CN102659844A - Cr (III) chelate, and preparation method and application thereof - Google Patents
Cr (III) chelate, and preparation method and application thereof Download PDFInfo
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- CN102659844A CN102659844A CN2012101566027A CN201210156602A CN102659844A CN 102659844 A CN102659844 A CN 102659844A CN 2012101566027 A CN2012101566027 A CN 2012101566027A CN 201210156602 A CN201210156602 A CN 201210156602A CN 102659844 A CN102659844 A CN 102659844A
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Abstract
The invention provides a Cr (III) chelate, and a preparation method and application thereof. The preparation method for the chelate comprises the following steps: preparing 5,5-methylene di(2-hydroxybenzoic acid); putting Cr (III) Cl3.6H2O and the 5,5-methylene di(2-hydroxybenzoic acid) into a reactor, dissolving by using organic alcohol, adding zinc particles, dripping ethanediamine in a reflux state, and continuously reacting for 15 to 60 minutes, wherein 1.85g of 5,5-methylene di(2-hydroxybenzoic acid), 0.1 to 1g of zinc particles, 10 to 30ml of organic alcohol and 0.5 to 1g of ethanediamine are added into each 1g of Cr(III)Cl3.6H2O; and cooling and filtering a reaction liquid to obtain a target product. The chelate is high in water solubility, has a sustained release function, is easily absorbed and can be applied to preparing weight-reducing medicines.
Description
Technical field
The present invention relates to metallo-chelate, be specially a kind of Cr (III) inner complex and preparation method, and the application of this inner complex in the preparation slimming medicine.
Background technology
Cr (III) ion (trivalent chromic ion) has the effect that strengthens insulin function, promotes the metabolism of sugar, protein and lipid.The intravital Cr of people (III) content lacks Cr (III) tissue is reduced the susceptibility of Regular Insulin along with the increase at age reduces gradually.Chromium (III) title complex demonstrates vital role as the supplement of Cr (III) in the process of treatment type ii diabetes.Replenish effect, the glucose tolerance that the slowly-releasing human body is impaired, lowering blood glucose level and the cholesterol in serum content that The addition of C r (III) title complex can strengthen Regular Insulin to the diabetics.The benefit chromium article of selling in the market have nicotinic acid chromium, various amino acid chromium and CrP etc.; Wherein CrP is current the most salable nutrition chromium supplementing agent; Its annual sales amount in the U.S. is about 500,000,000 dollars, nearlyly surpasses 10,000,000 people and is taking CrP (NBI, 2001).Because CrP exists and possibly cause chromosome damage, the sudden change of DNA and bring out shortcoming such as cancer generation, its use causes that gradually people suspect.Therefore the novel organic chromium inner complex of synthesizing efficient, low toxicity, easy absorption is significant.
Shrestha found 5 in 2007, and 5 '-methylene-bis (2 hydroxybenzoic acid) is a PTP1B enzyme potential suppressor factor (L), IC
50=15 ~ 19 μ M can significantly reduce the blood triglyceride, and the concentration of SUV and lipid acid suppress the increase of body weight and the accumulation of fat, and spinoff is very little.But it is water-soluble low, the biological utilisation rate variance.
Summary of the invention:
The object of the present invention is to provide a kind of Cr (III) inner complex and preparation method thereof, this inner complex good water solubility has slow-release function, is beneficial to absorption, can in the preparation slimming medicine, use.
A kind of Cr provided by the invention (III) inner complex, its structural formula is:
The preparation method of a kind of Cr provided by the invention (III) inner complex comprises the steps:
1) according to document " organic synthesis topical reference book " P751, Fan Nengting, press of Beijing Institute of Technology; With 2 hydroxybenzoic acid and formaldehyde in molar ratio for the 1:2 ratio adds in the hydrochloric acid, 90 ℃ of reaction 8h down, crystallization in water; Can get the L part: 5,5 '-methylene-bis (2 hydroxybenzoic acid).
2) with Cr (III) Cl
36H
2O and 5,5 '-methylene-bis (2 hydroxybenzoic acid) add in the reactor drum, with organic alcohol dissolving, add zinc granule again, splash into quadrol under the reflux state, continue reaction 15 ~ 60min time; By every 1gCr (III) Cl
36H
2O adds 1.85g 5, and the quadrol of 5 '-methylene-bis (2 hydroxybenzoic acid), 0.1-2g zinc granule, the organic pure and mild 0.5-1g of 10-30ml feeds intake;
3) with reaction solution cooling, filter, washing, dry pink title product, reaction formula is following:
Described CrCl
36H
2O can use CrCl
3Replace.
Described organic alcohol is organic alcohol of 1 carbon to 5 carbon.
Described zinc granule is 20-50 purpose arsenic-free zinc granule or zinc powder.
