CN1224383C - Blood sugar reducing compound - Google Patents
Blood sugar reducing compound Download PDFInfo
- Publication number
- CN1224383C CN1224383C CN 99122378 CN99122378A CN1224383C CN 1224383 C CN1224383 C CN 1224383C CN 99122378 CN99122378 CN 99122378 CN 99122378 A CN99122378 A CN 99122378A CN 1224383 C CN1224383 C CN 1224383C
- Authority
- CN
- China
- Prior art keywords
- blood sugar
- group
- metformin
- dosage
- rhubarb
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The present invention discloses a new compound for reducing blood sugar, which contains diphenyl ethylene ingredients extracted and separated from natural medicine--polygonaceae rhubarb wave leaved plants, such as rhubarb obtained from Tibet, rhubarb obtained from Hetao, etc. The ingredients have the function of blood sugar activity reduction, so the ingredients provide a new medicament for treating diabetic patients in clinical application.
Description
The invention belongs to the new purposes of plant compound.What specifically the present invention relates to is that the plant compound that separates the stilbene constituents that obtains from Polygonaceae Rheum plant is used for hypoglycemic purposes clinically.
Diabetes are clinical common endocrine metabolism diseases.In recent years, along with the development of society, the change of people's dietary structure, this disease sickness rate worldwide raises rapidly.According to statistics, global patient's sum can reach about 100,012,000.As seen diabetes have become the another serious disease of the serious harm human health after cardiovascular, tumor disease.Diabetic duration is long, and recuperating under medical treatment improperly often has complication to take place, and as chronic vascular complications (comprising cerebrovascular disorders, ischemic heart desease), diabetic nephropathy etc., the mortality rate due to the complication increases year by year.Therefore, the control to diabetes and complication thereof is global research hot subject.
Blood sugar lowering medicine of using clinically such as sulfonylurea, its effect of biguanides at present is slow, and certain toxic and side effects is arranged.Though effective in cure, the no obvious toxic-side effects of Chinese medicine compound, it is of less types that patent medicine is sold.And by the monomeric compound in the natural drug source hypoglycemic drug as clinical practice, not seeing as yet so far has open report.
First purpose of the present invention provides the novel blood sugar reducing component of a class.
Another object of the present invention provides a kind of pharmaceutical composition that has good action for blood sugar lowering.
Purpose according to the present invention, the novel blood sugar lowing composition that is provided is a diphenylethylene compounds, this chemical compound mainly is from plant, can be from natural drug such as Polygonaceae Rheum ripple leaf group plant Radix Rhei emodi, Rheum hotaoense C. Y. Cheng et C. T. Kao etc. extraction separation.Extraction separation in the multiple rheum rhabarbarum such as Rheum hotaoense C. Y. Cheng et C. T. Kao.Such plant China distribute wide, reserves are big, and habit is suitable for a large amount of cultivating and growings, and above-mentioned blood sugar lowering constituents content in such plant is rich, easy, the easy row of the means of obtaining its effective monomer component.
This chemical compound has following structure:
R
1=H, OH, OCH
3, or the O-glucosyl group
R
2=H, or glucosyl group
R
3=H, or glucosyl group
The invention still further relates to a kind of hypoglycemic pharmaceutical composition, it comprises the stilbene analog derivative with said structure and pharmaceutical excipient or carrier as active component.According to the present invention, the stilbene analog derivative can be made into the preparation of intestinal or non-intestinal combination medicine by known method.As tablet, capsule, granule, injection etc.
Useful effect: chemical compound of the present invention has potential applicability in clinical practice, and it can blood sugar lowering and do not have obvious toxic and side effects.Simultaneously, this compounds might improve the complication state of an illness of diabetes again, then more helps the prospect of clinical practice.
The following examples will describe the present invention in detail.
Embodiment 1: the extraction of stilbene analog derivative and structure are identified:
Get the rheum rhabarbarum decoction pieces, add 8 times of amount 95% alcohol reflux three times, each 2 hours.Merge extractive liquid,, concentrating under reduced pressure.Ethanol extract disperses with kieselguhr, drying.With chloroform flush away liposoluble constituent, continue with eluent ethyl acetate, obtain the ethyl acetate soluble fraction.This part row silica gel column chromatography (60-100 order) with eluent ethyl acetate, continues with ethyl acetate/methanol (4: 1～2) eluting, promptly gets crude product, and crude product through water/acetone recrystallization promptly.
