CN102617584A - Irinotecan hydrochloride compound and medicinal composition thereof - Google Patents
Irinotecan hydrochloride compound and medicinal composition thereof Download PDFInfo
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Abstract
The invention belongs to the technical field of medicine, and relates to an irinotecan hydrochloride compound and a medicinal composition thereof. The molecular formula of irinotecan hydrochloride is C33H38N4O6.HCl.1.5H2O. A preparation method of the irinotecan hydrochloride comprises the following steps of: adding a mixed solvent of water/ethylene glycol into an irinotecan hydrochloride bulk pharmaceutical, wherein the volume ratio of water to ethylene glycol is (2-4):1; stirring and heating to 40-60 DEG C; adding active carbon; stirring and adsorbing; filtering, removing carbon and degerming to obtain a clear solution; transferring the clear solution into a reaction kettle; standing at the temperature of 160-180 DEG C for 24-36 hours; uniformly cooling to 55-75 DEG C; opening a reaction kettle; dropwise adding acetone slowly; devitrifying; slowly cooling to 0-5 DEG C; filtering; washing with deionized water; and drying under reduced pressure to obtain the irinotecan hydrochloride compound. The irinotecan hydrochloride provided by the invention does not absorb moisture easily, and has low impurity content, high storage stability and higher safety performance.
Description
Technical field
The invention belongs to medical technical field, relate to a kind of U 101440E compound and pharmaceutical composition thereof.
Background technology
U 101440E, English name: Irinotecan Hydrochloride Injection, molecular formula is C
33H
38N
4O
6HCl3H
2O, molecular weight are 677.19, and its chemical name is (+)-(4S)-4,11-diethylammonium-4-hydroxyl-9-[(4-piperidinyl piperidine) carbonyl]-1H-pyrans also [3; 4:6,7] indolizine [1,2b] quinoline-3; 14-(4H, 12H)-the dione hydrochloride trihydrate, under the room temperature pale yellow powder or light yellow crystalline powder; Odorless, slightly soluble in water, ethanol or chloroform, insoluble in acetone.Be Japanese first pharmacy and Yakult Honsha company in the antitumor drug of exploitation listing in 1994, antitumour activity is strong, exists with the form of hydrochloride, and structural formula is following:
U 101440E (CPT-11) is a kind of semisynthetic solubility camptothecin verivate, mainly acts on the cell cycle S phase, through suppressing topoisomerase I, disturbs dna replication dna and cell fission.Through the katalysis of Procaine esterase, be metabolized to active result 7-ethyl-10-hydroxycamptothecine (SN-38) in vivo, its antitumour activity is the former 100～1000 times.The U 101440E injection liquid is a kind of effective, representative anti-cancer agent, and is as specific topoisomerase I (Topo I) suppressor factor, different with traditional enzyme inhibitors; It does not hinder the combination of Topo I, but this ribozyme is transformed into the deleterious material to DNA, with the mixture mortise of Topo I enzyme and DNA formation; Specificity suppresses DNA and reconnects step; Cause the dna single splitting of chain, make DNA produce irreversible damage, cause necrocytosis.
The mortality ratio that China's tumour causes occupies the 2nd (accounting for 17.9%) in all causes of disease, and sickness rate is in rising trend, and wherein the sickness rate of lung cancer, intestinal cancer is higher.U 101440E is the specific medicament of treatment advanced CRC, and it is still effective that 5 FU 5 fluorouracil is produced chemical sproof case, and is also effective in cure to minicell and nonsmall-cell lung cancer and cervical cancer and ovarian cancer simultaneously.This medicine has obtained the common approval of U.S. FDA and European Union, more than 100 country's listings in the whole world, and it is that U.S. FDA has continued over more than 40 year since the 5 FU 5 fluorouracil (5-FU), unique approval is used for the chemotherapeutic of advanced CRC first-line treatment.
Interaction between irinotecan and the neuromuscular blocking agent is very important, has anticholinesterase activity, can prolong the neuromuscular blockade effect of lake choline, and the neuromuscular blockade effect of non depolarization medicine maybe be by antagonism.
