CN1096031A - The medicine and the method for making thereof that beta-2 adrenoceptor and M cholinocepter are had dual regulation - Google Patents
The medicine and the method for making thereof that beta-2 adrenoceptor and M cholinocepter are had dual regulation Download PDFInfo
- Publication number
- CN1096031A CN1096031A CN 93112451 CN93112451A CN1096031A CN 1096031 A CN1096031 A CN 1096031A CN 93112451 CN93112451 CN 93112451 CN 93112451 A CN93112451 A CN 93112451A CN 1096031 A CN1096031 A CN 1096031A
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- China
- Prior art keywords
- medicine
- beta
- adrenoceptor
- cholinocepter
- making
- Prior art date
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Links
- 239000003814 drug Substances 0.000 title abstract description 11
- 102000014974 beta2-adrenergic receptor activity proteins Human genes 0.000 title description 6
- 108040006828 beta2-adrenergic receptor activity proteins Proteins 0.000 title description 6
- 238000000034 method Methods 0.000 title description 5
- 230000009977 dual effect Effects 0.000 title description 3
- 102000005962 receptors Human genes 0.000 claims abstract description 6
- 108020003175 receptors Proteins 0.000 claims abstract description 6
- 238000004519 manufacturing process Methods 0.000 claims abstract description 4
- 102000012740 beta Adrenergic Receptors Human genes 0.000 claims abstract 2
- 108010079452 beta Adrenergic Receptors Proteins 0.000 claims abstract 2
- 229960001231 choline Drugs 0.000 claims abstract 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- 230000000694 effects Effects 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 230000007935 neutral effect Effects 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
- 241000605447 Anemarrhena Species 0.000 claims 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims 1
- 229930191283 anemarrhena Natural products 0.000 claims 1
- 235000011149 sulphuric acid Nutrition 0.000 claims 1
- 239000000556 agonist Substances 0.000 abstract description 4
- 239000005557 antagonist Substances 0.000 abstract description 4
- 229940079593 drug Drugs 0.000 abstract description 2
- 230000001105 regulatory effect Effects 0.000 abstract description 2
- 230000002457 bidirectional effect Effects 0.000 abstract 1
- 238000011031 large-scale manufacturing process Methods 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- 229930193981 timosaponin Natural products 0.000 abstract 1
- VQMZQKBLIKANMK-IKFJEIPGSA-N (2S,3R,4S,5S,6R)-2-[(2R,3R,4S,5R,6R)-4,5-dihydroxy-6-(hydroxymethyl)-2-[(1R,2S,4S,5'S,6R,7S,8R,9S,12S,13S,16S,18R)-5',7,9,13-tetramethylspiro[5-oxapentacyclo[10.8.0.02,9.04,8.013,18]icosane-6,2'-oxane]-16-yl]oxyoxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol (2S,3R,4S,5S,6R)-2-[(2R,3S,4S,5R,6R)-4,5-dihydroxy-6-(hydroxymethyl)-2-[(1S,2R,4R,5'S,6R,7R,8S,9S,12R,13S,16R,18S)-5',7,9,13-tetramethylspiro[5-oxapentacyclo[10.8.0.02,9.04,8.013,18]icosane-6,2'-oxane]-16-yl]oxyoxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical group C[C@H]1CC[C@@]2([C@@H]([C@@H]3[C@H](O2)C[C@H]4[C@@]3(CC[C@@H]5[C@@H]4CC[C@@H]6[C@@]5(CC[C@H](C6)O[C@H]7[C@H]([C@H]([C@H]([C@H](O7)CO)O)O)O[C@H]8[C@@H]([C@H]([C@@H]([C@H](O8)CO)O)O)O)C)C)C)OC1.C[C@H]1CC[C@@]2([C@H]([C@H]3[C@@H](O2)C[C@@H]4[C@@]3(CC[C@H]5[C@H]4CC[C@H]6[C@@]5(CC[C@@H](C6)O[C@H]7[C@@H]([C@H]([C@H]([C@H](O7)CO)O)O)O[C@H]8[C@@H]([C@H]([C@@H]([C@H](O8)CO)O)O)O)C)C)C)OC1 VQMZQKBLIKANMK-IKFJEIPGSA-N 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 238000002791 soaking Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 210000001835 viscera Anatomy 0.000 description 2
- 241000605445 Anemarrhena asphodeloides Species 0.000 description 1
- 241000612118 Samolus valerandi Species 0.000 description 1
