CN102872045B - Application of gypensapogenin A to hypoglycemic drugs - Google Patents
Application of gypensapogenin A to hypoglycemic drugs Download PDFInfo
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- CN102872045B CN102872045B CN 201210417465 CN201210417465A CN102872045B CN 102872045 B CN102872045 B CN 102872045B CN 201210417465 CN201210417465 CN 201210417465 CN 201210417465 A CN201210417465 A CN 201210417465A CN 102872045 B CN102872045 B CN 102872045B
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- PYGRZYXAMLFMOS-IBMFSSKUSA-N gypensapogenin a Chemical compound O=C1C(=C(C)C)CC=C1[C@@H]1[C@@H](CC[C@H]2[C@]3(CCC4=C2[C@H]2CC[C@H](O2)C4(C)C)C)[C@@]3(C)CC1 PYGRZYXAMLFMOS-IBMFSSKUSA-N 0.000 title abstract description 68
- 239000003472 antidiabetic agent Substances 0.000 title abstract description 15
- 238000002360 preparation method Methods 0.000 claims abstract description 16
- 239000008280 blood Substances 0.000 claims description 27
- 210000004369 blood Anatomy 0.000 claims description 27
- 239000003814 drug Substances 0.000 claims description 16
- 229930192112 gypensapogenin Natural products 0.000 claims 1
- 230000003178 anti-diabetic effect Effects 0.000 abstract description 13
- 150000001875 compounds Chemical class 0.000 abstract description 12
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 12
- 229940127003 anti-diabetic drug Drugs 0.000 abstract 4
- 239000000126 substance Substances 0.000 abstract 1
- 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 16
- 239000008103 glucose Substances 0.000 description 16
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 8
- 241000700159 Rattus Species 0.000 description 7
- 229940079593 drug Drugs 0.000 description 5
- 238000011552 rat model Methods 0.000 description 5
- 238000003304 gavage Methods 0.000 description 4
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 4
- 210000003462 vein Anatomy 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 240000006509 Gynostemma pentaphyllum Species 0.000 description 3
- 235000002956 Gynostemma pentaphyllum Nutrition 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 235000013336 milk Nutrition 0.000 description 3
- 239000008267 milk Substances 0.000 description 3
- 210000004080 milk Anatomy 0.000 description 3
- 229930182490 saponin Natural products 0.000 description 3
- 150000007949 saponins Chemical class 0.000 description 3
- 235000017709 saponins Nutrition 0.000 description 3
- 150000003648 triterpenes Chemical class 0.000 description 3
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 210000005252 bulbus oculi Anatomy 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 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 2
- 238000000034 method Methods 0.000 description 2
- 229960001052 streptozocin Drugs 0.000 description 2
- INLFWQCRAJUDCR-IQVMEADQSA-N (1R,2S,4S,5'S,6R,7S,8R,9S,12S,13S)-5',7,9,13-tetramethylspiro[5-oxapentacyclo[10.8.0.02,9.04,8.013,18]icosane-6,2'-oxane] Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CCCCC4CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@H](C)CO1 INLFWQCRAJUDCR-IQVMEADQSA-N 0.000 description 1
- BOVGTQGAOIONJV-BETUJISGSA-N 1-[(3ar,6as)-3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrol-2-yl]-3-(4-methylphenyl)sulfonylurea Chemical group C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1C[C@H]2CCC[C@H]2C1 BOVGTQGAOIONJV-BETUJISGSA-N 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 235000003143 Panax notoginseng Nutrition 0.000 description 1
- 241000180649 Panax notoginseng Species 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 238000013295 T2DM animal model Methods 0.000 description 1
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- OORMXZNMRWBSTK-UHFFFAOYSA-N dammaran Natural products C1CCC(C)(C)C2CCC3(C)C4(C)CCC(C(C)CCCC(C)C)C4CCC3C21C OORMXZNMRWBSTK-UHFFFAOYSA-N 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000003716 rejuvenation Effects 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
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- Steroid Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention discloses application of gypensapogenin A to preparation of antidiabetic drugs. According to the application of gypensapogenin A, brand-new selection and thought are provided to the existing antidiabetic drugs, the selection field of the antidiabetic drugs is widened and a contribution is made for the technical field; and the application of gypensapogenin A is proven to have remarkable antidiabetic effect. According to the application of gypensapogenin A, compounds with distinct chemical structures are selected. The application of gypensapogenin A to the preparation of the antidiabetic drugs is firstly publicized, the skeleton type is brand-new, the antidiabetic activity is unexpectedly strong and the possibility of giving any revelation by other compounds does not exist, sothat prominent substantive features are provided and a remarkable progress in the treatment of the diabetes mellitus is made at the same time.
Description
Technical field
The present invention relates to a kind of new purposes of Gypensapogenin A, the specifically application of Gypensapogenin A in the preparation antidiabetic medicine.
