CN101633661B - Process for preparing sodium cantharidinate - Google Patents
Process for preparing sodium cantharidinate Download PDFInfo
- Publication number
- CN101633661B CN101633661B CN2009101693745A CN200910169374A CN101633661B CN 101633661 B CN101633661 B CN 101633661B CN 2009101693745 A CN2009101693745 A CN 2009101693745A CN 200910169374 A CN200910169374 A CN 200910169374A CN 101633661 B CN101633661 B CN 101633661B
- Authority
- CN
- China
- Prior art keywords
- cantharidin
- disodium cantharidinate
- cantharidinate
- blister beetle
- water
- 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.)
- Active
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a process for preparing sodium cantharidinate, which comprises the following steps: treating cantharis; extracting cantharidin; purifying; refining; synthesizing the sodium cantharidinate; purifying and refining the sodium cantharidinate, and the like. The invention has the advantages of simplicity, practicability, good safety, high purity of prepared finished products, stable quality, low production cost, and the like and can be applied to the production of various dosage forms of big injections, big transfusions, tablets, granules, capsules, oral liquid, ointments, and the like.
Description
Technical field
The present invention relates to a kind of preparation technology of anti-tumor medicine, particularly a kind of preparation technology of disodium cantharidinate.
Background technology
The traditional Chinese medical science of China is brought into use cantharis treatment tumour very early: just having put down in writing Chinese blister beetle in 13rd century " Renzhai Zhi Zhi Fang, Effective Recipes from Renzhai House " has the effect for the treatment of breast cancer and belly cancer.Ancients''s " the Chinese blister beetle boiled egg is abandoned Chinese blister beetle food egg " commonly used folk prescription treatment liver cancer and other cancer in digestive system are still continued to use among the people so far.This property of medicine flavor is hot, heat; Very toxic, can attack malicious phagedenoma, return liver, stomach, kidney channel.Have broken blood to disappear { note of the ancient Chinese }, merit poison phagedenoma is drawn the function of red foaming, is used for { note of the ancient Chinese } lump in the abdomen lump, stubborn dermatitis for many years, and scrofula, wart, ulcer are not burst, and dislike the treatment of the dead flesh of sore.But toxic side effect is very big.In recent years find that its anticancer effective component is a naturally occurring Cantharidin in the body.China shows that to the clinical study of Cantharidin Cantharidin and derivative thereof etc. are evident in efficacy to the treatment primary hepatocarcinoma, obviously are better than operative treatment or radiotherapy.In addition, it can also treat chronic hepatitis and neurodermatitis oligoleukocythemia etc.Other has the report proof, and Cantharidin and derivative thereof also have certain curative effect to diseases such as mammary cancer, esophagus cancer, lung cancer, intestinal cancer, liver cirrhosis; Can be used for treating mange simultaneously, the scrofula that disappears disease; All right tonneau water channel is a kind of very strong diuretic(s).External application is a dermerethistica, and the effect of drawing red foaming, setation is arranged, and can control and dislike sore and burst that pain, ulcer are drawn out the pus, tinea sore, wart mole black mole etc. for many years.Though extract the Cantharidin easy administration that obtains through science, toxic side effect is still very big, the effective dose of Cantharidin and toxicity dose are very approaching.And disodium cantharidinate is the derivative of Cantharidin, outside the pharmacologically active that has kept Cantharidin, has reduced its toxic side effect.Its molecular weight is little, easily goes in the cell, produces cytotoxicity, has stronger antitumor action, be a kind of comparatively ideal cancer therapy drug, have pharmacologically actives such as antitumor, immunomodulatory, leukocyte increasing, be mainly used in the treatment that is used for late primary liver cancer and advanced lung cancer clinically.Disodium cantharidinate is as antineoplastic pioneer's medicine, make the application modern biotechnology from cantharis, extract its effective constituent, the bound drug synthetic technology, through the processing of Chinese blister beetle polypide, the extraction of Cantharidin, purification refine, the purification refine synthetic, disodium cantharidinate of disodium cantharidinate forms, its antitumor mechanism mainly is the protein synthesis by anticancer, influence its RNA and DNA, the growth of anticancer is divided, thereby reaches the purpose of treatment.
