CN101129374B - Vinflunine pharmaceutical composition and method of producing the same and application of the same - Google Patents
Vinflunine pharmaceutical composition and method of producing the same and application of the same Download PDFInfo
- Publication number
- CN101129374B CN101129374B CN2007100166045A CN200710016604A CN101129374B CN 101129374 B CN101129374 B CN 101129374B CN 2007100166045 A CN2007100166045 A CN 2007100166045A CN 200710016604 A CN200710016604 A CN 200710016604A CN 101129374 B CN101129374 B CN 101129374B
- Authority
- CN
- China
- Prior art keywords
- vinflunine
- solution
- injection
- bitartrate
- dissolving
- 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.)
- Expired - Fee Related
Links
Abstract
The invention relates to a pharmaceutical composition of Vinflunine, which comprises Vinflunine as the active constituent, pharmaceutically acceptable salts and cyclodextrin, wherein each 1 part of Vinflunine and its pharmaceutically acceptable salt are mixed with a maximum of 0. 5-100 parts by weight ratio of cyclodextrin, and freeze dried injection is prepared. The invention also relates to the process for preparing the composition, and its use in preparing non-stomach administering pharmaceutical products for the treatment of cancer.
Description
Technical field
The present invention relates to a kind of vinflunine pharmaceutical composition, the vinflunine freeze-dried powder injecta medicine composition and method of making the same that relates in particular to a kind of parenteral administration is used for the treatment of the medicinal usage of cancer with it, belongs to medical technical field.
Background technology
Vinflunine is by the up-to-date vinca medicine of French Pierre's method C Compaq screening the earliest, is derived by vinorelbine, by the inhibition tubulin polymerization, makes cell division stop at mitosis metaphase, is the period specific cancer therapy drug.Can be used for nonsmall-cell lung cancer, bladder cancer, tumor treatment such as breast carcinoma, mesothelioma, melanoma, renal carcinoma.
The pharmaceutically acceptable salt of bibliographical information vinflunine has forms such as bitartrate, sulfate.Liquor epinephrinae bitartratis ophthalmicus vinflunine raw material is very unstable, must be under inert gas shielding, and subzero (15 ℃) stores.But the aqueous solution of liquor epinephrinae bitartratis ophthalmicus vinflunine but can be preserved 2-8 ℃ of condition.Therefore, Pierre's method C Compaq of France applied on the 17th at December in 2004 that the liquor epinephrinae bitartratis ophthalmicus vinflunine was used for the patent of the stable aqueous solution preparation of antineoplaston, and publication number is WO2005070425.Patent disclosure with citric acid/sodium citrate or acetic acid/sodium-acetate buffer or directly be stabilized between the 3-4 with the pH of water for injection with solution, aseptic filtration makes aseptic parenteral solution, places under 5 ℃ ± 3 ℃ the condition, at least 36 months stable.
The specification of liquor epinephrinae bitartratis ophthalmicus vinflunine injection is subjected to the restriction of packing container and the medicine steady concentration in aqueous solution, disclosed optimum medicine concentration is 25mg/ml (containing vinflunine) among the WO2005070425, but the clinical large usage quantity (320mg/m of vinflunine
2), like this, single dose strengthens, and will certainly cause packing to strengthen; Make troubles to medicine preparation, transportation and application.
Because the liquor epinephrinae bitartratis ophthalmicus vinflunine is very easily water-soluble, so liquor epinephrinae bitartratis ophthalmicus vinflunine injectable powder can be avoided this defective, carries out specifications design according to clinical needs, for doctors and patients' medication provides better facility.But, studies show that, the liquor epinephrinae bitartratis ophthalmicus vinflunine injectable powder sample that lyophilizing adjuvant commonly used such as mannitol prepare under conventional amount used, its clarity is greater than No. 2, stability is poor than medicinal liquid before the lyophilizing of liquor epinephrinae bitartratis ophthalmicus vinflunine, can not obtain vinflunine salt lyophilized formulations ideal, high stability.Result of study sees Table 1.
In the experiment: liquor epinephrinae bitartratis ophthalmicus vinflunine and mannitol weight ratio 1:1, water-soluble, drug level is counted 25mg/ml with vinflunine, lyophilization.
