CN101863755A - Chromium malate complex and preparation method and application thereof - Google Patents
Chromium malate complex and preparation method and application thereof Download PDFInfo
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Abstract
The invention relates to a chromium malate complex and a preparation method and application thereof, belonging to the technical field of pharmaceutical chemicals industrial production technology. The molecular formula of the chromium malate complex is Cr2 (C4H4O5) 3.5 H2O. The method of the invention comprises the following steps: obtaining malate by the reaction of malic acid and alkali liquor; and obtaining the chromium malate complex by the reaction of the malate and chromium trichloride; or mixing the malic acid and the chromium trichloride solution and then adding the alkali liquor for reaction to obtain the chromium malate complex, wherein the concentration of the malic acid and the chromium trichloride is 0.1-5mol/L, the mol ratio of the chromium ion to the malic acid is 1:1-1:3, and the reaction temperature is normal temperature-100 DEG C. The reaction solution is under the condition of pH 3-7, the reaction medium can be water, 20%-80% methanol or ethanol solution, and the used alkali is ammonia or sodium hydroxide solution or potassium hydroxide solution. The chromium malate complex can be used for preparing antidiabetic drugs for treating diabetes and hypoglycemic health products. The chromium malate complex of the invention has obvious blood sugar lowering activity, has obvious promoting action on the synthesis of hepatic glycogen, and has stable structure and simple preparation method.
Description
Technical field
The present invention relates to chromium malate and its production and use, refer in particular to chromium malate complex, belong to medication chemistry industrial manufacture process technical field with hypoglycemic activity.
Background technology
Along with development of human society, diabetes have become the third-largest disease after cardiovascular disorder, tumour.According to The World Health Organization (WHO) and International Diabetes Federation (IDF) 1997 annual reports, nineteen ninety-five the whole world diabetic subject 1.25 hundred million people are arranged approximately, predict and will increase sharply in 2025 to 2.99 hundred million people.In China, along with growth in the living standard and aging population, diabetes prevalence also is ascendant trend year by year.According to estimates, China diabetic subject in 1999 is up to more than 4,000 ten thousand people, the crowd who still has fifty-five million not made a definite diagnosis, and constantly rise with annual 0.1% speed.Diabetes also can cause various severe complications, as fatal diseases of disabling such as ephrosis, retinopathy and lower limb vascular pathologies.Therefore the research and development of hypoglycemic drug and functional foodstuff have become one of research focus.
Present hypoglycemic medicine mainly contains yellow ureas, biguanides, alpha-glucosidase inhibitor, euglycemic agent, free fatty acids oxidation retarder etc., some toxic side effect of these ofhypoglycemic medicines is obvious, some easily produces uncomfortable disease, for example take yellow carbamide type medicine for a long time and be easy to cause hypoglycemia, appetite stimulator, urine ketosis, oxypathy etc., biguanides easily causes lactic acidosis, and taking for a long time increases liver kidney burden etc.
Cr
3+Being one of trace element of needed by human, is normal sugar and metabolism of fat essential trace element, and structure, function and the target tissue cell state of Regular Insulin all had a significant effect, and body lacks Cr
3+Can cause sugar, disorders of lipid metabolism, impel atherosclerosis, low-density lipoprotein increases, and causes diabetes, symptoms such as hyperlipidemia.Because the multi-form combination degree difference of chromium in tissue causes the specific absorption difference.Inorganic chromium not only toxicity is big, and the absorption level is low, is about 0.14～3.0%; Organic chromium absorbs rapidly and safety, and specific absorption can reach 10～25%.Pyridine acid chromium salt (picolinate chromium) is extensive use of as blood sugar reducing health product additive on American-European market.But the pyridine acid group is as part, and itself does not have biological activity, has bibliographical information to replenish pyridine acid chromium salt for a long time and can cause the pyridine acid group to be accumulated in vivo, produces toxic side effect.
