CN1112187C - Medicinal composition for treating diabetes - Google Patents
Medicinal composition for treating diabetes Download PDFInfo
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- CN1112187C CN1112187C CN99102823A CN99102823A CN1112187C CN 1112187 C CN1112187 C CN 1112187C CN 99102823 A CN99102823 A CN 99102823A CN 99102823 A CN99102823 A CN 99102823A CN 1112187 C CN1112187 C CN 1112187C
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- 206010012601 diabetes mellitus Diseases 0.000 title claims abstract description 13
- 239000000203 mixture Substances 0.000 title abstract description 10
- 229930182490 saponin Natural products 0.000 claims abstract description 14
- 150000007949 saponins Chemical class 0.000 claims abstract description 13
- 239000000654 additive Substances 0.000 claims abstract description 6
- 239000001397 quillaja saponaria molina bark Substances 0.000 claims abstract description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 82
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 14
- 235000017709 saponins Nutrition 0.000 claims description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 9
- 239000000741 silica gel Substances 0.000 claims description 9
- 229910002027 silica gel Inorganic materials 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 235000019359 magnesium stearate Nutrition 0.000 claims description 7
- 239000000080 wetting agent Substances 0.000 claims description 7
- 239000002775 capsule Substances 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 239000000314 lubricant Substances 0.000 claims description 5
- 239000002552 dosage form Substances 0.000 claims description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N lactose group Chemical group OC1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@@H](O)[C@H](O2)CO)[C@H](O1)CO GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 3
- 239000004375 Dextrin Substances 0.000 claims description 2
- 229920001353 Dextrin Polymers 0.000 claims description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 2
- 229920002472 Starch Polymers 0.000 claims description 2
- 235000019425 dextrin Nutrition 0.000 claims description 2
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical group O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 2
- 239000008101 lactose Substances 0.000 claims description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 2
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 2
- 239000008107 starch Substances 0.000 claims description 2
- 235000019698 starch Nutrition 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 abstract 1
- 230000000996 additive effect Effects 0.000 abstract 1
- 210000004369 blood Anatomy 0.000 description 58
- 239000008280 blood Substances 0.000 description 58
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 41
- 239000008103 glucose Substances 0.000 description 41
- 241000700159 Rattus Species 0.000 description 39
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 24
- 210000002966 serum Anatomy 0.000 description 21
- ICFJFFQQTFMIBG-UHFFFAOYSA-N phenformin Chemical compound NC(=N)NC(=N)NCCC1=CC=CC=C1 ICFJFFQQTFMIBG-UHFFFAOYSA-N 0.000 description 18
- 241000699670 Mus sp. Species 0.000 description 16
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 14
- 238000012360 testing method Methods 0.000 description 14
- 102000004877 Insulin Human genes 0.000 description 12
- 108090001061 Insulin Proteins 0.000 description 12
- 229940125396 insulin Drugs 0.000 description 12
- 230000037396 body weight Effects 0.000 description 11
- 241000699666 Mus <mouse, genus> Species 0.000 description 9
- 239000003651 drinking water Substances 0.000 description 9
- 235000020188 drinking water Nutrition 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 229960004580 glibenclamide Drugs 0.000 description 9
- ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 9
- HIMXGTXNXJYFGB-UHFFFAOYSA-N alloxan Chemical compound O=C1NC(=O)C(=O)C(=O)N1 HIMXGTXNXJYFGB-UHFFFAOYSA-N 0.000 description 8
- 239000012153 distilled water Substances 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 239000013641 positive control Substances 0.000 description 7
- 208000007241 Experimental Diabetes Mellitus Diseases 0.000 description 6
- 230000037406 food intake Effects 0.000 description 6
- 235000012631 food intake Nutrition 0.000 description 6
- 150000002632 lipids Chemical class 0.000 description 6
- 210000004279 orbit Anatomy 0.000 description 6
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 5
- 229930006000 Sucrose Natural products 0.000 description 5
- KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 description 5
- 229960001214 clofibrate Drugs 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 239000005720 sucrose Substances 0.000 description 5
- 208000031226 Hyperlipidaemia Diseases 0.000 description 4
- 235000013305 food Nutrition 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 150000003626 triacylglycerols Chemical class 0.000 description 4
- 235000019786 weight gain Nutrition 0.000 description 4
- JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 230000003203 everyday effect Effects 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 235000021590 normal diet Nutrition 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 229960005371 tolbutamide Drugs 0.000 description 3
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- CRHNHRRTNMVEFW-UHFFFAOYSA-L [Mg++].CCO.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O Chemical compound [Mg++].CCO.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CRHNHRRTNMVEFW-UHFFFAOYSA-L 0.000 description 2
- 238000010241 blood sampling Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- -1 saponin compounds Chemical class 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
- 239000004380 Cholic acid Substances 0.000 description 1
- 239000004366 Glucose oxidase Substances 0.000 description 1
- 108010015776 Glucose oxidase Proteins 0.000 description 1
- 208000005374 Poisoning Diseases 0.000 description 1
- 241000282894 Sus scrofa domesticus Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 235000019416 cholic acid Nutrition 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 229960002471 cholic acid Drugs 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229940116332 glucose oxidase Drugs 0.000 description 1
- 235000019420 glucose oxidase Nutrition 0.000 description 1
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- PMRYVIKBURPHAH-UHFFFAOYSA-N methimazole Chemical compound CN1C=CNC1=S PMRYVIKBURPHAH-UHFFFAOYSA-N 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000007779 soft material Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229960002178 thiamazole Drugs 0.000 description 1
- 230000035922 thirst Effects 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
The present invention relates to a medicinal composition for treating diabetes, which contains 6 kinds of saponin as active ingredients, and/or acceptable additive in pharmacology.
