CN1054606C - Preparation method of antiviral compound eight-treasures extract - Google Patents
Preparation method of antiviral compound eight-treasures extract Download PDFInfo
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- CN1054606C CN1054606C CN96115901A CN96115901A CN1054606C CN 1054606 C CN1054606 C CN 1054606C CN 96115901 A CN96115901 A CN 96115901A CN 96115901 A CN96115901 A CN 96115901A CN 1054606 C CN1054606 C CN 1054606C
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- ketose
- treasures
- compound
- scape
- isopropylidene
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Abstract
The present invention relates to a new antiviral active compound; sedum ketose anhydride is extracted and separated from sedum; the sedum ketose anhydride is condensed with acetone by one step for obtaining a compound of showy sedum prime with activity; the showy sedum prime is isopropylidene sedum ketose anhydride by structural identification, and the structural formula is *. The compound can be used as a preparation for preparing new medicine of resisting duck hepatitis B viruses and bidirectional immunity.
Description
The present invention relates to field of medicaments, is to have the active compound of antiviral property, a kind of anti-duck hepatitis B virus and a two-way immunoregulatory active compound of being used for of more specifically saying so about a kind of.
Hepatitis B is one of main transmissible disease of harm humans health, and domestic have 10% population to carry hepatitis B surface antigen approximately.Though the medicine of treatment hepatitis B and the research of Hepatitis B virus vaccine thereof get along with at present, still do not have good specifics so far.The Crassulaceae plant is clearing heat and detoxicating at Ceng Zuowei among the people, dissipating blood stasis for subsidence of swelling and wound herbal medicine use, but to all further investigations of its intrinsic pharmaceutical activity.
The object of the present invention is to provide a kind of new compound with anti-hepatitis B virus activities, and the method for synthesizing this compound from the Crassulaceae plant milk extract.
The anti-hepatitis B virus activities compound of the present invention development is extraction in the herb of long medicine eight treasures (choice ingredients of certain special dishes) (H.spectabile) or Crassulaceae plant eight treasures (choice ingredients of certain special dishes) (Hylotelephium erythrosticlum) or Orostachys fimbriatus plants such as (Orostachys fimbriatus), separation and purification and obtain scape ketose acid anhydride, obtain to have active compound, called after Isopropylidene Sedoheptulosan (Hylotelephin) here with this scape ketose anhydridization compound and acetone one step condensation again.Synthetic this active compound mainly comprises following operation steps:
1, pulverizes dry Crassulaceae plant herb, with the boiling water leaching, generally leach twice earlier, merge leaching liquid;
2, leaching liquid is about 1/5th of a former leaching liquid volume to be evaporated to concentrated back volume earlier through thin film concentration thereafter again.The ethanol constant volume that adds equivalent is about about 50% alcoholic degree, places;
3, get supernatant liquor, by strong-acid type cation exchange fat post, handle by the strong basic type anion-exchange resin post more earlier;
4. effluent liquid steams and removes ethanol, and reclaims ethanol, obtains medicinal extract;
5, medicinal extract with diatomite and acidic alumina spice after, last alumina column with ethanol elution, obtains scape ketose acid anhydride;
6, the ketose acid anhydride of finding a view in the presence of an amount of sulfuric acid, adds acetone one and goes on foot condensation and obtain Isopropylidene Sedoheptulosan;
This antiviral activity compound Isopropylidene Sedoheptulosan that obtains as stated above.With modern spectral methods such as chemical, infrared, nucleus magnetic resonance and mass spectrums, the structure of this compound is identified qualification result is as follows:
Isopropylidene Sedoheptulosan is a white, needle-shaped crystals, m.p 224-225 ℃, distils [α] during fusion
D 28=-125.2 ° (aqueous solution), molecular formula C
10H
16O
6, M+232.Ultimate analysis: calculated value, C 51.72%, and H 6.94%; Measured value C51.32%, H 6.74%, and Molish reacts strong positive, orcinol reacting positive, Liebermann-Burchard reacting positive, the aubepine-sulfuric acid reaction positive.