China Patent No. CN 1431228A discloses " chitosan chromium and its production and use " on July 23rd, 2003, though the application of chitosan chromium aspect hypoglycemic has result preferably, can eliminate toxic side effect or harm that pyridine chromium etc. may bring to human body, but the molecular weight of chitosan is bigger, is difficult to directly be absorbed by the body.Zhao's book waits clearly that (2003,20 (3): 115-118.) reported a kind of preparation method of chromium citrate, this method at first is Cr for the research of chromium citrate synthetic method, Heilongjiang University's natural science journal
2(SO
4)
36H
2O and ammoniacal liquor reaction generate chromium hydroxide precipitation, generate chromium citrate with citric acid reactions again.But chromium malate complex and preparation method thereof does not appear in the newspapers so far both at home and abroad with hypoglycemic activity, does not see corresponding patent disclosure yet.
Summary of the invention
The objective of the invention is provides a kind of chromium malate and preparation method thereof for solving the deficiency that the above-mentioned background technology exists.This chromium malate is easily absorbed by the body, and can effectively replenish the required trivalent chromium of body, can eliminate the potential hazard that pyridine acid chromium salt etc. may bring to human body.The hypoglycemic purposes of this chromium malate is provided simultaneously, and it has the effect of lowering blood glucose, total cholesterol and triglyceride level, can be used as the healthcare products or the foodstuff additive of treatment diabetes medicament and prevent diabetes.
The invention provides a kind of preparation method of novel complexes chromium malate, this method comprises the steps:
Oxysuccinic acid and alkaline reaction are obtained malate; With malate and chromium trichloride reaction, obtain chromium malate complex.
The present invention also provides another kind of chromium malate preparation method of the present invention, and this method comprises the steps:
Oxysuccinic acid is mixed with chromium trichloride solution, add alkaline reaction again, obtain chromium malate complex.When synthesizing chromium malate complex of the present invention,
Wherein said oxysuccinic acid and chromium trichloride concentration 0.1～5mol.L
-1, the mol ratio of chromium ion and oxysuccinic acid is 1: 1～1: 3, temperature of reaction is normal temperature～100 ℃.
Wherein reaction soln can be to carry out under pH3～7 conditions under neutrallty condition in acidity, and reaction medium can make water, 20～80% methyl alcohol or ethanolic soln, and used alkali is ammoniacal liquor or sodium hydroxide solution or potassium hydroxide solution.
After synthetic the finishing, adopt easy method to isolate chromium malate, for example, can add the solubleness that alcohols or ketone equal solvent reduce chromium malate, settlement separate or centrifugation is after use the little solvent wash of chromium malate solvability, drying.
This title complex is confirmed as a kind of novel oxysuccinic acid title complex through ultraviolet-visible spectrum, infrared spectra, atomic absorption spectrum, ultimate analysis, heat analysis etc., and its molecular formula is Cr
2(C
4H
4O
5)
35H
2O.
Chromium malate of the present invention can be used for preparing the ofhypoglycemic medicine and the health-caring product capable of reducing blood sugar for the treatment of diabetes, can the liquid or solid form foodstuff additive of organic trace element chromium (III) as a supplement; Can on various pharmaceutical preparations such as tablet, capsule and other medicines, use with composition forms.
Chromium malate provided by the invention and composition thereof mainly adopt oral method.
Chromium malate of the present invention has the lowering blood glucose effect, can make any formulation, for example tablet, capsule, solution, suspension agent, ointment, lyophilisate, pill, film, liposome etc.; Can make protective foods with function of blood sugar reduction; Use as foodstuff additive, add to the liquid or solid powder type in the food such as beverage, cheese, bread, flour.
Chromium malate of the present invention is made and is used for hypoglycemic medicine composition or health food composition, comprises chromium malate and other component drug carrier or auxiliary material.
In the chromium malate composition of the present invention, functional component is a chromium malate.According to pharmacy and preparation needs, carrier in the composition or auxiliary material are acceptable any with medicine.
Of the present invention be used for the treatment of the pharmaceutical composition of diabetes or be used for the blood glucose-lowering health-care product composition can be formulations such as tablet, injection, capsule, injection liquid or oral liquid.
The usage quantity of chromium malate of the present invention can be determined the needs of different preparations according to pharmacy.
The invention has the advantages that: chromium malate of the present invention has the obvious functions of blood sugar activity, can regulate triglyceride level and total cholesterol preferably, and the synthetic of liver starch had obvious facilitation, and Stability Analysis of Structures, and the preparation method is easy.
