CN102068407A - Cabazitaxel injection and preparation method thereof - Google Patents
Cabazitaxel injection and preparation method thereof Download PDFInfo
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- CN102068407A CN102068407A CN2010106069661A CN201010606966A CN102068407A CN 102068407 A CN102068407 A CN 102068407A CN 2010106069661 A CN2010106069661 A CN 2010106069661A CN 201010606966 A CN201010606966 A CN 201010606966A CN 102068407 A CN102068407 A CN 102068407A
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
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- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
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- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
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- A—HUMAN NECESSITIES
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- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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Abstract
The invention provides cabazitaxel injection. The injection of each milliliter comprises the following components by weight: 10 to 100 milligrams of cabazitaxel, 250 to 800 milligrams of polysorbate 80, 200 to 600 milligrams of absolute ethanol, and 0.05 to 20 milligrams of citric acid. The cabazitaxel injection is a single preparation, does not need to be previously dissolved and prepared by using a special solvent, and can be directly diluted for administration; compared with the conventional preparation technology, the preparation has simple preparation process, low cost and good stability; meanwhile, the preparation shortens the time for preparing the medicinal liquor, improves the stability of clinical medicinal liquor, enhances the accuracy of administration dose, and reduces toxic or side reaction; and the preparation simplifies the preparation process of medicinal personnel, and reduces the risks of the preparation process on harm to the medicinal personnel and environmental pollution.
Description
Technical field
What the present invention relates to is a kind of cabazitaxel injection and preparation method thereof, belongs to the pharmaceutical chemistry technical field.
Background technology
Cabazitaxel is a kind of microtubule inhibitor class antineoplastic agent of being developed by Sanofi-Aventis (Sanofi-aventis), U.S. food Drug Administration ratifies Cabazitaxel injection (trade name: Jevtana) listing in June, 2010, with prednisone (Prednisone) coupling treatment prostate cancer, this medicine is that first-selection is used for the treatment of the medicine of late period, hormone antagonist type carcinoma of prostate when using the invalid even state of an illness of advanced prostate cancer medicine docetaxel to increase the weight of.
In prior art, Chinese patent CN1152870 and CN1213042 disclose the preparation of Cabazitaxel; Chinese patent CN1200707 discloses the new purposes of Cabazitaxel; U.S. Pat 2005/0065138 discloses the novel crystal forms and preparation method thereof of the acetone solvate of Cabazitaxel.The open WO2009/115655 of international monopoly discloses other new crystal formations of Cabazitaxel and preparation method thereof.
(trade name: Jevtan) be an assembly packaging, wherein one is the Cabazitaxel injection to the Cabazitaxel injection of U.S. food Drug Administration approval, and one is the diluent of Cabazitaxel injection (claiming dedicated solvent again).Cabazitaxel injection specification is 60mg/1.5ml, contains in its every 1.5ml injection of writing out a prescription: the Cabazitaxel of 60mg (anhydrous or solvent-free) and 1.56g polyoxyethylene sorbitan monoleate; The concentration that is to say the Cabazitaxel injection is Cabazitaxel (anhydrous or solvent-free) and the 1.04g polyoxyethylene sorbitan monoleate that every 1ml contains 40mg.The diluent of Cabazitaxel injection (claiming dedicated solvent again) prescription is the ethanol water of 13% (w/w).The Cabazitaxel injection of U.S. food Drug Administration approval (trade name: Jevtan) clinical using method is: 1, with a syringe that syringe needle is housed will be corresponding with the Cabazitaxel injection whole aseptic the separating out of dedicated solvent, bottle inclination that will the dress solvent; 2, whole solvents in the syringe are injected the Cabazitaxel injection, to avoid scratch cillin bottle inwall or to cause foamy generation.Topple over cillin bottle then gently, repeat 45 times, make the Cabazitaxel dissolving fully also avoid foamy generation to greatest extent.The solution of making (following abbreviation " is pre-mixed liquid ") needs to place 5 minutes, makes froth breaking, and too much foam will influence the accuracy of dosage in the cillin bottle.JEVTANA is pre-mixed liquid, should use in 30 minutes immediately; 3, draw required " being pre-mixed liquid " with another syringe at last and inject transfusion bag, mix gently.This preparation method operation is quite loaded down with trivial details, and the time is long; And " being pre-mixed liquid " be a kind of metastable solution, and physical stability is poor.If firmly excessive in ' being pre-mixed liquid ' process for preparation, can cause that precipitation takes place, perhaps bubble too much, can't guarantee the clinical medicine dose accuracy; If firmly not enough in ' being pre-mixed liquid ' process for preparation, Cabazitaxel not dissolving is difficult to guarantee the clinical medicine dose accuracy fully equally.' being pre-mixed liquid ' life-span generally has only 30 minutes, and clinical use is extremely inconvenient; Overlong time will cause the degraded of principal agent Cabazitaxel to produce impurity, certainly will affect the treatment and may bring in various degree toxicity to the patient.Though producer has spent a lot of manpower and materials big and small hospital nurse is carried out " being pre-mixed liquid " preparation training, but according to incompletely statistics, during product quality over the years was complained, the case of relevant " being pre-mixed liquid " quality still accounted for all product qualities and complains more than 95%.