Description
The present invention relates to a kind of pharmaceutical composition for the treatment of diabetes, specifically, this pharmaceutical composition contains 6 kinds of Saponins and makes active component.
Diabetes are to threaten a human big disease always, for a long time, physician in the world feels simply helpless to treating this disease always, expensive injection of insulin can only be postponed this sick process, but be difficult to for most people bear, because never in a single day the obvious results Drug therapy so suffer from diabetes, almost just equals to have suffered from incurable disease.People thirst for finding a kind of treatment diabetes obvious results medicine.The inventor extracts from foliage filter screening and has found six kinds of new saponin compounds through long term studies, their combinations is used for the treatment of diabetes has excellent effect, thereby finished the present invention.
Purpose of the present invention just provides a kind of pharmaceutical composition for the treatment of diabetes.
Pharmaceutical composition of the present invention comprises that 6 kinds of Saponins make active component and/or pharmaceutically acceptable additives.Wherein these 6 kinds of Saponins are represented with GA-1, GA-2, GA-3, GA-4, GA-5 and GA-6 respectively, and wherein GA-1 and GA-2 are for having two kinds of Saponins of following general formula (I):
Work as R
1During=H, be GA-1; Work as R
1=
The time, be GA-2;
Wherein said GA-3 to GA-6 is for having four kinds of Saponins of following general formula (II):
Work as R
1=H and R
2=
The time, be GA-3;
Work as R
1=
And R
2During=H, be GA-4;
Work as R
1=
And R
2=
The time,
Be GA-5;
Work as R
1=H and R
2=
The time, be GA-6.
The content of these six kinds of Saponins is respectively in pharmaceutical composition of the present invention
GA-1 12～21 weight portions, GA-2 8～15 weight portions,
GA-3 24～38 weight portions, GA-4 21～34 weight portions,
GA-5 27～46 weight portions, GA-6 32～54 weight portions;
Wherein their preferred content is
GA-1 16 weight portions, GA-2 12 weight portions, GA-3 31 weight portions,
GA-4 27 weight portions, GA-5 36 weight portions, GA-6 43 weight portions.
Can choose wantonly in the pharmaceutical composition of the present invention and contain pharmaceutically acceptable various additives, these additives comprise filler, binding agent, wetting agent, disintegrating agent, surfactant, lubricant, diluent etc.Wherein diluent comprises lactose, starch, dextrin, microcrystalline Cellulose, micropowder silica gel etc., preferred micropowder silica gel.Wetting agent comprises water and ethanol etc., the ethanol of preferred 50-85%, more preferably 80% ethanol.Lubricant comprises Pulvis Talci, magnesium stearate etc., preferred magnesium stearate.
According to the present invention, use this area conventional formulation technology to make pharmaceutically various preparations to pharmaceutical composition of the present invention, the preferred oral form of administration, exemplary dosage form wherein is oral liquid, tablet, powder agent, capsule etc., capsule the best.Prepare capsular technology and be the various conventional methods on the pharmaceutics, preferably the present composition is made granule earlier and reinstall capsule.Particulate method for making can be selected wet granulation or dry granulation for use.