The different vinflunine preparation of table 1 clarity relatively
Given this, research and development with vinflunine and pharmaceutically acceptable salt thereof be the prescription of the stable lyophilized formulations of principal agent form and preparation method very necessary.
Summary of the invention
At the deficiencies in the prior art, the object of the present invention is to provide a kind of is that the vinflunine freeze-dried powder injecta medicine composition and method of making the same of the parenteral administration made of principal agent and its are used for the treatment of the medicinal usage of cancer with vinflunine and pharmaceutically acceptable salt thereof.
Vinflunine powder medicine administered by injection compositions of the present invention, it is characterized in that: contain active component vinflunine and pharmaceutically acceptable salt thereof, and be mixed with the cyclodextrin of 0.5-100 part part by weight at the most and make powderous preparations in 1 part of vinflunine and pharmaceutically acceptable salt thereof, wherein water content can be controlled in 12%.
Wherein: the preferred vinflunine bitartrate of the pharmaceutically acceptable salt of described vinflunine; The preferred HP-of described cyclodextrin or acetyl-gamma-cyclodextrin.
Vinflunine powder medicine administered by injection compositions of the present invention is characterized in that: contain the pH buffer system, described pH buffer system is made up of acetic acid/sodium acetate buffer agent or citric acid/sodium citrate buffer agent, and its pH value maintains 3.0-4.5.
Wherein: the molar concentration of the pH buffer agent in the described pH buffer system is 0.002M-0.2M.
The preparation method of vinflunine powder medicine administered by injection compositions of the present invention comprises following successive step:
(a) cyclodextrin is water-soluble or optionally add in the aqueous solution of pH buffer agent and dissolve;
(b) vinflunine and pharmaceutically acceptable salt thereof are added by weight proportion be dissolved to the solution clarification in the above-mentioned solution;
(c) with conventional method above-mentioned settled solution is removed thermal source and filtration sterilization;
(d) aseptic powdery solid composite medicament is made in lyophilization.
In the preparation method of above-mentioned vinflunine powder medicine administered by injection compositions:
Freeze-drying method described in the step (d) can be sub-packed in medical unit dose package and directly be loaded on the lyophilizing cabinet, carries out lyophilization;
Freeze-drying method described in the step (d), also directly sabot lyophilization, aseptic subpackaged then in medical unit dose package container;
The described freezing dry process of step (d) can blanketing with inert gas.
The aseptic powdery solid composite medicament of gained after the described lyophilization of step (d) seals, packs the vinflunine lyophilized injectable powder that makes parenteral administration through gland.
Utilize the vinflunine freeze-dried powder injecta medicine compositions of the parenteral administration of the method for the invention preparation to be used for the treatment of the application of the medical product of cancer as preparation.
Utilize the vinflunine freeze-dried powder injecta medicine compositions of the parenteral administration of the method for the invention preparation to can be used for treatment for cancer such as nonsmall-cell lung cancer, breast carcinoma, ovarian cancer, lymphoma, the solvent load of described preparation gets final product with enough principal agents and adjuvant dissolving, volume according to the lyophilized solid thing can suitably increase quantity of solvent, and the quantity of solvent that preparation commonly used is every bottle can be at 1-20ml.
The content of principal agent can prepare the 1mg-800mg/ bottle usually in vinflunine.
Vinflunine injectable powder of the present invention is identical with injection in the clinical scope of application.When using clinically, injectable powder is diluted in the normal saline then earlier with behind a small amount of physiological saline solution, and in short time angular vein input, the normal saline flushing vein that instils a large amount of then reduces this product to the venous zest.Clinical administration dosage is 320mg/m
2Once in a week, continuous 4-6 time is a course of treatment.
The vinflunine injectable powder product stability that the present invention makes is better, and product clarity is good, and the effective active composition is difficult for decomposing, and reduces medicine storage life catabolite especially, improves curative effect, the minimizing toxic and side effects of product.
Injectable powder of the present invention can be placed under 5 ℃ ± 3 ℃ condition for a long time.
Injectable powder convenient transportation of the present invention, product appearance is attractive in appearance, helps applying on a large scale clinically.
