CN1557830A - Process for preparing 20(R)-ginsenoside Rh2 - Google Patents
Process for preparing 20(R)-ginsenoside Rh2 Download PDFInfo
- Publication number
- CN1557830A CN1557830A CNA2004100218351A CN200410021835A CN1557830A CN 1557830 A CN1557830 A CN 1557830A CN A2004100218351 A CNA2004100218351 A CN A2004100218351A CN 200410021835 A CN200410021835 A CN 200410021835A CN 1557830 A CN1557830 A CN 1557830A
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- China
- Prior art keywords
- acid
- preparation
- ginsenoside
- rhs
- saponin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- CKUVNOCSBYYHIS-SUEBGMEDSA-N (2r,3r,4s,5s,6r)-2-[[(3s,5r,8r,9r,10r,12r,13r,14r,17s)-12-hydroxy-17-[(2r)-2-hydroxy-6-methylhept-5-en-2-yl]-4,4,8,10,14-pentamethyl-2,3,5,6,7,9,11,12,13,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound O([C@H]1CC[C@]2(C)[C@H]3C[C@@H](O)[C@H]4[C@@]([C@@]3(CC[C@H]2C1(C)C)C)(C)CC[C@@H]4[C@](C)(O)CCC=C(C)C)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O CKUVNOCSBYYHIS-SUEBGMEDSA-N 0.000 title claims abstract description 33
- CKUVNOCSBYYHIS-UHFFFAOYSA-N (20R)-ginsenoside Rg3 Natural products CC(C)=CCCC(C)(O)C1CCC(C2(CCC3C4(C)C)C)(C)C1C(O)CC2C3(C)CCC4OC1OC(CO)C(O)C(O)C1O CKUVNOCSBYYHIS-UHFFFAOYSA-N 0.000 title abstract 3
- CKUVNOCSBYYHIS-LGYUXIIVSA-N 20(R)-Ginsenoside Rh2 Natural products O([C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1)[C@@H]1C(C)(C)[C@H]2[C@@](C)([C@H]3[C@](C)([C@@]4(C)[C@H]([C@H](O)C3)[C@@H]([C@](O)(CC/C=C(\C)/C)C)CC4)CC2)CC1 CKUVNOCSBYYHIS-LGYUXIIVSA-N 0.000 title abstract 3
- 238000004519 manufacturing process Methods 0.000 title description 2
- 229930182490 saponin Natural products 0.000 claims abstract description 24
- 150000007949 saponins Chemical class 0.000 claims abstract description 24
- 238000002360 preparation method Methods 0.000 claims abstract description 22
- 238000000034 method Methods 0.000 claims abstract description 21
- 239000001397 quillaja saponaria molina bark Substances 0.000 claims abstract description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 8
- 150000007524 organic acids Chemical class 0.000 claims abstract description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000000463 material Substances 0.000 claims abstract description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000005903 acid hydrolysis reaction Methods 0.000 claims abstract description 5
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims abstract description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims abstract description 3
- 235000019253 formic acid Nutrition 0.000 claims abstract description 3
- 229910017604 nitric acid Inorganic materials 0.000 claims abstract description 3
- 235000017709 saponins Nutrition 0.000 claims description 22
- 238000006243 chemical reaction Methods 0.000 claims description 12
- 241000208340 Araliaceae Species 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- 238000001953 recrystallisation Methods 0.000 claims description 6
- 238000010898 silica gel chromatography Methods 0.000 claims description 6
- 239000002775 capsule Substances 0.000 claims description 5
- 239000000376 reactant Substances 0.000 claims description 5
- 239000007924 injection Substances 0.000 claims description 4
- 238000002347 injection Methods 0.000 claims description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 4
- 239000011707 mineral Substances 0.000 claims description 4
- 239000000243 solution Substances 0.000 claims description 4
- 241000196324 Embryophyta Species 0.000 claims description 3
- 239000007901 soft capsule Substances 0.000 claims description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- 230000001476 alcoholic effect Effects 0.000 claims description 2
- 239000011260 aqueous acid Substances 0.000 claims description 2
- 230000003301 hydrolyzing effect Effects 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 abstract description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 5
- 241000208343 Panax Species 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 4
- 239000000203 mixture Substances 0.000 abstract description 3
- 230000008569 process Effects 0.000 abstract description 3
- 239000007795 chemical reaction product Substances 0.000 abstract description 2