Summary of the invention
The objective of the invention is to overcome the deficiencies in the prior art part, a kind of Cabazitaxel injection and preparation method thereof is provided.
Cabazitaxel injection of the present invention, the component and the weight of every milliliter of injection are as follows: cabazitaxel 10～100mg, polyoxyethylene sorbitan monoleate 250～800mg, dehydrated alcohol 200～600mg, citric acid 0.05～20mg.
Preferably,
The pH value of said injection is 3.5～6.0.
The preparation method of cabazitaxel injection of the present invention comprises the following steps:
(1) earlier cabazitaxel and citric acid are dissolved in the part dehydrated alcohol, add polyoxyethylene sorbitan monoleate, the back that stirs adds remaining dehydrated alcohol to full dose, continues to stir, and sampling detects pH;
(2) carry out aseptic filtration by 0.22 μ m microporous filter membrane or 0.22 μ m degerming filter bulb, fill is sealed and is formed the cabazitaxel injection formulation.
Preferably,
The weight of said part dehydrated alcohol accounts for the 78-90% of dehydrated alcohol full dose.
The pH value of said injection is 3.5～6.0.
Cabazitaxel injection of the present invention and preparation method thereof has solved existing preparation complex operation, the cost height, and poor stability, clinical use complexity is prone to the shortcoming of mistake, has following technique effect:
1, preparation of the present invention, preparation process is simple, need not to remove troublesome operation such as solvent by distillation or lyophilized form, has reduced cost, has shortened the production time, has reduced operator and anticarcinogen Long contact time and the adverse consequences brought.
2, preparation process of the present invention is simple, and energy consumption is low; Reduce the cillin bottle of splendid attire medicinal liquid and the use of disposable syringe, met the requirement of low-carbon environment-friendly.
3, better stability of preparation of the present invention detects purity and content through HPLC, and purity is singly mixed below 0.3% more than 99%; Said preparation is tested through study on the stability, and this product related substance and content are not seen significant change, steady quality.
4, the clinical use compound method of preparation of the present invention is simplified greatly, need not preparation " being pre-mixed liquid ", can directly draw required dosage injection transfusion mixing back with syringe and use.Clinical compound method is simplified, and clinical stability in use and dosage accuracy strengthen; Can thoroughly solve the quality that causes because of " being pre-mixed liquid " preparation complains.
5, preparation of the present invention can be used for advanced prostate cancer patient's treatment, and often treatment means is few to have solved such disease patient, owing to the long problem of delaying treatment time of clinical use preparation time, gives the more therapy apparatus meeting of patient.Reduce the toxicity that existing preparation causes because of dosage is inaccurate, complied with the clinical application custom, alleviated patient's misery.
The specific embodiment
Further specify the present invention below by embodiment.Should correct understanding be: the method in the embodiments of the invention is only used for the present invention is described and provides, rather than limitation of the present invention, so, under method prerequisite of the present invention, simple modifications of the present invention is all belonged to the scope of protection of present invention.
Embodiment 1: preparation Cabazitaxel injection
(1) preparation is formed:
Cabazitaxel 0.6g
Polyoxyethylene sorbitan monoleate 15.6g
Citric acid 0.02g
Dehydrated alcohol 11.9g
Be total to 30ml
(2) preparation method:
0.6 gram cabazitaxel and 0.02g citric acid are dissolved in the 10.7 gram dehydrated alcohol, add 15.6 gram polyoxyethylene sorbitan monoleates, add dehydrated alcohol 1.2g after stirring to full dose 30ml, continue to stir, get intermediate and detect PH, PH is 4.91; Carry out aseptic filtration by 0.22 μ m microporous filter membrane, in the 10ml cillin bottle, the preparation of cabazitaxel injection (specification 60mg/ props up) is made in tamponade to filtrate with every 3ml sterile filling.