Test confirmation through the inventor, pharmaceutical composition of the present invention has intestinal absorbs and recover the insulin β emiocytosis insulin of damage to glucose the effect that suppresses, can reduce the hyperglycemia and the blood lipid level of diabetics, can be used for treating and/or preventing II phase diabetes.The effective dose of this pharmaceutical composition is 100～450mg/kg, and preferred dose 100-400mg/kg, optimal dose are 200mg/kg, oral 3 times of every day.
Further specify the present invention below in conjunction with embodiment and test example.
Embodiment 1
Select the active component of following consumption for use:
GA-1 16mg、GA-2 12mg、GA-3 31mg、
GA-4 27mg、GA-5 36mg、GA-6 43mg；
With above-mentioned component and 30mg micropowder silica gel mix homogeneously, make wetting agent with an amount of 70% ethanol the powder of above-mentioned mix homogeneously is made soft material, make granule more according to a conventional method, add an amount of magnesium stearate, mix, the snap fit capsule of packing into forms.
Embodiment 2
Select following raw materials according for use:
GA-1 20mg、GA-2 12mg、GA-3 38mg、
GA-4 30mg、GA-5 46mg、GA-6 54mg、
Micropowder silica gel 135mg, magnesium stearate are an amount of;
With above-mentioned component GA1-6 mix homogeneously, mix with micropowder silica gel again, cross 100 mesh sieves, add magnesium stearate, to mix, dry method is made granule, incapsulates.
Embodiment 3
Press the step preparation of embodiment 1, difference is to select for use following raw materials according:
GA-1 10mg、GA-2 5.5mg、GA-3 17.5mg、
GA-4 17mg、GA-5 23mg、 GA-6 27mg、
Micropowder silica gel 200mg, magnesium stearate ethanol an amount of, 80% is an amount of.
Embodiment 4
Press the step preparation of embodiment 1, difference is to select for use following raw materials according:
GA-1 36mg、GA-2 24mg、 GA-3 90mg、
GA-4 90mg、GA-5 105mg、GA-6 105mg、
Micropowder silica gel 50mg, magnesium stearate ethanol an amount of, 60% is an amount of.
The toxicological test of test example 1 pharmaceutical composition of the present invention
Get 50 of mices, male and female half and half are by the body weight random packet, every group 10, contain the present composition of above-mentioned 6 kinds of Saponins for the oral and lumbar injection of mice, raise continuously after the administration, observed 7 days, poisoning symptom and the death condition that occurs after the administration respectively organized in record, calculates LD with the Bliss method
50Value is respectively 5120mg/kg and 112.5mg/kg.
Test example 2 pharmaceutical compositions of the present invention are to the influence of normal mouse blood sugar
Male mice in kunming, random packet, experimental group orally give pharmaceutical composition 50 of the present invention, 100,200mg/kg, positive controls is orally give tolbutamide 100mg/kg respectively, the blank group waits the capacity distilled water, and the administration volume is 20ml/kg, continuous 14 days, respectively at behind the administration first day and the medicine the 3rd, 7,14 days, pre-fasting administration after 5 hours, separation of serum was pressed the test kit method and is measured the mice serum concentration of glucose by eye socket about 100 μ l that take a blood sample in 3 hours behind the medicine.
As a result, pharmaceutical composition 50,100 of the present invention, 200mg/kg, continuous oral administration 14 days does not have obvious influence to normal mouse blood sugar, and the 3rd day beginning behind the tolbutamide self administration of medication promptly shows significant blood sugar reducing function, sees Table 1.
Table 1: pharmaceutical composition of the present invention is to the influence of normal mice serum glucose content
(X±SD，n＝10)
| Group | Dosage mg/kg | Blood sugar concentration (mmol/L) | |||
| 1 | 3 | 7 | 14 (my god) | ||
| Matched group | 5.21±1.10 | 7.10±1.30 | 8.56±0.74 | 7.52±1.29 | |
| Pharmaceutical composition of the present invention | 50 | 5.84±0.94 | 7.56±0.92 | 8.51±1.06 | 8.27±0.66 |
| 100 | 6.48±1.28 | 7.73±2.26 | 8.71±0.97 | 7.45±1.59 | |
| 200 | 6.41±1.04 | 6.28±1.19 | 8.46±0.88 | 7.86±1.56 | |
| Tolbutamide | 100 | 6.48±1.18 | 5.22±0.80 ** | 6.62±0.96 ** | 5.75±1.02 ** |
*Compare with matched group p＜0.05.