Identify:
Compd E is white amorphous powder (rare acetone), mp.138-140 ℃.Be bluish violet fluorescence under the ultraviolet light, the Molisch reacting positive.
1HNMR (the δ ppm:7.14 (1H, d, J=8.5Hz, H-5 ') of acetone-d6), 7.06 (1H, d, J=2.1Hz, H-2 '), 6.97 (1H, d, J=16.3Hz, H-β), (6.94 1H, dd, J=2.1/8.5Hz, H-6 '), 6.89 (1H, d, H=16.3Hz, H-α), 6.52 (2H, d, J=2.1Hz, H-2,6), 6.24 (1H, t, J=2.1Hz, H-4), 4.79 (1H, d, J=7.5Hz, the end group isomery-H), 3.9-3.3 (sugar-H);
13CNMR (the δ ppm of acetone-d6): aglucon 159.5 (C-3,5), 148.5 (C-4 '), 146.0 (C-3 '), 140.3 (C-1), 134.2 (C-1 '), 128.6 (C-α, β), (119.3 C-5 '), 118.9 (C-6 '), 114.2 (C-2 '), (105.6 C-2,6), 104.0 (C-4), glucosyl group 102.9 (C-1 "), 77.8 (C-3 "), 77.1 (C-5 "); 74.4 (C-2 "), 70.9 (C-4 "), 62.2 (C-6 ").
1HNMR and
13(2 Yoshiki Kashiwada et al.Chem.Pharm.Bull.988 such as CNMR data and Yoshiki Kashiwada, 36 (4): 1545) Bao Dao data consistent, compd E be accredited as 3,3 ' 4 ' 5-tetrahydroxystilbene-4 '-the O-glucoside (Piceatannol-4 '-O-β-D-glucopyranoside).
Compd B
50Be white, needle-shaped crystals (rare acetone), mp.222-224 ℃.Be bluish violet fluorescence Molisch reacting positive under the ultraviolet light.
1HNMR (the δ ppm:7.46 (1H, d, J=2Hz, H-2 ') of acetone-d6), 7.10 (1H, dd, J=2/8.3Hz, H-6 '), 6.96 (1H, d, J=16.3Hz, H-β), (6.87 1H, d, H=16.3Hz, H-α), 6.82 (1H, d, J=8.2Hz, H-5 '), 6.50 (2H, d, J=2.1Hz, H-2,6), 6.22 (1H, t, J=2.1Hz, H-4), 4.82 (1H, d, J=7.5Hz, the end group isomery-H), 4.0-3.3 (sugar-H);
13CNMR (the δ ppm of acetone-d6): aglucon 159.5 (C-3,5), 148.1 (C-3 '), (146.5 C-4 '), 140.5 (C-1), 130.5 (C-1 '), (128.7 C-β), (127.5 C-α), 123.3 (C-6 '), 116.8 (C2 '), (116.5 C-5 '), (105.4 C-2,6), 104.1 (C-4); Glucosyl group 102.6 (C-1 "), 78.0 (C-3 "), 77.2 (C-"), 74.4 (C-2 "), 71.1 (C-4 "), 62.3 (C-6 ").
1HNMR and
13(2 Yoshiki Kashiwada etal.Chem.Pharm.Bull.1984,32 (9): 3501) Bao Dao data consistent, compd B such as CNMR data and Yoshiki Kashiwada
50Be accredited as 3,3 ' 4 ' 5-tetrahydroxystilbenes-3 '-O-glucoside (Piceatannol-3 '-O-β-D-glucopyranoside).
Compound F 17-hydroxy-corticosterone is white, needle-shaped crystals (dilute methanol), mp.228-230 ℃.Be bluish violet fluorescence under the ultraviolet light, the Molisch reacting positive.