For further embodying stability of formulation of the present invention, emphasize the particularly effect of HP-of the selected lyophilizing adjuvant of the present invention cyclodextrin, in the list of experiments mode beneficial effect of the present invention is further described in detail below:
(medicinal liquid is sub-packed in the cillin bottle with the injectable powder that contains different proportioning HP-and vinflunine bitartrate and the correlated steadiness of liquor epinephrinae bitartratis ophthalmicus vinflunine aqueous solution, investigating index with high performance liquid chromatography detects) investigate, the results are shown in Table 2:
Table 2: the study on the stability information slip of vinflunine bitartrate (25mg/ml) and cyclodextrin composite
| Liquor epinephrinae bitartratis ophthalmicus vinflunine: HP-weight ratio | 1：1 | 1：2 | 1：3 | 1：4 | 1：5 | 1：6 | Aqueous solution |
| Dried frozen aquatic products clarity | No. 2 turbidity liquid | <2 | <1 | <1 | ≤0.5 | ≤0.5 | ≤0.5 |
| 0 day total impurities % | 0.69 | 0.70 | 0.72 | 0.68 | 0.64 | 0.71 | 0.70 |
| 5 days total impurities % of cold preservation | 0.71 | 0.75 | 0.74 | 0.710 | 0.66 | 0.75 | 0.71 |
| 10 days total impurities % of cold preservation | 0.84 | 0.89 | 0.71 | 0.76 | 0.73 | 0.84 | 0.85 |
| 40 ℃ of 5 days total impurities % | 1.23 | 1.22 | 1.20 | 0.99 | 1.04 | 1.06 | 1.1 |
| 40 ℃ of 10 days total impurities % | 1.51 | 1.42 | 1.34 | 1.08 | 1.04 | 1.03 | 1.04 |
| 60 ℃ of 5 days total impurities % | 1.73 | 1.52 | 1.52 | 1.35 | 1.23 | 1.24 | 1.37 |
| 60 ℃ of 10 days total impurities % | 3.15 | 2.53 | 2.2 | 1.73 | 2.01 | 2.13 | 2.87 |
| 5 days total impurities % of illumination | 3.67 | 2.8 | 2.5 | 1.6 | 1.4 | 1.4 | 6.7 |
| 10 days total impurities % of illumination | 4.50 | 3.53 | 3.1 | 2.50 | 2.40 | 2.45 | 8.0 |
Annotate: the solid preparation sample is diluted to the concentration that principal agent is 25mg/ml with water for injection, carries out the medicinal liquid turbidity relatively.
By above result as can be seen, along with the increasing of HP-consumption, vinflunine is made after the injectable powder, stability significantly increases, especially heat stability significantly increases, and its stability is compared with WO2005070425 patent prescription aqueous solution, and is more stable.
In view of liquor epinephrinae bitartratis ophthalmicus vinflunine raw material must be under inert gas shielding, subzero (15 ℃) stores, and therefore can also confirm that the present invention has obtained the solid composite medicament more stable than liquor epinephrinae bitartratis ophthalmicus vinflunine.Vinflunine is to photo-labile, and preferably lucifuge stores.
With the liquor epinephrinae bitartratis ophthalmicus vinflunine: the HP-weight ratio is respectively 1:6 and 1:4 water dissolution, vinflunine concentration is 25mg/ml, the concentration of citric acid and sodium citrate buffer salt is 4mM, pH is controlled at 3.0-5.5, lyophilizing preparing product, brown bottle packing, 2-8 ℃ of lucifuge are placed 6 months impurity data and aqueous solution according to WO2005070425 patent prescription preparation liquor epinephrinae bitartratis ophthalmicus vinflunine, be sub-packed in brown ampoule fusion sealing, 2-8 ℃ of lucifuge placed 6 months impurity data and compared.The results are shown in Table 3:
The impurity of table 3 vinflunine injectable powder and aqueous solution is investigated information slip
With the liquor epinephrinae bitartratis ophthalmicus vinflunine: the HP-weight ratio is respectively the 1:4 water dissolution, and vinflunine concentration is 25mg/ml, and the concentration of citric acid and sodium citrate buffer salt is 4mM, and pH is controlled at 3.0-5.5, lyophilizing preparing product, brown bottle packing.With the compatibility stability test of the concentration of vinflunine 12.8mg/ml and 1.5mg/ml and 0.9% sodium chloride and 5% glucose injection, the results are shown in Table 4 and table 5:
Table 4 vinflunine concentration is the stability test result of 12.8mg/ml
Table 5 vinflunine concentration is the stability test result of 1.5mg/ml
Toxicological test proves that also liquor epinephrinae bitartratis ophthalmicus vinflunine aqueous solution compares in liquor epinephrinae bitartratis ophthalmicus vinflunine powder medicine administered by injection compositions of the present invention and the WO2005070425 patent, and toxicity is not seen increase.
