CN103877533B - Pharmaceutical composition of a kind for the treatment of diabetes containing metformin and preparation method thereof - Google Patents
Pharmaceutical composition of a kind for the treatment of diabetes containing metformin and preparation method thereof Download PDFInfo
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Abstract
The invention belongs to medical art, be specifically related to pharmaceutical composition of a kind for the treatment of diabetes containing metformin and preparation method thereof.The pharmaceutical composition of the treatment diabetes containing metformin of the present invention, is made up of the crude drug of following weight: metformin 250-750 part, Rhizoma Pinelliae 1500-2500 part, Rhizoma Zingiberis Recens 2500-3500 part, Fructus Aurantii 2500-3500 part, Pericarpium Citri Reticulatae 1500-2500 part, Rhizoma Coptidis 1500-2500 part.Chinese medicine combines with metformin by the present invention, can avoid the common gastrointestinal side effect of metformin, and improves the therapeutic effect to diabetes.
Description
Technical field
The invention belongs to medical art, be specifically related to pharmaceutical composition of a kind for the treatment of diabetes containing metformin and preparation method thereof.
Background technology
Diabetes are second killers in modern diseases, and it is only second to cancer to the harm of human body.In fact, diabetes itself are not fearful, and the complication of diabetes that fearful is, the harm that diabetes are brought, nearly all from its complication.In China's diabetics, complicated hypertension person reaches 1,200 ten thousand, apoplexy person 5,000,000, coronary disease patient 6,000,000, and the person of losing the sight of both eyes 450,000, uremia person 500,000.
Diabetes are a kind of complex diseases because of syndrome, be because the hormone of insulin deficit in body or antagonism insulin increases, or insulin can not be brought into normal play physiological action and a kind of syndrome of glucose, protein and lipid metabolic disorder of causing in target cell.To it is characterized by blood circulation that concentration of glucose is abnormal to be raised and glucose in urine, blood glucose occur typical " three-many-one-little " symptom time too high, namely to eat more, polyuria, polyphagia and lose weight, and with fatigue and weak.Can be there is ketoacidosis, hypertonicity diabetic coma in severe patient, and easily merge multi-infection.Along with the prolongation of the course of disease, its metabolism disorder can cause the chronic disease of the histoorgans such as eye, kidney, nerve, blood vessel and heart.If can not get timely, appropriate treatment, then there is heart change, cerebrovascular disease, renal failure, lose the sight of both eyes, the situation such as lower limbs necrosis, become disable, lethal main cause.
Metformin is the biguanides of clinical conventional treatment diabetes, is applicable to alone diet and exercise therapy and can not obtains the good type 2 diabetes mellitus patient controlled.This product can medication separately, also can share with sulphanylureas or insulin.The diabetes effect being used for the treatment of obese type is fine, therefore clinical practice is extensive, the common untoward reaction of metformin is gastrointestinal upset, as nausea,vomiting,diarrhea, stomachache, constipation, abdominal distention, dyspepsia, heartburn, this untoward reaction is up to 30%, and this untoward reaction limits the use of metformin.
Summary of the invention
In order to solve the technical problem of metformin gastrointestinal side effect large restriction end user group, the invention provides the compositions of a kind of metformin and Chinese medicine, by the compatibility with Chinese medicine, alleviating the untoward reaction of metformin, thus realize the object of attenuation synergistic.
The present invention is realized by following technical scheme:
A pharmaceutical composition for treatment diabetes containing metformin, is made up of the crude drug of following weight proportion: metformin 250-750 part, Rhizoma Pinelliae 1500-2500 part, Rhizoma Zingiberis Recens 2500-3500 part, Fructus Aurantii 2500-3500 part, Pericarpium Citri Reticulatae 1500-2500 part, Rhizoma Coptidis 1500-2500 part.
The pharmaceutical composition of the above-mentioned treatment diabetes containing metformin, its weight is preferably: metformin 400-600 part, Rhizoma Pinelliae 1800-2200 part, Rhizoma Zingiberis Recens 2800-3200 part, Fructus Aurantii 2800-3200 part, Pericarpium Citri Reticulatae 450-2200 part, Rhizoma Coptidis 1800-2200 part.