CN101277694A discloses a kind of new crystal of U 101440E, and new crystal formation of U 101440E and preparation method thereof is provided, and contains the pharmaceutical composition and the method for utilizing its treatment colon or rectum metastatic carcinoma of said new crystal formation.
CN101318964A discloses a kind of crystal of U 101440E, and the U 101440E of this crystal formation has stability in storage preferably, and foreign matter content is few.
In the prior art; The U 101440E of different crystal forms all has 3 crystal water, and the change crystal formation that passes through that has has improved stability, and the change crystal formation that passes through that has has improved water-soluble; In order to find the more good irinotecan hydrochloride medicines of a kind of performance, special proposition the present invention.
Summary of the invention
The object of the present invention is to provide a kind of U 101440E compound, the U 101440E compound that is provided is easily dilutable not, is easy to store, and has better stability in storage, and foreign matter content is few, has improved drug safety greatly.
Another object of the present invention is to provide the pharmaceutical composition that contains above-mentioned U 101440E compound.
In order to realize the foregoing invention purpose, the present invention takes following technical scheme:
A kind of U 101440E, the molecular formula of said U 101440E are C
33H
38N
4O
6HCl1.5H
2O.
In the U 101440E compound provided by the invention, only have 1.5 crystal water in its molecular formula, individual molecule is in piling up the crystalline process, because the minimizing of crystal water, variation has also taken place its internal crystal structure.U 101440E is prone to moisture absorption in the prior art, and the unexpected special crystallized form of U 101440E compound provided by the present invention of finding is difficult for moisture absorption, has stronger stability in storage.
The X-ray powder diffraction that said U 101440E crystal uses the Cu-K alpha-ray to measure is 9.7 °, 10.1 °, 13.1 °, 13.3 °, 16.1 °, 19.0 °, 20.5 °, 21.6 °, 23.4 °, 28.6 °, 29.2 °, 30.7 °, 33.2 °, 35.7 ° at 2 θ and locates to show characteristic peak.
The fusing point of said U 101440E is 278-280 ℃.
The preparation of described U 101440E comprises: get the U 101440E bulk drug, add the mixed solvent of entry/terepthaloyl moietie, wherein the volume ratio of water and terepthaloyl moietie is 2～4: 1, stirs and be heated to 40～60 ℃; Add gac again, whip attachment is filtered the decarburization degerming, obtains settled solution; Settled solution is moved in the reaction kettle, and in 160～180 ℃ of held 24～36h, reaction kettle is opened in uniform decrease in temperature to 55～75 ℃; Slowly drip acetone, crystallization slowly is cooled to 0～5 ℃, filters; Use deionized water wash, drying under reduced pressure promptly gets.
Among the above-mentioned preparation method, the ratio of the weight of said U 101440E and the volume of mixed solvent is 1g: 10～15ml.
Among the above-mentioned preparation method, said dropping is under mixing speed 25～30rmp, at the uniform velocity to drip.
Among the above-mentioned preparation method, the volume ratio of said acetone and mixed solvent is 3～4: 1.
The degerming of described adding activated carbon is this area common technology means; Can handle referring to any decolouring; Those skilled in the art need not to pay any creative work, can carry out appropriate selection according to the prior art of himself grasping, and realize the object of the invention.
In order further to improve the formulation products quality, the present invention also can be preferably be filtered into the use ultrafiltration membrance filter after decolouring.
The contriver passes through experiment repeatedly, finally comprises under the experiment conditions such as temperature, pressure, pH, solvent, with C in change
33H
38N
4O
6HCl3H
2O is that raw material has obtained C
33H
38N
4O
6HCl1.5H
2O; Because variation has taken place in the position and the environment of water molecules in the compound; Huge variation has taken place in this new U 101440E compound inner solid-state structure in the process of packing of molecules crystallization; The contriver draws through water absorbability experiment and stability experiment, and the present invention provides not easily dilutable of U 101440E, and stability in storage is good.
The present invention also provides a kind of pharmaceutical composition that contains foregoing U 101440E.
Said pharmaceutical composition is the U 101440E injection liquid, and by weight, said U 101440E injection liquid comprises U 101440E 30-100 part, Sorbitol Powder 50-250 part, lactic acid 1-5 part, water for injection 150-2000 part.