- GMBQZIIUCVWOCD-WWASVFFGSA-N Sarsasapogenin Natural products O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CC[C@H](O)C[C@H]4CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@H](C)CO1 GMBQZIIUCVWOCD-WWASVFFGSA-N 0.000 description 1
- RTMWIZOXNKJHRE-UHFFFAOYSA-N Tigogenin Natural products CC1COC2CC(C)(OC12)C3CCC4C5CCC6CC(O)CCC6(C)C5CCC34C RTMWIZOXNKJHRE-UHFFFAOYSA-N 0.000 description 1
- 230000004308 accommodation Effects 0.000 description 1
- YBCVMFKXIKNREZ-UHFFFAOYSA-N acoh acetic acid Chemical compound CC(O)=O.CC(O)=O YBCVMFKXIKNREZ-UHFFFAOYSA-N 0.000 description 1
- 239000000048 adrenergic agonist Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000007365 immunoregulation Effects 0.000 description 1
- 230000000955 neuroendocrine Effects 0.000 description 1
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明是一种对β肾上腺素受体和M胆碱受 体有双向调节作用的药——知母皂苷元及其制法。 它具有对两种受体有双向调节作用的特殊优点，并且 不同于西药中的激动剂或拮抗剂，不存在停药“反跳” 现象。其制造工艺亦具有成本低，得率高，操作简便， 适用于大规模生产等特点。The present invention is a kind of beta adrenergic receptor and M choline receptor Medicine with two-way regulating effect on the body - timosaponin and its preparation method. It has the particular advantage of bidirectional modulation of both receptors, and Unlike agonists or antagonists in Western medicine, there is no withdrawal "rebound" Phenomenon. Its manufacturing process also has low cost, high yield, easy operation, Suitable for large-scale production and other characteristics.
Description
The present invention discloses a kind ofly has the medicine-zhimusaponin unit and the method for making thereof of dual regulation to beta-2 adrenoceptor and M cholinocepter, belongs to medicine and makes the field.
The biology and the medical significance of cell receptor are more and more paid attention to by people, the activity of it and central nervous system, the regulating effect of neuroendocrine pair cell, and drug effect, immunoregulation etc. all have substantial connection.Cell receptor and clinical relation also are familiar with by people day by day.The researchdevelopment of acceptor medicine is very fast in the world, but mainly is synthetic drug, and is agonist or the antagonist that plays association reaction with acceptor basically.The effect of these medicines belongs to suiting the medicine to the illness property, and their common drawback is: side effect is more, and action time is short, and drug withdrawal " knock-on " phenomenon may occur.
The objective of the invention is to: proposing a kind ofly has the medicine of Accommodation and is suitable for scale operation beta-2 adrenoceptor and M cholinocepter, and easy and simple to handle, cost is low, the method for making that yield is high.
The objective of the invention is to realize by following technical proposals:
At first, dry, beat powder,, add the 3%H of 3.5 times of volumes with warm water soaking with the wind-weed (Anemarrhena asphodeloides Bunge) chopping
2SO
4, at 0.7-1.2Kgf/cm
2Pressure under, temperature is 115 ℃ of-122 ℃ of hydrolysis 6 hours; Filter after washing to neutral, oven dry; Again with ethyl acetate backflow, through twice extraction, at last with acetone recrystallization, obtain purity and be more than 95% zhimusaponin unit (sarsasapogenin)-(3 β, 5 β, 25s)-Spironstan-30l.Structure is:
Evident characteristic of the present invention is:
1, the internal organ (comprising brain) that pathologic is raise and the beta-2 adrenoceptor number of peripheral blood lymphocyte, and the plasma C AMP that the beta-2 adrenoceptor agonist causes excessively raises, and tangible downward modulation effect is arranged, and these variations are returned to normally.
2, internal organ (comprising brain) the M cholinocepter that pathologic is reduced has tangible rise effect, makes it to return near normal.
3, the brain m receptor that the naturally-aged animal is reduced has tangible rise effect, simultaneously its mean lifetime of significant prolongation.