Notification number is the preparation technology that the Chinese patent of CN1166669C discloses a kind of disodium cantharidinate, comprise that Cantharidin extracts, crystallization, the several steps of preparation disodium cantharidinate, concrete grammar is Chinese blister beetle polypide powder to be added hydrochloric acid soaked into 24 hours, adds the acetone cold soaking again, filters, divide and get organic phase, reclaim acetone to the ointment shape, add the washing of sherwood oil and dehydrated alcohol mixing solutions, get yellow-white Cantharidin crude product; Get the ratio adding acetone of Cantharidin crude product in 1: 30 weight, refluxed 30 minutes, suction filtration gets achromatism and clarity filtrate while hot, reclaims acetone, and cooling back suction filtration gets white crystals, gets the Cantharidin elaboration; Get the ratio adding acetone soln of Cantharidin elaboration again in 1: 20 weight, the dissolving that refluxes, getting with the Cantharidin mol ratio is the solution of 1: 2 sodium hydroxide 20% again, reacted 1 hour, distillation then adds gac and refluxes, concentrate, drying gets white disodium cantharidinate crystalline powder.Yet this method has been used a large amount of acetone, the cost height, and acetone is toxic solvents, and the operator is easily produced harm.
Publication number discloses a kind of disodium cantharidinate injection and preparation method thereof for the CN1586500A Chinese patent application, the preparation process of disodium cantharidinate is wherein also disclosed, comprising steps such as cantharis pulverizing, Cantharidin extraction, Cantharidin degreasing, disodium cantharidinate synthesize.This application has also adopted a large amount of acetone in steps such as extraction, degreasing, therefore exist the shortcoming same with CN1166669C.
Prior art still need a kind of easy and simple to handle, pollute the preparation method who endangers little preparation disodium cantharidinate less, to operator.
Summary of the invention
The applicant, adopts ethyl acetate to substitute acetone and extracts as solvent in the Cantharidin extraction step through discovering in a large number, the operating time is shortened, and reach better extraction effect.
Simultaneously, in the Cantharidin purification step, only carry out the degreasing washing, also can reach purification effect preferably with sherwood oil.
In the synthesis step of disodium cantharidinate, applicant also other people surprisingly finds, with Virahol Cantharidin is dissolved earlier, and then adopts 5%-20%, and preferred 15% sodium hydroxide solution can make the generated time of disodium cantharidinate shorten gain in yield.Wherein, the weight ratio of Cantharidin and Virahol can be 1: 5～200, preferred 1: 10～100, most preferably 1: 30～70.
Therefore, the preparation method who the purpose of this invention is to provide a kind of disodium cantharidinate that meets the state-promulgated pharmacopoeia requirement newly, this method comprises and adopts the Chinese blister beetle polypide, obtains the Cantharidin elaboration through polypide pre-treatment, extraction, purification refine, again through semi-synthetic and obtain the technology of disodium cantharidinate elaboration.Do not adopt toxic solvents such as acetone in this method, technology is simple, safe, convenient, fast, economical, constant product quality, and the purity height, and can reach good yield.
The present invention realizes by the following technical solutions, specifically comprises the processing of Chinese blister beetle polypide, the extraction of Cantharidin, purification refine, and the purification refine step of synthetic, the disodium cantharidinate of disodium cantharidinate:
(1) processing of Chinese blister beetle polypide.
The dry Chinese blister beetle polypide that will meet the state-promulgated pharmacopoeia standard picks, and removes foreign material such as soil block, pulverizes.
(2) extraction of Cantharidin.
The saturated ethyl acetate of hydrochloric acid is used in the adding of Chinese blister beetle polypide powder in advance, soaked 10～20 hours.Leach liquor is discarded in the storage tank, adds again to soak with the saturated ethyl acetate of hydrochloric acid in advance and extract once.Emitting leach liquor is incorporated into and is steam heated to 50 ℃ in the withdrawer and concentrates.Wherein the weight ratio of the ethyl acetate that Chinese blister beetle polypide powder and hydrochloric acid are saturated is 1: 7～9.
(3) purification refine of Cantharidin.
Concentrated solution is transferred in the revolving bottle, the about 1 times of amount sherwood oil (bp:60 ℃～90 ℃) of heating in water bath to 50 ℃ adding, heat is 5 minutes altogether, pour into the silk is in the B of filter material, decompress filter is to doing, to obtaining white Cantharidin crystallization, the normal temperature drying under reduced pressure promptly obtains Cantharidin elaboration (purity is more than 97%) with the drip washing of about 2.5 times of amount sherwood oils.