It is 99.62% (related substance total impurities 0.38%) that product detects purity through HPLC, and maximum single mixing is 0.18%;
The HPLC testing conditions is:
Chromatographic column: octadecylsilane chemically bonded silica is filler (150mm*4.6mm, 5 μ m);
Mobile phase: acetonitrile: methanol: water (26: 32: 42);
Detect wavelength: 232nm;
Flow velocity: 1ml/min;
Column temperature: 30 ℃.
Reference examples 1: preparation Cabazitaxel injection (with reference to the preparation of Chinese patent CN1291713 method)
0.6 gram cabazitaxel is dissolved in the 5ml dehydrated alcohol, add the 15.6g polyoxyethylene sorbitan monoleate, after stirring, carry out aseptic filtration by 0.22 μ m microporous filter membrane, filtrate with every 2ml sterile filling in the 10ml cillin bottle, half tamponade is sent into the freeze dryer volatilization of reducing pressure and is removed ethanol, and the total head plug is made the preparation of cabazitaxel injection (specification 60mg/ props up).
It is 98.97% (related substance total impurities 1.03%) that product detects purity through HPLC, and maximum single mixing is 0.58%; The HPLC testing conditions is with embodiment 1.
Embodiment 2: preparation Cabazitaxel injection
(1) preparation is formed:
Cabazitaxel 0.2g
Polyoxyethylene sorbitan monoleate 16g
Citric acid 1mg
Dehydrated alcohol 4g
Be total to 20ml
(2) preparation method:
0.2 gram cabazitaxel and 1 milligram of citric acid are dissolved in the 3.2 gram dehydrated alcohol, add 16 gram polyoxyethylene sorbitan monoleates, add dehydrated alcohol 0.8g after stirring to full dose 20ml, continue to stir, get intermediate and detect pH, pH is 6.0; Carry out aseptic filtration by 0.22 μ m microporous filter membrane, in the 10ml cillin bottle, tamponade forms the preparation of cabazitaxel injection (specification 20mg/ props up) to filtrate with every 2ml sterile filling.
It is 99.72% (related substance total impurities 0.28%) that product detects purity through HPLC, and maximum single mixing is 0.09%; The HPLC testing conditions is with embodiment 1.
Embodiment 3: preparation Cabazitaxel injection
(1) preparation is formed:
Cabazitaxel 1.2g
Polyoxyethylene sorbitan monoleate 6g
Citric acid 0.1g
Dehydrated alcohol 11.3g
Be total to 20ml
(2) preparation method:
1.2 gram cabazitaxel and 0.1g citric acid are dissolved in the 9 gram dehydrated alcohol, add 6 gram polyoxyethylene sorbitan monoleates, add dehydrated alcohol 2.3g after stirring to full dose 20ml, continue to stir, get intermediate and detect pH, pH is 4.43; Carry out aseptic filtration by 0.22 μ m degerming filter bulb, in the 10ml cillin bottle, tamponade forms the preparation of cabazitaxel injection (specification 120mg/ props up) to filtrate with every 2ml sterile filling.
It is 99.65% (related substance total impurities 0.35%) that product detects purity through HPLC, and maximum single mixing is 0.12%; The HPLC testing conditions is with embodiment 1.
Embodiment 4: preparation Cabazitaxel injection
(1) preparation is formed:
Cabazitaxel 3g
Polyoxyethylene sorbitan monoleate 12.8g
Citric acid 0.3g
Dehydrated alcohol 14.2g
Be total to 30ml
(2) preparation method:
3 gram cabazitaxel and 0.3g citric acid are dissolved in the 11.4 gram dehydrated alcohol, add 12.8 gram polyoxyethylene sorbitan monoleates, add dehydrated alcohol 2.8g after stirring to full dose 30ml, continue to stir, get intermediate and detect pH, pH is 3.98; Carry out aseptic filtration by 0.22 μ m filter membrane, in cillin bottle, tamponade forms the preparation of cabazitaxel injection (specification 100mg/ props up) to filtrate with every 1ml sterile filling.