4, different with agonist or antagonist in the Western medicine, be not that binding site with acceptor plays association reaction, but regulate the generating rate and the degradation rate of acceptor molecule, therefore there is not the drug withdrawal knock-on side effect of agonist or antagonist.
5, manufacture method is easy and simple to handle, and cost is low, and the productive rate height is suitable for suitability for industrialized production.
Below in conjunction with embodiment, the present invention is further described:
Embodiment 1: powder is beaten in 100g wind-weed chopping, warm water soaking, the 3%H of 3.5 times of volumes in addition again
2SO
4, at 0.7Kgf/cm
2115 ℃ of following acidolysis 8 hours, washing residue is to neutral; 80 ℃ of oven dry; With the reflux extraction of acetate acetate, reclaim solvent again, residue gets the zhimusaponin unit (yield 1.2%) more than 95% with acetone recrystallization twice.
Embodiment 2: with 300g wind-weed chopping, beat powder, warm water soaking, the 3%H of 3.5 times of volumes in addition again
2SO
4, at 1.05Kgf/cm
2, 121 ℃, 10 hours washing residue of following acidolysis are extremely neutral, 80 ℃ of oven dry, and solvent is reclaimed in the ethyl acetate backflow extraction, and residue gets the zhimusaponin unit (yield 2.0%) more than 95% with acetone recrystallization twice.
Claims (2)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 93112451 CN1033754C (en) | 1993-05-31 | 1993-05-31 | Use of timosaponin as a bidirectional modulator of β-adrenergic and M choline receptors and its preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 93112451 CN1033754C (en) | 1993-05-31 | 1993-05-31 | Use of timosaponin as a bidirectional modulator of β-adrenergic and M choline receptors and its preparation method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1096031A true CN1096031A (en) | 1994-12-07 |
| CN1033754C CN1033754C (en) | 1997-01-08 |
Family
ID=4990063
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 93112451 Expired - Lifetime CN1033754C (en) | 1993-05-31 | 1993-05-31 | Use of timosaponin as a bidirectional modulator of β-adrenergic and M choline receptors and its preparation method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1033754C (en) |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999048507A3 (en) * | 1998-03-26 | 1999-11-25 | Phytopharm Plc | Steroidal saponins for treating alzheimer's disease |
| CN1061985C (en) * | 1996-04-03 | 2001-02-14 | 中国科学院上海有机化学研究所 | Method for preparation of progestol by degradation of steroidal saponin |
| WO2001023408A1 (en) * | 1999-09-29 | 2001-04-05 | Phytopharm Plc | 5-hydroxysapogenin derivatives with anti-dementia activity |
| WO2001023407A1 (en) * | 1999-09-29 | 2001-04-05 | Phytopharm Plc | Sapogenin derivatives and their use in the treatment of cognitive dysfunction |
| WO2001049703A3 (en) * | 2000-01-06 | 2002-02-21 | Phytopharm Plc | Substituted sapogenins and their use |
| JP2003510332A (en) * | 1999-09-29 | 2003-03-18 | ファイトファーム・ピーエルシー | 5-β-sapogenin and pseudosapogenin derivatives and their use in treating dementia |
| AU781810B2 (en) * | 1998-03-26 | 2005-06-16 | Phytopharm Plc. | Steroidal sapogenins and their derivatives for treating Alzheimer's disease |
| US7166308B2 (en) | 1999-03-08 | 2007-01-23 | Zongqin Xia | Smilagenin and its use |
| CN1692914B (en) * | 2004-04-29 | 2010-05-26 | 中国人民解放军军事医学科学院放射医学研究所 | Use of timosaponin BⅡ in the preparation of drugs or products for preventing and treating stroke |
| EP2479183A3 (en) * | 2004-11-05 | 2013-08-28 | Phytopharm PLC | Polymorphs of sarsasapogenin |
-
1993
- 1993-05-31 CN CN 93112451 patent/CN1033754C/en not_active Expired - Lifetime