Test example 3 pharmaceutical compositions of the present invention cause the influence of large and small Mus blood sugar increasing to glucose
(1) influence that mouse blood sugar is raise: male mice in kunming, be divided into experimental group at random, difference orally give pharmaceutical composition 50,100 of the present invention, 200mg/kg, positive controls is orally give glyburide 50mg/kg respectively, blank group and normal control group orally give equivalent distilled water, the administration volume is 20ml/kg, fasting is 10 hours before the last administration in continuous 7 days, except that the normal control group, each organizes orally give glucose solution 2.5g/kg (10ml/kg).Respectively at giving before the glucose and behind the glucose 30 minutes,, press glucose oxidase method, glucose content in the mensuration serum by the eye socket 100 μ l that take a blood sample.
As a result, mice oral glucose 30 minutes, blood glucose obviously rises, and pharmaceutical composition 100 of the present invention, 200mg/kg and glyburide 50mg/kg all significantly suppress mouse blood sugar and raise.The blood sugar reducing function of pharmaceutical composition 200mg/kg of the present invention is close with glyburide 50mg/kg, sees Table 2.
Table 2: pharmaceutical composition of the present invention causes the influence that mouse blood sugar raises to glucose
| Group | Dosage (mg/kg) | Blood glucose value (mmol/l) | |
| 0 | 30 (minute) | ||
| Normal group | 6.20±1.01 | 6.64±1.04 | |
| Matched group | 6.55±1.16 | 13.94±3.22 ΔΔ | |
| Pharmaceutical composition of the present invention | 50 | 6.79±1.16 | 12.01±1.88 |
| 100 | 6.09±1.34 | 9.59±2.25 ** | |
| 200 | 6.42±0.99 | 9.16±1.08 ** | |
| Glyburide | 50 | 4.48±0.83 ** | 8.18±1.72 ** |
The Δ ΔCompare with normal group p＜0.01;
*Compare with matched group p＜0.01.
(2) influence that rat blood sugar is raise: male SD rat, body weight 130-170g, fasting was divided into experimental group by body weight after 24 hours, an orally give pharmaceutical composition 50 of the present invention, 100,200mg/kg, positive controls is orally give glyburide 100mg/kg respectively, capacity distilled water such as normal control group and blank group orally give, the administration volume is 10ml/kg, and except that normal group, each organizes rat orally give glucose solution 1g/kg (5ml/kg) after 30 minutes, and respectively at thereafter 30,60,120 minutes, by the rat eye socket 100 μ l that take a blood sample, preparation serum is measured blood sugar content.
The result, behind the oral glucose of rat in 120 minutes, blood glucose value is apparently higher than the normal control group, pharmaceutical composition 100mg/kg of the present invention behind oral glucose 30 minutes, pharmaceutical composition 200mg/kg of the present invention behind oral glucose 30-120 minute, glyburide 100mg/kg is 30, the blood glucose value that rat is raise significantly reduces, the blood sugar reducing function of pharmaceutical composition 200mg/kg of the present invention is close with glyburide 100mg/kg, but lasts longer than the latter, sees Table 3.
Table 3: pharmaceutical composition of the present invention causes the influence that rat blood sugar raises to oral glucose
(X±SD，n＝10)
| Group | Dosage (mg/kg) | Blood glucose value (mmol/L) | ||
| 30 | 60 | 120 (minute) | ||
| Normal group | 4.42±0.67 | 4.62±0.66 | 4.20±0.63 | |
| Matched group | 8.36±1.13 ΔΔ | 7.40±0.81 ΔΔ | 5.78±1.14 ΔΔ | |
| Pharmaceutical composition of the present invention | 50 | 7.72±1.96 | 7.63±1.74 | 6.38±1.59 |
| 100 | 6.32±1.34 ** | 6.69±1.81 | 5.35±1.50 | |
| 200 | 5.62±0.90 ** | 5.25±0.86 ** | 4.78±0.89 * | |
| Glyburide | 100 | 5.12±1.02 ** | 5.70±1.36 ** | 6.03±1.43 |
The Δ ΔCompare with normal group p＜0.01;
*P＜0.05,
*Compare with matched group p＜0.01.