The pharmaceutical composition of the above-mentioned treatment diabetes containing metformin, its weight the best is:: metformin 500 parts, the Rhizoma Pinelliae 2000 parts, 3000 parts, Rhizoma Zingiberis Recens, Fructus Aurantii 3000 parts, Pericarpium Citri Reticulatae 2000 parts, Rhizoma Coptidis 2000 parts.
In above composition of the present invention, the weight of each taste Chinese medicine calculates, if in grams, as made preparation, then because varying in size of preparation can be made into 100-1000 agent with crude drug.Described 100-1000 agent refers to the dosage form of unit dose, as tablet 100-1000 sheet, and capsule 100-1000 grain, granule l00-1000g, oral liquid l00-l000ml, unguentum l00-l000g, pill 100-1000 ball etc.
More than composition is by weight as proportioning, can increase according to corresponding proportion when producing or reduce, as large-scale production can in units of kg, or with t (ton) for unit; Preparation also can in units of g on a small scale.Weight can increase or reduce, but the constant rate of raw medicinal herbs weight proportion between each composition.
The ratio of above weight proportion is through that science screening obtains, and for especial patient, as serious symptom or mild, fat or modest patient, can the proportioning of amount of corresponding adjustment composition, and increase or reduce being no more than 100%, drug effect is substantially constant.
Chinese medicine composition of the present invention, can add the acceptable adjuvant of some medicines separately or as required, galenic pharmacy routine techniques can be adopted to prepare this pharmaceutical preparation, as mixed by acceptable to pharmaceutically active substance and medicine adjuvant.Can make any pharmaceutically useful peroral dosage form when making pharmaceutical preparation, these dosage forms are selected from: granule, tablet, capsule, oral liquid, suck agent, pill, powder, preferably granule.
The preparation method of the pharmaceutical composition of the above-mentioned treatment diabetes containing metformin, comprises following steps:
A. the Rhizoma Pinelliae, Rhizoma Zingiberis Recens, Fructus Aurantii, Pericarpium Citri Reticulatae, Rhizoma Coptidis are decocted with water 2 times, add 6 ~ 8 times of water gagings the 1st time, decoct 1 ~ 2 hour, second time adds 4 ~ 6 times of water gagings, decocts 0.5 ~ 1.5 hour, merges decoction liquor, for subsequent use;
B. by decoction liquor 55 ~ 65 DEG C, be condensed into the clear paste that relative density is 1.08 ~ 1.12 under-0.04 ~-0.08Mpa condition, adding ethanol to alcohol content is 75%, places 12 hours, filters, filtrate is concentrated into the clear paste that relative density is 1.15 ~ 1.20, and spraying dry obtains dry medicated powder;
C. metformin and dry medicated powder are mixed, granulate, obtain the active substance of Chinese medicine composition of the present invention;
D. this active substance separately or mix with medicine acceptable adjuvant, obtained according to galenic pharmacy conventional method.
In the preparation method of the pharmaceutical composition of the above-mentioned treatment diabetes containing metformin, add 7 times of water gagings the 1st time, decoct 1.5 hours in institute portion step a, second time adds 5 times of water gagings, decocts 1 hour; In described step b, thickening temperature is 60 DEG C, concentrated pressure is-0.06Mpa.
Preferably, state the preparation method of the pharmaceutical composition of the treatment diabetes containing metformin, detailed step is as follows:
A. the Rhizoma Pinelliae, Rhizoma Zingiberis Recens, Fructus Aurantii, Pericarpium Citri Reticulatae, Rhizoma Coptidis are decocted with water 2 times, add 7 times of water gagings the 1st time, decoct 1.5 hours, second time adds 5 times of water gagings, decocts 1 hour, merges decoction liquor, for subsequent use;
B. by decoction liquor 60 DEG C, be condensed into the clear paste that relative density is 1.08 ~ 1.12 under-0.06Mpa condition, adding ethanol to alcohol content is 75%, places 12 hours, and filter, filtrate is concentrated into the clear paste that relative density is 1.15 ~ 1.20, and spraying dry obtains dry medicated powder;
C. metformin and dry medicated powder are mixed, granulate, obtain the active substance of Chinese medicine composition of the present invention;
D. this active substance separately or mix with medicine acceptable adjuvant, obtained according to galenic pharmacy conventional method.