1HNMR (acetone-d6) δ H-β), 6.96 (1H, dd, J=2/8.3Hz, H-6 '), (6.90 1H, d, J=7.9Hz, H-5 '), 6.89 (1H, d, H=16.5Hz, H α), 6.77 (1H, br.s, H-2), 6.66 (1H, br.s, H-2), 6.48 (1H, t, J=1.8Hz, H-4), 4.90 (1H, d, J=7.7Hz, the end group isomery-H), 3.82 (3H, s ,-OCH
3), 4.0-3.3 (sugar-H);
13CNMR (the δ ppm of acetone-d6): aglucon 160.1 (C-5), 159.5 (C-3), 148.4 (C-4 '), (147.5 C-3 '), 140.5 (C-1), 131.5 (C-1 '), (129.5 C-β), 127.2 (C-α), 119.7 (C-6 '), (113.3 C-2 '), (112.5 C-5 '), 108.0 (C-2), 106.5 (C-6), 103.8 (C-4), 56.2 (OCH3); Glucosyl group 1101.9 (C-1 "), 77.7 (C-3 ", 5 "), 74.4 (C-2 "), 71.1 (C-4 "), 62.5 (C-6 ").
1HNMR and
13(2Yoshiki Kashiwada et al.Chem.Pharm.Bull.1984,32 (9): 3501) Bao Dao data consistent, compound F 17-hydroxy-corticosterone are accredited as ponticin (rhaponticin) for CNMR data and Yoshiki Kashiwada etc.
Embodiment 2 biological assessments
One, mainly observes the therapeutical effect of above-claimed cpd in the biotic experiment below, make positive control drug, its drug effect is estimated with the two croaks (to call metformin in the following text) of dimethyl to the hyperglycemia mice of alloxan modeling.
1 materials and methods
1.1 material
1.1.1 medicine and animal
Metformin, lot number 96064, Chinese-foreign joint Zhengan County pharmacy (Tianjin) company limited production.
Kunming mouse, body weight 22-24g, male, animal housing of Beijing Drug Control Inst. provides, the quality certification number: No. the 037th, the accurate word (1994) of the moving pipe in capital
1.1.2 instrument and reagent
The UV-265 spectrophotometer, day island proper Tianjin company produces; Alloxan, lot number 42011-3E, Hong Kong produces; Glucoseoxidase (GOD), the packing of Beijing hundred safe Biochem Technology, INC.; Peroxidase (POD), lot number 9712193, the beautiful pearl east wind in Shanghai Bioisystech Co., Ltd produces.
1.2 method
Above-mentioned healthy mice behind the fasting 20hr., with alloxan normal saline solution tail vein injection 80mg/Kg body weight, makes into hyperglycemia model.
With determination of glucose oxidase mice fasting blood sugar, select blood glucose value the mice of 7-25mmol/L be divided at random six groups (between group mean blood glucose differ＜0.6mmol/L), each is organized dosage and sees Table.Every day, gastric infusion continuous 12 days, was surveyed the fasting blood sugar of respectively organizing mice in 30 minutes, with comparison between the blood glucose difference is organized before and after each group mouse blood sugar mean and the administration after the last administration.
2. result
Blood glucose value difference value after the blood glucose value administration before the group animals administer dosed administration
Number mg/kg mmol/L mmol/L mmol/L
Blank 11 ordinary water 20ml/Kg 7.08 ± 1.17 7.02 ± 1.31 0.22 ± 1.38
Model contrasts 12 ordinary water 20ml/Kg 22.70 ± 3.91 22.77 ± 2.92
Δ Δ Δ-0.76 ± 3.07
Metformin group 13 500 22.63 ± 4.85 17.35 ± 5.29
※5.85 ± 6.46
※
E is big by 13 1,000 22.47 ± and 3.52 16.41 ± 5.44
※6.41 ± 7.54
※
Among the E 13 500 22.58 ± 3.15 16.26 ± 5.27
※ ※6.93 ± 6.27
E is little by 13 250 22.51 ± and 4.60 20.93 ± 5.68 1.58 ± 6.73
Glyburide 13 6.6 22.25 ± 2.46 21.06.0 ± 4.29 0.06 ± 7.03
Annotate: compare Δ Δ Δ p＜0.01 with the blank group; Compare ※ p＜0.05, ※ ※ p＜0.01 with model group;
Negative value is represented blood sugar increasing.
As seen from the above table, the positive control drug metformin demonstrates good blood sugar reducing function, and the illustrative experiment method is reliable.The big or middle dosage of compd E all can obviously reduce the blood glucose value of high sugared model mice, and (500mg/Kg) its effect is similar or slightly be better than the metformin group when equal dosage, illustrates that this medicine blood sugar reducing function is obvious.
