CN102885828B - Application of Gypensapogenin B in medicament for treating rheumatoid arthritis - Google Patents
Application of Gypensapogenin B in medicament for treating rheumatoid arthritis Download PDFInfo
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- CN102885828B CN102885828B CN201210417398.XA CN201210417398A CN102885828B CN 102885828 B CN102885828 B CN 102885828B CN 201210417398 A CN201210417398 A CN 201210417398A CN 102885828 B CN102885828 B CN 102885828B
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- gypensapogenin
- rheumatoid arthritis
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- NNUMQZNZQGQGCN-AGHUFMIKSA-N gypensapogenin b Chemical compound O=C1C(=C(C)C)CC([C@@H]2[C@@H]3[C@@]([C@@]4(CCC5=C([C@H]6CC[C@H](O6)C5(C)C)[C@H]4CC3)C)(C)CC2)=C1 NNUMQZNZQGQGCN-AGHUFMIKSA-N 0.000 title claims abstract description 64
- 206010039073 rheumatoid arthritis Diseases 0.000 title claims abstract description 20
- 239000003814 drug Substances 0.000 title claims abstract description 13
- 229940079593 drug Drugs 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 abstract description 15
- 238000002360 preparation method Methods 0.000 abstract description 4
- 206010061218 Inflammation Diseases 0.000 abstract description 2
- 230000004054 inflammatory process Effects 0.000 abstract description 2
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 abstract 1
- 229960001193 diclofenac sodium Drugs 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 230000002265 prevention Effects 0.000 abstract 1
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 abstract 1
- 229960000351 terfenadine Drugs 0.000 abstract 1
- 230000008961 swelling Effects 0.000 description 16
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 239000002671 adjuvant Substances 0.000 description 6
- 206010003246 arthritis Diseases 0.000 description 5
- 108010084652 homeobox protein PITX1 Proteins 0.000 description 5
- 229920001525 carrageenan Polymers 0.000 description 4
- 235000010418 carrageenan Nutrition 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 208000009386 Experimental Arthritis Diseases 0.000 description 3
- 240000006509 Gynostemma pentaphyllum Species 0.000 description 3
- 235000002956 Gynostemma pentaphyllum Nutrition 0.000 description 3
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 3
- 229960001259 diclofenac Drugs 0.000 description 3
- 210000002683 foot Anatomy 0.000 description 3
- 239000000203 mixture Substances 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
- 241000699670 Mus sp. Species 0.000 description 2
- 210000000544 articulatio talocruralis Anatomy 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 229940113118 carrageenan Drugs 0.000 description 2
- 239000000679 carrageenan Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 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
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000186359 Mycobacterium Species 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 235000003143 Panax notoginseng Nutrition 0.000 description 1
- 241000180649 Panax notoginseng Species 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 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
- 238000011161 development Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000000454 fifth toe Anatomy 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 1
- 208000011906 peptic ulcer disease Diseases 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000010517 secondary reaction Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 210000001226 toe joint Anatomy 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention relates to Gypensapogenin B for treating immune inflammation and preparing a medicament for treating rheumatoid arthritis. By using terfenadine and diclofenac sodium as contrasts, the Gypensapogenin B has definite treatment effect. The application of the Gypensapogenin B in preparation of the medicament for treating rheumatoid arthritis is disclosed for the first time, the skeleton type is a brand-new skeleton type, the Gypensapogenin B has unexpected strong inhibiting activity on the rheumatoid arthritis, the probability of giving any revelation by other compounds does not exit, and the Gypensapogenin B has predominant substantial characteristics and obviously has a remarkable progress in prevention and treatment of the rheumatoid arthritis.
Description
Technical field
The present invention relates to the application of Gypensapogenin B in preparing drugs for rheumatoid arthritis.