- 239000000047 product Substances 0.000 abstract description 2
- 150000007522 mineralic acids Chemical class 0.000 abstract 2
- 235000002791 Panax Nutrition 0.000 abstract 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 abstract 1
- 239000000741 silica gel Substances 0.000 abstract 1
- 229910002027 silica gel Inorganic materials 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 11
- 229940089161 ginsenoside Drugs 0.000 description 10
- 239000013078 crystal Substances 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical group ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 206010028980 Neoplasm Diseases 0.000 description 6
- 201000011510 cancer Diseases 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- CKUVNOCSBYYHIS-IRFFNABBSA-N (20S)-ginsenoside Rh2 Chemical compound O([C@H]1CC[C@]2(C)[C@H]3C[C@@H](O)[C@H]4[C@@]([C@@]3(CC[C@H]2C1(C)C)C)(C)CC[C@@H]4[C@@](C)(O)CCC=C(C)C)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O CKUVNOCSBYYHIS-IRFFNABBSA-N 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 4
- 235000003140 Panax quinquefolius Nutrition 0.000 description 4
- 238000011097 chromatography purification Methods 0.000 description 4
- 235000008434 ginseng Nutrition 0.000 description 4
- 229930182494 ginsenoside Natural products 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 206010013786 Dry skin Diseases 0.000 description 3
- 239000000890 drug combination Substances 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000000413 hydrolysate Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 235000002789 Panax ginseng Nutrition 0.000 description 2
- 230000018199 S phase Effects 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 150000001243 acetic acids Chemical class 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 238000005100 correlation spectroscopy Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000000227 grinding Methods 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 201000007270 liver cancer Diseases 0.000 description 2
- 208000014018 liver neoplasm Diseases 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- RWXIFXNRCLMQCD-JBVRGBGGSA-N (20S)-ginsenoside Rg3 Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H]1CC[C@]2(C)[C@H]3C[C@@H](O)[C@H]4[C@@]([C@@]3(CC[C@H]2C1(C)C)C)(C)CC[C@@H]4[C@@](C)(O)CCC=C(C)C)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O RWXIFXNRCLMQCD-JBVRGBGGSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 208000001382 Experimental Melanoma Diseases 0.000 description 1
- XIRZPICFRDZXPF-UHFFFAOYSA-N Ginsenoside Rg3 Natural products CC(C)=CCCC(C)(O)C1CCC(C2(CC(O)C3C4(C)C)C)(C)C1C(O)CC2C3(C)CCC4OC1OC(CO)C(O)C(O)C1OC1OC(CO)C(O)C(O)C1O XIRZPICFRDZXPF-UHFFFAOYSA-N 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241001529246 Platymiscium Species 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000004069 differentiation Effects 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
- 238000007908 dry granulation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000005096 rolling process Methods 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000002476 tumorcidal effect Effects 0.000 description 1
- 235000020985 whole grains Nutrition 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
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/582—Recycling of unreacted starting or intermediate materials
Landscapes
- Steroid Compounds (AREA)
Abstract
The present invention is the preparation process of 20(R)-ginsenoside Rh2 with panax leaf and stem total saponin or protopanoxadiol saponin as initial material. The preparation process includes dissolving the material in the water solution or alcohol solution of organic acid or inorganic acid for acid hydrolysis and collecting the reaction product. The product may be silica gel chromatographic column separated and re-crystallized to purify. The acid hydrolysis is completed at 30-100 deg.c and 0.05-1 MPa, and the organic acid and the inorganic acid include formic acid, acetic acid, hydrochloric acid, sulfuric acid and nitric acid. In addition, the prepare process of medicine composition with 20(R)-ginsenoside Rh2 is also disclosed. The present invention has reasonable technological process and high yield.