IR (Vcm): 3,410 3280 (wide) 1,380 1,365 982 955 932 850 820 810,785 740 720
H-NMR L (CD
3)
2SO adds trifluoracetic acid δ:
1.31(S，3H，-CH
3)，1.43(S，3H，-CH
3)，3.43(d，1H，J＝12，C
1-H)，3.65(d，1H，C
1-H′)，3.61(d，1H，J
3，4＝5，C3-H)，3.73(d，1H，J
6，7＝5.4，C
7-H
8x)，3.85(d，1H，J
6，7 8n＝1.5，C
7-H
8n)，4.01(q，1H，J
4，5＝6，C
4-H)，4.21(q，1H，J
5，6＝1.2，C
6-H)4.78(m，1H，C
6-H)
MS m/e (%) electron-bombardment: 232 (M
+0.17), 217 (100), 156 (11.2), 101 (27.0), 85 (6.99), 70 (46.3), 59 (48.6), 43 (35.6); Field desorption(FD): 217 (100, m-CH
3), 232 (10.7, M
+), 233 (16, M
+ 1), 234 (29, M
+ 2)
13C-NMR：δ(OFR)61.4(t，c-1)，110.9(s，c-2)，73.30(d，c-3)，76.79(d，c-4)，74.85(d，c-5)，79.47(d，c-6)，67.78(t，c-7)，108.05(s，c-8)，26.55)q，c-9)，28.17(q，c-10)。
Through the ownership of chemical reaction and spectral data, and with known allied compound relatively, the structural formula of this active compound is decided to be:
Chemistry isopropylidene scape ketose acid anhydride (Isopropylidene Sedoheptulosan) by name, this compound can be used as the preparation of anti-duck hepatitis B virus of preparation and two-way immune new drug.
For the result of treatment of proof the present invention, in duck hepatitis B virus infection duck body, carry out the result of treatment test both at home and abroad with the animal experimental model of recognizing altogether at present to duck hepatitis B virus.An age in days Beijing duck intravenous injection duck hepatitis B virus is adopted in experiment, begin after seven days to duck abdominal injection injection liquid of the present invention, one day twice, administration 10 days (B idx10) or 14 days (B idx14) is observed medicine to toxicity of duck and the influence of duck serum duck hepatitis B virus DNA (DHBV-DNA).Experimental result shows, 200,100 and 50mg/kg dosage group, one day secondary, 10 days or 14 days, equal nontoxicity, two dosage groups of 200mg/kg and 100mg/kg all can reduce DHBA infected duck serum DHBR-DNA level, do statistical study in groups relatively, administration the 7th day (T7) or the 14th day (T with the virus control group
14) DHBV-DNA has significance to reduce, 50mg/kg dosage group, significant difference does not appear in the experiment, show that injection liquid of the present invention has restraining effect to duck serum DHBV-DNA, simultaneously, experimental result also shows, injection liquid of the present invention, under this experiment condition, its 200mg/kg and 100mg/kg group are the effective dose of treatment duck hepatitis B virus.
Further observed the immunoregulatory activity of injection of the present invention to body with kunming mice.In vivo test of the present invention has tangible enhancement (P＜0.01) to Turnover of Mouse Peritoneal Macrophages lysosomal enzyme-acid phosphatase (ACP) activity.The activity of cell membrane enzyme-alkaline phosphatase (AKP) has tangible immunoregulation effect.To tumour ring necrosis factor (TNF) activity, tangible enhancement (P＜0.01) is also arranged, experiment in vitro shows that the present invention and CONA and LPS share, can strengthen the two silk, split former effect, promote lymphocyte transformation, both have share synergy (the P value is respectively＜0.01 and＜0.05), and therefore, injection liquid of the present invention is biological response modifier (Biological Response Modifer, BRM) immunomodulator in and/or immunostimulant have two-way immunologic function.
With a concrete instance the present invention is extracted scape ketose acid anhydride in the Crassulaceae plant more below, further the method for synthetic Isopropylidene Sedoheptulosan is further described.
Get eight treasures (choice ingredients of certain special dishes) (or Orostachys fimbriatus, long medicine eight treasures (choice ingredients of certain special dishes) (50kg, be ground into meal, added water boil 1 hour, emit leaching liquid after, added water boil again 1 hour, merging leaching liquid twice, earlier through thin film concentration, is about 1/5th of former leaching liquid volume through being evaporated to liquid volume again, the 95% ethanol constant volume that adds equivalent, determining alcohol is about about 50%, places, get supernatant liquor earlier by strongly-acid H
+The exchange of type cation exchange resin column, effluent liquid are again by strong basicity OH
-The exchange of type anion-exchange resin column.Effluent liquid steams ethanol, and reclaims ethanol usefulness again, makes medicinal extract.Gained medicinal extract with diatomite and acidic alumina spice after, last alumina column, with ethanol elution, can get scape ketose acid anhydride about 50 the gram.
Get above scape ketose acid anhydride 4 grams, add 80 milliliters in acetone, add an amount of sulfuric acid, induction stirring was placed after 24 hours, promptly had Isopropylidene Sedoheptulosan needle crystal to separate out, and reclaimed acetone, got product 4.1 grams, and yield is greater than 85%.
After quality test is qualified, under aseptic condition, be sub-packed in the penicillin peace bottle of 10ml capacity, every 100mg 105 ℃ of thermal sterilizations 20 minutes, promptly gets the Isopropylidene Sedoheptulosan injection.
During use, after facing with before adding about 5 milliliters of sterilizeds water for injection, making dissolving, intravenous drip, 200-300mg on the one.