The acceptable adjuvant of described medicine is selected from: starch, magnesium stearate, mannitol, sorbitol, sorbic acid or potassium salt, sodium pyrosulfite, sodium sulfite, sodium thiosulfate, cysteine hydrochloride, TGA, methionine, vitamin A, vitamin C, tie up main plain E, vitamin D, azone, EDETATE SODIUM, Ethylenediaminetetraacetic Acid Calcium Salt, the alkali-metal carbonate of monovalence, acetate, phosphate or its aqueous solution, hydrochloric acid, acetic acid, sulphuric acid, phosphoric acid, aminoacid, sodium chloride, potassium chloride, sodium lactate, xylitol, dextran, glycine, lactose, mannitol, silicon derivative, cellulose and its derivates, alginate, gelatin, polyvinylpyrrolidone, glycerol, propylene glycol, ethanol, polysorbate60 ~ 80, department class ~ 80, Cera Flava, lanoline, liquid paraffin, hexadecanol, gallate ester, fine jade, triethanolamine, basic amino acid, carbamide, allantoin, calcium carbonate, calcium bicarbonate, surfactant, Polyethylene Glycol, cyclodextrin, β ~ cyclodextrin, phospholipid material, Kaolin, Pulvis Talci, calcium stearate etc.
The pharmaceutical composition that the present invention treats diabetes is applicable to alone diet and exercise therapy can not obtain good control and the Body Mass Index BMI type 2 diabetes mellitus patient that is greater than 35.This product can medication separately, also can share with sulphanylureas or insulin, be particularly suitable for insulin resistant, and insulin or C peptide secretion test, higher than the patient of normal value, also can be share with antioxidant.
The present invention treats the pharmaceutical composition usage and dosage of diabetes:
Oral: cumulative dosage from low dose.Usual initial dose be one time 1 bag, 2 times on the one; Take with meal.
The pharmaceutical composition that the present invention treats diabetes to be forbidden in type 2 diabetes mellitus with ketoacidosis, hepatic and kidney function obstacle, heart failure, acute myocardial infarction, severe infections and wound, capital operation, clinically has hypotension and anaerobic condition, is previously had lactic acidosis history person, and forbids this product allergy sufferers.
Beneficial effect of the present invention is: Chinese medicine combines with metformin by the present invention, to avoid the common gastrointestinal side effect of metformin, and improves the therapeutic effect to diabetes.Clinical test results shows: oral the present invention containing the patient of combination with metformin thing, preliminary judgement in the blood glucose fluctuation time, improve carbohydrate tolerance, improve in insulin and the release of C peptide and be better than simple application base metformin person.In addition, the metformin pharmaceutical composition that contains of the present invention is improving in metformin medicine gastrointestinal side effect than simple application metformin person's Be very effective (P < 0.05).Illustrate and of the present inventionly truly have curative effect containing metformin pharmaceutical composition improving in insulin resistant, protection islet cell function, and there is the little advantage of side effect.
Accompanying drawing explanation
Accompanying drawing 1 is C peptide release profiles after two groups of patient treatments in clinical trial data of the present invention.
Detailed description of the invention
Below in conjunction with specific embodiment, the present invention is further described, so that those skilled in the art more understands the present invention, but does not therefore limit the present invention.
Embodiment 1
Treat a pharmaceutical composition for diabetes, be made up of the crude drug of following weight:
Metformin 500g, Rhizoma Pinelliae 2000g, Rhizoma Zingiberis Recens 3000g, Fructus Aurantii 3000g, Pericarpium Citri Reticulatae 2000g, Rhizoma Coptidis 2000g.
The preparation method of the pharmaceutical composition of these treatment diabetes:
A. the Rhizoma Pinelliae, Rhizoma Zingiberis Recens, Fructus Aurantii, Pericarpium Citri Reticulatae, Rhizoma Coptidis are decocted with water 2 times, add 7 water gagings the 1st time, decoct 1.5 hours, second time adds 5 times of water gagings, decocts 1 hour, merges decoction liquor, for subsequent use;
B. by decoction liquor 60 DEG C, be condensed into the clear paste that relative density is 1.08 ~ 1.12 under-0.06Mpa condition, adding ethanol to alcohol content is 75%, places 12 hours, and filter, filtrate is concentrated into the clear paste that relative density is 1.15 ~ 1.20, and spraying dry obtains dry medicated powder;
C. metformin and dry medicated powder are mixed, granulate, obtain the active substance of Chinese medicine composition of the present invention;
D. this active substance adds xylitol, mannitol and β ~ cyclodextrin, and binding agent makes granule in right amount.
Prepare 1000 bags altogether, every bag heavy 5g.