Description
Technical field
The present invention relates to 20 (R)-ginsenoside Rhs
2The preparation method.
Background technology
Cancer is the disease of serious harm human health.Statistical information according to The World Health Organization (WHO) shows, about 1,000 ten thousand people of the annual morbidity of whole world cancer, and dead about 7,000,000 people have become the mankind second killer who is only second to cardiovascular diseases.The cancer therapy drug of clinical application at present has bigger toxic side effect more.Therefore, the medicine of developing new treatment cancer is very urgent, especially seeks the focus that the person that always is the drug research of anticancer active constituent safely and efficiently pays close attention to from the traditional plant amedica of China.
The eighties in 20th century, a large amount of research reports shows that ginsenoside has certain anti-tumor activity, (pharmaceutical journals [day] 1983.103 such as particularly Japanese scholar's Beichuan merit; 612) from red ginseng, isolate 20 (S)-ginsenoside Rhs
2Content only be 100,000 of red ginseng/, and by the respectful husband of Xiao Tiandao (ginseng for medicinal use ' 85, Tokyo: the upright altogether Co., Ltd. that publishes, 1990:84) carry out cell in vitro and cultivated inhibition test, found that this composition is to the mice lung cancer cell, the B16 melanoma cell, the propagation of rat Morris liver cancer cell has tangible specificity tumor-inhibiting action, i.e. inducing cancer cell differentiation reverse effect.From then on, the lot of domestic and foreign scholar to 20 (S)-ginsenosides produce and research has extensively and profoundly been carried out in the pharmacology aspect.
Studies show that, 20 (S)-ginsenosides also can be induced the HL-60 cell, the differentiation of F9 deformity cancer cells, suppress the growth of Proliferation of Human Ovarian Cell HT1080 people fiber inner tumour cell, to the S180 sarcoma cell, S phase cell capable of blocking was divided a word with a hyphen at the end of a line to positive 2 phases, cause the accumulation of S phase tumour cell, thereby suppress the propagation of S180 sarcoma cell, induce human liver cancer cell SK-HEP-1, C
6The glioma cell apoptosis.People such as Chen Yingjie (herbal medicine 1988.19 (3): 4) from Stem and leaf of Radix Ginseng, isolate epimer 20 (the R)-ginsenoside of 20 (S)-ginsenosides, this compound just has stronger tumoricidal activity when concentration 0.1 μ g/ml, can suppress human body children's grain leukemia HL60 early when 2 μ g/ml significantly.Studies show that further (Shenyang Pharmacy College's journal, 1999,16 (2): 152) the ginsenoside anti-tumor activity is subjected to C
20The strong and weak rule of position configuration influence is: 20 (R)-ginsenoside＞20 (S)-ginsenosides.
Yet no matter be 20 (R)-ginsenosides or 20 (S)-ginsenosides content in the natural ginseng platymiscium extremely low (0.001%～0.006%), directly extraction and application does not have practical significance.In recent years, people successfully utilize mild hydrolysis method under biological enzyme or the alkaline condition by making great efforts exploration, and from genseng and stem and leaf of Radix Panacis Quinquefolii saponin, the total saponin of panax species or its protopanoxadiol group saponin make 20 (S)-ginsenoside Rhs
2, above method can make 20 (S)-ginsenoside Rhs
2Higher yields (1.4%～5.6%) is arranged, thereby make it be applied to the clinical possibility that becomes.But from the total saponin of panax species, haulm general saponin or its protopanoxadiol group saponin make 20 (R)-ginsenoside Rhs
2Do not appear in the newspapers as yet.Korea S genseng Dohanykutato Intezet discloses a kind of 20 (R)-ginsenoside Rhs that prepare from constituent of ginseng
2Method (korean patent application bulletin 94-8291), be at first to use acid hydrolysis ginsenoside protopanoxadiol component, obtain 20 (R﹠amp through acetylize and hydrolysis treatment again; S)-ginsenoside Rg3, and then carry out basic hydrolysis with alkaline butanol solution and obtain 20 (R﹠amp; S)-and ginsenoside, after the silicic acid column chromatography for separation obtains 20 (R)-ginsenoside Rhs
2With 20 (S)-ginsenoside Rhs
2
It is emphasized that aforesaid method is unfavorable for 20 (R)-ginsenoside Rhs
2Suitability for industrialized production, its major defect is at first to obtain protopanoxadiol group saponin, has increased the step of the separation and purification of this group saponin, transforms in the preparation and has passed through 20 (R﹠amp; S)-and numerous and diverse reactions steps such as the preparation of ginsenoside Rg3, acetylize, catalytic hydrolysis, cause the reaction product composition to increase, and products therefrom is 20 (R﹠amp; S)-ginsenoside Rh
2, be difficult to obtain 20 pure (R)-ginsenoside Rhs
2With the raising productive rate.This is technical barrier that urgency is to be solved in this problem.