Background technology
Diabetes (diabetes mellitus) are one of current modal chronic diseases, type 2 diabetes mellitus (Type II diabetes mellitus wherein, be again non-insulin-dependent diabetes mellitus, non-insulin-depentdiabetes mellitus, NIDDM) account for more than 90% of diabetics.Diabetes all are day by day serious problems in developed country and developing country, and it has caused serious and costly consequence, comprise blind, heart disease and nephropathy etc.According to estimates, from 2000 to the year two thousand fifty, the number of whole world diabetics will increase by 165%.According to the statistics of IDF, at present in state-owned 4.3% population suffer from diabetes, patient's number will break through 5,000 ten thousand in following 20 years.Diabetes are second killers in the modern disease, it is only second to cancer to the harm of human body, human health in serious threat, and present diabetes have the tendency of extension and rejuvenation, how to prevent that diabetes from having become the large problem that present the world of medicine pays close attention to.
The chemical compound Gypensapogenin A that the present invention relates to is one and delivered (Li in 2012, N. et al., 2012. Triterpenes possessing an unprecedented skeleton isolated from hydrolyzate of total saponins from Gynostemma pentaphyllum. European Journal of Medicinal Chemistry 50,173 – 178.) New skeleton compound, this chemical compound has brand-new framework types, present purposes only relates to the cytotoxic activity (Li of human tumor cell line, N. et al., 2012. Triterpenes possessing an unprecedented skeleton isolated from hydrolyzate of total saponins from Gynostemma pentaphyllum. European Journal of Medicinal Chemistry 50,173 – 178.), belong to open first for the purposes of the Gypensapogenin A that the present invention relates in preparation treatment antidiabetic medicine, because framework types belongs to brand-new framework types, and its control diabetic activity is unexpectedly strong, there is not the possibility that is provided any enlightenment by other chemical compounds, possess outstanding substantive distinguishing features, be used for the treatment of simultaneously anti-diabetic and obviously have significant progress.
Summary of the invention
The objective of the invention is provides a kind of new way for the technical field of existing preparation antidiabetic medicine, and the application of Gypensapogenin A in the preparation antidiabetic medicine is provided.
The structural formula of Gypensapogenin A such as formula I:
Technical scheme of the present invention is: the application of Gypensapogenin A specifically is applied to prepare antidiabetic medicine.
The invention has the beneficial effects as follows:
1) the present invention has widened diabetes and has selected the field for present antidiabetic medicine provides a kind of brand-new selection and thinking, also contributes for the development of this technical field; 2) application of Gypensapogenin A of the present invention has been proved to be significant anti-diabetic effect.
The most important thing is: the present invention carries out the blood sugar lowering experiment of laboratory animal to Gypensapogenin A, at lasting gavage fat milk rat is produced on the basis of insulin resistant, use low dose of streptozotocin damage beta Cell of islet, cause rat blood sugar to raise, institute makes animal model and type 2 diabetes mellitus is similar.After rat model of type 2 diabetes mellitus gives Gypensapogenin A treatment, Gypensapogenin A is high, in and the blood glucose value and the comparison of model group blood glucose value of low dose group, also has significant difference (P＜0.01), Gypensapogenin A is high, in and the blood glucose value before and after the low dose group administration relatively, also have significant difference (P＜0.01), illustrate that Gypensapogenin A has good hypoglycemic activity to experimental type 2 diabetes mellitus.
The purposes of the Gypensapogenin A that the present invention relates in preparation treatment antidiabetic medicine belongs to open first, because framework types belongs to brand-new framework types, and its control diabetic activity is unexpectedly strong, there is not the possibility that is provided any enlightenment by other chemical compounds, possess outstanding substantive distinguishing features, be used for the treatment of simultaneously anti-diabetic and obviously have significant progress.
The specific embodiment
The preparation method of chemical compound Gypensapogenin A involved in the present invention is referring to document (Li, N. et al., 2012. Triterpenes possessing an unprecedented skeleton isolated from hydrolyzate of total saponins from Gynostemma pentaphyllum. European Journal of Medicinal Chemistry 50,173 – 178. and Wei, J.X. et al., 1982. Two new dammaran sapogenins from leaves of Panax notoginseng. Planta Medica, 45 (3): 167-171.).
The present invention is further detailed explanation by the following examples, but protection scope of the present invention is not subjected to any restriction of specific embodiment, but limited by claim.
Embodiment 1: the preparation of chemical compound Gypensapogenin A tablet involved in the present invention:
Get 20 and digest compound Gypensapogenin A, add conventional adjuvant 180 grams of preparation tablet, mixing, conventional tablet machine are made 1000.
Embodiment 2: the preparation of chemical compound Gypensapogenin A capsule involved in the present invention:
Get 20 and digest compound Gypensapogenin A, add conventional adjuvant such as starch 180 grams of preparation capsule, mixing is encapsulatedly made 1000.
