CN1586500A - Disodium cantharidinate injection for treating tumor and its preparing method - Google Patents
Disodium cantharidinate injection for treating tumor and its preparing method Download PDFInfo
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- CN1586500A CN1586500A CNA2004100529384A CN200410052938A CN1586500A CN 1586500 A CN1586500 A CN 1586500A CN A2004100529384 A CNA2004100529384 A CN A2004100529384A CN 200410052938 A CN200410052938 A CN 200410052938A CN 1586500 A CN1586500 A CN 1586500A
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- disodium cantharidinate
- injection
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- cantharis
- cantharidin
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- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 title claims abstract description 56
- 238000002347 injection Methods 0.000 title claims abstract description 38
- 239000007924 injection Substances 0.000 title claims abstract description 38
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 24
- 238000000034 method Methods 0.000 title claims description 6
- DHZBEENLJMYSHQ-XCVPVQRUSA-N cantharidin Chemical compound C([C@@H]1O2)C[C@@H]2[C@]2(C)[C@@]1(C)C(=O)OC2=O DHZBEENLJMYSHQ-XCVPVQRUSA-N 0.000 claims abstract description 25
- 229940095758 cantharidin Drugs 0.000 claims abstract description 25
- 229930008397 cantharidin Natural products 0.000 claims abstract description 25
- DHZBEENLJMYSHQ-UHFFFAOYSA-N cantharidine Natural products O1C2CCC1C1(C)C2(C)C(=O)OC1=O DHZBEENLJMYSHQ-UHFFFAOYSA-N 0.000 claims abstract description 25
- 239000003814 drug Substances 0.000 claims abstract description 10
- 230000001954 sterilising effect Effects 0.000 claims abstract description 6
- 238000007670 refining Methods 0.000 claims abstract description 4
- 241000131283 Cantharis Species 0.000 claims description 27
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 24
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 16
- 238000003756 stirring Methods 0.000 claims description 15
- 239000000047 product Substances 0.000 claims description 13
- 239000000243 solution Substances 0.000 claims description 13
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- 238000010438 heat treatment Methods 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 10
- 239000000284 extract Substances 0.000 claims description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 238000004140 cleaning Methods 0.000 claims description 8
- 239000012043 crude product Substances 0.000 claims description 8
- 238000000605 extraction Methods 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 239000000843 powder Substances 0.000 claims description 8
- 235000010265 sodium sulphite Nutrition 0.000 claims description 8
- 239000008215 water for injection Substances 0.000 claims description 8
- 229910001220 stainless steel Inorganic materials 0.000 claims description 7
- 239000010935 stainless steel Substances 0.000 claims description 7
- 229910000831 Steel Inorganic materials 0.000 claims description 6
- 239000012141 concentrate Substances 0.000 claims description 6
- 238000005516 engineering process Methods 0.000 claims description 6
- 238000009413 insulation Methods 0.000 claims description 6
- 239000000463 material Substances 0.000 claims description 6
- 239000010959 steel Substances 0.000 claims description 6
- 238000004659 sterilization and disinfection Methods 0.000 claims description 5
- 238000010792 warming Methods 0.000 claims description 5
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 239000003610 charcoal Substances 0.000 claims description 4
- 238000002425 crystallisation Methods 0.000 claims description 4
- 230000008025 crystallization Effects 0.000 claims description 4
- 239000012153 distilled water Substances 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 4
- 239000003208 petroleum Substances 0.000 claims description 4
- 239000008213 purified water Substances 0.000 claims description 4
- 230000001093 anti-cancer Effects 0.000 claims description 3
- 239000002246 antineoplastic agent Substances 0.000 claims description 3
- 229940041181 antineoplastic drug Drugs 0.000 claims description 3
- 238000009835 boiling Methods 0.000 claims description 3
- 230000007797 corrosion Effects 0.000 claims description 3
- 238000005260 corrosion Methods 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000002893 slag Substances 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims description 2
- 239000013078 crystal Substances 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- 238000005485 electric heating Methods 0.000 claims description 2