Test example 4 pharmaceutical compositions of the present invention cause the influence that rat blood sugar raises to sucrose
Female sd inbred rats, after the fasting 24 hours, be divided into experimental group at random, an orally give pharmaceutical composition 50 of the present invention, 100,200mg/kg, positive controls gives insoral 100mg/kg respectively, capacity distilled water such as normal group, matched group and blank group orally give, the administration volume is 10ml/kg, after 30 minutes, except that normal group, each organizes orally give sucrose solution 1g/kg (5ml/kg), and respectively at 30,60,120 minutes thereafter, by the rat eye socket 100 μ l that take a blood sample, measure serum glucose content.
The result, after the oral sucrose of rat 30, in 60 minutes, blood glucose value obviously rises, pharmaceutical composition 100mg/kg of the present invention was at 30 minutes, and pharmaceutical composition 200mg/kg of the present invention and insoral 100mg/kg all made rat raise at 30,60 minutes blood glucose value significantly descends, and both action intensities are close, see Table 4.
Table 4: pharmaceutical composition of the present invention causes the influence that rat blood sugar raises to sucrose
(X±SD，n＝10)
| Group | Dosage mg/kg | Blood glucose value (mmol/L) | ||
| 30 | 60 | 120 (minute) | ||
| Normal group | 3.56±0.64 | 4.12±0.72 | 3.76±0.69 | |
| Matched group | 6.58±0.87 ΔΔ | 5.93±1.27 ΔΔ | 4.54±1.37 | |
| Pharmaceutical composition of the present invention | 50 | 6.03±0.86 | 6.42±0.78 | 4.26±1.03 |
| 100 | 5.12±1.29 * | 5.77±1.09 | 4.53±0.94 | |
| 200 | 4.43±0.72 ** | 4.73±0.83 * | 4.07±0.70 | |
| Insoral | 100 | 4.24±0.87 ** | 4.74±0.90 * | 4.79±1.03 |
The Δ ΔCompare with normal group p＜0.01;
*P＜0.05,
*Compare with matched group p＜0.01.
Test example 5 pharmaceutical compositions of the present invention cause the influence that mouse blood sugar raises to alloxan
Male mice in kunming, fasting be after 24 hours, except that normal group, and tail vein injection alloxan normal saline solution 90mg/kg (10ml/kg), after 72 hours, the pre-fasting of mice 5 hours by eye socket about 100 μ l that take a blood sample, is measured the glucose content in the serum.Select mice between blood glucose value 11-26mmol/L, and press the blood glucose value random packet, experimental group gives pharmaceutical composition 50,100 of the present invention, 200mg/kg, positive controls is orally give insoral 100mg/kg respectively, the distilled water of capacity such as blank group orally give, and the administration volume is 20ml/kg, respectively behind medicine the 3rd, the 5th day, mice fasting administration after 5 hours, 3 hours blood glucose value after the mensuration administration.In addition, measure after the administration between the 3rd to the 5th day, every day every mice average amount of drinking water.
As a result, pharmaceutical composition 100 of the present invention, 200mg/kg, insoral 100mg/kg all significantly suppressed mouse blood sugar on the the 3rd, the 5 day and raise after administration.The blood sugar reducing function of pharmaceutical composition 200mg/kg of the present invention is close with insoral 100mg/kg, and the daily drink amount that pharmaceutical composition 200mg/kg of the present invention, insoral 100mg/kg increase diabetic mice obviously reduces.See Table 5.
Table 5: pharmaceutical composition of the present invention is to the influence of alloxan diabetes mice
(X±SD，n＝10-14)
| Group | Dosage mg/kg | Blood glucose value mmol/L before the medicine | Blood glucose value mmol/L behind the medicine | Amount of drinking water | |
| 3 | 5 (my god) | Ml//day | |||
| Normal group | 5.24±1.08 | 6.61±1.02 | 7.36±1.27 | 4.5±0.2 | |
| Matched group | 20.00±3.89 | 18.43±4.24 ΔΔ | 19.35±4.9 ΔΔ | 14.3±0.8 ΔΔ | |
| Pharmaceutical composition of the present invention | 50 | 19.56±4.08 | 15.04±4.59 | 15.89±6.30 | 14.2±1.4 |
| 100 | 20.15±3.92 | 11.94±3.78 ** | 11.71±4.18 ** | 12.8±1.4 | |
| 200 | 19.06±4.52 | 9.07±2.93 ** | 7.73±3.86 ** | 11.8±0.9 * | |
| Insoral | 100 | 19.34±4.59 | 8.31±3.02 ** | 9.34±4.44 ** | 11.1±2.0 |
The Δ ΔCompare with normal group p＜0.01;
*P＜0.05,
*Compare with matched group p＜0.01.