The specific embodiment
Following examples will further specify the present invention, but not limit the present invention.
Embodiment 1
Take by weighing HP-205.05g, sterilized water for injection 800ml stirring and dissolving, add liquor epinephrinae bitartratis ophthalmicus vinflunine 34.175g (being equivalent to vinflunine 25g) stirring and make its dissolving, measure the pH value 3.0-4.5 of solution, be settled to 1000ml, add needle-use activated carbon, filter, the filtrate reuse is equipped with 0.22 μ m filtering with microporous membrane, and is canned in aseptic cillin bottle.Freezingly in the lyophilizing cabinet kept 2-3 hour to about-45 ℃ ,-10 ℃～0 ℃ 9 hours sublimation drying, 38 ℃ after dry again 5-10 hour, the inflated with nitrogen outlet is jumped a queue, gland seals, and packing promptly gets injection vinflunine injectable powder.
Embodiment 2
Take by weighing HP-136.7g and citric acid 0.6g, sodium citrate 0.6g, add sterilized water for injection 800ml stirring and dissolving, add liquor epinephrinae bitartratis ophthalmicus vinflunine 34.175g (being equivalent to vinflunine 25g) stirring and make its dissolving, measure the pH value 3.0-4.5 of solution, be settled to 1000ml, add needle-use activated carbon, filter, the filtrate reuse is equipped with 0.22 μ m filtering with microporous membrane, and is canned in aseptic cillin bottle.Freezingly in the lyophilizing cabinet kept 2-3 hour to about-45 ℃ ,-10～0 ℃ of 9 hours sublimation drying, 38 ℃ after dry again 8-10 hour, outlet is jumped a queue, gland seals, and packing promptly gets injection vinflunine injectable powder.
Embodiment 3
Take by weighing acetyl group-gamma-cyclodextrin 160.0g and citric acid 0.6g, sodium citrate 0.8g; add sterilized water for injection 800ml stirring and dissolving; add liquor epinephrinae bitartratis ophthalmicus vinflunine 34.175g (being equivalent to vinflunine 25g) stirring and make its dissolving; measure the pH value 3.0-4.5 of solution; be settled to 1000ml, add needle-use activated carbon, filter; the filtrate reuse is equipped with 0.22 micropore considers membrane filtration, canned in aseptic cillin bottle.Freezingly in the lyophilizing cabinet kept 2-3 hour to about-45 ℃ ,-10～0 ℃ of 9 hours sublimation drying, 38 ℃ after dry again 5-10 hour, the inflated with nitrogen outlet is jumped a queue, gland seals, and packing is promptly.
Embodiment 4
Take by weighing HP-136.7g and acetic acid 0.3g, sodium acetate 2.5g, add sterilized water for injection 800ml stirring and dissolving, add liquor epinephrinae bitartratis ophthalmicus vinflunine 34.175g (being equivalent to vinflunine 25g) stirring and make its dissolving, measure the pH value 3.0-4.5 of solution, be settled to 1000ml, add needle-use activated carbon, filter, the filtrate reuse is equipped with 0.22 μ m filtering with microporous membrane, and is canned in aseptic cillin bottle.Freezingly in the lyophilizing cabinet kept 2-3 hour to about-45 ℃ ,-10～0 ℃ of 9 hours sublimation drying, 38 ℃ after dry again 5-10 hour, the inflated with nitrogen outlet is jumped a queue, gland seals, and packing promptly gets injection vinflunine injectable powder.