- 239000010413 mother solution Substances 0.000 claims description 2
- 229910052573 porcelain Inorganic materials 0.000 claims description 2
- -1 transfusion Substances 0.000 claims description 2
- 238000005303 weighing Methods 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 abstract description 2
- 230000000259 anti-tumor effect Effects 0.000 abstract description 2
- 201000011510 cancer Diseases 0.000 abstract description 2
- 208000019425 cirrhosis of liver Diseases 0.000 abstract description 2
- 208000006454 hepatitis Diseases 0.000 abstract description 2
- 231100000283 hepatitis Toxicity 0.000 abstract description 2
- 241000254173 Coleoptera Species 0.000 abstract 1
- 201000007270 liver cancer Diseases 0.000 abstract 1
- 201000005202 lung cancer Diseases 0.000 abstract 1
- 208000020816 lung neoplasm Diseases 0.000 abstract 1
- 238000012856 packing Methods 0.000 abstract 1
- 238000001228 spectrum Methods 0.000 abstract 1
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- 229940090044 injection Drugs 0.000 description 22
- 230000000694 effects Effects 0.000 description 7
- 238000001990 intravenous administration Methods 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 210000000214 mouth Anatomy 0.000 description 2
- 231100000614 poison Toxicity 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 206010058019 Cancer Pain Diseases 0.000 description 1
- 208000017897 Carcinoma of esophagus Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 206010020565 Hyperaemia Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 241000124079 Mylabris Species 0.000 description 1
- 208000002454 Nasopharyngeal Carcinoma Diseases 0.000 description 1
- 206010061306 Nasopharyngeal cancer Diseases 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000001784 detoxification Methods 0.000 description 1
- 230000003028 elevating effect Effects 0.000 description 1
- 201000005619 esophageal carcinoma Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229940093181 glucose injection Drugs 0.000 description 1
- 210000000777 hematopoietic system Anatomy 0.000 description 1
- 208000006750 hematuria Diseases 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 230000027939 micturition Effects 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 201000011216 nasopharynx carcinoma Diseases 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The disodium cantharidinate injection for treating tumor is prepared through crushing blistere beetle, extracting cantharidin, defatting cantharidin, synthesizing disodium cantharidinate, refining disodium cantharidinate, forming disodium cantharidinate injection, packing and sterilizing. As one kind of wide spectrum antitumor medicine, the present invention is suitable for treating primary liver cancer, lung cancer, oesophagus cancer and other cancers, and may be used in treating hepatitis, liver cirrhosis, etc.
Description
The present invention relates to a kind of intravenous drip type injection, is a kind of injection agent in a new generation's treatment tumor that great role is all arranged aspect anticancer and the liter white two, is a kind of disodium cantharidinate injection for the treatment of tumor.
Before more than 2,000 years, the Chinese medicine of China is just brought into use cantharis treatment tumor.This property of medicine acrid in the mouth is cold, and is poisonous, but the counteracting toxic substances phagedenoma, and the removing blood stasis eliminating stagnation is to act on significantly attacking by class Chinese medicine.But toxic and side effects is very big, takes oral cavity, back, pharyngeal mucosa hyperemia, nausea and vomiting, loss of appetite, diarrhoea, dysurea, frequent micturition, hematuria etc.And can not grasp the dosage of medicine, be difficult to clinically use.The active ingredient of Mylabris treatment tumor is a cantharidin.Though the cantharidin taking convenience that extracts through science, and pharmaceutical quantities also is easy to grasp, toxic and side effects is still very big, and the effective dose of cantharidin and toxicity dose are very approaching.
The natural resources of cantharis is very deficient, 10 tons of China's annual production less thaies.Wild cantharis mainly is grown in the South China Tropical humid region, and based on the food leguminous plant, the conservation of natural environment of life requires very high.Natural environment polluted in recent years, and the output of wild cantharis is reduced significantly, and the artificial cultivation cantharis does not also have successful experience.