Description of drawings
The infrared spectrogram of Fig. 1 chromium malate complex of the present invention;
Fig. 2 chromium malate complex of the present invention and the chromium trichloride ultraviolet-visible spectrogram in water; Wherein a is a chromium trichloride, the b chromium malate complex;
The heat of Fig. 3 chromium malate complex of the present invention is analyzed the TG-DSC-DTG curve.
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.
Take by weighing 532mg (about 2mmol) six hydrated chromium trichlorides and 804mg (about 6mmol) oxysuccinic acid in the 100mL there-necked flask, 50% ethanolic soln that adds 20mL, stirring makes its dissolving, the sodium hydroxide solution that dropwise adds 2mol/L is again regulated pH3, at 100 ℃ of following heated and stirred reaction 10h, along with the prolongation in reaction times, the reaction solution color gradually becomes purple by green.Centrifugal concentrate, it is original 1/2～1/4 that its volume is become, and adds the dehydrated alcohol of 4 times of amounts in concentrated solution, precipitation in a large number occurs, leaves standstill, centrifugal, collecting precipitation.With absolute ethanol washing for several times, remove chromium trichloride and the oxysuccinic acid of not participating in reaction, collecting precipitation, vacuum-drying promptly gets hepatic pulverulent solids.
Compositional analysis, Cr
2(C
4H
4O
5)
35H
2O theoretical value: C 24.42, H 3.75, and Cr 17.61%, trial value: C 23.97, and H 3.82, and Cr 17.45%.Infrared spectra (accompanying drawing 1): 3399cm
-1, 1725cm
-1, 1605cm
-1, 1386cm
-1, 623cm
-1, 572cm
-1, 492cm
-1, 424cm
-1Ultraviolet-visible absorption spectroscopy (H
2O, accompanying drawing 2): chromium trichloride (a) maximum absorption band λ
1Max=594nm, λ
2Max=422nm, chromium malate (b) maximum absorption band λ
1Max=565nm, λ
2Max=391nm, heat is analyzed (accompanying drawing 3): the chromium malate complex heat absorption loses crystal water, and corresponding to thermogravimetric curve, rate of weight loss is 15.3%, loses the 5mol crystal water in the molecular formula of rate of weight loss and supposition and conforms to.
Take by weighing 804mg (about 6mmol) oxysuccinic acid in the 100mL there-necked flask, add 50% methanol solution of 20mL, stir and make its dissolving, the potassium hydroxide solution that dropwise adds 2mol/L is regulated pH5, adds 0.2mol/L CrCl again
36H
2The 50% methanol solution 20mL of O, at 60 ℃ of following heated and stirred reaction 10h, along with the prolongation in reaction times, the reaction solution color gradually becomes purple by green.Subsequent disposal is carried out with embodiment 1, and through signs such as ultimate analysis, spectroscopic analysis, heat analyses, the gained material is identical with embodiment 1.
Take by weighing 11320mg (about 50mmol) six hydrated chromium trichlorides and 6700mg (about 50mmol) oxysuccinic acid in the 100mL there-necked flask, the deionized water that adds 20mL, stirring makes its dissolving, dropwise weak ammonia is regulated pH7 again, the 10h of heated and stirred reaction at normal temperatures, along with the prolongation in reaction times, the reaction solution color gradually becomes purple by green.Subsequent disposal is carried out with embodiment 1, and through signs such as ultimate analysis, spectroscopic analysis, heat analyses, the gained material is identical with embodiment 1.
The hypoglycemic test of chromium malate complex:
1 material and equipment
1.1 animal
The ICR mouse, male and female half and half, body weight 20 ± 2g, the cleaning level is purchased in Yangzhou University comparative medicine center, conformity certification numbering: SCXK (Soviet Union) 2007-0001.Quarantine 3d raises and stabilizes to 21 ± 1 ℃ before the experiment, and humidity is 60 ± 5%.
1.2 medicine and reagent
Tetraoxypyrimidine, the rich U.S. biotechnology in Hefei limited liability company
Chromium malate complex: laboratory self-control (is 17.56% through its chrome content of atomic absorption detecting)
CrCl
36H
2O: Chemical Reagent Co., Ltd., Sinopharm Group, analytical pure.
Glyburide: Beijing Pharma Pacific Pty. Ltd.