Two, above-claimed cpd is to the influence of normal mouse carbohydrate tolerance
2. materials and methods
2.1 material
2.1.1 medicine and animal
Metformin, lot number 96064.Sino-foreign joint venture Zhengan County's pharmacy (Tianjin) company limited production.
Animal: Kunming mouse, body weight 20-23g, male and female are usefulness all, and the quality certification numbers 921103 is provided by Military Medical Science Institute's Experimental Animal Center.
2.1.2 instrument and reagent
Semi-automatic production analyser, IMPACT 400 types, U.S. GILFORD company produces.
Adopt the determination of glucose oxidase blood glucose value, provide the blood glucose test kit by Beijing Zhongsheng Biological Engineering High Technology Company.
2.2 method
Above-mentioned healthy mice is according to body weight size random packet.Each is organized dosage and sees the following form.Mice gastric infusion every day was taken 12 days continuously.Before the carbohydrate tolerance test, each treated animal fasting blood sugar is measured in animal fasting 12 hours, administration then, 1 hour pneumoretroperitoneum injectable dextrose monohydrate 2g/kg.Measure after the administration 0,0.5,1.0 and 2.0 hours blood glucose value at once, and calculate area under the blood glucose curve, between organizing relatively.
2. result
E is to the influence of normal mouse carbohydrate tolerance
| Group | Number of animals | Dosage (mg/kg) | Blood glucose value (mmol/L) | Area AUC under the blood glucose curve | ||||
| Before the administration | After the administration 0 ' | 30’ | 60’ | 120’ | ||||
| Among the blank metformin E | 7 7 7 | Water 500 500 | 2.7±1.0 2.4±0.9 1.8±0.8 | 5.2±1.1 4.0±0.9 4.0±0.6 * | 13.5±3.0 9.6±2.0 * 6.4±1.0 # | 7.2±1.1 4.1±2.0 # 3.7±0.6 # | 5.0±0.7 0.6±0.6 # 0.8±1.1 # | 953.2±135.4 552.6±100.3 #40.6±69.6 #@ |
| E is little for the blank metformin | 5 5 5 | Water 250 250 | 4.3±1.1 4.1±0.6 4.9±0.5 | 6.7±1.5 4.5±1.0 5.2±0.9 | 17.4±2.2 13.2±2.6 14.6±2.5 | 11.1±3.3 7.2±1.6 9.4±1.8 | 6.8±1.0 4.2±1.1 5.5±0.8 | 1327.6±227.6 917.0±143.5 1076.4±135.7 |
Annotate: compare * P＜0.01 #P＜0.001 with the blank group, compare @P＜0.05 with metformin
As seen from the above table, normal mouse gavages E 500mg/kg or metformin 500mg/kg, continuous 12 days.Behind glucose load in 30-120 minute, blood glucose value is starkly lower than the blank group, and (P＜0.005-0.001): area is also significantly less than blank group (P＜0.001) under the blood glucose curve.Illustrate that metformin and E all have good blood sugar reducing function.With equal drug dose (500mg/kg), area is than metformin smaller (P＜0.05) under the blood glucose curve of E.The hypoglycemic effect that E is described slightly is better than metformin.When dosage is reduced to 250mg/kg, also show certain blood sugar reducing function, but its effect weakens.