Background technology
Rheumatoid arthritis is common clinical and frequently-occurring disease, and rheumatoid arthritis belongs to autoimmune disease, belongs to the category of immune inflammation.At present, for rheumatoid arthritis, main NSAID (non-steroidal anti-inflammatory drug) (diclofenac, aspirin etc.) and the immunosuppressant (Ismipur etc.) of adopting administered at present, but all there is obvious untoward reaction in these medicines, as the former damages the gastrointestinal tract mucous peptic ulcer that causes, the latter acts on poor selectivity, is easy to bring out infection etc.Therefore, definite ingredients, quality controllable and safely and efficiently compound aspect development treating rheumatoid arthritis medicine, there is potential value.
The compound Gypensapogenin B the present invention relates to is one and within 2012, delivers (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.) New skeleton compound, this compound has brand-new framework types, current 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.), it is open first that purposes for the Gypensapogenin B the present invention relates in preparing drugs for rheumatoid arthritis belongs to, because framework types belongs to brand-new framework types, and it suppresses active unexpectedly strong for rheumatoid arthritis, there is not the possibility that is provided any enlightenment by other compounds, possesses outstanding substantive distinguishing features, control for rheumatoid arthritis simultaneously obviously has significant progress.
Summary of the invention
The technical problem to be solved in the present invention is the application of research Gypensapogenin B in preparing drugs for rheumatoid arthritis.
Gypensapogenin B of the present invention is 3.428 g/kg to the oral LD50 of mice, compound Gypensapogenin B 10,20mg/kg oral administration, the constitutional and Secondary cases sufficient waste time swelling and the acetic acid induced mice writhing response that obviously suppress adjuvant arthritis rat, show that compound Gypensapogenin B suppresses active chronic inflammation and pain.Therefore, compound Gypensapogenin B can be used as the medicine for the treatment of rheumatoid arthritis.
Described compound Gypensapogenin B structure is as shown in formula I:
It is open first that the purposes of the Gypensapogenin B the present invention relates in preparing drugs for rheumatoid arthritis belongs to, because framework types belongs to brand-new framework types, and it suppresses active unexpectedly strong for rheumatoid arthritis, there is not the possibility that is provided any enlightenment by other compounds, possess outstanding substantive distinguishing features, the control for rheumatoid arthritis simultaneously obviously has significant progress.
The specific embodiment
The preparation method of compound Gypensapogenin B 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 subject to any restriction of specific embodiment, but be limited by claim.
Embodiment 1: the preparation of compound Gypensapogenin B tablet involved in the present invention:
Get 20 and digest compound Gypensapogenin B, add 180 grams of conventional adjuvants preparing tablet, mix, conventional tablet machine is made 1000.
Embodiment 2: the preparation of compound Gypensapogenin B capsule involved in the present invention:
Get 20 and digest compound Gypensapogenin B, add the conventional adjuvant of preparing capsule as 180 grams of starch, mix, encapsulatedly make 1000.
Below by pharmacodynamic experiment, further illustrate its pharmaceutically active.
Experimental example 1, the impact of Gypensapogenin B of the present invention on rat assist agent arthritis
After mycobacterium butyricum (Difco) is ground, mix with liquid paraffin, be made into 10mg/ml, after autoclaving, make Freund's complete adjuvant.The right back foot of the male SD rat above-mentioned adjuvant 50ul of intradermal injection that wastes time, simultaneously at afterbody apart from the about 3cm of the root of the tail intradermal injection 50ul of place, respectively at different time before injection and after injection, measure the left and right foot of the rat volume of wasting time, to inject the difference of front and back, represent swelling.From latter the 16th day of adjuvant injection, the left back foot swelling of rat is obvious, by swelling and body weight, rat is divided into groups, experimental group is oral gives Gypensapogenin B 5.0 of the present invention, 10.0,20.0mg/kg, the oral diclofenac 10mg/kg that gives of positive controls, matched group gives isopyknic distilled water, every day 1 time, continuous 7 days, latter the 16th, 22 days of adjuvant injection, measure swelling (primary reaction) and the left back foot swelling (secondary reactions) of wasting time of wasting time of Rat Right metapedes, and in the 22nd day by the left back foot of the following standard evaluation rat lesion degree of wasting time.0: without red and swollen; 1: little toe joint is slightly swollen; 2: toe joint and the sufficient swelling of wasting time; 3: the sufficient pawl swelling below ankle joint; 4: comprise the whole sufficient pawl swelling of ankle joint.