(4) disodium cantharidinate is synthetic.
With Cantharidin add Virahol a little heat make its dissolving, sodium hydroxide and water are made into 5%-20% solution in proportion, join at 1: 2 in the above Cantharidin aqueous isopropanol with Cantharidin and sodium hydroxide mol ratio, in water-bath, be heated to 70 ℃～75 ℃ reactions 1 to 2 hour.Decompression steams solvent, obtains the disodium cantharidinate crude product.Wherein the weight ratio of Cantharidin and Virahol is 1: 30～70.
(5) purification refine of disodium cantharidinate.
The disodium cantharidinate crude product is added purified water, add the gac about 0.4% again, insulation is 1 to 1.5 hour in 60 ℃ of water-baths, and decompression steams moisture content, and drying promptly gets the disodium cantharidinate finished product.
Adopt the disodium cantharidinate of the inventive method preparation, the purity height, stable in properties can be used for the production of formulation such as big injection, infusion solutions, tablet, granule, capsule, oral liquid, ointment and multiple sustained-release preparation.
Embodiment:
Embodiment 1:
(1) processing of Chinese blister beetle polypide.
The dry Chinese blister beetle polypide that will meet the state-promulgated pharmacopoeia standard picks, and removes foreign material such as soil block, pulverizes, and the fineness that makes Chinese blister beetle polypide powder is at 20 orders～40 orders.
(2) extraction of Cantharidin.
With 100 kilograms in Chinese blister beetle polypide powder, add and use in advance in the stainless steel extractor of 700 kilograms to 2000 liters of the saturated ethyl acetate of hydrochloric acid, soaked 16 hours, preceding 10 hours are every stirring half an hour once.Leach liquor is discarded in the storage tank.Repeat above operation, add again to soak for 700 kilograms with the saturated ethyl acetate of hydrochloric acid in advance and extract once.Emit leach liquor and be incorporated into and be steam heated to 50 ℃ in the withdrawer and concentrate, stop heating, recovered solvent is used as extract next time.Leach liquor takes out the worm slag after putting and doing, and centralized collection is unified to be handled.
(3) purification refine of Cantharidin.
Concentrated solution is transferred in the revolving bottle, heating in water bath to 50 ℃ 1 times of amount of adding sherwood oil (bp:60 ℃～90 ℃), heat is 5 minutes altogether, pour into the silk is in the B of filter material, decompress filter is to doing, to obtaining white Cantharidin crystallization, the normal temperature drying under reduced pressure promptly obtains Cantharidin elaboration (purity 99.3%) with the drip washing of 2.5 times of amount sherwood oils.
(4) disodium cantharidinate is synthetic.
Add Cantharidin at 1000 milliliters to the round-bottomed flask of 5000ml, the Virahol that adds about 50 times of amounts heat a little makes its dissolving, with behind sodium hydroxide and the water wiring solution-forming, pours in the flask in proportion, is heated to 70 ℃～75 ℃ reactions 1 to 2 hour in water-bath.Decompression steams solvent, obtains the disodium cantharidinate crude product.Wherein, Cantharidin elaboration: Virahol: sodium hydroxide: distilled water=1.96: 50: 0.8: 4 (weight ratios).
(5) purification refine of disodium cantharidinate.
The disodium cantharidinate crude product put in 3000 milliliters to 5000 milliliters the flask, add the purified water of 10 times of amounts, add the gac about 0.4% again, insulation is 1 to 1.5 hour in 60 ℃ of water-baths, and decompression steams moisture content, and drying promptly gets the disodium cantharidinate finished product.
Embodiment 2:
(1) processing of Chinese blister beetle polypide.
The dry Chinese blister beetle polypide that will meet the state-promulgated pharmacopoeia standard picks, and removes foreign material such as soil block, pulverizes, and the fineness that makes Chinese blister beetle polypide powder is at 20 orders～30 orders.
(2) extraction of Cantharidin.