The objective of the invention is to overcome above-mentioned cantharis and the existing defective of cantharidin medicine, provide a kind of and can make full use of the cantharis resource, the medicine of the clinical treatment tumour that energy is long-term, safety clothes are used, it is the digestive tract reaction of antitumor drug as none both, the urinary system reaction of not having cantharidin again and being caused.By cantharidin again after semi-synthetic, the synergic disodium cantharidinate injection of detoxification.
The present invention is through reasonably prescription and processing technique are prepared from by cantharis.
Disodium cantharidinate injection of the present invention be synthetic by cantharis pulverizing, cantharidin extraction, cantharidin defat, disodium cantharidinate, disodium cantharidinate is refining, the disodium cantharidinate injection is synthetic and embedding, sterilization, obtains the disodium cantharidinate injection.Concrete grammar and preparation technology are as follows:
1. cantharis is pulverized.
Cantharis is picked, remove foreign material, put into then on the rustless steel drip pan, drying is 10 hours in the temperature of about 50 ℃ in drying room, and exsiccant cantharis is put into high speed disintegrator smashing fineness to 40 order.
2. cantharidin extracts.
Formula proportion is:
Cantharis powder: acetone: hydrochloric acid=1 (kg): 2～5 (kg): 3～7 (ml)
With 200 kilograms in cantharis powder, 400 kilograms to 1000 kilograms in acetone, hydrochloric acid drops into 500 for 600 milliliters to 1400 milliliters and rises in 2000 liters of rustless steel extraction pot, opens steam and is warming up to 30 ℃ to 40 ℃, and insulation was soaked 24 hours, and preceding 10 hours every stirring in 2 hours 5 minutes.With corrosion resisting centrifugal pump leachate in the extraction pot is evacuated in the basin.Repeat above operation, soak with 400 kilograms to 1000 kilograms acetone insulations respectively and extract three times.Last leachate is evacuated in the recover and concentrates, and applies mechanically as extract next time.Open vacuum, leachate in the basin is evacuated in the recover, open Steam Heating, concentrate, when liquid temperature boiling point rises to 78 ℃, stop heating, emit concentrated solution, contain in the stainless steel cask, at room temperature natural crystallize is more than 12 hours.After leachate is drained, take out the worm slag, centralized collection is handled.
3. cantharidin defat.
Formula proportion is:
Cantharidin crude product: cleaning mixture=1: 2.8
Cleaning mixture proportioning: petroleum ether (bp:60～90 ℃): ethanol (95%)=1: 1
With crystallize completely concentrated solution be the buchner funnel of filter material in order to silk, decompress filter is to doing.Crystal after draining is moved in the stainless steel disc, add the cleaning mixture that 0.5 times of petroleum ether and ethanol are made into, stir, basin is placed in the water-bath heats again, stir and be warming up to 30 ℃ with stainless steel knife.Be the buchner funnel of filter material in order to silk while hot, drain the back and drain with 0.2 times of cleaning mixture post rinse.And then repeat above operation three times, the crystallization of leukasmus Cantharidin, and this be contained in the porcelain dish dry, promptly get the cantharidin elaboration.
4. disodium cantharidinate is synthetic.
Formula proportion is:
Cantharidin elaboration (more than 95%): 40% sodium hydroxide solution: distilled water=1: 1.4: 8
In 1000 milliliters to 4000 milliliters there-necked flasks, add cantharidin, add 40% sodium hydroxide solution and distilled water again by above-mentioned formula proportion, heating made its dissolving in the electric heating chuck, 75 ℃ to 85 ℃ back flow reaction 1 to 2 hour.Distill out moisture content, be distilled to when the mother solution amount remains 1/3rd left and right sides in the flask, pour out product and cooled off 4 hours in the time of 20 ℃, the gap is stirred to crystallize, gets the disodium cantharidinate crude product.
5. disodium cantharidinate is refining.