It is 99.78% (related substance total impurities 0.22%) that product detects purity through HPLC, and maximum single mixing is 0.08%; The HPLC testing conditions is with embodiment 1.
Embodiment 5: preparation Cabazitaxel injection
(1) preparation is formed:
Cabazitaxel 1.7g
Polyoxyethylene sorbitan monoleate 5g
Citric acid 0.4g
Dehydrated alcohol 12g
Be total to 20ml
(2) preparation method:
1.7 gram cabazitaxel and 0.4g citric acid are dissolved in the 9.6 gram dehydrated alcohol, add 5 gram polyoxyethylene sorbitan monoleates, add dehydrated alcohol 2.4g after stirring to full dose 20ml, continue to stir, get intermediate and detect PH, PH is 3.50; Carry out aseptic filtration by 0.22 μ m microporous filter membrane, in cillin bottle, tamponade forms the preparation of cabazitaxel injection (specification 60mg/ props up) to filtrate with every 0.7ml sterile filling.
It is 99.60% (related substance total impurities 0.40%) that product detects purity through HPLC, and maximum single mixing is 0.13%; The HPLC testing conditions is with embodiment 1.
Embodiment 6: preparation Cabazitaxel injection
(1) preparation is formed:
Cabazitaxel 1.5g
Polyoxyethylene sorbitan monoleate 7.8g
Citric acid 0.3g
Dehydrated alcohol 10g
Be total to 20ml
(2) preparation method:
1.5 gram cabazitaxel and 0.3g citric acid are dissolved in the 8 gram dehydrated alcohol, add 7.8 gram polyoxyethylene sorbitan monoleates, add dehydrated alcohol 2g after stirring to full dose 20ml, continue to stir, get intermediate and detect pH, pH is 3.81; Carry out aseptic filtration by 0.22 μ m microporous filter membrane, in cillin bottle, tamponade forms the preparation of cabazitaxel injection (specification 60mg/ props up) to filtrate with every 0.8ml sterile filling.
It is 99.54% (related substance total impurities 0.46%) that product detects purity through HPLC, and maximum single mixing is 0.12%; The HPLC testing conditions is with embodiment 1.
Embodiment 7: preparation Cabazitaxel injection
(1) preparation is formed:
Cabazitaxel 0.7g
Polyoxyethylene sorbitan monoleate 9.6g
Citric acid 6mg
Dehydrated alcohol 8.7g
Be total to 20ml
(2) preparation method:
0.7 gram cabazitaxel and 6mg citric acid are dissolved in the 7 gram dehydrated alcohol, add 9.6 gram polyoxyethylene sorbitan monoleates, add dehydrated alcohol 1.7g after stirring to full dose 20ml, continue to stir, get intermediate and detect pH, pH is 5.79; Carry out aseptic filtration by 0.22 μ m microporous filter membrane, in cillin bottle, tamponade forms the preparation of cabazitaxel injection (specification 60mg/ props up) to filtrate with every 1.7ml sterile filling.
It is 99.79% (related substance total impurities 0.21%) that product detects purity through HPLC, and maximum single mixing is 0.07%; The HPLC testing conditions is with embodiment 1.
Embodiment 8: preparation Cabazitaxel injection
(1) preparation is formed:
Cabazitaxel 2g
Polyoxyethylene sorbitan monoleate 31.7g
Citric acid 5mg
Dehydrated alcohol 16g
Be total to 50ml
(2) preparation method:
2 gram cabazitaxel and 5mg citric acid are dissolved in the 12.8 gram dehydrated alcohol, add 31.7 gram polyoxyethylene sorbitan monoleates, add dehydrated alcohol 3.2g after stirring to full dose 50ml, continue to stir, get intermediate and detect pH, pH is 5.87; Carry out aseptic filtration by 0.22 μ m microporous filter membrane, in cillin bottle, tamponade forms the preparation of cabazitaxel injection (specification 60mg/ props up) to filtrate with every 1.5ml sterile filling.
It is 99.56% (related substance total impurities 0.44%) that product detects purity through HPLC, and maximum single mixing is 0.14%; The HPLC testing conditions is with embodiment 1.
Embodiment 9: preparation Cabazitaxel injection
(1) preparation is formed:
Cabazitaxel 2.5g
Polyoxyethylene sorbitan monoleate 35.6g
Citric acid 0.05g
Dehydrated alcohol 13g
Be total to 50ml
(2) preparation method:
2.5 gram cabazitaxel and 0.05g citric acid are dissolved in the 10.4 gram dehydrated alcohol, add 35.6 gram polyoxyethylene sorbitan monoleates, add dehydrated alcohol 2.6g after stirring to full dose 50ml, continue to stir, get intermediate and detect pH, pH is 5.62; Carry out aseptic filtration by 0.22 μ m degerming filter bulb, in cillin bottle, tamponade forms the preparation of cabazitaxel injection (specification 60mg/ props up) to filtrate with every 1.2ml sterile filling.
It is 99.48% (related substance total impurities 0.52%) that product detects purity through HPLC, and maximum single mixing is 0.11%; The HPLC testing conditions is with embodiment 1.
Embodiment 10 investigates the injection and the former control formulation stability of sample of grinding producer of embodiment 1～9, reference examples 1 preparation
Cabazitaxel injection and former control formulation Cabazitaxel injection (trade name: Jevtana of grinding producer according to embodiment 1～9, reference examples 1 preparation gained, specification 60mg/1.5ml) carry out the test of 40 ℃ of study on the stability, related substance of the present invention and content detection can be with reference to following standard methods:
Assay: measure according to high performance liquid chromatography (Chinese Pharmacopoeia 2010 version two ones).Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; With acetonitrile-methanol-water (26: 32: 42) is mobile phase; The detection wavelength is 232nm.Get each 20mg of reference substance and naphthalene, the accurate title, decide, and puts in the 100ml measuring bottle, adds ethanol 5ml, and jolting makes dissolving, adds mobile phase again and is diluted to scale, shakes up, and precision is measured 20 μ l and injected chromatograph of liquid, the record chromatogram; Number of theoretical plate calculates by main peak should be not less than 4000, and the separating degree at main peak and naphthalene peak should be not less than 4.
Assay method: it is an amount of that precision takes by weighing this product, puts in the 25ml measuring bottle, adds ethanol and make dissolving in right amount, adds the mobile phase dilution again and make the solution that contains 0.8mg among every 1ml approximately, shakes up, and precision is measured 20 μ l, injects chromatograph of liquid, the record chromatogram; Other gets reference substance 20mg, and accurate the title decides, and puts in the 25ml measuring bottle, adds ethanol and makes dissolving in right amount, adds mobile phase again and is diluted to scale, shakes up, and measures with method.Press external standard method with calculated by peak area.
Related substance: get under the assay item need testing solution as need testing solution.Precision is measured need testing solution 1ml, puts in the 100ml measuring bottle, is diluted to scale with mobile phase, shakes up, in contrast solution.According to the chromatographic condition under the assay item, get contrast solution 20 μ l injecting chromatographs, regulate detection sensitivity, making the main constituent peak height is 10%～25% of full scale; Precision is measured need testing solution and each 20 μ l of contrast solution again, injects chromatograph of liquid respectively, and the record chromatogram is to 2.5 times of main constituent peak retention time.In the chromatogram of need testing solution if any impurity peaks, deduction adjuvant peak, single impurity peak area must not be greater than contrast solution main peak area (1.0%), each impurity peak area and must not be greater than 1.5 times (1.5%) of contrast solution main peak area.Result of study is as shown in table 1.
40 ℃ of stability experiment results of the lyophilized formulations sample of table 1 embodiment 1～9, reference examples 1 preparation
Conclusion: from above result of study as can be known, cabazitaxel injection of the present invention, related substance is low, the purity height, in put procedure, related substance and content are not seen significant change, steady quality.
Claims (5)
1. a cabazitaxel injection is characterized in that, the component and the weight of every milliliter of injection are as follows: cabazitaxel 10 ~ 100mg, polyoxyethylene sorbitan monoleate 250 ~ 800 mg, dehydrated alcohol 200 ~ 600 mg, citric acid 0.05 ~ 20 mg.
2. cabazitaxel injection according to claim 1 is characterized in that, the pH value of said injection is 3.5 ~ 6.0.
3. the preparation method of a cabazitaxel injection is characterized in that, comprises the following steps:
(1) earlier cabazitaxel and citric acid are dissolved in the part dehydrated alcohol, add polyoxyethylene sorbitan monoleate, the back that stirs adds remaining dehydrated alcohol to full dose, continues to stir, and sampling detects pH;
(2) carry out aseptic filtration by 0.22 μ m microporous filter membrane or 0.22 μ m degerming filter bulb, fill is sealed and is formed the cabazitaxel injection formulation.
4. the preparation method of cabazitaxel injection according to claim 3 is characterized in that, the weight of said part dehydrated alcohol accounts for 78-90% of dehydrated alcohol full dose.
5. the preparation method of cabazitaxel injection according to claim 3 is characterized in that, the pH value of said injection is 3.5 ~ 6.0.
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102895183A (en) * | 2012-11-05 | 2013-01-30 | 江苏红豆杉生物科技股份有限公司 | Cabazitaxel for injection and preparation method thereof |
| WO2013024495A1 (en) * | 2011-08-18 | 2013-02-21 | Dr. Reddys Laboratories Limited | Pharmaceutical formulations of cabazitaxel |
| WO2014028704A1 (en) * | 2012-08-15 | 2014-02-20 | Yung Shin Pharm. Ind. Co., Ltd. | Stable pharmaceutical formulation of cabazitaxel |
| WO2014115168A2 (en) * | 2013-01-23 | 2014-07-31 | Leiutis Pharmaceuticals Private Limited | Novel solvate forms of cabazitaxel and process for preparation thereof |
| CN103961345A (en) * | 2013-01-31 | 2014-08-06 | 江苏奥赛康药业股份有限公司 | Jevtana-containing injection composition and preparation method thereof |
| CN104546694A (en) * | 2013-10-15 | 2015-04-29 | 悦康药业集团有限公司 | Docetaxel injection and preparation method thereof |
| CN106619493A (en) * | 2015-11-04 | 2017-05-10 | 四川科伦药物研究院有限公司 | Cabazitaxel injection and preparation method thereof |
| US20180280295A1 (en) * | 2016-03-14 | 2018-10-04 | Song Lin | Single vial ready to use cabazitaxel formulations with increased stability and methods of preparations |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010128258A1 (en) * | 2009-05-06 | 2010-11-11 | Sanofi-Aventis | Antitumor combination including cabazitaxel and capecitabine |
-
2010
- 2010-12-27 CN CN2010106069661A patent/CN102068407B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010128258A1 (en) * | 2009-05-06 | 2010-11-11 | Sanofi-Aventis | Antitumor combination including cabazitaxel and capecitabine |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013024495A1 (en) * | 2011-08-18 | 2013-02-21 | Dr. Reddys Laboratories Limited | Pharmaceutical formulations of cabazitaxel |
| WO2014028704A1 (en) * | 2012-08-15 | 2014-02-20 | Yung Shin Pharm. Ind. Co., Ltd. | Stable pharmaceutical formulation of cabazitaxel |
| CN102895183A (en) * | 2012-11-05 | 2013-01-30 | 江苏红豆杉生物科技股份有限公司 | Cabazitaxel for injection and preparation method thereof |
| WO2014115168A2 (en) * | 2013-01-23 | 2014-07-31 | Leiutis Pharmaceuticals Private Limited | Novel solvate forms of cabazitaxel and process for preparation thereof |
| WO2014115168A3 (en) * | 2013-01-23 | 2014-12-04 | Leiutis Pharmaceuticals Private Limited | Novel solvate forms of cabazitaxel and process for preparation thereof |
| CN103961345A (en) * | 2013-01-31 | 2014-08-06 | 江苏奥赛康药业股份有限公司 | Jevtana-containing injection composition and preparation method thereof |
| CN104546694A (en) * | 2013-10-15 | 2015-04-29 | 悦康药业集团有限公司 | Docetaxel injection and preparation method thereof |
| CN106619493A (en) * | 2015-11-04 | 2017-05-10 | 四川科伦药物研究院有限公司 | Cabazitaxel injection and preparation method thereof |
| CN106619493B (en) * | 2015-11-04 | 2019-09-13 | 四川科伦药物研究院有限公司 | A kind of Cabazitaxel injection and preparation method thereof |
| US20180280295A1 (en) * | 2016-03-14 | 2018-10-04 | Song Lin | Single vial ready to use cabazitaxel formulations with increased stability and methods of preparations |
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