With 100 kilograms in Chinese blister beetle polypide powder, add and use in advance in the stainless steel extractor of 800 kilograms to 2000 liters of the saturated ethyl acetate of hydrochloric acid, soaked 16 hours, preceding 10 hours are every stirring half an hour once.Leach liquor is discarded in the storage tank.Repeat above operation, add again to soak for 700 kilograms with the saturated ethyl acetate of hydrochloric acid in advance and extract once.Emit leach liquor and be incorporated into and be steam heated to 50 ℃ in the withdrawer and concentrate, stop heating, recovered solvent is used as extract next time.Leach liquor takes out the worm slag after putting and doing, and centralized collection is unified to be handled.
(3) purification refine of Cantharidin.
Concentrated solution is transferred in the revolving bottle, heating in water bath to 50 ℃ 2 times of amounts of adding sherwood oils, heat is 5 minutes altogether, pour into the silk is in the B of filter material, decompress filter is to doing, to obtaining white Cantharidin crystallization, the normal temperature drying under reduced pressure promptly obtains Cantharidin elaboration (purity 98.6%) with the drip washing of 1.5 times of amount sherwood oils.
(4) disodium cantharidinate is synthetic.
Add Cantharidin at 1000 milliliters to the round-bottomed flask of 5000ml, the Virahol that adds about 20 times of amounts heat a little makes its dissolving, with behind sodium hydroxide and the water wiring solution-forming, pours in the flask in proportion, is heated to 70 ℃～75 ℃ reactions 1 to 2 hour in water-bath.Decompression steams solvent, obtains the disodium cantharidinate crude product.Wherein, Cantharidin elaboration: Virahol: sodium hydroxide: distilled water=1.96: 77: 0.80: 5.50 (weight ratios)
(5) purification refine of disodium cantharidinate.
The disodium cantharidinate crude product put in 3000 milliliters to 5000 milliliters the flask, add the purified water of 8 times of amounts, add the gac about 0.4% again, insulation is 1 to 1.5 hour in 60 ℃ of water-baths, and decompression steams moisture content, and drying promptly gets the disodium cantharidinate finished product.
Embodiment 3:
(1) processing of Chinese blister beetle polypide.
The dry Chinese blister beetle polypide that will meet the state-promulgated pharmacopoeia standard picks, and removes foreign material such as soil block, pulverizes, and the fineness that makes Chinese blister beetle polypide powder is at 30 orders～40 orders.
(2) extraction of Cantharidin.
Formula rate is:
With 100 kilograms in Chinese blister beetle polypide powder, add and use in advance in the stainless steel extractor of 900 kilograms to 2000 liters of the saturated ethyl acetate of hydrochloric acid, soaked 16 hours, preceding 10 hours are every stirring half an hour once.Leach liquor is discarded in the storage tank.Repeat above operation, add again to soak for 700 kilograms with the saturated ethyl acetate of hydrochloric acid in advance and extract once.Emit leach liquor and be incorporated into and be steam heated to 50 ℃ in the withdrawer and concentrate, stop heating, recovered solvent is used as extract next time.Leach liquor takes out the worm slag after putting and doing, and centralized collection is unified to be handled.
(3) purification refine of Cantharidin.
Concentrated solution is transferred in the revolving bottle, heating in water bath to 50 ℃ 1 times of amount of adding sherwood oil, heat is 5 minutes altogether, pour into the silk is in the B of filter material, decompress filter is to doing, to obtaining white Cantharidin crystallization, the normal temperature drying under reduced pressure promptly obtains Cantharidin elaboration (purity 98.8%) with the drip washing of 2.5 times of amount sherwood oils.
(4) disodium cantharidinate is synthetic.
Add Cantharidin at 1000 milliliters to the round-bottomed flask of 5000ml, the Virahol that adds about 65 times of amounts heat a little makes its dissolving, with behind sodium hydroxide and the water wiring solution-forming, pours in the flask in proportion, is heated to 70 ℃～75 ℃ reactions 1 to 2 hour in water-bath.Decompression steams solvent, obtains the disodium cantharidinate crude product.Wherein, Cantharidin elaboration: Virahol: sodium hydroxide: distilled water=1.96: 107.55: 0.8: 16 (weight ratios)
(5) purification refine of disodium cantharidinate.
The disodium cantharidinate crude product put in 3000 milliliters to 5000 milliliters the flask, add the purified water of 12 times of amounts, add the gac about 0.4% again, insulation is 1 to 1.5 hour in 60 ℃ of water-baths, and decompression steams moisture content, and drying promptly gets the disodium cantharidinate finished product.