Physiological saline: Hunan Cologne Pharmaceutical Co., Ltd, the accurate word H51021158 of traditional Chinese medicines
The anthrone of anthrone reagent: 0.2g is dissolved in (adapted on the same day) in the 100mL vitriol oil;
The triglyceride level test kit: bio-engineering research institute is built up in Nanjing;
The cholesterol reagent box: bio-engineering research institute is built up in Nanjing.
1.3 key instrument equipment
Steady bold and unconstrained type blood glucose meter and supporting blood sugar test paper thereof: medicine equipment company limited of Johnson ﹠ Johnson (China);
Spectra Max 190 microplate reader: U.S. molecular device company;
1.4 statistical method
Data are handled with the Excel statistical software.The result uses
Expression is checked the significance that compares difference between each administration group and the control group with ANOVA between group.* represent p＜0.05, represent this administration group and control group significant difference.
2 experimental techniques
2.1 alloxan diabetes Preparation of model
Except that the blank group, all mouse shift to an earlier date fasting 12h, freely drink water, tetraoxypyrimidine is mixed with 0.8% injection liquid with physiological saline, every mouse is pressed the disposable injection in 200mg/kg dosage abdominal cavity, afterbody is got blood and is surveyed fasting plasma glucose behind the injection 5d, and fasting blood sugar is included diabetes model in the above person of 11.1mmol/L.
2.2 grouping
Get 10 not mouse of modeling, be the blank group; With hyperglycemia mouse random packet, 10 every group, totally 6 groups: dosage group, chromium malate complex high dose group, chromium trichloride group in hyperglycemia model control group, positive drug group, chromium malate complex low dose group, the chromium malate complex.
2.3 dosage design
As shown in table 1, be the dosage of each administration group, each administration group administration 14d.
Each administration group dosage of table 1
Annotate: dosage calculates with chromium malate complex and six hydrated chromium trichlorides, and wherein the chromium malate complex chrome content is that 17.45%, six hydrated chromium trichloride chrome content is 19.51%.
2.4 detection index
(1) growth of animal situation
Observe animal every day once, observing animal mental status, behavior and hair color has no abnormally, weighs and writes down to understand the weight of animals growth pattern.
(2) fasting plasma glucose pH-value determination pH
Behind fasting 3h after the administration of 14d last, deduct the mouse tail point, test paper is inserted blood glucose meter, droplets of whole blood writes down reading on blood sugar test paper.
(3) mensuration of blood fat (comprising total cholesterol TCH, triglyceride level TG)
Administration is got blood with mouse orbit after finishing, and collects the about 1.5mL of whole blood, the centrifugal 10min of 3000rpm.Get supernatant liquor 100 μ L, measure the content of total cholesterol and triglyceride level in strict accordance with the test kit operation instructions.
(4) mensuration of liver starch level
Put to death mouse, get liver, blot, accurately take by weighing liver 100mg, add 8mL trichoroacetic acid(TCA) homogenate 1min, 3000r/min, centrifugal 15min in vitro through the blank rinsing filter paper of physiological saline.Get supernatant liquor in vitro, with the content of anthrone colorimetric method for determining liver starch in another.
3 experimental results
3.1 each medicine is to the impact effect of diabetic mice body weight.
Each medicine of table 2 is to the influence of diabetic mice body weight (g)
Compare with the blank group,
*P＜0.05
As can be seen from Table 2, the diabetic mice body weight of modeling success significantly is lower than the blank mouse of organizing behind the 14d.Wanting that diabetic mice weight ratio model group mouse after giving medicine increases is many, shows that chromium malate has certain effect to the increase of diabetic mice body weight
3.2 each medicine is to the influence of blood glucose in diabetic mice
Each medicine of table 3 is to the influence of blood glucose in diabetic mice (mmol/L)
Compare with the blank group,
*P＜0.05
As shown in table 3, the blood glucose value of blank group mouse remains on normal value behind the 14d, and the mouse blood sugar value of model group is organized mouse apparently higher than blank.Compare the decline that all has in various degree before basic, normal, high three the dosage groups of chromium malate complex and the administration, its inhibiting rate all is higher than the chromium trichloride group, and visible chromium malate complex blood sugar decreasing effect is better than chromium trichloride.