Formula proportion is:
Disodium cantharidinate crude product: purified water: active carbon=1: 8: 0.01
The disodium cantharidinate crude product is dropped into 1500 milliliters to 6000 ml flasks, add 8 times of amount purified water, add 1% left and right sides active carbon again.Distill out moisture content, cooling crystallization promptly gets the disodium cantharidinate finished product.
6. the disodium cantharidinate injection is synthetic.
Formula proportion is: per ten thousand consumptions of per 500 consumptions of every content of supplementary material
Disodium cantharidinate 0.1mg 50mg 1g
Sodium sulfite 2mg～6mg 1000mg～3000mg 20g～60g
EDTA 0.2mg 100mg 2g
Propylene glycol 0.2ml～0.6ml 100ml～200ml 21～61
Water for injection is an amount of an amount of
Get 100ml～300ml propylene glycol, add an amount of water for injection, during 50 ℃～60 ℃ of agitating heating, add 1000mg～3000mg sodium sulfite solution and 100mgEDTA according to the above ratio, regulate pH value about 7.0, add disodium cantharidinate finished product 50mg again, stir and make dissolving, add injection water volume to 1000ml, adding needle-use activated carbon stirs, coarse filtration detects intermediate after taking off charcoal, and qualified back fine straining leads to N to clear and bright
2Embedding, 100 ℃ of flowing steam sterilizations 30 minutes promptly get the disodium cantharidinate injection that the present invention treats tumor.
Prescription of the present invention and technology are reasonable, practical, the disodium cantharidinate finished product stable in properties of above-mentioned 1 to 5 preparation, and safety is good, is easy to detect.Can be applicable to the production of the antitumor drug of multiple dosage forms such as injection, transfusion, capsule, tablet.
The disodium cantharidinate injection of the treatment tumor by above-mentioned prescription and preparation technology's gained has the following advantages and curative effect.
1. the present invention treats the disodium cantharidinate injection intravenous drip of tumor.1 time on the one, each 2 to 10ml, dilutes the back in right amount with 0.9% sodium chloride or 5% to 10% glucose injection and instils.
2. injection of the present invention has the effect of obvious alleviation cancer pain after the tumour patient intravenous drip, improve the clinical symptoms of tumour patient, improves patient's quality of life.
3. the present invention is the derivant of cantharidin, aspect anticancer and the liter white two very big effect being arranged all, cancerous cell is had directly kill and inhibitory action; Stimulate medulla hematopoietic system, the elevating blood leukocyte.
4. after the intravenous drip of this injection, most of medicine is discharged from urine.Significantly improve body's immunological function; With put, chemotherapy combined uses and to heighten the effect of a treatment; Before the surgical oncology art, postoperative uses, but the after treatment effect.
5. disodium cantharidinate is the broad-spectrum anti-tumor medicine, is applicable to the treatment of kinds of tumors such as primary hepatocarcinoma, pulmonary carcinoma, esophageal carcinoma, nasopharyngeal carcinoma, malignant lymphoma, bladder cancer, gynecologic malignant tumor, also can be used for hepatitis, liver cirrhosis and hepatitis b virus carrier.
The disodium cantharidinate injection that the present invention treats tumor is the injection according to the processing technique preparation process gained of above-mentioned cantharis.Embodiments of the invention are as follows:
After cantharis selected, pulverizes, in the cantharis powder: acetone: hydrochloric acid=1 (kg): 3 (kg): 5 (ml) ratio, take by weighing in 200 kilograms in cantharis powder, 600 kilograms in acetone, 1000 liters of rustless steel extraction pot of 1000 milliliters of inputs of hydrochloric acid, open steam and be warming up to 30 ℃ to 40 ℃, insulation was soaked 24 hours, and preceding 10 hours every stirring in 2 hours 5 minutes.With corrosion resisting centrifugal pump leachate in the extraction pot is evacuated in the basin.Repeat above operation, soak with 600 kilograms of acetone insulations respectively and extract three times.Last leachate is evacuated in the recover and concentrates, and applies mechanically as extract next time.Open vacuum, leachate in the basin is evacuated in the recover, open Steam Heating, concentrate, when liquid temperature boiling point rises to 78 ℃, stop heating, emit concentrated solution, contain in the stainless steel cask, at room temperature natural crystallize is more than 12 hours.After leachate is drained, take out the worm slag, centralized collection is handled.Processing technique preparation process according to above-mentioned 3 to 5.Get 1.2 kilograms of disodium cantharidinate finished products.