Test example 6 pharmaceutical compositions of the present invention are to the influence of alloxan diabetes rats blood glucose
Female sd inbred rats, body weight 160-200g, fasting is after 24 hours, and except that normal group, tail vein injection alloxan normal saline solution 40mg/kg (5ml/kg) after 72 hours, surveys fasting blood sugar.Select rat between blood glucose value 12-29mmol/L, and press the blood glucose value random packet, the experimental group orally give that begins next day pharmaceutical composition 50 of the present invention, 100,200mg/kg, positive controls is orally give insoral 50mg/kg respectively, blank group orally give distilled water, the administration volume is 10ml/kg, continuous 15 days, respectively at after the administration the 5th, 10,15 days, fasting was 5 hours before the administration, measured the rat blood serum glucose content of administration after 3 hours.Measure average amount of drinking water, the food-intake of every rat every day after the administration, and after the last administration next day, with rat fasting 5 hours, the eye socket blood sampling, separation of serum is pressed the insulin content of serum measured by radioimmunoassay shown in the test kit.(1) to the influence of blood glucose: in administration 15 days, modeling group blood glucose is apparently higher than normal group, and pharmaceutical composition 200mg/kg of the present invention, insoral 50mg/kg all significantly suppressed rat blood sugar on the 10th, the 15 day and raise after administration; At the 15th day, blood sugar reducing function and the insoral of pharmaceutical composition 200mg/kg of the present invention were close, and pharmaceutical composition 100mg/kg of the present invention also presents significant hypoglycemic activity, sees Table 6.(2) to the influence of rat body weight, amount of drinking water, food-intake and serum insulin content:
The body weight gain of pharmaceutical composition 200mg/kg group rat of the present invention is apparently higher than model control group, and insoral only is enhancing trend to body weight gain; Pharmaceutical composition 50,100 of the present invention, 200mg/kg and insoral 50mg/kg all make the diabetes rat amount of drinking water obviously descend, and food-intake significantly reduces; Alloxan modeling rat blood serum insulin content significantly descends, and pharmaceutical composition 200mg/kg of the present invention makes the serum insulin levels rebound significantly, and pharmaceutical composition of the present invention 50,100mg/kg and insoral only are enhancing trend, see Table 7.
Table 6: pharmaceutical composition of the present invention is to the influence of alloxan diabetes rats blood glucose
(X±SD，n＝10-14)
| Group | Dosage mg/kg | Blood glucose value mmol/L before the medicine | Blood glucose value mmol/L behind the medicine | ||
| 5 | 10 | 15 (my god) | |||
| Normal group | 6.44±0.53 | 5.93±0.53 | 6.59±0.50 | 6.09±0.51 | |
| Matched group | 24.78±3.89 ΔΔ | 23.15±4.48 ΔΔ | 27.79±3.55 ΔΔ | 27.96±3.72 ΔΔ | |
| Pharmaceutical composition of the present invention | 50 | 24.52±4.48 | 24.01±4.15 | 26.06±4.14 | 24.96±4.73 |
| 100 | 25.00±3.72 | 21.20±5.39 | 24.48±6.21 | 18.72±5.98 * | |
| 200 | 24.82±4.39 | 20.00±5.97 | 18.87±6.00 ** | 15.13±6.39 ** | |
| Insoral | 100 | 24.08±4.63 | 19.45±5.87 | 20.50±6.42 ** | 13.54±6.08 * |
The Δ ΔCompare with normal group p＜0.01;
*P＜0.05,
*Compare with matched group p＜0.01.
Table 7 pharmaceutical composition of the present invention to alloxan diabetes rats serum insulin, body weight,
The influence of food-intake and amount of drinking water (X ± SD, n=10-14)
| Group | Dosage mg/kg | Insulin mmol/L | Body weight gain g | Food-intake g//day | Amount of drinking water ml//day |
| Normal group | 24.2±6.6 | 45.4±5.8 | 18.5±1.3 | 30.3±2.9 | |
| Matched group | 11.8±3.0 ΔΔ | 16.2±15.6 ΔΔ | 40.9±3.7 ΔΔ | 147.1±20.3 ΔΔ | |
| Pharmaceutical composition of the present invention | 50 | 12.4±3.2 | 19.0±14.2 | 38.2±3.8 | 127.6±12.7 * |
| 100 | 16.0±9.9 | 25.4±10.7 | 35.1±4.0 * | 124.4±13.5 | |
| 200 | 19.4±7.2 ** | 34.0±11.4 * | 36.5±4.3 * | 120.1±8.2 ** | |
| Insoral | 100 | 14.1±4.2 | 31.5±19.4 | 32.4±3.7 ** | 118.1±10.1 ** |
The Δ ΔCompare with normal group p＜0.01;
*P＜0.05,
*Compare with matched group p＜0.01.