Embodiment 5
Take by weighing HP-136.7g and citric acid 0.6g, sodium citrate 0.6g, add sterilized water for injection 800ml stirring and dissolving, add liquor epinephrinae bitartratis ophthalmicus vinflunine 34.175g (being equivalent to vinflunine 25g) stirring and make its dissolving, measure the pH value 3.0-4.5 of solution, be settled to 1000ml, add needle-use activated carbon, filter, the filtrate reuse is equipped with 0.22 μ m filtering with microporous membrane, sterile solution is positioned in the deep bid aseptic freeze-dried, pulverizes.Measure the vinflunine content of lyophilized powder, in vinflunine conversion weight packing cillin bottle, behind the inflated with nitrogen, jump a queue, gland seals, packing promptly gets injection vinflunine injectable powder.
Embodiment 6
Take by weighing HP-34.175g and citric acid 0.3g, sodium citrate 0.4g, add sterilized water for injection 500ml stirring and dissolving, add liquor epinephrinae bitartratis ophthalmicus vinflunine 34.175g (being equivalent to vinflunine 25g) stirring and make its dissolving, measure the pH value 3.0-4.5 of solution, be settled to 1000ml, add needle-use activated carbon, filter, the filtrate reuse is equipped with 0.22 μ m filtering with microporous membrane, and is canned in aseptic cillin bottle.Freezingly in the lyophilizing cabinet kept 2-3 hour to about-45 ℃ ,-10～0 ℃ of 9 hours sublimation drying, 38 ℃ after dry again 5-10 hour, outlet is jumped a queue, gland seals, and packing promptly gets injection vinflunine injectable powder.
Embodiment 7
Take by weighing acetyl group-gamma-cyclodextrin 320.0g and citric acid 1.0g, sodium citrate 1.2g; add sterilized water for injection 800ml stirring and dissolving; add liquor epinephrinae bitartratis ophthalmicus vinflunine 34.175g (being equivalent to vinflunine 25g) stirring and make its dissolving; measure the pH value 3.0-4.5 of solution; be settled to 1000ml, add needle-use activated carbon, filter; the filtrate reuse is equipped with 0.22 micropore considers membrane filtration, canned in aseptic cillin bottle.Freezingly in the lyophilizing cabinet kept 2-3 hour to about-45 ℃ ,-10～0 ℃ of 9 hours sublimation drying, 38 ℃ after dry again 5-10 hour, the inflated with nitrogen outlet is jumped a queue, gland seals, and packing is promptly.
Embodiment 8
Take by weighing HP-1708.75g and citric acid 1.6g, sodium citrate 1.6g, add sterilized water for injection 800ml stirring and dissolving, add liquor epinephrinae bitartratis ophthalmicus vinflunine 34.175g (being equivalent to vinflunine 25g) stirring and make its dissolving, measure the pH value 3.0-4.5 of solution, be settled to 1000ml, add needle-use activated carbon, filter, the filtrate reuse is equipped with 0.22 μ m filtering with microporous membrane, sterile solution is positioned in the deep bid aseptic freeze-dried, pulverizes.Measure the vinflunine content of lyophilized powder, in vinflunine conversion weight packing cillin bottle, behind the inflated with nitrogen, jump a queue, gland seals, packing promptly gets injection vinflunine injectable powder.
Embodiment 9
Take by weighing HP-2734.0g and acetic acid 0.9g, sodium acetate 5.5g, add sterilized water for injection 800ml stirring and dissolving, add liquor epinephrinae bitartratis ophthalmicus vinflunine 34.175g (being equivalent to vinflunine 25g) stirring and make its dissolving, measure the pH value 3.0-4.5 of solution, be settled to 1000ml, add needle-use activated carbon, filter, the filtrate reuse is equipped with 0.22 μ m filtering with microporous membrane, and is canned in aseptic cillin bottle.Freezingly in the lyophilizing cabinet kept 2-3 hour to about-45 ℃ ,-10～0 ℃ of 9 hours sublimation drying, 38 ℃ after dry again 5-10 hour, the inflated with nitrogen outlet is jumped a queue, gland seals, and packing promptly gets injection vinflunine injectable powder.