Embodiment 2
Treat a pharmaceutical composition for diabetes, be made up of the crude drug of following weight:
Metformin 400g, Rhizoma Pinelliae 2200g, Rhizoma Zingiberis Recens 2800g, Fructus Aurantii 3200g, Pericarpium Citri Reticulatae 1800g, Rhizoma Coptidis 1800g.
The preparation method of the pharmaceutical composition of these treatment diabetes:
A. the Rhizoma Pinelliae, Rhizoma Zingiberis Recens, Fructus Aurantii, Pericarpium Citri Reticulatae, Rhizoma Coptidis are decocted with water 2 times, add 8 water gagings the 1st time, decoct 2 hours, second time adds 6 times of water gagings, decocts 1.5 hours, merges decoction liquor, for subsequent use;
B. by decoction liquor 55 DEG C, be condensed into the clear paste that relative density is 1.08 ~ 1.12 under-0.08Mpa condition, adding ethanol to alcohol content is 75%, places 12 hours, and filter, filtrate is concentrated into the clear paste that relative density is 1.15 ~ 1.20, and spraying dry obtains dry medicated powder;
C. metformin and dry medicated powder are mixed, granulate, obtain the active substance of Chinese medicine composition of the present invention;
D. this active substance adds xylitol, mannitol and β ~ cyclodextrin, binding agent makes granule in right amount.
Prepare 1000 bags altogether, every bag heavy 5g.
Embodiment 3
Treat a pharmaceutical composition for diabetes, be made up of the crude drug of following weight:
Metformin 600g, Rhizoma Pinelliae 1800g, Rhizoma Zingiberis Recens 3200g, Fructus Aurantii 2800g, Pericarpium Citri Reticulatae 2200g, Rhizoma Coptidis 2200g.
The preparation method of the pharmaceutical composition of these treatment diabetes:
A. the Rhizoma Pinelliae, Rhizoma Zingiberis Recens, Fructus Aurantii, Pericarpium Citri Reticulatae, Rhizoma Coptidis are decocted with water 2 times, add 6 water gagings the 1st time, decoct 1 hour, second time adds 4 times of water gagings, decocts 0.5 hour, merges decoction liquor, for subsequent use;
B. by decoction liquor 65 DEG C, be condensed into the clear paste that relative density is 1.08 ~ 1.12 under-0.04Mpa condition, adding ethanol to alcohol content is 75%, places 12 hours, and filter, filtrate is concentrated into the clear paste that relative density is 1.15 ~ 1.20, and spraying dry obtains dry medicated powder;
C. metformin and dry medicated powder are mixed, granulate, obtain the active substance of Chinese medicine composition of the present invention;
D. this active substance adds xylitol, mannitol and β ~ cyclodextrin, and binding agent makes granule in right amount.
Prepare 1000 bags altogether, every bag heavy 5g.
Embodiment 4
Treat a pharmaceutical composition for diabetes, be made up of the crude drug of following weight:
Metformin 250g, Rhizoma Pinelliae 2500g, Rhizoma Zingiberis Recens 2500g, Fructus Aurantii 3500g, Pericarpium Citri Reticulatae 1500g, Rhizoma Coptidis 2500g.
The preparation method of the pharmaceutical composition of these treatment diabetes:
A. the Rhizoma Pinelliae, Rhizoma Zingiberis Recens, Fructus Aurantii, Pericarpium Citri Reticulatae, Rhizoma Coptidis are decocted with water 2 times, add 7 water gagings the 1st time, decoct 1.5 hours, second time adds 5 times of water gagings, decocts 1 hour, merges decoction liquor, for subsequent use;
B. by decoction liquor 60 DEG C, be condensed into the clear paste that relative density is 1.08 ~ 1.12 under-0.06Mpa condition, adding ethanol to alcohol content is 75%, places 12 hours, and filter, filtrate is concentrated into the clear paste that relative density is 1.15 ~ 1.20, and spraying dry obtains dry medicated powder;
C. metformin and dry medicated powder are mixed, granulate, obtain the active substance of Chinese medicine composition of the present invention;
D. this active substance adds xylitol, mannitol and β ~ cyclodextrin, and binding agent makes granule in right amount.
Prepare 1000 bags altogether, every bag heavy 5g.