Test example 7 pharmaceutical compositions of the present invention are to hyperlipidemia rats serum triglycerides, cholesterol
The influence of content
Male SD rat, body weight 130-170g, normal group gives normal diet, and other each group gives high lipid food (1% cholesterol, 10% Adeps Sus domestica, 0.3% cholic acid, 0.2% thiamazole and 88.5% normal diet are made into cubed feed by oneself).Continuous 14 days, the rat fasting was pressed the test kit method and is measured rat blood serum triglyceride and cholesterol level after 12 hours, then, carried out random packet by the blood fat value.Experimental group orally give pharmaceutical composition 50,100 of the present invention, 200mg/kg, positive controls is oral clofibrate 100mg/kg respectively, matched group gives distilled water, the administration volume is 10ml/kg, and continuous 10 days, each group was still raised with high lipid food in administration in preceding 5 days, raised with normal diet in 5 days the back, fasting is 11 hours before the last administration, and triglyceride and cholesterol level in the serum surveyed in blood sampling in 1 hour after the administration.
The result, rat gave high lipid food after 10 days, serum triglycerides and cholesterol level obviously raise, pharmaceutical composition 50,100 of the present invention, 200mg/kg and clofibrate 100mg/kg all make hyperlipidemia rats serum triglycerides and cholesterol levels obviously descend, the effect for reducing blood fat of pharmaceutical composition 200mg/kg of the present invention is close with clofibrate 100mg/kg, sees Table 8.
Table 8: pharmaceutical composition of the present invention is to the influence of hyperlipidemia rats lipids contents
(X±SD，n＝9-10)
| Group | Dosage mg/kg | Triglyceride (mmol/L) | T-CHOL (mmol/L) | ||
| Before the administration | After the administration | Before the administration | After the administration | ||
| Normal group | 1.02±0.22 | 1.04±0.15 | 2.43±0.41 | 1.99±0.47 | |
| Matched group | 2.64±0.82 | 3.04±0.93 | 4.10±0.51 ΔΔ | 4.77±0.63 ΔΔ | |
| Pharmaceutical composition of the present invention | 50 | 2.72±0.61 | 2.41±0.44 | 4.29±0.60 | 3.92±0.58 ** |
| 100 | 2.54±0.90 | 1.75±0.53 ** | 4.02±0.59 | 2.94±0.66 ** | |
| 200 | 2.72±0.76 | 1.37±0.40 ** | 4.18±0.61 | 2.31±0.74 ** | |
| Clofibrate | 100 | 2.51±0.77 | 2.72±0.74 | 4.33±0.51 | 2.15±0.76 ** |
The Δ ΔCompare with normal group P＜0.01;
*Compare with matched group P＜0.01
Show that thus pharmaceutical composition of the present invention does not have obvious influence to normal mouse blood sugar, but suppress glucose or sucrose induced mice, rat blood sugar raises, in rat test, the blood sugar reducing function of pharmaceutical composition 200mg/kg of the present invention is close with glyburide 100mg/kg; Blood sugar increasing and amount of drinking water that pharmaceutical composition of the present invention suppresses the alloxan diabetes mice increase, and the action intensity of pharmaceutical composition 200mg/kg of the present invention is suitable with insoral 100mg/kg; In addition, blood glucose, food-intake and amount of drinking water that pharmaceutical composition of the present invention still suppresses alloxan diabetes rats raise, and the serum insulin content rebound significantly that rat is reduced, accelerate the body weight gain of rat, pharmaceutical composition 200mg/kg action intensity of the present invention is weaker than insoral 50mg/kg slightly, shows that pharmaceutical composition of the present invention is by suppressing intestinal to the absorption of glucose and the β emiocytosis insulin performance blood sugar reducing function of recovery damage insulin.
Pharmaceutical composition of the present invention reduces high lipid food and causes hyperlipidemia rats serum triglycerides and cholesterol level, and the effect for reducing fat of pharmaceutical composition 200mg/kg of the present invention is suitable with clofibrate 100mg/kg.
So pharmaceutical composition of the present invention has effects such as blood sugar lowering, blood fat reducing.
