food per-cent is 5%-99%.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104892663A (en) * | 2015-05-25 | 2015-09-09 | 北京大学 | Vanadium coordination compound using aminotriacetic acid derivative as ligand, and preparation method and application thereof |
| CN108558935A (en) * | 2018-04-08 | 2018-09-21 | 广西师范大学 | Vanadic anhydride crystalline material and its synthetic method based on the modification of tartaric acid chiral derivatives |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3617388A (en) * | 1966-07-25 | 1971-11-02 | Monsanto Res Corp | Method of activating fuel cell anodes |
| CN101205236A (en) * | 2006-12-18 | 2008-06-25 | 金文正 | Pyridinedicarboxylic acid vanadyl complexes as well as agent, tablet, capsule and uses thereof |
-
2015
- 2015-01-14 CN CN201510018112.4A patent/CN104628765B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3617388A (en) * | 1966-07-25 | 1971-11-02 | Monsanto Res Corp | Method of activating fuel cell anodes |
| CN101205236A (en) * | 2006-12-18 | 2008-06-25 | 金文正 | Pyridinedicarboxylic acid vanadyl complexes as well as agent, tablet, capsule and uses thereof |
Non-Patent Citations (2)
| Title |
|---|
| WALKER, RUTH A.: "Metal complexes of 1-hydroxy-9,10-anthraquinone. I. Infrared spectra (4000-350 cm-1) of complexes formed with divalent cations", 《SPECTROCHIMICA ACTA, PART A: MOLECULAR AND BIOMOLECULAR》 * |
| 谢明进等: "双(α-呋喃甲酸)氧钒的合成和抗糖尿病活性研究", 《化学学报》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104892663A (en) * | 2015-05-25 | 2015-09-09 | 北京大学 | Vanadium coordination compound using aminotriacetic acid derivative as ligand, and preparation method and application thereof |
| CN108558935A (en) * | 2018-04-08 | 2018-09-21 | 广西师范大学 | Vanadic anhydride crystalline material and its synthetic method based on the modification of tartaric acid chiral derivatives |
| CN108558935B (en) * | 2018-04-08 | 2019-06-14 | 广西师范大学 | Vanadic anhydride crystalline material and its synthetic method based on the modification of tartaric acid chiral derivatives |
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