3 toxicity relatively
Drug toxicity
Mice, the Kunming kind, body weight 19-21g Military Medical Science Institute Animal Experimental Study central supply,
The quality certification numbers 921103
1. acute toxicity test
Lumbar injection
LD
50♀ 1242.5mg/kg MTD 641.3mg/kg
LD
50♂ 1139.2mg/kg MTD 641.3mg/kg
Oral
LD
50♀ 9007.5mg/kg MTD 5625mg/kg
LD
50♂ 8578.9mg/kg MTD 4219mg/kg
2. cumulative toxicity test
Mouse peritoneal is injected 1/10 LD
50Dosage (123.5mg/kg) once a day, totally 30 days
Mouse peritoneal is injected 1/2 LD
10Dosage (336.5mg/kg) once a day, totally 30 days
The above-mentioned two groups of mices of result (10 every group) all do not have dead, show no obvious depot action.But its influence for mice body weight and some index is as follows:
E is to the influence of body weight
Before the medicine behind (g) medicine 30 days (g)
Normal control 20.0 ± 0.4 32.0 ± 3.8
1/2 LD
10Dosage 20.0 ± 0.4 30.4 ± 1.6
1/10 LD
50Dosage 20.2 ± 0.6 29.6 ± 1.3
E is to the influence of some serum biochemistry index
GOT GPT Glu
Normal control 3004.8 ± 884.7 679.3 ± 114.2 6.96 ± 0.80
1/2 LD
10Dosage 3397.3 ± 690.8 994.5 ± 324.5 7.48 ± 0.48
1/10 LD
50Dosage 3097.3 ± 545.8 735.5 ± 23.6 6.86 ± 0.67
For some index such as body weight, GOT, GPT.1/2 LD
10Dosage (336.5mg/kg) connects was relatively had the trend that increases with the normal control group after 30 days, but did not have the statistics difference.1/10LD
50Dosage connects gives 30 days, and only body weight is low slightly like comparative control person, does not have the statistics difference.
It seems that by above-mentioned mouse test this toxicity of compound is quite low, in general the oral LD of mice
50Dosage should belong to low toxicity or non-toxic type material, and this chemical compound does not also have accumulative effect greater than 5g/kg person.
Metformin LD
50Be 247mg/Kg (ip)
Compd E LD
50About 1100mg/Kg (ip)
Therefore it seems that compd E is low to the toxicity of mice than metformin.
Claims (3)
1. the purposes of the stilbene analog derivative with following structure in the preparation hypoglycemic drug.
R
1=H, OH, OCH
3, or the O-glucosyl group
R
2=H, or glucosyl group
R
3=H, or glucosyl group
2. one kind is used for hypoglycemic medicine composition, and its feature comprises as the stilbene analog derivative in the claim 1 of active ingredient and pharmaceutical excipient or carrier.
3. pharmaceutical composition according to claim 2, it can be tablet, capsule, granule or injection type.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 99122378 CN1224383C (en) | 1999-11-05 | 1999-11-05 | Blood sugar reducing compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 99122378 CN1224383C (en) | 1999-11-05 | 1999-11-05 | Blood sugar reducing compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1294912A CN1294912A (en) | 2001-05-16 |
| CN1224383C true CN1224383C (en) | 2005-10-26 |
Family
ID=5282476
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 99122378 Expired - Fee Related CN1224383C (en) | 1999-11-05 | 1999-11-05 | Blood sugar reducing compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1224383C (en) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7384920B2 (en) * | 2001-07-26 | 2008-06-10 | Institute Of Radiation Medicine, Academy Of Military Medical Sciences, Pla | Use of stilbene compounds in the manufacture of medicament for the prevention and treatment of diabetes or retrovirus-associated diseases |
| CN1308002C (en) * | 2003-11-01 | 2007-04-04 | 胡群 | Compound preparation of notoginseng total saponin and quzaqi aglycone and its preparing method |
| CN1723884A (en) * | 2004-07-21 | 2006-01-25 | 中国人民解放军军事医学科学院放射医学研究所 | Cis-1, the diphenyl ethylene derivatives that 2-replaces are used to prepare the purposes of the medicine of treatment or prevent diabetes |
| CN100421583C (en) * | 2006-01-19 | 2008-10-01 | 拉萨乌孜食品饮料发展有限公司 | Rheumefmodiwdll extract and its application |
| CN100421582C (en) * | 2006-01-19 | 2008-10-01 | 拉萨乌孜食品饮料发展有限公司 | Tibet rhubarb extract and its application |
| JP5224648B2 (en) * | 2006-02-21 | 2013-07-03 | 丸善製薬株式会社 | Anti-dermatitis agent, whitening agent and anti-skin aging agent |
| CN102887925B (en) * | 2011-07-21 | 2015-08-12 | 中国科学院兰州化学物理研究所 | The method of ponticin is extracted from Rheum hotaoense C. Y. Cheng et C. T. Kao |