Preferably, by weight, said U 101440E injection liquid comprises 40 parts of U 101440Es, 90 parts of Sorbitol Powders, 1.8 parts of lactic acid, 2000 parts of waters for injection.
Preferably, by weight, said U 101440E injection liquid comprises 100 parts of U 101440Es, 225 parts of Sorbitol Powders, 4.5 parts of lactic acid, 2000 parts of waters for injection.
The preparation method of said U 101440E injection liquid comprises the steps:
(1) water for injection preparation: purified water is carried out multi-effect distilling prepare sterile water for injection;
(2) dosing: after recipe quantity U 101440E, Sorbitol Powder, lactic acid mixed, slowly add down in 90% the water for injection in stirring, using pH regulator agent regulator solution pH value is 3.0～4.0, adds remaining 10% water for injection;
(3) sterilization: solution is warming up to 117～125 ℃ under stirring, and stops heat tracing 10～15min, is cooled to 40～50 ℃;
(4) decolouring: in clear and bright solution, add gac, whip attachment 30min, through taking off a charcoal and a sterilization filter filtration, the secondary terminals degerming filters filter, and gained is filtrated to the soup bottle, can after the passed examination, tamponade promptly gets.
Among the preparation method of above-mentioned U 101440E injection liquid, step (2), (3) said stirring are rotating speed 100～160 commentaries on classics/min.
Among the preparation method of above-mentioned U 101440E injection liquid, the said water for injection temperature of step (2) is 70～75 ℃.
Among the preparation method of above-mentioned U 101440E injection liquid, the said multiple-effect of step (1) is 3～6 effects.
Among the preparation method of above-mentioned U 101440E injection liquid, the activated carbon consumption is 0.3～0.5% (g/ml) of liquor capacity in the said decolouring of step (4).
Among the preparation method of above-mentioned U 101440E injection liquid, millipore filtration aperture described in the step (4) is 0.22 μ m.
PH regulator agent of the present invention is well known in the art, and those skilled in the art know the concrete kind of pH regulator agent usually, such as mineral acid or mineral alkali, but the present invention's one or more combination in sodium hydroxide, Pottasium Hydroxide or the hydrochloric acid preferably.With pH regulator to 3.0～4.0 of soup, U 101440E all being in the more stable system from be formulated into the whole process of can in this scope, this has helped improving the stability of U 101440E injection liquid.
Among the present invention, amount of activated and adsorption time have been carried out strict control, it is proper that gac uses, can the active adsorption degerming, can reduce the adsorption of gac again to bulk drug, and make prepared U 101440E injection liquid solution clarification.
Preparation technology's simple possible of U 101440E injection liquid provided by the invention, good reproducibility is prone to realize industrialized production; Practice thrift manpower, short production cycle, lower scrap rate and lower human cost reduce production cost significantly; Can produce considerable economic and social benefit; Prepared U 101440E clarity of injection is good, and foreign matter content is low, and little to human body spinoff and potential harm.
Compared with prior art, U 101440E provided by the invention and compsn thereof have following advantage:
(1) U 101440E of the present invention is difficult for moisture absorption, and foreign matter content is few, and stability in storage is good;
(2) U 101440E safety performance of the present invention is higher.
Description of drawings
The X-powder diagram of the U 101440E that Fig. 1 provides for the embodiment of the invention 1;
The thermogravimetric curve of the U 101440E that Fig. 2 provides for the embodiment of the invention 1.
Embodiment
Through specific embodiment summary of the invention of the present invention is further specified below, but therefore do not limit content of the present invention.
Embodiment 1
Get U 101440E bulk drug 50g, add the mixed solvent 500ml of entry/terepthaloyl moietie, wherein the volume ratio of water and terepthaloyl moietie is 2: 1, stirs and be heated to 40 ℃; Add the 0.15g gac again, whip attachment is filtered the decarburization degerming, obtains settled solution; Settled solution is moved in the reaction kettle, and in 160 ℃ of held 24h, uniform decrease in temperature to 55 ℃ is opened reaction kettle; Slowly drip 1500ml acetone and stir with the speed of 25rmp, crystallization slowly is cooled to 0 ℃, filters; With deionized water wash 3 times, drying under reduced pressure 3h promptly gets.Yield 65.4%, HPLC content 99.74%.mp：278-280℃。
The X-ray powder diffraction that the U 101440E crystal that obtains uses the Cu-K alpha-ray to measure is 9.7 °, 10.1 °, 13.1 °, 13.3 °, 16.1 °, 19.0 °, 20.5 °, 21.6 °, 23.4 °, 28.6 °, 29.2 °, 30.7 °, 33.2 °, 35.7 ° at 2 θ and locates to show characteristic peak.
Adopt the U.S. PE Pyris Diamond TG of Perkin-Elmer company thermal analyzer, the thermogravimetric analysis experiment shows: the U 101440E crystal of present embodiment 1 preparation loses 1.5 H in the time of 137～161 ℃
2The O molecule.
Embodiment 2
Get U 101440E bulk drug 50g, add the mixed solvent 750ml of entry/terepthaloyl moietie, wherein the volume ratio of water and terepthaloyl moietie is 4: 1, stirs and be heated to 60 ℃; Add the 0.3g gac again, whip attachment is filtered the decarburization degerming, obtains settled solution; Settled solution is moved in the reaction kettle, and in 180 ℃ of held 36h, uniform decrease in temperature to 75 ℃ is opened reaction kettle; Slowly drip 3000ml acetone and stir with the speed of 30rmp, crystallization slowly is cooled to 5 ℃, filters; With deionized water wash 3 times, drying under reduced pressure 3h promptly gets.Yield 68.5%, HPLC content 99.79%.mp：278-280℃。
X-ray powder diffraction collection of illustrative plates, the thermogravimetric curve of U 101440E crystal that obtains and embodiment 1 product have identical parameters.
Embodiment 3
Get U 101440E bulk drug 50g, add the mixed solvent 600ml of entry/terepthaloyl moietie, wherein the volume ratio of water and terepthaloyl moietie is 3: 1, stirs and be heated to 55 ℃; Add the 0.2g gac again, whip attachment is filtered the decarburization degerming, obtains settled solution; Settled solution is moved in the reaction kettle, and in 170 ℃ of held 30h, uniform decrease in temperature to 70 ℃ is opened reaction kettle; Slowly drip 2400ml acetone and stir with the speed of 30rmp, crystallization slowly is cooled to 0 ℃, filters; With deionized water wash 3 times, drying under reduced pressure 3h promptly gets.Yield 68.8%, HPLC content 99.77%.mp：278-280℃。
X-ray powder diffraction collection of illustrative plates, the thermogravimetric curve of U 101440E crystal that obtains and embodiment 1 product have identical parameters.
Embodiment 4
The preparation of U 101440E injection liquid
Purified water is carried out distillation preparation sterile water for injection 3 times; After U 101440E 30g, Sorbitol Powder 50g, the lactic acid 1g that gets embodiment 1 preparation mixes; Slowly add 70 ℃ of water for injection 135ml down in stirring; The rotating speed that stirs is 100 commentaries on classics/min, and using sodium hydroxide or hydrochloric acid conditioning solution pH value is 3.0, adds 70 ℃ water for injection 15ml; Solution is warming up to 117 ℃ under stirring, and the rotating speed of stirring is 100 commentaries on classics/min, stops heat tracing 10min, is cooled to 40 ℃; In clear and bright solution, add gac 0.45g, whip attachment 30min, the rotating speed of stirring are 100 commentaries on classics/min; Through taking off a charcoal and a sterilization filter filtration; The secondary terminals degerming filters filter, and filtering millipore filtration aperture is 0.22 μ m, and gained is filtrated to the soup bottle; Can after the passed examination, tamponade promptly gets.Every bottle loading amount is 0.4g: 2ml.
Embodiment 5
The preparation of U 101440E injection liquid
Purified water is carried out distillation preparation sterile water for injection 6 times; After U 101440E 100g, Sorbitol Powder 250g, the lactic acid 5g that gets embodiment 2 preparation mixes; Slowly add 75 ℃ of water for injection 1800ml down in stirring; The rotating speed that stirs is 100 commentaries on classics/min; Using sodium hydroxide or hydrochloric acid conditioning solution pH value is 4.0, adds 75 ℃ water for injection 200ml; Solution is warming up to 125 ℃ under stirring, and the rotating speed of stirring is 100 commentaries on classics/min, stops heat tracing 15min, is cooled to 50 ℃; In clear and bright solution, add gac 10g, whip attachment 30min, the rotating speed of stirring are 100 commentaries on classics/min; Through taking off a charcoal and a sterilization filter filtration, the secondary terminals degerming filters filter, and filtering millipore filtration aperture is 0.22 μ m; Gained is filtrated to the soup bottle, can after the passed examination, and tamponade promptly gets.Every bottle loading amount is 0.1g: 2ml.
Embodiment 6
The preparation of U 101440E injection liquid
Purified water is carried out distillation preparation sterile water for injection 4 times; After U 101440E 40g, Sorbitol Powder 90g, the lactic acid 1.8g that gets embodiment 3 preparation mixes; Slowly add 75 ℃ of water for injection 1800ml down in stirring; The rotating speed that stirs is 160 commentaries on classics/min; Using sodium hydroxide or hydrochloric acid conditioning solution pH value is 4.0, adds 75 ℃ water for injection 200ml; Solution is warming up to 125 ℃ under stirring, and the rotating speed of stirring is 160 commentaries on classics/min, stops heat tracing 15min, is cooled to 50 ℃; In clear and bright solution, add gac 6g, whip attachment 30min, the rotating speed of stirring are 160 commentaries on classics/min; Through taking off a charcoal and a sterilization filter filtration, the secondary terminals degerming filters filter, and filtering millipore filtration aperture is 0.22 μ m; Gained is filtrated to the soup bottle, can after the passed examination, and tamponade promptly gets.Every bottle loading amount is 0.1g: 5ml.
Embodiment 7
The preparation of U 101440E injection liquid
Purified water is carried out distillation preparation sterile water for injection 4 times; After U 101440E 40g, Sorbitol Powder 90g, the lactic acid 1.8g that gets embodiment 3 preparation mixes; Slowly add 75 ℃ of water for injection 1800ml down in stirring; The rotating speed that stirs is 160 commentaries on classics/min; Using sodium hydroxide or hydrochloric acid conditioning solution pH value is 4.0, adds 75 ℃ water for injection 200ml; Solution is warming up to 125 ℃ under stirring, and the rotating speed of stirring is 160 commentaries on classics/min, stops heat tracing 15min, is cooled to 50 ℃; In clear and bright solution, add gac 6g, whip attachment 30min, the rotating speed of stirring are 160 commentaries on classics/min; Through taking off a charcoal and a sterilization filter filtration, the secondary terminals degerming filters filter, and filtering millipore filtration aperture is 0.22 μ m; Gained is filtrated to the soup bottle, can after the passed examination, and tamponade promptly gets.Every bottle loading amount is 0.04g: 2ml.
Embodiment 8
The preparation of U 101440E injection liquid
Purified water is carried out distillation preparation sterile water for injection 4 times; After U 101440E 100g, Sorbitol Powder 225g, the lactic acid 4.5g that gets embodiment 3 preparation mixes; Slowly add 75 ℃ of water for injection 1800ml down in stirring; The rotating speed that stirs is 160 commentaries on classics/min; Using sodium hydroxide or hydrochloric acid conditioning solution pH value is 4.0, adds 75 ℃ water for injection 200ml; Solution is warming up to 125 ℃ under stirring, and the rotating speed of stirring is 160 commentaries on classics/min, stops heat tracing 15min, is cooled to 50 ℃; In clear and bright solution, add gac 6g, whip attachment 30min, the rotating speed of stirring are 160 commentaries on classics/min; Through taking off a charcoal and a sterilization filter filtration, the secondary terminals degerming filters filter, and filtering millipore filtration aperture is 0.22 μ m; Gained is filtrated to the soup bottle, can after the passed examination, and tamponade promptly gets.Every bottle loading amount is 0.1g: 2ml.
Experimental example 1
This Test Example detects related substance in the prepared U 101440E of embodiment 1～3; This test is carried out according to 2010 editions second appendix VIII P of Chinese Pharmacopoeia residual solvent assay method, appendix XIX F medicine impurity analysis governing principle, and its result sees table 1:
The assay of table 2 related substance
| Preparation | Terepthaloyl moietie | Acetone | Other related substance |
| Embodiment 1 product | Up to specification | Up to specification | Up to specification |
| Embodiment 2 products | Up to specification | Up to specification | Up to specification |
| Embodiment 3 products | Up to specification | Up to specification | Up to specification |
Experimental example 2
This Test Example has been investigated the water absorbability of U 101440E provided by the invention.
Under the condition of humidity 80% and 90%, each sample thief 1g places on the electronic balance this Test Example respectively, and time recording weight is to detect the moisture absorption degree.
Table 2 wettability test result
Wherein sample 1 is embodiment 1 product;
Sample 2 is embodiment 2 products;
Sample 3 is that HPLC content is 99.58% with reference to the U 101440E crystal of CN201110247797.1 embodiment 1 preparation;
Sample 4 is commercially available U 101440E, originates from Shanghai Ya Ji bio tech ltd, and content is 98.8%.
This Test Example has also been investigated other embodiment preparing products, draws and go up table rule identical result, i.e. the prepared U 101440E water absorbability of the present invention is little.
Experimental example 3
This Test Example has been investigated the stability of U 101440E provided by the invention
This test is carried out according to 2005 editions second appendix XIX C of Chinese Pharmacopoeia medicine stability test governing principle, and the result is following:
Table 3, accelerated test result
| 1 month | 2 months | 3 months | 6 months | 12 months | |
| 1 | 99.86％ | 99.86％ | 99.84％ | 99.82％ | 99.61％ |
| 2 | 99.80％ | 99.79％ | 99.76％ | 99.73％ | 99.56％ |
| 3 | 99.85％ | 99.84％ | 99.78％ | 99.47％ | 98.64％ |
| 4 | 99.86％ | 99.83％ | 99.77％ | 99.44％ | 97.63％ |
| 5 | 99.84％ | 99.82％ | 99.72％ | 99.40％ | 98.58％ |
Table 4, long-term test results
| 3 months | 6 months | 9 months | 12 months | 18 months | |
| 1 | 99.86％ | 99.86％ | 99.86％ | 99.85％ | 99.83％ |
| 2 | 99.80％ | 99.80％ | 99.80％ | 99.78％ | 99.75％ |
| 3 | 99.85％ | 99.85％ | 99.84％ | 99.80％ | 99.48％ |
| 4 | 99.86％ | 99.86％ | 99.84％ | 99.79％ | 99.41％ |
| 5 | 99.84％ | 99.84％ | 99.82％ | 99.75％ | 99.35％ |
Wherein sample 1 is embodiment 1 product, and sample 2 is embodiment 2 products;
Sample 3 is for getting commercially available common U 101440E, the water recrystallization, and recrystallization is approaching to HPLC content and embodiment 1 repeatedly;
Sample 4 is that HPLC content is 99.62% with reference to the U 101440E of CN200710041738.2 embodiment 1 preparation;
Sample 5 originates from Shanghai Ya Ji bio tech ltd for getting commercially available common U 101440E, and content is 98.8%;
This description of test, compared with prior art, U 101440E good stability provided by the invention quickens, test of long duration purity content is little.
Other embodiment products of the present invention have also carried out identical experiment, and obtain the experimental result of same trend, but length limits, and the present invention enumerates no longer one by one.
Claims (9)
1. a U 101440E is characterized in that, the molecular formula of said U 101440E is C
33H
38N
4O
6HCl1.5H
2O.
2. U 101440E according to claim 1 is characterized in that, the preparation of said U 101440E comprises: get the U 101440E bulk drug, add the mixed solvent of entry/terepthaloyl moietie, wherein the volume ratio of water and terepthaloyl moietie is 2～4: 1; Stirring also is heated to 40～60 ℃, adds gac again, and whip attachment is filtered the decarburization degerming; Obtain settled solution, settled solution is moved in the reaction kettle, in 160～180 ℃ of held 24～36h, uniform decrease in temperature to 55～75 ℃; Open reaction kettle, slowly drip acetone, crystallization slowly is cooled to 0～5 ℃; Filter, use deionized water wash, drying under reduced pressure promptly gets.
3. U 101440E according to claim 2 is characterized in that, the ratio of the weight of said U 101440E and the volume of mixed solvent is 1g: 10～15ml.
4. U 101440E according to claim 2 is characterized in that, said dropping is under mixing speed 25～30rmp, at the uniform velocity to drip.
5. U 101440E according to claim 2 is characterized in that, the volume ratio of said acetone and mixed solvent is 3～4: 1.
6. pharmaceutical composition that contains each described U 101440E of claim 1～5.
7. pharmaceutical composition according to claim 6; It is characterized in that; Said pharmaceutical composition is the U 101440E injection liquid; By weight, said U 101440E injection liquid comprises U 101440E 30-100 part, Sorbitol Powder 50-250 part, lactic acid 1-5 part, water for injection 150-2000 part.
8. pharmaceutical composition according to claim 7 is characterized in that, by weight, said U 101440E injection liquid comprises 40 parts of U 101440Es, 90 parts of Sorbitol Powders, 1.8 parts of lactic acid, 2000 parts of waters for injection.
9. pharmaceutical composition according to claim 7 is characterized in that, by weight, said U 101440E injection liquid comprises 100 parts of U 101440Es, 225 parts of Sorbitol Powders, 4.5 parts of lactic acid, 2000 parts of waters for injection.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102824345A (en) * | 2012-09-20 | 2012-12-19 | 江苏奥赛康药业股份有限公司 | Irinotecan hydrochloride composition and preparation method thereof |
| CN102885765A (en) * | 2012-10-25 | 2013-01-23 | 哈药集团生物工程有限公司 | Irinotecan hydrochloride injection and preparation method thereof |
| RU2552289C1 (en) * | 2014-02-05 | 2015-06-10 | ФЕДЕРАЛЬНОЕ ГОСУДАРСТВЕННОЕ БЮДЖЕТНОЕ УЧРЕЖДЕНИЕ "РОССИЙСКИЙ НАУЧНЫЙ ЦЕНТР РАДИОЛОГИИ И ХИРУРГИЧЕСКИХ ТЕХНОЛОГИЙ" МИНИСТЕРСТВА ЗДРАВООХРАНЕНИЯ РОССИЙСКОЙ ФЕДЕРАЦИИ /ФГБУ "РНЦРХТ" Минздрава России/ | Method of treating locally advanced stomach cancer with high metabolic and proliferative activity |
| CN107949375A (en) * | 2015-06-30 | 2018-04-20 | 韩美药品株式会社 | Oral solid formulation containing Irinotecan and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102824345A (en) * | 2012-09-20 | 2012-12-19 | 江苏奥赛康药业股份有限公司 | Irinotecan hydrochloride composition and preparation method thereof |
| CN102824345B (en) * | 2012-09-20 | 2014-03-26 | 江苏奥赛康药业股份有限公司 | Irinotecan hydrochloride composition and preparation method thereof |
| CN102885765A (en) * | 2012-10-25 | 2013-01-23 | 哈药集团生物工程有限公司 | Irinotecan hydrochloride injection and preparation method thereof |
| RU2552289C1 (en) * | 2014-02-05 | 2015-06-10 | ФЕДЕРАЛЬНОЕ ГОСУДАРСТВЕННОЕ БЮДЖЕТНОЕ УЧРЕЖДЕНИЕ "РОССИЙСКИЙ НАУЧНЫЙ ЦЕНТР РАДИОЛОГИИ И ХИРУРГИЧЕСКИХ ТЕХНОЛОГИЙ" МИНИСТЕРСТВА ЗДРАВООХРАНЕНИЯ РОССИЙСКОЙ ФЕДЕРАЦИИ /ФГБУ "РНЦРХТ" Минздрава России/ | Method of treating locally advanced stomach cancer with high metabolic and proliferative activity |
| CN107949375A (en) * | 2015-06-30 | 2018-04-20 | 韩美药品株式会社 | Oral solid formulation containing Irinotecan and preparation method thereof |
| US11090299B2 (en) | 2015-06-30 | 2021-08-17 | Hanmi Pharm. Co., Ltd. | Oral solid formulation containing irinotecan and method of preparing the same |
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