Summary of the invention
The objective of the invention is at the deficiencies in the prior art and blank, a kind of 20 (R)-ginsenoside Rhs are provided
2The preparation method.This method realizes that by new path for transformation high yield conversion obtains 20 purer (R)-ginsenoside Rhs from the total saponin of panax species, haulm general saponin or protopanoxadiol group saponin
2Simultaneously, the present invention also aims to provide and contain 20 (R)-ginsenoside Rhs
2The preparation of drug combination method.
Purpose of the present invention is achieved by following technical proposals.
The invention provides a kind of is parent material preparation 20 (R)-ginsenoside Rhs with araliaceae ginseng plant's stem and leaf total saponins or protopanoxadiol group saponin
2Method, this method comprises dissolves in described plant stem-leaf total saponins in organic acid or inorganic aqueous acid or the alcoholic solution, carries out acid hydrolytic reaction, collects reactant then.
Described reactant is further carried out silica gel column chromatography and recrystallization purifying; Described acid hydrolysis step is carried out under 30 ℃～100 ℃ and 0.05Mpa～1MPa; The concentration of described organic acid or mineral acid is 0.01%～80% (w/v); Described organic acid or mineral acid comprise formic acid, acetate, hydrochloric acid, sulfuric acid or nitric acid.
The present invention also further provides and has contained 20 (R)-ginsenoside Rhs
2The preparation of drug combination method, described preparation of drug combination method is select to add the auxiliary material that pharmaceutically is suitable for to make capsule, soft capsule, tablet or injection etc. respectively.
Embodiment
By specific embodiment given below, can further be well understood to the present invention.But they are not limitation of the invention.
Embodiment 1
100 milliliters of the aqueous acetic acids of preparation 60%, add panoxadiol saponins dry powder 20 grams, under 0.1 MPa pressure, stirring heating, the reaction 2 hours that is hydrolyzed under 100 ℃ is after reaction is finished, water is washed till neutrality with reaction mixture, filter, the filter thing gets hydrolysate 12 grams 100 ℃ of dryings.With silica gel column chromatography, elutriant is a chloroform: methyl alcohol: ethyl acetate: water=2: 2: 4: 1 (volume ratio) chromatography purification, collect eluate recrystallization in methanol-water, and obtain 20 (R)-ginsenoside Rhs
2983 milligrams of white crystals bodies, yield 4.92%.Crystal purity is determined as 97.6% through the HPLC method.Process TLC, MS,
13C-NMR,
1H-NMR,
13C-
1HCOSY,
1H-
1HCOSY, specific rotatory power and fusing point test, and with 20 (R)-ginsenoside Rhs
2Data in literature examine, confirm that this white crystal is 20 (R)-ginsenoside Rhs
2
Embodiment 2
In the ethanol with 40 milliliter 95% of 60 milliliters of Glacial acetic acid adding, add panoxadiol saponins dry powder 20 grams, under 0.1 MPa pressure, stirring heating, the reaction 1.5 hours that is hydrolyzed under 75 ℃ is after reaction is finished, pour into while hot in 400 milliliters of 25 ℃ of water and dilute decompression recycling ethanol.Reactant continues to wash with water to neutrality, filters, and the filter thing is dry under 80 ℃, gets hydrolysate 13.6 grams.With silica gel column chromatography, elutriant is a chloroform: methyl alcohol: ethyl acetate: water=2: 2: 4: 1 (volume ratio) chromatography purification, collect eluate recrystallization in methanol-water, and obtain 20 (R)-ginsenoside Rhs