| CN102512507A (en) * | 2012-01-12 | 2012-06-27 | 西藏金哈达药业有限公司 | Application of rheum australe extract to preparation of medicament for preventing and treating diabetes |
| CN103505468B (en) * | 2012-06-19 | 2016-08-31 | 昆药集团股份有限公司 | Bent letter glycosides improves the application in microcirculation disturbance medicine in preparation |
| CN104147024A (en) * | 2014-08-20 | 2014-11-19 | 安树君 | Novel application of resveratrol derivatives |
| CN104147026A (en) * | 2014-08-20 | 2014-11-19 | 安树君 | New application of resveratrol derivative |
| CN104147023A (en) * | 2014-08-20 | 2014-11-19 | 安树君 | New application of resveratrol derivative |
| CN106038668B8 (en) * | 2016-05-28 | 2024-06-28 | 楚雄彝族自治州彝族医药研究所 | Medicine for controlling blood sugar concentration |
| CN111000854B (en) * | 2019-12-30 | 2023-06-09 | 昆药集团股份有限公司 | Application of Quzhazhigan in preparing products for treating and/or preventing non-alcoholic fatty liver disease |
-
1999
- 1999-11-05 CN CN 99122378 patent/CN1224383C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1294912A (en) | 2001-05-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1237961C (en) | Use of stilbene compounds in preparing medicaments for treating and preventing diabetes or diseases associated with retrovirus | |
| CN1224383C (en) | Blood sugar reducing compound | |
| CN101033245A (en) | Preparation method and application of pedunculoside | |
| CN1806821A (en) | Rhinitis-treating medicine | |
| CN1965873A (en) | Chinese medicinal extract having blood sugar-lowering activity, its preparation process, composition and use | |
| CN1733054A (en) | Dogwood fruit extract and its preparation process | |
| CN1799582A (en) | Blood sugar- and blood pressure-lowering medicine | |
| CN1850167A (en) | Thirsty-relieving blood-sugar-reducing dropping pills and preparing method | |
| CN101322738A (en) | Preparation of red sandalwood extract for treating diabetic and uses thereof | |
| CN103815397B (en) | Downgrade food compositions of blood pressure, blood fat and blood sugar and preparation method thereof | |
| CN102579530A (en) | Preparation method of aralia taibaiensis total saponin having diabetes mellitus resisting effect and medicament | |
| CN102976943A (en) | Alpha-crystal form substance of danshinolic acid A, preparation method, pharmaceutical composition and application | |
| CN106632378A (en) | Compound capable of inhibiting mast cell degranulation and preparation method and application thereof | |
| CN1864740A (en) | A Chinese medicinal composition for clearing heat and expelling toxin and preparation method thereof | |
| CN1927289A (en) | Pharmaceutical composition for treating diabetes and impaired glucose tolerance and its preparation | |
| CN1248698C (en) | Drug for treating coronary heart disease or coronary disease and cardiac insufficiency, and its preparation method | |
| CN100337654C (en) | Composition of Chinese medicine effective ingredients for treating cardiovascular disease | |
| CN1548142A (en) | Medicine for improving sugar tolerance and treating diabetes and its prepn process | |
| CN1575803A (en) | Application method of Aloe vera L. extract in preventing and curing diabetes | |
| CN101032534A (en) | Method of preparing jiubiying total saponins and the application thereof | |
| CN1803155A (en) | Medicine for curing rhinitis | |
| CN1224390C (en) | Pharmaceutical composition comprising pyrroloquinoline quinone for curing and preventing fatty liver | |
| CN102225082A (en) | Medicament for preventing and treating diabetes and complications thereof and preparation method thereof | |
| CN1171594C (en) | Composition containing pearl powder and ascorbic acid | |
| CN101053598A (en) | Medicinal composition for treating cardio-cerebralvascular diseases and diabetes |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C56 | Change in the name or address of the patentee |
Owner name: EMISSION AND RADIATION MEDICAL RESEARCH INSTITUTE Free format text: FORMER NAME: RADIATION MEDICINE INST., MILITARY MEDICINE ACADEMY, P.L.A. |
|
| CP01 | Change in the name or title of a patent holder |
Address after: 100850 No. 27, Taiping Road, Beijing, two Patentee after: Emission and Radiation Medical Research Institute Address before: 100850 No. 27, Taiping Road, Beijing, two Patentee before: Institute of Radiation Medicine of Academy of Military Medical Sciences of Chinese People's Liberation Army |
|
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20051026 Termination date: 20171105 |