Embodiment 4 quality product researchs
The disodium cantharidinate national drug standards [standard No.: WS-10001-(HD-0044)-2002] regulation disodium cantharidinate content calculates according to dry product, must not be less than 85%, and carrying out assay and purity test according to the disodium cantharidinate that the foregoing description makes, the result is all more than 98%.Explanation will obviously be better than the commercially available prod according to the disodium cantharidinate quality that the present invention makes, and assay and purity test concrete grammar are as follows:
1 assay
Chromatographic condition and system suitability test are weighting agent with the octadecylsilane chemically bonded silica; Methanol-water (51: 49) is a moving phase; Flow velocity is 1.0ml/min; The detection wavelength is 227nm; Sensitivity is 0.005AUFS.Theoretical plate number is pressed the Cantharidin peak and is calculated, and should be not less than 2000.
The preparation of reference substance solution: it is an amount of to get the Cantharidin reference substance, and accurate the title decides, and adds methyl alcohol and makes the solution that every 1ml contains Cantharidin 0.15mg, in contrast product solution.
The preparation of need testing solution: precision takes by weighing this product 10mg, to the 100ml flask, adds the 50ml water dissolution, adds 1mol/LH again
2SO
4Solution 10ml, shake up, put in 65 ℃ of water-baths and to reflux 30 minutes, move in separating funnel after cold slightly, with chloroform 25ml, 15ml, 10ml extraction three times, each 10 minutes, combining extraction liquid was put in 70 ℃ of water-baths and is volatilized solvent, residue holds to the 50ml measuring bottle with the methyl alcohol commentaries on classics, constant volume shakes up, and is need testing solution.
Assay method: accurate respectively reference substance solution and each 20 μ l of need testing solution of drawing, inject liquid chromatograph, the record color atlas calculates Cantharidin content with external standard method, multiply by 1.316 again, promptly gets disodium cantharidinate content.
The disodium cantharidinate actual content is more than 98% as a result.
2 purity tests
Chromatographic condition and system suitability test are weighting agent with octyl silane group silica gel; Methyl alcohol-0.5% triethylamine (28: 72) is a moving phase; Flow velocity is 1.0ml/min; The detection wavelength is 210nm; Sensitivity is 0.005AUFS.Theoretical plate number is pressed the disodium cantharidinate peak and is calculated, and should be not less than 2000.
The need testing solution preparation: precision takes by weighing this product 10mg, to the 10ml measuring bottle, is dissolved in water and constant volume, shakes up, and is need testing solution.
Measure: the accurate need testing solution 20 μ l that draw, inject liquid chromatograph, write down color atlas, check the purity of disodium cantharidinate with area normalization method.
Disodium cantharidinate purity is greater than 98% as a result.
3 measurement results
Claims (2)
1. the preparation method of a disodium cantharidinate is characterized in that comprising Chinese blister beetle polypide powder is added the step of soaking the extraction Cantharidin with the saturated ethyl acetate of hydrochloric acid in advance.
2. according to the preparation method of claim 1, wherein the weight ratio of the ethyl acetate that Chinese blister beetle polypide powder and hydrochloric acid are saturated is 1: 7～9.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009101693745A CN101633661B (en) | 2007-02-13 | 2007-02-13 | Process for preparing sodium cantharidinate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009101693745A CN101633661B (en) | 2007-02-13 | 2007-02-13 | Process for preparing sodium cantharidinate |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2007100638506A Division CN100545164C (en) | 2007-02-13 | 2007-02-13 | The preparation technology of disodium cantharidinate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101633661A CN101633661A (en) | 2010-01-27 |
| CN101633661B true CN101633661B (en) | 2011-06-01 |
Family
ID=41593015
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009101693745A Active CN101633661B (en) | 2007-02-13 | 2007-02-13 | Process for preparing sodium cantharidinate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101633661B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102268006B (en) * | 2011-06-15 | 2013-08-14 | 北京联合大学生物化学工程学院 | Method for extracting cantharidin from compound enzyme |