The disodium cantharidinate injection is synthetic.
Formula proportion is: per ten thousand consumptions of per 500 consumptions of every content of supplementary material
Disodium cantharidinate 0.1mg 50mg 1g
Sodium sulfite 3mg 1500mg 30g
EDTA 0.2mg 100mg 2g
Propylene glycol 0.6ml 300ml 61
Water for injection is an amount of an amount of
Get the 300ml propylene glycol, add an amount of water for injection, during 50 ℃～60 ℃ of agitating heating, add 1500mg sodium sulfite solution and 100mgEDTA according to the above ratio, regulate pH value about 7.0, add disodium cantharidinate finished product 50mg again, stir and make dissolving, add injection water volume to 1000ml, adding needle-use activated carbon stirs, coarse filtration detects intermediate after taking off charcoal, and qualified back fine straining leads to N to clear and bright
2Embedding, 100 ℃ of flowing steam sterilizations 30 minutes promptly get the disodium cantharidinate injection that the present invention treats tumor.1000ml can be made into 500 of the injections of 2ml specification, and every disodium cantharidinate injection contains disodium cantharidinate 0.1mg.
Claims (3)
1. the injection agent in a new generation's treatment tumor that great role is all arranged aspect anticancer and the liter white two is a kind of disodium cantharidinate injection for the treatment of tumor.It is characterized in that it is the medicament that is prepared from by following processing technique by cantharis.
A. cantharis is pulverized.
Cantharis is picked, remove foreign material, put into then on the rustless steel drip pan, drying is 10 hours in the temperature of about 50 ℃ in drying room, and exsiccant cantharis is put into high speed disintegrator smashing fineness to 40 order.
B. cantharidin extracts.
Formula proportion is:
Cantharis powder: acetone: hydrochloric acid=1 (kg): 2～5 (kg): 3～7 (ml)
With 200 kilograms in cantharis powder, 400 kilograms to 1000 kilograms in acetone, hydrochloric acid drops into 500 for 600 milliliters to 1400 milliliters and rises in 2000 liters of rustless steel extraction pot, opens steam and is warming up to 30 ℃ to 40 ℃, and insulation was soaked 24 hours, and preceding 10 hours every stirring in 2 hours 5 minutes.With corrosion resisting centrifugal pump leachate in the extraction pot is evacuated in the basin.Repeat above operation, soak with 400 kilograms to 1000 kilograms acetone insulations respectively and extract three times.Last leachate is evacuated in the recover and concentrates, and applies mechanically as extract next time.Open vacuum, leachate in the basin is evacuated in the recover, open Steam Heating, concentrate, when liquid temperature boiling point rises to 78 ℃, stop heating, emit concentrated solution, contain in the stainless steel cask, at room temperature natural crystallize is more than 12 hours.After leachate is drained, take out the worm slag, centralized collection is handled.
C. cantharidin defat.
Formula proportion is:
Cantharidin crude product: cleaning mixture=1: 2.8
Cleaning mixture proportioning: petroleum ether (bp:60～90 ℃): ethanol (95%)=1: 1
With crystallize completely concentrated solution be the buchner funnel of filter material in order to silk, decompress filter is to doing.Crystal after draining is moved in the stainless steel disc, add the cleaning mixture that 0.5 times of petroleum ether and ethanol are made into, stir, basin is placed in the water-bath heats again, stir and be warming up to 30 ℃ with stainless steel knife.Be the buchner funnel of filter material in order to silk while hot, drain the back and drain with 0.2 times of cleaning mixture post rinse.And then repeat above operation three times, the crystallization of leukasmus Cantharidin, and this be contained in the porcelain dish dry, promptly get the cantharidin elaboration.