Cited By (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1061985C (en) * | 1996-04-03 | 2001-02-14 | 中国科学院上海有机化学研究所 | Method for preparation of progestol by degradation of steroidal saponin |
| KR100632052B1 (en) * | 1998-03-26 | 2006-10-04 | 파이토팜 피엘씨 | Steroidal Sapogenin and its Derivatives for the Treatment of Alzheimer's Disease |
| EP1719512A2 (en) | 1998-03-26 | 2006-11-08 | Phytopharm Plc | Sarsasapogenin and smilagenin for treating cognitive dysfunctions |
| US7507720B2 (en) | 1998-03-26 | 2009-03-24 | Phytopharm Plc | 5-Beta-sapogenin and pseudosapogenin derivatives and their use in the treatment of dementia |
| RU2297228C2 (en) * | 1998-03-26 | 2007-04-20 | Фитофарм Плк | Steroid sapogenins and their derivatives usable in medical treatment |
| CN100377714C (en) * | 1998-03-26 | 2008-04-02 | 植物药物公共有限公司 | Steroidal sapogenins and their derivatives for treating alzheimer's disease |
| AU748138B2 (en) * | 1998-03-26 | 2002-05-30 | Phytopharm Plc. | Steroidal sapogenins and their derivatives for treating alzheimers disease |
| AU781810B2 (en) * | 1998-03-26 | 2005-06-16 | Phytopharm Plc. | Steroidal sapogenins and their derivatives for treating Alzheimer's disease |
| KR100713311B1 (en) * | 1998-03-26 | 2007-05-04 | 파이토팜 피엘씨 | Smilagenin and Azurogeniin-D to Treat Alzheimer's Disease |
| WO1999048507A3 (en) * | 1998-03-26 | 1999-11-25 | Phytopharm Plc | Steroidal saponins for treating alzheimer's disease |
| US6812213B2 (en) | 1998-03-26 | 2004-11-02 | Phytopharm, Plc | Steroidal sapogenins and their derivatives for treating alzheimer's disease |
| WO1999048482A3 (en) * | 1998-03-26 | 2000-11-23 | Phytopharm Plc | Smilagenin and anzurogenin-d for the treatment of alzheimer's disease |
| US7166308B2 (en) | 1999-03-08 | 2007-01-23 | Zongqin Xia | Smilagenin and its use |
| US7368137B2 (en) | 1999-03-08 | 2008-05-06 | Phytopharm Plc | Smilagenin and its use |
| US7138427B2 (en) | 1999-03-26 | 2006-11-21 | Phytopharm Plc. | 5-β-sapogenin and pseudosapogenin derivatives and their use in the treatment of dementia |
| JP2003510332A (en) * | 1999-09-29 | 2003-03-18 | ファイトファーム・ピーエルシー | 5-β-sapogenin and pseudosapogenin derivatives and their use in treating dementia |
| JP2003510333A (en) * | 1999-09-29 | 2003-03-18 | ファイトファーム・ピーエルシー | Sapogenin derivatives and their use in the treatment of cognitive dysfunction |
| JP2003525869A (en) * | 1999-09-29 | 2003-09-02 | ファイトファーム・ピーエルシー | 5-hydroxysapogenin having anti-dementia activity |
| WO2001023407A1 (en) * | 1999-09-29 | 2001-04-05 | Phytopharm Plc | Sapogenin derivatives and their use in the treatment of cognitive dysfunction |
| EP1548025A3 (en) * | 1999-09-29 | 2008-11-19 | Phytopharm Plc | Sapogenin derivatives and their use in the treatment of cognitive dysfunction |
| WO2001023408A1 (en) * | 1999-09-29 | 2001-04-05 | Phytopharm Plc | 5-hydroxysapogenin derivatives with anti-dementia activity |
| WO2001049703A3 (en) * | 2000-01-06 | 2002-02-21 | Phytopharm Plc | Substituted sapogenins and their use |
| CN1692914B (en) * | 2004-04-29 | 2010-05-26 | 中国人民解放军军事医学科学院放射医学研究所 | Use of timosaponin BⅡ in the preparation of drugs or products for preventing and treating stroke |
| EP2479183A3 (en) * | 2004-11-05 | 2013-08-28 | Phytopharm PLC | Polymorphs of sarsasapogenin |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1033754C (en) | 1997-01-08 |
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| PB01 | Publication | ||
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| SE01 | Entry into force of request for substantive examination | ||
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Expiration termination date: 20130531 Granted publication date: 19970108 |