The present invention extracts scape ketose acid anhydride from Crassulaceae plant eight treasures (choice ingredients of certain special dishes) or long medicine eight treasures (choice ingredients of certain special dishes) in the herb of plants such as Orostachys fimbriatus, the resynthesis Isopropylidene Sedoheptulosan has significant antiviral activity and two-way immunologic function through this new compound of experiment confirm to hepatitis B virus.Can be used as the bidirectional immune regulator of diseases such as treatment hepatitis B.
Claims (2)
1, a kind of preparation method of antiviral activity compound is characterized in that:
1-1 extracts from the herb of Crassulaceae plant eight treasures (choice ingredients of certain special dishes) or Orostachys fimbriatus or long medicine eight treasures (choice ingredients of certain special dishes), separate and obtain scape ketose anhydridization compound;
1-2 obtains to have active compound Isopropylidene Sedoheptulosan with this scape ketose anhydridization compound and acetone one step condensation, chemistry isopropylidene scape ketose acid anhydride by name, and its structural formula is:
2,, it is characterized in that comprising following operation steps according to the preparation method of the described antiviral activity compound of claim 1:
2-1 pulverizes the herb of dry Crassulaceae plant eight treasures (choice ingredients of certain special dishes) or Orostachys fimbriatus or long medicine eight treasures (choice ingredients of certain special dishes), leaches with boiling water;
After 2-2 concentrates leaching liquid, add equivalent ethanol and do the constant volume adjusting;
2-3 gets supernatant liquor, separates with the strong base ion exchange resin column with strong acid type successively;
The steaming of 2-4 effluent liquid removes ethanol and obtains medicinal extract;
2-5 medicinal extract is made alumina column with diatomite and acidic alumina spice, obtains scape ketose acid anhydride with ethanol elution;
2-6 one step of ketose acid anhydride and acetone of finding a view is condensed into Isopropylidene Sedoheptulosan.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN96115901A CN1054606C (en) | 1996-07-26 | 1996-07-26 | Preparation method of antiviral compound eight-treasures extract |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN96115901A CN1054606C (en) | 1996-07-26 | 1996-07-26 | Preparation method of antiviral compound eight-treasures extract |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 99112550 Division CN1110303C (en) | 1999-11-17 | 1999-11-17 | Application of eight precious extract in preparing antiviral medicine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1145366A CN1145366A (en) | 1997-03-19 |
| CN1054606C true CN1054606C (en) | 2000-07-19 |
Family
ID=5123108
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN96115901A Expired - Lifetime CN1054606C (en) | 1996-07-26 | 1996-07-26 | Preparation method of antiviral compound eight-treasures extract |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1054606C (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101485672B (en) * | 2008-12-05 | 2010-08-25 | 广东粤龙药业有限公司 | Application of hylotelephin in preparing medicament for treating human HBeAg-positive chronic hepatitis B |
| CN101919872B (en) * | 2010-07-21 | 2011-12-07 | 广东粤龙药业有限公司 | Application of sedoheptulose to preparation of new anti-hepatitis B medicament |
| CN113197803B (en) * | 2021-04-29 | 2022-04-19 | 浙江吉叶生物科技有限公司 | Antibacterial mouth wash and preparation method thereof |
-
1996
- 1996-07-26 CN CN96115901A patent/CN1054606C/en not_active Expired - Lifetime
Non-Patent Citations (1)
| Title |
|---|
| ACTA CRY STALLOGR SECT C CRYST STRUCT COMMUN 1994.1.1 KOPF JUERGCM等，STRUCTURE OF ISOPROPYLI SEDOHEP RU LOSAN * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1145366A (en) | 1997-03-19 |
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Owner name: DARI BIOLOGY CHEMICALS MEDICINE CO., LTD., GUANGD Free format text: FORMER OWNER: PHARMACEUTICAL RESEARCH INST. OF SHANDONG PROV. MEDICAL SCIENCE ACADEMY Effective date: 20011123 |
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Effective date of registration: 20011123 Address after: 510507, Yan Tang Industrial Park, Guangzhou, Guangdong, Tianhe District Patentee after: Dari Biological Chemical Pharmceutical Co., Ltd., Guangdong Prov. Address before: 250062, No. ten, No. 89, Ji'nan, Shandong Patentee before: Medicine Research Inst., Shandong Prov. Medical Science Academy |
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Owner name: GUANGDONG YUELONG PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: DARI BIOLOGY CHEMICALS MEDICINE CO., LTD., GUANGDONG PROVINCE Effective date: 20080912 |
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Effective date of registration: 20080912 Address after: Green Industrial Park, Jiedong County, Jieyang, Guangdong Patentee after: Guangdong Yuelong Pharmaceutical Co., Ltd. Address before: Swallow pond Industrial Park, Guangzhou, Guangdong, Tianhe District Patentee before: Dari Biological Chemical Pharmceutical Co., Ltd., Guangdong Prov. |
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