D. disodium cantharidinate is synthetic.
Formula proportion is:
Cantharidin elaboration (more than 95%): 40% sodium hydroxide solution: distilled water=1: 1.4: 8
In 1000 milliliters to 4000 milliliters there-necked flasks, add cantharidin, add 40% sodium hydroxide solution and distilled water again by above-mentioned formula proportion, heating made its dissolving in the electric heating chuck, 75 ℃ to 85 ℃ back flow reaction 1 to 2 hour.Distill out moisture content, be distilled to when the mother solution amount remains 1/3rd left and right sides in the flask, pour out product and cooled off 4 hours in the time of 20 ℃, the gap is stirred to crystallize, gets the disodium cantharidinate crude product.
E. disodium cantharidinate is refining.
Formula proportion is:
Disodium cantharidinate crude product: purified water: active carbon=1: 8: 0.01
The disodium cantharidinate crude product is dropped into 1500 milliliters to 6000 ml flasks, add 8 times of amount purified water, add 1% left and right sides active carbon again.Distill out moisture content, cooling crystallization promptly gets the disodium cantharidinate finished product.
F. the disodium cantharidinate injection is synthetic.
Formula proportion is: per ten thousand consumptions of per 500 consumptions of every content of supplementary material
Disodium cantharidinate 0.1mg 50mg 1g
Sodium sulfite 2mg～6mg 1000mg～3000mg 20g～60g
EDTA 0.2mg 100mg 2g
Propylene glycol 0.2ml～0.6ml 100ml～300ml 2l～6l
Water for injection is an amount of an amount of
Get 100ml～300ml propylene glycol, add an amount of water for injection, during 50 ℃～60 ℃ of agitating heating, add 1000mg～3000mg sodium sulfite solution and 100mgEDTA according to the above ratio, regulate pH value about 7.0, add disodium cantharidinate finished product 50mg again, stir and make dissolving, add injection water volume to 1000ml, adding needle-use activated carbon stirs, coarse filtration detects intermediate after taking off charcoal, and qualified back fine straining leads to N to clear and bright
2Embedding, 100 ℃ of flowing steam sterilizations 30 minutes promptly get the disodium cantharidinate injection that the present invention treats tumor.
2. according to the disodium cantharidinate finished product of the described treatment tumor of the A to E in the claim 1, it is characterized in that optimum formula and preparation technology are as follows among above-mentioned prescription and the preparation technology:
After cantharis selected, pulverizes, in cantharis powder 1 (kg): acetone 3 (kg): the ratio of hydrochloric acid 5 (ml), take by weighing 200 kilograms in cantharis powder, 600 kilograms in acetone, 1000 milliliters of hydrochloric acid, drop in 1000 liters of rustless steel extraction pot, through the processing technique preparation process of above-mentioned B to E, get 1.2 kilograms of disodium cantharidinate finished products.
Prescription of the present invention and technology are reasonable, practical, the disodium cantharidinate finished product stable in properties of above-mentioned A to E preparation, and safety is good, is easy to detect.Can be applicable to the production of the antitumor drug of multiple dosage forms such as injection, transfusion, capsule, tablet.