3.3 each medicine is to the influence of diabetic mice blood fat
(1) each medicine is to the influence of diabetic mice triglyceride level
As shown in table 4, chromium malate complex has certain regulating effect to triglyceride level.
(2) each medicine is to the influence of diabetic mice total cholesterol
As shown in table 5, chromium malate complex has regulating effect preferably to the hypercholesterolemia symptom.
Each medicine of table 4 is to the influence of diabetic mice triglyceride level (mg/dl)
The group triglyceride level
Blank group 0.815 ± 0.27
Model group 1.17 ± 0.36
Positive drug group 1.13 ± 0.34
Chromium malate low dose group 1.13 ± 0.21
Dosage group 0.815 ± 0.37 in the chromium malate
*
Chromium malate high dose group 0.951 ± 0.46
Chromium trichloride group 1.07 ± 0.16
Compare with model group,
*P＜0.05
Each medicine of table 5 is to the influence of diabetic mice total cholesterol (mg/dl)
The group total cholesterol
Blank group 2.30 ± 0.34
Model group 2.69 ± 0.47
Positive drug group 2.09 ± 0.39
Chromium malate low dose group 2.34 ± 0.20
Dosage group 2.09 ± 0.66 in the chromium malate
Chromium malate high dose group 2.34 ± 0.27
Chromium trichloride group 2.35 ± 0.41
3.4 each medicine is to the influence of diabetic mice liver starch
As shown in table 6, chromium malate complex liver starch synthetic has obvious facilitation, and its influence to liver starch is better than Glyburide and chromium trichloride.
Each medicine of table 6 is to the influence of diabetic mice liver starch (μ g/100mg)
The group liver starch
Model group 315.95 ± 198.93
Positive drug group 379.82 ± 253.31
Chromium malate low dose group 387.38 ± 238.20
Dosage group 473.75 ± 190.42 in the chromium malate
Chromium malate high dose group 622.95 ± 210.20
*
Chromium trichloride group 348.09 ± 217.46
Compare with the blank group,
*P＜0.05
4 conclusion chromium malates have the obvious functions of blood sugar activity, can regulate triglyceride level and total cholesterol preferably, and liver starch synthetic had obvious facilitation.
The chromium malate complex acute toxicity test
1 material and instrument
1.1 animal
The ICR mouse, male and female half and half, body weight 20 ± 2g, the cleaning level is purchased in Yangzhou University comparative medicine center, conformity certification numbering: SCXK (Soviet Union) 2007-0001.Quarantine 3d raises and stabilizes to 21 ± 1 ℃ before the experiment, and humidity is 60 ± 5%.
1.2 medicine and reagent
Chromium malate complex, laboratory self-control (is 17.56% through its chrome content of atomic absorption detecting).
1.3 key instrument equipment
B3200S ultrasonic cleaning machine must be believed ultrasonic Shanghai company limited
BS124S type analysis balance Beijing Sai Duolisi instrument system company limited
Electronic balance BS124S Beijing Sai Duolisi Instr Ltd.
2 experimental techniques
Quarantine 3d before the experiment, getting 10 healthy mices respectively immediately is blank group and administration group, presses dosage 15231mg/kg, the 0.15mL/10g per os is irritated stomach and is tried thing.Irritate the preceding animal overnight fasting of stomach, freely drink water, continue after the administration to give normal diet behind the fasting 4h.Observe a week, observe animal every day once, record mouse mental status, behavior and hair color have no abnormal, weigh and write down to understand the weight of animals growth pattern.
After 7d is observed in mouse contamination, put to death mouse, each composition is not 1 of blank group mouse and 2 of chromium malate groups.Take out the mouse liver of fritter at random rapidly, heart and kidney are fixed (size of tissue block is 2.0cm * 2.0cm * 0.3cm, and the ratio of tissue block and formalin solution is 1: 10) with 10% formalin immediately.The dehydration of tissue block, embedding, section, HE dyeing are finished by the technician of Pathology Deparment of Zhenjiang City No.1 People's Hospital.