21082 milligrams of white crystals bodies, yield 7.95%.Its purity is determined as 95.3% through the HPLC method.Through TLC, MS,
13C-NMR,
1H-NMR,
13C-
1H COSY,
1H-
1HCOSY, specific rotatory power and fusing point test, and with 20 (R)-ginsenoside Rhs
2Data in literature examine, confirm that this white crystal is 20 (R)-ginsenoside Rhs
2
Embodiment 3
10 milliliter 36% hydrochloric acid is dissolved in the water, make and be 100 milliliters, add panoxadiol saponins dry powder 20 grams, under 0.1 MPa pressure, stirring heating, reaction 1.5 hours is hydrolyzed under 100 ℃, after reaction was finished, water was washed till neutrality with reaction mixture, filtered, the filter thing gets hydrolysate 11.4 grams 100 ℃ of dryings.With silica gel column chromatography, elutriant is a chloroform: methyl alcohol: ethyl acetate: water=2: 2: 4: 1 (volume ratio) chromatography purification, collect eluate recrystallization in methanol-water, and obtain 20 (R)-ginsenoside Rhs
2869 milligrams of white crystals bodies, yield 4.35%.Its purity is determined as 96.2% through the HPLC method.Through TLC, MS,
13C-NMR,
1H-NMR,
13C-
1HCOSY,
1H-
1HCOSY. specific rotatory power and fusing point test, and with 20 (R)-ginsenoside Rhs
2Data in literature examine, confirm that this white crystal is 20 (R)-ginsenoside Rhs
2
Embodiment 4
10 liters of the aqueous acetic acids of preparation 60%, add 2 kilograms in panoxadiol saponins dry powder, under 0.1 MPa pressure, stirring heating, the reaction 2 hours that is hydrolyzed under 100 ℃ is after reaction is finished, water is washed till neutrality with reaction mixture, filter, the filter thing gets 1.18 kilograms of hydrolysates 100 ℃ of dryings.With silica gel column chromatography, elutriant is a chloroform: methyl alcohol: ethyl acetate: water=2: 2: 4: 1 (volume ratio) chromatography purification, collect eluate recrystallization in methanol-water, and obtain 20 (R)-ginsenoside Rhs
2White crystals body 89 gram, yield 4.45%.Its purity is determined as 95.8% through the HPLC method.Through TLC, MS,
13C-NMR,
1H-NMR,
13C-
1H COSY,
1H-
1HCOSY. specific rotatory power and fusing point test, and with 20 (R)-ginsenoside Rhs
2Data in literature examine, confirm that this white crystal is 20 (R)-ginsenoside Rhs
2
Embodiment 5
With 20 (R)-ginsenoside Rhs
2Powder 10%, Microcrystalline Cellulose 90% mixes, the Place grinding machine ground 2 hours, crossed 120 mesh sieves, abundant mixing, inspect qualified after, branch is packed in the capsulae vacuus, promptly gets 20 required (R)-ginsenoside Rhs
2Capsule.
Embodiment 6
With 20 (R)-ginsenoside Rhs
2Powder dissolves in the hydrogenated vegetable oil, and both weight ratios are 1: 9, is uniform oil solution, adopts rotation rolling capsule machine or capsule and pill dropping method automatically then, makes 20 required (R)-ginsenoside Rhs
2Soft capsule preparation.
Embodiment 7
With 20 (R)-ginsenoside Rhs
2Powder 10%; Microcrystalline Cellulose 90% mixes; the Place grinding machine ground 2 hours, crossed 120 mesh sieves, added proper quantity of medicinal auxiliary material; abundant mixing; making granularity through dry granulation or one-step-granulating method is 40～80 purpose particles, adds the Magnesium Stearate of particle weight 0.5%～1.0% in dried particle, and the back compacting of the whole grain of mixing in flakes; behind the bag book film clothing, make 20 required (R)-ginsenoside Rhs
2Tablet.