3. the disodium cantharidinate injection according to the described treatment tumor of the F in the claim 1 is characterized in that the optimum formula ratio of disodium cantharidinate injection is:
Per ten thousand consumptions of per 500 consumptions of every content of supplementary material
Disodium cantharidinate 0.1mg 50mg 1g
Sodium sulfite 3mg 1500mg 30g
EDTA 0.2mg 100mg 2g
Propylene glycol 0.6ml 300ml 6l
Water for injection is an amount of an amount of
Get the 300ml propylene glycol, add an amount of water for injection, during 50 ℃～60 ℃ of agitating heating, add 1500mg sodium sulfite solution and 100mgEDTA according to the above ratio, regulate pH value about 7.0, add disodium cantharidinate finished product 50mg again, stir and make dissolving, add injection water volume to 1000ml, adding needle-use activated carbon stirs, coarse filtration detects intermediate after taking off charcoal, and qualified back fine straining leads to N to clear and bright
2Embedding, 100 ℃ of flowing steam sterilizations 30 minutes promptly get the disodium cantharidinate injection that the present invention treats tumor.1000ml can be made into 500 of the injections of 2ml specification, and every disodium cantharidinate injection contains disodium cantharidinate 0.1mg.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2004100529384A CN1586500A (en) | 2004-07-19 | 2004-07-19 | Disodium cantharidinate injection for treating tumor and its preparing method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2004100529384A CN1586500A (en) | 2004-07-19 | 2004-07-19 | Disodium cantharidinate injection for treating tumor and its preparing method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1586500A true CN1586500A (en) | 2005-03-02 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2004100529384A Pending CN1586500A (en) | 2004-07-19 | 2004-07-19 | Disodium cantharidinate injection for treating tumor and its preparing method |
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| Country | Link |
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| CN (1) | CN1586500A (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100386089C (en) * | 2006-03-02 | 2008-05-07 | 上海慈瑞医药科技有限公司 | Compound lentinan preparation and its preparing method |
| CN100545164C (en) * | 2007-02-13 | 2009-09-30 | 北京世纪博康医药科技有限公司 | Preparation process of sodium cantharidate |
| CN101633661B (en) * | 2007-02-13 | 2011-06-01 | 北京世纪博康医药科技有限公司 | Process for preparing sodium cantharidinate |
| CN102146086A (en) * | 2011-04-12 | 2011-08-10 | 贵州金桥药业有限公司 | Preparation method of sodium cantharidate |
| EP2309853A4 (en) * | 2008-08-01 | 2012-04-25 | Lixte Biotechnology Inc | METHODS OF REGULATING CELL MITOSIS BY INHIBITING SERINE / THREONINE PHOSPHATASE |
| US11931354B2 (en) | 2013-04-09 | 2024-03-19 | Lixte Biotechnology, Inc. | Formulations of oxabicycloheptanes and oxabicycloheptenes |
| US12168008B2 (en) | 2016-12-08 | 2024-12-17 | Lixte Biotechnology, Inc. | Oxabicycloheptanes for modulation of immune response |
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- 2004-07-19 CN CNA2004100529384A patent/CN1586500A/en active Pending
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100386089C (en) * | 2006-03-02 | 2008-05-07 | 上海慈瑞医药科技有限公司 | Compound lentinan preparation and its preparing method |
| CN100545164C (en) * | 2007-02-13 | 2009-09-30 | 北京世纪博康医药科技有限公司 | Preparation process of sodium cantharidate |
| CN101633661B (en) * | 2007-02-13 | 2011-06-01 | 北京世纪博康医药科技有限公司 | Process for preparing sodium cantharidinate |
| EP2309853A4 (en) * | 2008-08-01 | 2012-04-25 | Lixte Biotechnology Inc | METHODS OF REGULATING CELL MITOSIS BY INHIBITING SERINE / THREONINE PHOSPHATASE |
| CN102146086A (en) * | 2011-04-12 | 2011-08-10 | 贵州金桥药业有限公司 | Preparation method of sodium cantharidate |
| CN102146086B (en) * | 2011-04-12 | 2012-03-07 | 贵州金桥药业有限公司 | Preparation method of sodium cantharidate |
| US11931354B2 (en) | 2013-04-09 | 2024-03-19 | Lixte Biotechnology, Inc. | Formulations of oxabicycloheptanes and oxabicycloheptenes |
| US12343342B2 (en) | 2013-04-09 | 2025-07-01 | Lixte Biotechnology, Inc. | Methods for treating soft tissue sarcoma |
| US12168008B2 (en) | 2016-12-08 | 2024-12-17 | Lixte Biotechnology, Inc. | Oxabicycloheptanes for modulation of immune response |
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