3 results
3.1 overview
1 all interior mouse do not occur unusual and dead after the mouse administration.Credit is analysed by statistics, behind administration 3d and the 7d, and oxysuccinic acid group and control group body weight change there was no significant difference (seeing Table 1); Mouse all increases weight, and 1 week back is put to death and dissected, the visual inspection heart, liver, spleen, lung, kidney, stomach, intestines, and thoracic cavity, abdominal cavity, each organ are all no abnormal.Female, male its mouse oral LD
50Greater than 15000mg/kg.According to acute toxicity grading criteria regulation in " food safety toxicity assessment process and method ", chromium malate complex belongs to nontoxic level to chmice acute per os toxicity.
3.2 influence to each tissue of mouse
The heart of blank group and chromium malate group test mice, liver, kidney is made section, after dyeing with the HE staining, examines under a microscope.Heart, liver, the kidney of finding chromium malate group mouse do not see that parenchyma sex change, necrosis, weave construction do not see variation.As seen chromium malate is to the heart of mouse, and liver, kidney also have no side effect.
Table 1 chromium malate complex maximum dosage-feeding is measured the body weight of mouse
4 conclusions
Studies on acute toxicity to chromium malate complex shows that in the observation period of 7d, abnormal conditions and death do not appear in mouse, the postmortem no abnormality seen.The tissue slice of heart, liver, kidney is not seen parenchymatous degeneration, necrosis, and weave construction is not seen variation.Female, male mice per os LD
50Greater than 15000mg/kg.And female, the male mice per os LD50 of bibliographical information chromium trichloride are 2143.3mg/kg, and toxicity obviously reduced after visible chromium trichloride and oxysuccinic acid formed title complex.
Claims (7)
1. the preparation method of chromium malate complex is characterized in that this method comprises the steps: oxysuccinic acid and alkaline reaction are obtained malate; With malate and chromium trichloride reaction, obtain chromium malate complex.
2. the preparation method of chromium malate complex according to claim 1 is characterized in that this method can also be undertaken by following step: oxysuccinic acid is mixed with chromium trichloride solution, add alkaline reaction again, obtain chromium malate complex.
3. the preparation method of chromium malate complex according to claim 1 and 2 is characterized in that described oxysuccinic acid and chromium trichloride concentration 0.1～5mol.L
-1, the mol ratio of chromium ion and oxysuccinic acid is 1: 1～1: 3, temperature of reaction is normal temperature～100 ℃.
4. the preparation method of chromium malate complex according to claim 1 and 2, it is characterized in that described reaction soln can be to carry out under pH3～7 conditions in acidity under neutrallty condition, reaction medium can make water, 20～80% methyl alcohol or ethanolic soln, and used alkali is ammoniacal liquor or sodium hydroxide solution or potassium hydroxide solution.
5. chromium malate complex is characterized in that its molecular formula is Cr
2(C
4H
4O
5)
35H
2O.
6. chromium malate complex is in the application of the ofhypoglycemic medicine of preparation treatment diabetes.
7. chromium malate complex is in the application of the health-caring product capable of reducing blood sugar of preparation treatment diabetes.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102302520A (en) * | 2011-09-02 | 2012-01-04 | 江苏大学 | Composition of chromium malate and bee glue and application thereof |
| CN111996522A (en) * | 2020-08-03 | 2020-11-27 | 鞍钢股份有限公司 | Zinc-aluminum-magnesium steel plate environment-friendly passivator and preparation and use method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101117316A (en) * | 2007-07-07 | 2008-02-06 | 李恕勤 | Oral liquid for preventing and remitting diabetes |
| CN101495439A (en) * | 2006-07-10 | 2009-07-29 | 日本化学工业株式会社 | Aqueous solutions of organic acid chromium(III) salts and process for preparation thereof |
-
2009
- 2009-09-24 CN CN2009100352781A patent/CN101863755B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101495439A (en) * | 2006-07-10 | 2009-07-29 | 日本化学工业株式会社 | Aqueous solutions of organic acid chromium(III) salts and process for preparation thereof |
| CN101117316A (en) * | 2007-07-07 | 2008-02-06 | 李恕勤 | Oral liquid for preventing and remitting diabetes |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102302520A (en) * | 2011-09-02 | 2012-01-04 | 江苏大学 | Composition of chromium malate and bee glue and application thereof |
| CN111996522A (en) * | 2020-08-03 | 2020-11-27 | 鞍钢股份有限公司 | Zinc-aluminum-magnesium steel plate environment-friendly passivator and preparation and use method thereof |
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