Further specify its pharmaceutically active below by pharmacodynamic experiment.
Experimental example 1 Gypensapogenin A is on the impact of rat model of type 2 diabetes mellitus
1, animal grouping
Healthy Wistar rat (SPF level), male, body weight 180-220g(is provided by Nanfang Medical Univ's Experimental Animal Center), the feed of freely drinking water, be divided at random Normal group and modeling group, the modeling group is set up model as follows, the model group animal is divided at random high, normal, basic group of model control group, positive drug gliclazide group, Gypensapogenin A after the modeling success, 1 week of according to the form below successive administration again.
Administration time and dosage see Table 1:
The grouping of table 1 Gypensapogenin A effect experiment animal
| Group | Number of animals (only) | Dosage (mg/kgBW) |
| Normal group | 12 | ? |
| Model control group | 12 | ? |
| The positive drug group | 12 | 35.5 |
| Low dose group | 12 | 0.16 |
| Middle dosage group | 12 | 0.5 |
| High dose group | 12 | 1.5 |
2, rat model preparation
Normal rats gavage every day distilled water, high fat group rat sooner or later gavage self-control every day fat milk (1ml/100gBW).Continuously the gavage fat milk is after 2 weeks, and water 24h is can't help in the animal fasting, 10 tail vein injection salines of blank group, the equal tail vein injection 30mg/kgBW of all the other rats streptozotocin (below be abbreviated as STZ) solution (before use preparation).Behind the administration 48h, water 12h is can't help in fasting, gets blood every 3 hours eyeball rear vein beards, according to blood sugar detection test kit time-and-motion study fasting blood sugar, and METHOD FOR CONTINUOUS DETERMINATION 3 times, fasting blood sugar 〉=16.7mmol/L's is modeling success rat.
3, the mensuration of blood glucose
After the last administration, water 12h is can't help in the animal fasting, and the eyeball rear vein beard is got blood, measures respectively blood glucose value according to the method for test kit.Adopt the SPSS13.0 statistical software, analyze and respectively organize the situation of change of blood glucose value.
4, Gypensapogenin A is on the impact of rat model of type 2 diabetes mellitus blood glucose
Experimental result sees Table 2, and as known from Table 2, behind the injection STZ, rat blood sugar rises, and fasting blood sugar 〉=16.7mmol/L behind the 72h illustrates the diabetes model success.After the administration, the positive drug group, Gypensapogenin A is high, in and the blood glucose value and the comparison of model group blood glucose value of low dose group, significant difference (P＜0.01) is all arranged.
Each is organized before the administration, and the T check of blood glucose shows behind the blood glucose and administration, the positive drug group, Gypensapogenin A is high, in and the blood glucose value before and after the low dose group administration relatively, have significant difference (P＜0.01).Above result shows that Gypensapogenin A can reduce the blood glucose of rat model of type 2 diabetes mellitus.
Table 2 experimental result
| Group | Number of animals (only) | Blood glucose value before the administration | Blood glucose value after the administration |
| Normal group | 10 | 5.5±0.27 | 5.27±0.30 |
| Model control group | 9 | 13.02±2.23 | 31.16±2.46 |
| The positive drug group | 9 | 31.33±2.42 | 18.74±2.32** △△ |
| Low dose group | 8 | 31.94±2.24 | 23.61±2.24** △△ |
| Middle dosage group | 10 | 32.96±1.93 | 19.65±2.68** △△ |
| High dose group | 9 | 35.37±2.55 | 18.81±3.01** △△ |
* p＜0.05vs model group * * p＜0.01vs model group
△P＜0.05vs is on the same group before the administration
△ △P＜0.01vs is on the same group before the administration
Conclusion: Gypensapogenin A can significantly reduce the blood glucose of type 2 diabetes mellitus animal model, can be used for preparing antidiabetic medicine.
Claims (1)
1.Gypensapogenin the application of A in preparation blood sugar lowering medicine, described chemical compound Gypensapogenin A structure as
Formula IShown in:
Formula I.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201210417465 CN102872045B (en) | 2012-10-26 | 2012-10-26 | Application of gypensapogenin A to hypoglycemic drugs |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201210417465 CN102872045B (en) | 2012-10-26 | 2012-10-26 | Application of gypensapogenin A to hypoglycemic drugs |
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| Publication Number | Publication Date |
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| CN102872045A CN102872045A (en) | 2013-01-16 |
| CN102872045B true CN102872045B (en) | 2013-10-23 |
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| CN 201210417465 Expired - Fee Related CN102872045B (en) | 2012-10-26 | 2012-10-26 | Application of gypensapogenin A to hypoglycemic drugs |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105902527A (en) * | 2016-04-19 | 2016-08-31 | 马苏州 | Medicine composition having blood glucose reduction effect, preparation method and application thereof |
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