Embodiment 5
Treat a pharmaceutical composition for diabetes, be made up of the crude drug of following weight:
Metformin 750g, Rhizoma Pinelliae 1500g, Rhizoma Zingiberis Recens 3500g, Fructus Aurantii 2500g, Pericarpium Citri Reticulatae 2500g, Rhizoma Coptidis 1500g.
The preparation method of the pharmaceutical composition of these treatment diabetes:
A. the Rhizoma Pinelliae, Rhizoma Zingiberis Recens, Fructus Aurantii, Pericarpium Citri Reticulatae, Rhizoma Coptidis are decocted with water 2 times, add 7 water gagings the 1st time, decoct 1.5 hours, second time adds 5 times of water gagings, decocts 1 hour, merges decoction liquor, for subsequent use;
B. by decoction liquor 60 DEG C, be condensed into the clear paste that relative density is 1.08 ~ 1.12 under-0.06Mpa condition, adding ethanol to alcohol content is 75%, places 12 hours, and filter, filtrate is concentrated into the clear paste that relative density is 1.15 ~ 1.20, and spraying dry obtains dry medicated powder;
C. metformin and dry medicated powder are mixed, granulate, obtain the active substance of Chinese medicine composition of the present invention;
D. this active substance adds xylitol, mannitol and β ~ cyclodextrin, and binding agent makes granule in right amount.
Prepare 1000 bags altogether, every bag heavy 5g.
Carried out clinical trial to the pharmaceutical composition containing metformin prepared by embodiment 1, result is as follows:
1. data and method
Object of study
This research of 60 routine type 2 diabetes mellitus patient selection, all meets WHO diagnostic criteria in 1999, and meets following condition: 1. make a definite diagnosis for the first time or make a definite diagnosis and be no more than half a year and do not treat and fasting glucose >=11.1mmol/L; 2. without serious acute and chronic complication.
Therapeutic Method
Qualified 60 routine patients are divided into two groups at random.1. matched group: use in conjunction metformin on the basis of patient being carried out to the education of diabetes health knowledge and Diet Therapy, each 0.5g of metformin, every day 2 times.2. treatment group: use in conjunction contains the pharmaceutical composition of metformin on the basis of patient being carried out to the education of diabetes health knowledge and Diet Therapy, each 1 bag, every day 2 times.Two groups of patients no significant difference in sex, age, Body Mass Index, glycolated hemoglobin, the distribution of fasting glucose, roughly disease time.
Observation index
1. safety indexes: as routine blood test, stool routine examination, liver function, kidney function test, electrocardiogram etc.; 2. health giving quality index: Body Mass Index, blood glucose fluctuation time before and after treatment; 3. lab testing: the experiment of the glycolated hemoglobin after treatment, carbohydrate tolerance, insulin and C peptide release test.3. gastrointestinal side effect index: as Nausea and vomiting, abdominal distention, stomachache etc.
Statistical method
SPSS17.0 is adopted to carry out the statistical analysis of data.Measurement data adopts t inspection (representing by mean ± standard deviation); Group data adopts χ
2inspection, using P≤0.05 as there being statistical significance, using P≤0.01 as there being height statistical significance.
2. result
Clinical efficacy result
Difference (P > 0.05) that before and after Body Mass Index treatment, there are no significant.Blood glucose fluctuation chronotherapy is obviously less than matched group (P < 0.05), in table 1.
Table 1 liang group patient blood glucose reaching standard time
relatively (X ± s)
Laboratory examination results after treatment
Glycolated hemoglobin treatment group lower than matched group, result there was no significant difference (P > 0.05).Carbohydrate tolerance test: 3h two groups of there was no significant differences (P > 0.05) after the meal, remaining chronotherapy group reduction (P < 0.05) more obvious than matched group.C peptide release test: treatment group comparatively matched group discharges showed increased (P < 0.05), 2h, 3h there was no significant difference (P > 0.05) after the meal on an empty stomach and after the meal 1h.Insulin release test: 1h treatment group is matched group insulin releasing showed increased (P < 0.01) comparatively; The remaining time two groups of there was no significant differences (P > 0.05).Analyze insulin releasing curve, treatment group secretion peak is more obvious and obvious in the falling of 2h amount of insulin secretion, shows that islet function recovers to be better than matched group.In Table 2-5 and accompanying drawing 1.