The present invention utilizes Cr (III) and 5, and a kind of novel inner complex has been synthesized in 5 '-methylene-bis (2 hydroxybenzoic acid) reaction.Characteristics are to utilize 5; The phenolic hydroxyl group of 5 '-methylene-bis (2 hydroxybenzoic acid) and carboxyl and Cr (III) ionic sequestering action; Significantly reduce Cr (III) ionic positive polarity, in the complex physical environment, played the effect of stablizing Cr (III), increased the utilization ratio of Cr (III); Also improved simultaneously the hydrophile/lipophile ability of part self, it is active to strengthen its lowering blood-fat and reducing weight.This inner complex good water solubility has slow-release function, is beneficial to absorption, can in the preparation slimming medicine, use.
Description of drawings:
The uv-visible absorption spectra of Fig. 1 ligand L and inner complex
The fluorescence spectrum of Fig. 2 ligand L and inner complex (λ ex=280nm)
Embodiment:
The preparation of embodiment 1:Cr (III) inner complex
The first step: 13.8g 2 hydroxybenzoic acid and 25ml mixed in hydrochloric acid are stirred, be warming up to 70 ℃, add 10g 30% formaldehyde solution, reinforced process keeps temperature to be no more than 80 ℃, and reinforced finishing is warming up to 90 ℃ of insulation 8h.After the cooling, reaction solution is invaded in the 100mL water, filter the crystallization of separating out, water repetitive scrubbing disacidify, dry under 100 ℃, get 5,5 '-methylene-bis (2 hydroxybenzoic acid), productive rate 75%.C is pressed in ultimate analysis
15H
12O
6, theoretical value: C, 62.50; H, 4.20; Experimental value: C, 62.01, H, 4.28.
Second step: with 2.67g (10.0mmol) CrCl
36H
2O and 1.44g (5.0mmol) 5,5 '-methylene-bis (2 hydroxybenzoic acid) places the 50mL round-bottomed flask, with the organic alcohol dissolving of 10mL; Add 0.3 gram arsenic-free zinc granule, refluxing slowly splashes into the 1mL anhydrous ethylenediamine down, and the color of solution becomes redness by green; Continue reaction 30min, separate out a large amount of pink powder after the cooling, suction filtration; Successively wash three to five times with absolute ethyl alcohol and ether, drying at room temperature is to constant weight, and productive rate is 70%.
Determination of elemental analysis is by molecular formula Cr
2C
23H
40N
8O
6Cl
2, theoretical value: C, 39.49; H, 5.76, N, 16.02, Cr 14.86; Experimental value: C, 39.52, H, 5.99, N, 15.88, Cr, 14.6.
Uv-visible absorption spectra: part 5; 5 '-methylene-bis (2 hydroxybenzoic acid) has charateristic avsorption band (accompanying drawing 1 at the 300nm place; Curve a); Arrive 340nm (curve b) with the π-π * absorption peak red shift of its phenyl ring after Cr (III) coordination, explain that the electronic cloud on the pi-conjugated system shifts to the empty d track of Cr (III); Inner complex is the d-d transition peak (curve c) of Cr (III) in the inner complex in the absorption peak ownership that 521nm occurs.
Fluorescence spectrum: 5,5 '-methylene-bis (2 hydroxybenzoic acid) near 410nm, have strong fluorescence (see accompanying drawing 2, curve a), when itself and Cr (III) form behind the inner complex near the fluorescence the 410nm almost by complete cancellation (curve b).Uv-visible absorption spectra and fluorescence spectrum all show 5, and (phenolic hydroxyl group of 2 hydroxybenzoic acid and carboxyl are with bidentate mode and chromium coordination to 5 '-methylene-bis.
The preparation of embodiment 2:Cr (III) inner complex:
Take by weighing 2.67g (10.0mmol) CrCl
36H
2O and 1.44g (5.0mmol) 5,5 '-methylene-bis (2 hydroxybenzoic acid) places the 100mL round-bottomed flask, with the organic alcohol dissolving of 30mL; Add 1 gram arsenic-free zinc granule, splash into the 2mL anhydrous ethylenediamine under refluxing, the color of solution becomes redness by green; Continue reaction 30min, separate out a large amount of pink powder, suction filtration; Successively with anhydrous organic pure and mild ether washing three to five times, drying at room temperature is to constant weight, and productive rate is 78%.
The fat-reducing of embodiment 3:Cr (III) inner complex is active
The active experiment through the feeding small white mouse of fat-reducing verified.30 of Kunming mouses, male half and half, body weight (10-12g) is provided by Shanxi Institute of Traditional Chinese Medicine's Experimental Animal Center.Normal diet is provided by Guangzhou Sai Bainuo bio tech ltd.High lipid food prescription: normal diet 66.5%, sucrose 20%, lard 10%, SUV 2.5%, Sodium cholic acid 1%.Be divided into 3 groups (male half and half), 10 of normal group, 10 of model group, administration group 10 at random by body weight.From the experiment beginning, the normal group mouse gives normal diet, and all the other each groups all give high lipid food.Begin administration after feeding for 11 weeks.Dosage is 50g/kg every day, and every morning is irritated stomach 1 time, 19 weeks of Therapy lasted.Regularly claim the weight of animals.After experiment finished, fasting 18h weighed, and the eye socket venous plexus is got blood, the kit measurement related biochemical indicator.