The impact (x ± SD, n=8) of table 1 Gypensapogenin B of the present invention on the sufficient swelling of wasting time of adjuvant arthritis rat primary
* p<0.01, with matched group comparison
The impact (x ± SD, n=8) of table 2 Gypensapogenin B of the present invention on the sufficient swelling of wasting time of adjuvant arthritis rat Secondary cases
* p<0.05, * * p<0.01, with matched group comparison
From table 1, table 2, Gypensapogenin B 10.0 of the present invention, 20.0mg/kg oral administration, continuous 7 days, significantly suppress constitutional and the Secondary cases swelling of rat assist agent arthritis, alleviate the secondary arthritis that rat foot is wasted time.
Experimental example 2, Gypensapogenin B on Carrageenan of the present invention cause the impact of the sufficient swelling of wasting time of rat
Male SD rat, experimental group is oral gives Gypensapogenin B 5.0 of the present invention, 10.0,20.0mg/kg, the oral diclofenac 10mg/kg that gives of positive controls, matched group gives isopyknic distilled water, 1 as a child, the 1% carrageenin normal saline 0.1ml that the right back foot of each Mus is wasted time subcutaneous injection sterilizing, measures the sufficient volume of wasting time of Rat Right respectively at injection is front for latter 1,3 hour with injection, to inject the difference of front and back, represents swelling.
From table 3, Gypensapogenin B 10.0 of the present invention, 20.0mg/kg oral administration, obviously alleviates due to carrageenin the swelling of wasting time of rat foot.
Table 3 Gypensapogenin B of the present invention on Carrageenan causes the impact (x ± SD, n=8) of the sufficient swelling of wasting time of rat
* p<0.05, * * p<0.01, with matched group comparison
Conclusion: Gypensapogenin B can significantly suppress arthritis, can be used for preparing arthritis disease drug.
Claims (1)
- The application of 1.Gypensapogenin B in preparing drugs for rheumatoid arthritis, described compound Gypensapogenin B structure as formula Ishown in:
formula I.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210417398.XA CN102885828B (en) | 2012-10-26 | 2012-10-26 | Application of Gypensapogenin B in medicament for treating rheumatoid arthritis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210417398.XA CN102885828B (en) | 2012-10-26 | 2012-10-26 | Application of Gypensapogenin B in medicament for treating rheumatoid arthritis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102885828A CN102885828A (en) | 2013-01-23 |
| CN102885828B true CN102885828B (en) | 2014-04-16 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210417398.XA Active CN102885828B (en) | 2012-10-26 | 2012-10-26 | Application of Gypensapogenin B in medicament for treating rheumatoid arthritis |
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| Country | Link |
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| CN (1) | CN102885828B (en) |
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2012
- 2012-10-26 CN CN201210417398.XA patent/CN102885828B/en active Active
Non-Patent Citations (1)
| Title |
|---|
| Ning Li，等.Triterpenes possessing an unprecedented skeleton isolated from hydrolyzate of total saponins from Gynostemma pentaphyllum.《European Journal of Medicinal Chemistry》.2012,第50卷173-178. * |
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| CN102885828A (en) | 2013-01-23 |
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Owner name: QIDONG TIANFEN ELECTRIC TOOL TECHNOLOGY INNOVATION Free format text: FORMER OWNER: WU JUNHUA Effective date: 20141126 |
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Effective date of registration: 20141126 Address after: Qidong City, Jiangsu province 226241 Nantong lvsigang Tianfen electric tools trade city comprehensive building Patentee after: Qidong Tianfen Electric Tool Technology Innovation Center Address before: 210009 No. 22, Hankou Road, Gulou District, Jiangsu, Nanjing Patentee before: Wu Junhua |