| CN102276619A (en) * | 2011-06-21 | 2011-12-14 | 贵州金桥药业有限公司 | Method for preparing sodium canthanridate |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1586500A (en) * | 2004-07-19 | 2005-03-02 | 俞锋 | Disodium cantharidinate injection for treating tumor and its preparing method |
-
2007
- 2007-02-13 CN CN2009101693745A patent/CN101633661B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1586500A (en) * | 2004-07-19 | 2005-03-02 | 俞锋 | Disodium cantharidinate injection for treating tumor and its preparing method |
Non-Patent Citations (1)
| Title |
|---|
| 李晓飞等.昆虫斑蝥素的研究与利用.《山地农业生物学报》.2004,第23卷(第2期),169-175. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101633661A (en) | 2010-01-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN100545164C (en) | The preparation technology of disodium cantharidinate | |
| CN103880910B (en) | A kind of preparation method and its usage of Cyclosiversigenin | |
| CN103768534B (en) | A kind of Chinese medicine composition with antitumor activity | |
| CN102068535B (en) | Immature bitter orange or bitter orange total flavonoids extract prepared by ethanol reflux and extraction and application thereof | |
| CN102210737B (en) | Sweet potato leaf extract and preparation method and use thereof | |
| JP6389958B2 (en) | Medicinal use of anti-tumor for rutile pentacyclic triterpene saponins | |
| CN107412430A (en) | A kind of radix scrophulariae water extract and its application | |
| WO2008145064A1 (en) | The method for a sequoyitol-containing extract obtaining from the genus of trifolium, sobyean and ginkgo biloba and use thereof | |
| CN101633661B (en) | Process for preparing sodium cantharidinate | |
| CN102976943B (en) | The alpha-crystal form material of salvianolic acid A, method for making and pharmaceutical composition and purposes | |
| CN102688248B (en) | Use of bufadienolide compound in preparing medicines for treating oral mucosal malignant tumors | |
| CN101396373B (en) | Cinobufacini extract and preparation method thereof | |
| CN109602759A (en) | The purposes of kusamaki broad-leaved podocarpus seed and receptacle polysaccharide | |
| CN102048874B (en) | General flavone extractive of immature bitter orange or bitter orange extracted through water decoction and use of general flavone extractive | |
| CN102786418B (en) | Chlorogenic acid brilliant II type sign and preparation method and apply in medicine and health products | |
| CN107260777A (en) | A kind of fiveleaf akebia fruit with antitumor activity refines total saposins and its application | |
| CN1107680C (en) | Solasodine hydrochlorate and productive method and application in medicine | |
| CN1709418A (en) | Katsumadai seed extract and its preparation | |
| CN102670698B (en) | The application of Radix Flemingiae Philippinensis extract in preparation control diabetes medicament | |
| CN102093380B (en) | Cyclic icaritin aglycon as well as preparation method and application of cyclic icaritin aglycon | |
| CN102716231B (en) | A kind of Chinese medicine composition and application thereof for the treatment of brain injury and cerebral edema | |
| CN101502536B (en) | Cedar total flavone as well as preparation method and medical use | |
| CN104840747B (en) | Chinese medicine composition with antithyroid cancer activity and its preparation method and application | |
| CN106977561B (en) | Preparation of Sutherlandin-5-p-hydroxybenzoate and application thereof in preparation of drugs for treating rheumatoid arthritis | |
| CN106977560B (en) | Preparation of 2S-cardiospermin-5-benzoate and application thereof in preparation of drugs for treating rheumatoid arthritis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CP03 | "change of name, title or address" |
Address after: 210047 room 1203, building D, 606 ningliu Road, Changlu street, Jiangbei new district, Nanjing City, Jiangsu Province Patentee after: Nanjing century Bokang Pharmaceutical Technology Co., Ltd Address before: 100070 Beijing science and Technology Park of Fengtai District Haiying Road No. 9 Jintang building 3 203 Patentee before: BEIJING CENTURY BIOCOM PHARMACEUTICAL TECHNOLOGY Co.,Ltd. |
|
| CP03 | "change of name, title or address" | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20201230 Address after: 226300 1-2 / F, C6 building, 266 Century Avenue, Nantong hi tech Zone, Nantong City, Jiangsu Province Patentee after: JIANGSU REPODX BIOTECHNOLOGY Co.,Ltd. Address before: 210047 room 1203, building D, 606 ningliu Road, Changlu street, Jiangbei new district, Nanjing City, Jiangsu Province Patentee before: Nanjing century Bokang Pharmaceutical Technology Co., Ltd |
|
| TR01 | Transfer of patent right |