The result shows: 1) each item biochemical indicator of model group and compared with normal all have utmost point significant difference; Explain that high lipid food can produce utmost point remarkably influenced to the physiological situation of mouse; Blood pressure and blood lipoid concentration is raise; Increase the weight of fat and liver, improve ldl concn, reduce high-density lipoprotein concentration; 2) administration group all has utmost point significant difference with model group at the body weight gain degree in each period, and in every group negative growth is arranged all, explains that growth has remarkable effect (table 1) to this inner complex to management of body weight.The administration group is compared with model group, and in 7 indexs, except blood sugar concentration, all there were significant differences (table 2) for all the other indexs.
Table 1 weight of mice degree (
n=10)
Compare with normal group,
▲P<0.05,
▲ ▲p<0.01; Compare with model group,
*P ﹤ 0.05,
*P ﹤ 0.01
Table 2 each item physiological and biochemical index (
n=10)
Compare ▲ P with normal group<0.05 the p of, ▲ ▲<0.01; Compare with model group,
*P ﹤ 0.05,
*P ﹤ 0.01
Claims (5)
1. a Cr (III) inner complex is characterized in that structural formula is:
2. the preparation method of a kind of Cr provided by the invention (III) inner complex is characterized in that, comprises the steps:
1) preparation 5,5 '-methylene-bis (2 hydroxybenzoic acid);
2) with Cr (III) Cl
36H
2O and 5,5 '-methylene-bis (2 hydroxybenzoic acid) add in the reactor drum, with organic alcohol dissolving, add zinc granule again, splash into quadrol under the reflux state, continue reaction 15 ~ 60min time; By every 1gCr (III) Cl
36H
2O adds 1.85g 5, and the quadrol of 5 '-methylene-bis (2 hydroxybenzoic acid), 0.1-1g zinc granule, the organic pure and mild 0.5-1g of 10-30ml feeds intake;
3) with the reaction solution cooling, filter washing, the dry title product that gets.
3. by the preparation method of the described Cr of claim 2 (III) inner complex, it is characterized in that described CrCl
36H
2O uses CrCl
3Replace.
4. by the preparation method of the described Cr of claim 2 (III) inner complex, it is characterized in that described organic alcohol is organic alcohol of 1 carbon to 5 carbon.
5. by the preparation method of the described Cr of claim 2 (III) inner complex, it is characterized in that described zinc granule is 20-50 purpose arsenic-free zinc granule or zinc powder.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104513279A (en) * | 2015-01-15 | 2015-04-15 | 山西大学 | Cr (III) chelate compound as well as preparation method and application thereof |
| CN105601670A (en) * | 2016-03-15 | 2016-05-25 | 山西大学 | Chromium (III) complex as well as preparation method and application thereof |
| US11013750B2 (en) | 2017-01-20 | 2021-05-25 | Aurin Biotech Inc. | Methods for treating and preventing nociceptive pain |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1810250A (en) * | 2005-01-25 | 2006-08-02 | 尼普洛株式会社 | Inclusion compound of porphyrin metal complex and albumin |
| CN1844137A (en) * | 2006-04-27 | 2006-10-11 | 南京大学 | Preparation process of chromium glucosaminic acid and use thereof |
| WO2007002739A2 (en) * | 2005-06-28 | 2007-01-04 | The University Of Wyoming | Chromium-amino acid complexes in the treatment of diabetes and other diseases |
| US7547454B2 (en) * | 2002-11-07 | 2009-06-16 | Shyam K Gupta | Hydroxy acid complexes for antiaging and skin renovation |
-
2012
- 2012-05-21 CN CN2012101566027A patent/CN102659844A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7547454B2 (en) * | 2002-11-07 | 2009-06-16 | Shyam K Gupta | Hydroxy acid complexes for antiaging and skin renovation |
| CN1810250A (en) * | 2005-01-25 | 2006-08-02 | 尼普洛株式会社 | Inclusion compound of porphyrin metal complex and albumin |
| WO2007002739A2 (en) * | 2005-06-28 | 2007-01-04 | The University Of Wyoming | Chromium-amino acid complexes in the treatment of diabetes and other diseases |
| CN1844137A (en) * | 2006-04-27 | 2006-10-11 | 南京大学 | Preparation process of chromium glucosaminic acid and use thereof |
Non-Patent Citations (2)
| Title |
|---|
| SUJA SHRESTHA等，: "Mono- and disalicylic acid derivatives: PTP1B inhibitors as potential anti-obesity drugs", 《BIOORGANIC & MEDICINAL CHEMISTRY》 * |
| 刘斌: "水杨酸系列铬络合物合成及其性质研究", 《山西大学博士学位论文》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN105601670A (en) * | 2016-03-15 | 2016-05-25 | 山西大学 | Chromium (III) complex as well as preparation method and application thereof |
| US11013750B2 (en) | 2017-01-20 | 2021-05-25 | Aurin Biotech Inc. | Methods for treating and preventing nociceptive pain |
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Application publication date: 20120912 |