HbA1c (%) results contrast (X ± s) before and after table 2 liang group patient treatment
Carbohydrate tolerance test before and after table 3 liang group patient treatment
result (X ± s)
C peptide release test before and after table 4 liang group patient treatment
result (X ± s)
Insulin release test (Uu/ before and after table 5 liang group patient treatment
ml) result (X ± s)
Safety observations result
In this test, whole experimenter carries out safety indexes detection respectively before and after treatment, and result does not find obvious abnormal change, the pharmaceutical composition use safety containing metformin of the present invention is described, without obvious adverse reaction.
Gastrointestinal side effect result
Gastrointestinal side effect matched group is starkly lower than treatment group (P < 0.05).In table 6.
A table 6 liang group adverse reactions of patients number compares
3 conclusions
Oral the present invention containing the patient of combination with metformin thing, preliminary judgement in the blood glucose fluctuation time, improve carbohydrate tolerance, improve in insulin and the release of C peptide and be better than simple application base metformin person.In addition, the metformin pharmaceutical composition that contains of the present invention is improving in metformin medicine gastrointestinal side effect than simple application metformin person's Be very effective (P < 0.05).Illustrate and of the present inventionly truly have curative effect containing metformin pharmaceutical composition improving in insulin resistant, protection islet cell function, and there is the little advantage of side effect.
Claims (4)
1. a pharmaceutical composition for the treatment diabetes containing metformin, be made up of the crude drug of following weight:
Metformin 250-750 part, Rhizoma Pinelliae 1500-2500 part, Rhizoma Zingiberis Recens 2500-3500 part, Fructus Aurantii 2500-3500 part, Pericarpium Citri Reticulatae 1500-2500 part, Rhizoma Coptidis 1500-2500 part.
2. the pharmaceutical composition of the treatment diabetes containing metformin as claimed in claim 1, it is characterized in that, be made up of the crude drug of following weight: metformin 400-600 part, Rhizoma Pinelliae 1800-2200 part, Rhizoma Zingiberis Recens 2800-3200 part, Fructus Aurantii 2800-3200 part, Pericarpium Citri Reticulatae 1800-2200 part, Rhizoma Coptidis 1800-2200 part.
3. the pharmaceutical composition of the treatment diabetes containing metformin as claimed in claim 2, it is characterized in that, be made up of the crude drug of following weight: metformin 500 parts, the Rhizoma Pinelliae 2000 parts, 3000 parts, Rhizoma Zingiberis Recens, Fructus Aurantii 3000 parts, Pericarpium Citri Reticulatae 2000 parts, Rhizoma Coptidis 2000 parts.
4. the pharmaceutical composition of the treatment diabetes containing metformin as described in claim 1 or 2 or 3, it is characterized in that, its dosage form is granule.
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| CN101011561A (en) * | 2006-11-01 | 2007-08-08 | 黄达驹 | Modern traditional Chinese medicine oral preparation huanglianwendan decoction and production method thereof |
| CN101810849A (en) * | 2010-04-20 | 2010-08-25 | 南京凯瑞尔纳米生物技术有限公司 | Medicament for curing diabetes |
| CN102908599A (en) * | 2012-06-19 | 2013-02-06 | 谢文龙 | Medicine capable of reducing blood sugar, blood fat and blood pressure |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101011561A (en) * | 2006-11-01 | 2007-08-08 | 黄达驹 | Modern traditional Chinese medicine oral preparation huanglianwendan decoction and production method thereof |
| CN101810849A (en) * | 2010-04-20 | 2010-08-25 | 南京凯瑞尔纳米生物技术有限公司 | Medicament for curing diabetes |
| CN102908599A (en) * | 2012-06-19 | 2013-02-06 | 谢文龙 | Medicine capable of reducing blood sugar, blood fat and blood pressure |
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Effective date of registration: 20160322 Address after: 550018 Guizhou Province, Guiyang city Wudang District High Road No. 25 Applicant after: Xi'an Tian An Pharmaceutical Shares Co., Ltd. Address before: 250023 dormitory 7-4-201, Ji'nan boiler factory, 2 Huanggang Road, Tianqiao District, Shandong, Ji'nan Applicant before: Meng Xiaofei |
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