Embodiment 10
Take by weighing HP-683.5g and citric acid 0.9g, sodium citrate 0.9g, add sterilized water for injection 800ml stirring and dissolving, add liquor epinephrinae bitartratis ophthalmicus vinflunine 34.175g (being equivalent to vinflunine 25g) stirring and make its dissolving, measure the pH value 3.0-4.5 of solution, be settled to 1000ml, add needle-use activated carbon, filter, the filtrate reuse is equipped with 0.22 μ m filtering with microporous membrane, and is canned in aseptic cillin bottle.Freezingly in the lyophilizing cabinet kept 2-3 hour to about-45 ℃ ,-10～0 ℃ of 9 hours sublimation drying, 38 ℃ after dry again 5-10 hour, outlet is jumped a queue, gland seals, and packing promptly gets injection vinflunine injectable powder.
Embodiment 11
Take by weighing HP-2500.0g, add sterilized water for injection 800ml stirring and dissolving, add vinflunine 25g stirring and make its dissolving, measure the pH value 3.0-4.5 of solution, be settled to 1000ml, add needle-use activated carbon, filter, the filtrate reuse is equipped with 0.22 μ m filtering with microporous membrane, and is canned in aseptic cillin bottle.Freezingly in the lyophilizing cabinet kept 2-3 hour to about-45 ℃ ,-10～0 ℃ of 9 hours sublimation drying, 38 ℃ after dry again 5-10 hour, the inflated with nitrogen outlet is jumped a queue, gland seals, and packing promptly gets injection vinflunine injectable powder.
Embodiment 12
Take by weighing acetyl group-gamma-cyclodextrin 240.46g and citric acid 0.8g, sodium citrate 1.0g; add sterilized water for injection 800ml stirring and dissolving; add sulphuric acid vinflunine 25.868g (being equivalent to vinflunine 25g) stirring and make its dissolving; measure the pH value 3.0-4.5 of solution; be settled to 1000ml, add needle-use activated carbon, filter; the filtrate reuse is equipped with 0.22 micropore considers membrane filtration, canned in aseptic cillin bottle.Freezingly in the lyophilizing cabinet kept 2-3 hour to about-45 ℃ ,-10～0 ℃ of 9 hours sublimation drying, 38 ℃ after dry again 5-10 hour, the inflated with nitrogen outlet is jumped a queue, gland seals, and packing is promptly.
Claims (2)
1. vinflunine powder medicine administered by injection compositions, contain active component vinflunine bitartrate, HP-, it is characterized in that: the HP-that in 1 part of vinflunine bitartrate, is mixed with 6 parts of part by weight, the pH buffer system pH value that it contains maintains 3.0-4.5, described pH buffer system is made up of acetic acid/sodium acetate buffer agent or citric acid/sodium citrate buffer agent, and the molar concentration of buffer agent is 0.002M-0.2M.
2. one kind prepares the method for vinflunine powder medicine administered by injection compositions according to claim 1, comprises following successive step:
(a) HP-is dissolved in the aqueous solution that adds the pH buffer agent dissolving;
(b) the vinflunine bitartrate is added in the ratio that is mixed with the HP-of 6 parts of part by weight in 1 part of vinflunine bitartrate be dissolved to solution clarification in the above-mentioned solution;
(c) with conventional method above-mentioned settled solution is removed thermal source and filtration sterilization;
(d) aseptic powdery solid composite medicament is made in lyophilization, wherein lyophilization make the process of aseptic powdery solid composite medicament can blanketing with inert gas.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007100166045A CN101129374B (en) | 2007-06-26 | 2007-06-26 | Vinflunine pharmaceutical composition and method of producing the same and application of the same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007100166045A CN101129374B (en) | 2007-06-26 | 2007-06-26 | Vinflunine pharmaceutical composition and method of producing the same and application of the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101129374A CN101129374A (en) | 2008-02-27 |
| CN101129374B true CN101129374B (en) | 2010-09-08 |
Family
ID=39126884
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2007100166045A Expired - Fee Related CN101129374B (en) | 2007-06-26 | 2007-06-26 | Vinflunine pharmaceutical composition and method of producing the same and application of the same |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101129374B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102151249A (en) * | 2010-02-11 | 2011-08-17 | 石药集团中奇制药技术（石家庄）有限公司 | Medical composition of vinflunine |