Claims (12)
1. pharmaceutical composition for the treatment of diabetes is characterized in that it comprises that 6 kinds of Saponins make active component and pharmaceutically acceptable additives, and 6 kinds of Saponins of wherein contained this and content thereof are respectively
GA-1 12～21 weight portions, GA-2 8～15 weight portions,
GA-3 24～38 weight portions, GA-4 21～34 weight portions,
GA-5 27～46 weight portions, GA-6 32～54 weight portions; Wherein said GA-1 and GA-2 are two kinds of Saponins with following general formula:
Work as R
1During=H, be GA-1; Work as R
1=
The time, be GA-2;
Wherein said GA-3 to GA-6 is four kinds of Saponins with following general formula:
Work as R
1=H and R
2=
The time, be GA-3;
Work as R
1=
And R
2During=H, be GA-4;
Work as R
1=
And R
2=
The time,
Be GA-5;
Work as R
1=H and R
2=
The time, be GA-6.
2. pharmaceutical composition according to claim 1, wherein the content of its 6 kinds of contained Saponin is respectively
GA-1 16 weight portions, GA-2 12 weight portions, GA-3 31 weight portions,
GA-4 27 weight portions, GA-5 36 weight portions, GA-6 43 weight portions.
3. pharmaceutical composition according to claim 1 and 2, wherein contained additives are diluent, wetting agent and/or lubricant.
4. pharmaceutical composition according to claim 3, its contained diluent is lactose, starch, dextrin, microcrystalline Cellulose or micropowder silica gel.
5. pharmaceutical composition according to claim 4, its contained diluent is micropowder silica gel.
6. pharmaceutical composition according to claim 3, its contained lubricant is Pulvis Talci or magnesium stearate.
7. pharmaceutical composition according to claim 6, its contained lubricant is a magnesium stearate.
8. pharmaceutical composition according to claim 3, its contained wetting agent is water or ethanol.
9. pharmaceutical composition according to claim 8, its contained wetting agent is the ethanol of 50-85%.
10. pharmaceutical composition according to claim 9, its contained wetting agent are 80% ethanol.
11. according to arbitrary described pharmaceutical composition among the claim 1-10, its dosage form is a peroral dosage form.
12. pharmaceutical composition according to claim 11, its dosage form are capsule.
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN99102823A CN1112187C (en) | 1999-03-12 | 1999-03-12 | Medicinal composition for treating diabetes |
| US09/913,322 US6833443B1 (en) | 1999-02-11 | 2000-01-21 | Gymnemic acid derivatives, process for the preparation thereof and use thereof as medicine |
| EP00901035A EP1176149B1 (en) | 1999-02-11 | 2000-01-21 | Novel gymnemic acid derivatives, process for the preparation thereof and use thereof as medicine |
| AU20909/00A AU2090900A (en) | 1999-02-11 | 2000-01-21 | Novel gymnemic acid derivatives, process for the preparation thereof and use thereof as medicine |
| CA2362864A CA2362864C (en) | 1999-02-11 | 2000-01-21 | New gymnemic acid derivatives, their preparation, pharmaceutical composition containing them and their medical use |
| PCT/CN2000/000010 WO2000047594A1 (en) | 1999-02-11 | 2000-01-21 | Novel gymnemic acid derivatives, process for the preparation thereof and use thereof as medicine |
| DE60004353T DE60004353T2 (en) | 1999-02-11 | 2000-01-21 | DERIVATIVES OF GYMNEMIC ACID, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE AS MEDICINES |
| KR1020017010217A KR100625222B1 (en) | 1999-02-11 | 2000-01-21 | Novel gymnemic acid derivatives, process for the preparation thereof and use thereof as medicine |
| JP2000598513A JP4903309B2 (en) | 1999-02-11 | 2000-01-21 | Novel gymnemic acid derivatives, their production, pharmaceutical compositions containing them, and their pharmaceutical use |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN99102823A CN1112187C (en) | 1999-03-12 | 1999-03-12 | Medicinal composition for treating diabetes |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1266686A CN1266686A (en) | 2000-09-20 |
| CN1112187C true CN1112187C (en) | 2003-06-25 |
Family
ID=5270994
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN99102823A Expired - Fee Related CN1112187C (en) | 1999-02-11 | 1999-03-12 | Medicinal composition for treating diabetes |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1112187C (en) |
-
1999
- 1999-03-12 CN CN99102823A patent/CN1112187C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1266686A (en) | 2000-09-20 |
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