Embodiment 8
Get 200 milliliters of distilled water for injection, the adding tween-80 is an amount of, adds 200 milligram of 20 (R)-ginsenoside Rh again
2Powder, heating for dissolving, filtration, packing, sterilization are made every milliliter and are contained 1 milligram of 20 (R)-ginsenoside Rh
2Injection liquid, be sub-packed in ampoule.
Claims (7)
1. one kind is parent material preparation 20 (R)-ginsenoside Rhs with araliaceae ginseng plant's stem and leaf total saponins or protopanoxadiol group saponin
2Method, this method comprises dissolves in described plant stem-leaf total saponins or protopanoxadiol group saponin in organic acid or inorganic aqueous acid or the alcoholic solution, carries out acid hydrolytic reaction, collects reactant then.
2. preparation method according to claim 1 further comprises described reactant is carried out silica gel column chromatography and recrystallization purifying.
3. preparation method according to claim 1, wherein said acid hydrolysis step carry out under 30 ℃～100 ℃ and 0.05Mpa～1MPa.
4. preparation method according to claim 1, the concentration of wherein said described organic acid or mineral acid are 0.01%～80% (w/v).
5. according to claim 1 or 4 described preparation methods, wherein said organic acid or mineral acid comprise formic acid, acetate, hydrochloric acid, sulfuric acid or nitric acid.
6. preparation method according to claim 2 further comprises 20 (R)-ginsenoside Rhs
2Make pharmaceutical composition.
7. preparation method according to claim 6, wherein said pharmaceutical composition is pharmaceutically described capsule, soft capsule preparation, tablet or injection.
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| CNB2004100218351A CN100486988C (en) | 2004-02-13 | 2004-02-13 | Process for preparing 20(R)-ginsenoside Rh2 |
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| CNB2004100218351A CN100486988C (en) | 2004-02-13 | 2004-02-13 | Process for preparing 20(R)-ginsenoside Rh2 |
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| CN100486988C CN100486988C (en) | 2009-05-13 |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100423727C (en) * | 2006-01-19 | 2008-10-08 | 云南天秀植物科技开发有限公司 | Antineoplastic composition, and process for preparing the same |
| CN101828712A (en) * | 2010-04-30 | 2010-09-15 | 吉林大学 | Process for preparing ginsenoside acid degraded product and application of ginsenoside acid degraded product |
| CN101288475B (en) * | 2008-05-20 | 2012-05-30 | 吉林省宏久生物科技股份有限公司 | Production method of flavor panax ginseng |
| CN102731603A (en) * | 2011-03-31 | 2012-10-17 | 上海兰蒂斯生物医药科技有限公司 | Preparation method of panaxadiol and 20(R)-protopanaxadiol |
| CN107805270A (en) * | 2017-10-30 | 2018-03-16 | 江苏吉生源生物科技有限公司 | A kind of ginsenoside Rh2Extracting method |
-
2004
- 2004-02-13 CN CNB2004100218351A patent/CN100486988C/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100423727C (en) * | 2006-01-19 | 2008-10-08 | 云南天秀植物科技开发有限公司 | Antineoplastic composition, and process for preparing the same |
| CN101288475B (en) * | 2008-05-20 | 2012-05-30 | 吉林省宏久生物科技股份有限公司 | Production method of flavor panax ginseng |
| CN101828712A (en) * | 2010-04-30 | 2010-09-15 | 吉林大学 | Process for preparing ginsenoside acid degraded product and application of ginsenoside acid degraded product |
| CN102731603A (en) * | 2011-03-31 | 2012-10-17 | 上海兰蒂斯生物医药科技有限公司 | Preparation method of panaxadiol and 20(R)-protopanaxadiol |
| CN107805270A (en) * | 2017-10-30 | 2018-03-16 | 江苏吉生源生物科技有限公司 | A kind of ginsenoside Rh2Extracting method |
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|---|---|
| CN100486988C (en) | 2009-05-13 |
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