| CN102188394B (en) * | 2010-03-05 | 2013-03-27 | 石药集团中奇制药技术（石家庄）有限公司 | Vinflunine freeze-drying medicinal composition |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1839800A (en) * | 2006-01-19 | 2006-10-04 | 浙江大学 | Vinorelbine Bitartrate lipsome freeze-drying powder injection and its preparation method |
| CN1897940A (en) * | 2003-12-23 | 2007-01-17 | 皮埃尔法布雷医药公司 | Pharmaceutical composition of vinflunine which is intended for parenteral administration preparation method thereof and use of same |
-
2007
- 2007-06-26 CN CN2007100166045A patent/CN101129374B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1897940A (en) * | 2003-12-23 | 2007-01-17 | 皮埃尔法布雷医药公司 | Pharmaceutical composition of vinflunine which is intended for parenteral administration preparation method thereof and use of same |
| CN1839800A (en) * | 2006-01-19 | 2006-10-04 | 浙江大学 | Vinorelbine Bitartrate lipsome freeze-drying powder injection and its preparation method |
Non-Patent Citations (1)
| Title |
|---|
| Cserhati Tibor et al..Interaction of taxol and other anticancer drugswith hydroxypropyl-β-cyclodextrin.International Journal of Pharmaceutics108 1.1994,108(1),p.69右栏第2段-p.70左栏第1段,p.70左栏第3段,p.71表1. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101129374A (en) | 2008-02-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101502533B1 (en) | Stable pharmaceutical composition containing Taxane derivatives, and method of manufacturing the same | |
| TW457095B (en) | Pharmaceutical formulations comprising epothilones and lyophilised compositions comprising epothilones | |
| KR102465046B1 (en) | A composition comprising 5-cholestene-3, 25-diol, 3-sulfate (25HC3S) or a pharmaceutically acceptable salt thereof, and at least one cyclic oligosaccharide | |
| US20230285563A1 (en) | Formulations of bendamustine | |
| CN102525963B (en) | Netilmicin sulfate lyophiled powder injection and preparation method thereof | |
| CN101716149A (en) | New precursor medicinal preparation | |
| CN102342931B (en) | Injectable parenteral medicinal preparation of temozolomide and preparation method thereof | |
| CN101129374B (en) | Vinflunine pharmaceutical composition and method of producing the same and application of the same | |
| CN101961311A (en) | 5alpha-androstane (alkyl)-3beta,5,6beta-triol injection and preparation method thereof | |
| CN100525758C (en) | Garcinolic acid liposome and freezing-drying powdery preparation and its making method | |
| WO2002007708A1 (en) | Lyophilized powder of lentinan and the process of preparation thereof | |
| CN101513400B (en) | Ampelopsin and basic amino acid solubilizing system and antitumor activity research | |
| CN102210686A (en) | Pharmaceutical composition containing ganciclovir compound, and preparation method thereof | |
| CN104800172A (en) | Carbazochrome sodium sulfonate powder injection for injection and preparation method thereof | |
| CN111465389B (en) | Pharmaceutical composition of docetaxel conjugate and preparation method thereof | |
| CN102552923A (en) | Pharmaceutical composition containing L-carnitine and coenzyme Q10 as well as its preparation method | |
| CN102327239A (en) | Salmon calcitonin nano liposome injection and preparation method thereof | |
| CN102512360A (en) | Torasemide pharmaceutical composition with stabilization and safety for injection | |
| CN106902357A (en) | Pharmaceutical composition and its application, medicinal inclusion compound, intravenous formulations and preparation method | |
| US11957758B2 (en) | Pharmaceutical composition of docetaxel conjugate and preparation method | |
| CN106074399B (en) | A kind of SC 69124 sodium freeze-dried preparation and preparation method thereof | |
| CN113476398B (en) | Stable and safe argatroban injection and preparation method thereof | |
| CN100588405C (en) | Deoxyuridine powder injection and preparation method thereof | |
| CN106937944A (en) | A kind of injection metronidazole freeze-dried powder and preparation method thereof | |
| CN102008461A (en) | Ibuprofen drug composite for injection |
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 | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20100908 Termination date: 20170626 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |