CN101607968A - Vinflunine salt, its preparation method and pharmaceutical composition thereof - Google Patents
Vinflunine salt, its preparation method and pharmaceutical composition thereof Download PDFInfo
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- CN101607968A CN101607968A CNA2009101318379A CN200910131837A CN101607968A CN 101607968 A CN101607968 A CN 101607968A CN A2009101318379 A CNA2009101318379 A CN A2009101318379A CN 200910131837 A CN200910131837 A CN 200910131837A CN 101607968 A CN101607968 A CN 101607968A
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- acid
- vinflunine
- salt compound
- preparation
- vinflunine salt
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- NMDYYWFGPIMTKO-HBVLKOHWSA-N vinflunine Chemical class C([C@@](C1=C(C2=CC=CC=C2N1)C1)(C2=C(OC)C=C3N(C)[C@@H]4[C@@]5(C3=C2)CCN2CC=C[C@]([C@@H]52)([C@H]([C@]4(O)C(=O)OC)OC(C)=O)CC)C(=O)OC)[C@H]2C[C@@H](C(C)(F)F)CN1C2 NMDYYWFGPIMTKO-HBVLKOHWSA-N 0.000 title claims abstract description 39
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 7
- 238000002360 preparation method Methods 0.000 title abstract description 20
- 229960000922 vinflunine Drugs 0.000 claims description 32
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 30
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 26
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 14
- -1 Vinflunine salt compound Chemical class 0.000 claims description 14
- 239000001530 fumaric acid Substances 0.000 claims description 13
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 13
- CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 claims description 12
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 10
- 229960002989 glutamic acid Drugs 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 150000007524 organic acids Chemical class 0.000 claims description 8
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- 229960005261 aspartic acid Drugs 0.000 claims description 6
- 239000004310 lactic acid Substances 0.000 claims description 6
- 235000014655 lactic acid Nutrition 0.000 claims description 6
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 6
- 230000002378 acidificating effect Effects 0.000 claims description 5
- 229940024606 amino acid Drugs 0.000 claims description 5
- 150000001413 amino acids Chemical class 0.000 claims description 5
- 238000002425 crystallisation Methods 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 230000008025 crystallization Effects 0.000 claims description 4
- 239000012046 mixed solvent Substances 0.000 claims description 4
- 229940095064 tartrate Drugs 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 2
- 238000007670 refining Methods 0.000 claims description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 2
- 125000000570 L-alpha-aspartyl group Chemical group [H]OC(=O)C([H])([H])[C@]([H])(N([H])[H])C(*)=O 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 1
- 238000003756 stirring Methods 0.000 description 21
- 238000012360 testing method Methods 0.000 description 8
- 238000001291 vacuum drying Methods 0.000 description 8
- 239000007787 solid Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 230000001954 sterilising effect Effects 0.000 description 4
- 238000004659 sterilization and disinfection Methods 0.000 description 4
- 239000008215 water for injection Substances 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- 239000003814 drug Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000013557 residual solvent Substances 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000005286 illumination Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000012856 packing Methods 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000863480 Vinca Species 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 238000003822 preparative gas chromatography Methods 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- C07D519/04—Dimeric indole alkaloids, e.g. vincaleucoblastine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to vinflunine salt, its preparation method and the pharmaceutical composition thereof of general formula (I); In the general formula (I), M, n are defined as in the description.
Description
Technical field
The present invention relates to vinflunine salt, its preparation method and pharmaceutical composition thereof.
Background technology
Vinflunine (vinflunine) is the semi-synthetic derivative of latest generation vinca, is developed as far back as 1996 by French Pierre Fabre company, and US 5,620,985 and US 6,127, and 377 disclose its preparation method.At present, the liquor epinephrinae bitartratis ophthalmicus Vinflunine be in II, III phase clinical during.But the liquor epinephrinae bitartratis ophthalmicus Vinflunine has following deficiency: if with the preparation of crystallization method, sample residual solvent difficulty is qualified; If with the freeze drying process preparation, the easy moisture absorption of cost height and sample, less stable are difficult to preserve.
The inventor with Vinflunine and acidic amino acid or organic acid reaction, be easy to the crystallization salify, and gained salt residual solvent is qualified, is difficult for the moisture absorption by discovering, stability particularly light durability improves greatly, is beneficial to preservation, is suitable for drug research.
Summary of the invention
A first aspect of the present invention is to provide the Vinflunine salt compound shown in the formula (I).
Wherein, M is acidic amino acid or organic acid, but does not comprise tartrate.Described acidic amino acid is natural or non-natural, is selected from L-aspartic acid, L-L-glutamic acid, D-aspartic acid, D-L-glutamic acid, preferably L-aspartic acid, L-L-glutamic acid; Described organic acid is selected from but is not limited to following kind: fumaric acid, toxilic acid, Citric Acid, lactic acid, methylsulfonic acid, tosic acid or oxysuccinic acid, preferably toxilic acid, fumaric acid, lactic acid, Citric Acid, more preferably fumaric acid, Citric Acid.The salt of described formula (I) is a part or two molecules or three molecules or four fens alites, preferably two fens alites that Vinflunine and M form.
A second aspect of the present invention is to provide a kind of method for preparing general formula I Vinflunine salt compound of the present invention, it is characterized in that: with Vinflunine and M mixing salify, refining in organic solvent then, crystallization gets formula (I) compound.
Described organic solvent is selected from ethanol, methylene dichloride, chloroform, ethyl acetate, acetone, ether, normal hexane, isopropyl ether etc. or its mixed solvent, the preferably mixed solvent of methylene dichloride/ether or acetone.
A third aspect of the present invention is to provide a kind of pharmaceutical composition, and formula (I) the Vinflunine salt compound that it is characterized in that containing effective dose is as activeconstituents.
Embodiment
Present invention will be described in more detail for the following example, but can not be interpreted as limitation of the present invention.
Embodiment one
The preparation of tartrate Vinflunine
With Vinflunine (2.0g 2.45mmol) adds in the acetone (40ml), add tartrate (0.74g, 4.9mmol), 50 ℃ of thermosols of water-bath drip ether (40ml) under the stirring at room, freezing crystallization filters, vacuum-drying gets title compound: 1.6g.
Embodiment two
The preparation of toxilic acid Vinflunine
With Vinflunine (2.0g, 2.45mmol), (0.57g 4.9mmol) adds in the there-necked flask toxilic acid, adds methylene dichloride (10ml) and is stirred to dissolving fully.Be added dropwise to ether (50ml), stirring and crystallizing.Filter, vacuum-drying gets the title compound of little yellow solid shape: 1.78g.
Embodiment three
The preparation of two fumaric acid Vinflunines
With Vinflunine (6.5g, 7.96mmol), (1.85g 15.92mmol) puts into there-necked flask to fumaric acid, adds acetone (130ml) and ethanol (16ml) and stirs, and very fast clarification continues stirring 30min in 50 ℃ in water-bath.Add ether (200ml), stirring and crystallizing.Filter, vacuum-drying gets the title compound of white solid: 5.98g.
Embodiment four
The preparation of Citric Acid Vinflunine
With Vinflunine (5.7g, 6.98mmol), (2.93g 13.96mmol) puts into there-necked flask to a hydration Citric Acid, adds acetone (55ml) and is stirred to dissolving fully, continues to stir 30min in 50 ℃ in water-bath.Add ether (110ml), stirring and crystallizing.Filter, vacuum-drying gets the title compound of white solid: 7.6g.
Embodiment five
The preparation of oxysuccinic acid Vinflunine
With Vinflunine (5.7g, 6.98mmol), (1.87g 13.96mmol) puts into there-necked flask to oxysuccinic acid, adds acetone (55ml) and stirs a moment to dissolving, continues to stir 30min in 50 ℃ in water-bath.Add ether (110ml), stirring and crystallizing.Filter, vacuum-drying gets the title compound of white solid: 6.37g.
Embodiment six
The preparation of lactic acid Vinflunine
With Vinflunine (10.5g, 12.85mmol), (4.63g 51.4mmol) puts into there-necked flask to lactic acid, adds methylene dichloride (50ml) and stirs the dissolving in a moment, stirs 30min in 50 ℃ in water-bath.Add ether (200ml), stirring and crystallizing is spent the night.Filter, vacuum-drying gets the title compound of white solid: 7.3g.
Embodiment seven
The preparation of L-L-glutamic acid Vinflunine
With Vinflunine (10.5g, 12.85mmol), (3.8g 25.8mmol) puts into there-necked flask to L-L-glutamic acid, adds methylene dichloride (50ml) and stirs the dissolving in a moment, stirs 30min in 50 ℃ in water-bath.Add ether (200ml), stirring and crystallizing.Filter, vacuum-drying gets the title compound of white solid: 7.3g.
Embodiment eight
The preparation of L-aspartic acid Vinflunine
The preparation method is with embodiment six, and difference is to change L-L-glutamic acid (3.8g) into L-aspartic acid (3.4g).
Embodiment nine
The preparation of single fumaric acid Vinflunine
With fumaric acid (1.16g 10mmol) in 40 ℃ of mixing solutionss that are dissolved in acetone (100ml) and ethanol (5ml), moltenly reduces to 15 ℃ after clear, filters, in filtrate, add Vinflunine alkali (8.17g, 10mmol), molten rapidly clear.Solution kept 15 ℃ of stirring and crystallizing 1.5 hours, filtered, and filter cake is with cold acetone 10ml washing, vacuum-drying 2 hours, the title compound of white solid: 5.41g.
Embodiment ten
The preparation of Vinflunine saline injection
Prescription:
Fumaric acid Vinflunine 400mg (by Vinflunine)
Water for injection adds to 20ml
Preparation technology
Take by weighing the fumaric acid Vinflunine of recipe quantity, it is an amount of to add water for injection, stirring and dissolving, transfer pH3.2～3.6 with Citric Acid or Sodium Citrate, add the injection water again to total amount, after stirring, filter with the sterilization filter that 0.22 μ m millipore filtration is housed, with the filtrate packing, inflated with nitrogen adds the sterilization plug and rolls enclosing cover then.
Prescription:
Citric Acid Vinflunine 400mg (by Vinflunine)
Water for injection adds to 20ml
Preparation technology
Take by weighing the fumaric acid Vinflunine of recipe quantity, adding water for injection is an amount of, and stirring and dissolving adds the injection water again to total amount, after stirring, filters with the sterilization filter that 0.22 μ m millipore filtration is housed, and then with the filtrate packing, inflated with nitrogen adds sterilization and fills in and roll enclosing cover.
Test example one
The test of vinflunine salt gas phase
Undertaken by Chinese Pharmacopoeia version in 2005 two appendix V E vapor-phase chromatography and appendix VIII P residual solvent assay method.
Test example two
Vinflunine salt draws moist test
Undertaken by " medicine draws moist governing principle " (2005 editions appendix of Chinese Pharmacopoeia).
Experimental technique: get a certain amount of trial-product, accurate claim surely, put a precision (m that weighs
1) tool plug vial (external diameter is 50mm, and height is 15mm) in, the precision (m that weighs
2); Uncovered 25 ℃ ± 1 ℃ thermostatic drier (bottom place ammonium chloride saturated solution) that places of weighing bottle, placed 24 hours, build the weighing bottle lid again, the precision (m that weighs
3)
The weightening finish percentage
It is as follows to draw moist experiment judging criterion:
Very easily draw moist: X% 〉=15%;
Have draw moist: 2%≤X%＜15%
Slightly draw moist: 0.2%≤X%＜2%
Deliquescence: absorb enough water and divide formation liquid
Test example three
The test of vinflunine salt influence factor
(2005 editions two appendix XIX C of Chinese Pharmacopoeia) carry out according to " bulk drug and pharmaceutical preparation stability test governing principle ".
The high humidity test
This product divided to expose be positioned in the plate, place 25 ℃, the constant humidity encloses container of RH75% respectively, in the 5th day and 10 days sampling analysis;
The strong illumination test
Under the cold condition, this product divided being positioned in the plate, in lighting box, is to place 10 days under the condition of 4500lx in illumination, in the 5th day and 10 days sampling analysis;
Claims (12)
1, the Vinflunine salt compound shown in the formula (I),
Wherein, M is acidic amino acid or organic acid, but does not comprise tartrate; N is 1-4.
2, Vinflunine salt compound according to claim 1 is characterized in that M is an organic acid.
3, Vinflunine salt compound according to claim 2 is characterized in that described organic acid is selected from fumaric acid, toxilic acid, Citric Acid, lactic acid, methylsulfonic acid, tosic acid or oxysuccinic acid.
4, Vinflunine salt compound according to claim 3 is characterized in that described organic acid is selected from toxilic acid, fumaric acid, lactic acid or Citric Acid.
5, Vinflunine salt compound according to claim 4 is characterized in that described organic acid is fumaric acid or Citric Acid.
6, Vinflunine salt compound according to claim 1 is characterized in that M is an acidic amino acid, and it is selected from L-aspartic acid, L-L-glutamic acid, D-aspartic acid or D-L-glutamic acid.
7, Vinflunine salt compound according to claim 6 is characterized in that M is L-aspartic acid or L-L-glutamic acid.
8, according to any described Vinflunine salt compound of claim 1-7, wherein n is 1 or 2.
9, a kind of method for preparing the salt compound of Vinflunine described in the claim 1 is characterized in that: with Vinflunine and M mixing salify, refining in organic solvent then, crystallization gets formula (I) compound.
10, method according to claim 9 is characterized in that described organic solvent is selected from ethanol, methylene dichloride, chloroform, ethyl acetate, acetone, ether, normal hexane, isopropyl ether etc. or its mixed solvent.
11, method according to claim 10 is characterized in that described organic solvent is the mixed solvent of methylene dichloride/ether or acetone.
12, a kind of pharmaceutical composition, it is characterized in that containing effective dose as any described Vinflunine salt compound of claim 1-8 as activeconstituents and pharmaceutically acceptable carrier.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2009101318379A CN101607968A (en) | 2008-06-17 | 2009-04-08 | Vinflunine salt, its preparation method and pharmaceutical composition thereof |
| PCT/CN2009/071778 WO2009152712A1 (en) | 2008-06-17 | 2009-05-13 | Vinflunine salts, preparation process and pharmaceutical composition thereof |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810126653.9 | 2008-06-17 | ||
| CN200810126653 | 2008-06-17 | ||
| CNA2009101318379A CN101607968A (en) | 2008-06-17 | 2009-04-08 | Vinflunine salt, its preparation method and pharmaceutical composition thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101607968A true CN101607968A (en) | 2009-12-23 |
Family
ID=41433678
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2009101318379A Pending CN101607968A (en) | 2008-06-17 | 2009-04-08 | Vinflunine salt, its preparation method and pharmaceutical composition thereof |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN101607968A (en) |
| WO (1) | WO2009152712A1 (en) |
Cited By (3)
| 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 |
| CN102188394A (en) * | 2010-03-05 | 2011-09-21 | 石药集团中奇制药技术（石家庄）有限公司 | Vinflunine freeze-drying medicinal composition |
| CN103788117A (en) * | 2012-10-30 | 2014-05-14 | 何小解 | Technology for continuously synthesizing Dehydrate Catharanthine, vinorelbine and Vinflunine |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2863891B1 (en) * | 2003-12-23 | 2006-03-24 | Pf Medicament | PHARMACEUTICAL COMPOSITION OF VINFLUNIN FOR PARENTAL ADMINISTRATION, PROCESS FOR PREPARATION AND USE |
| WO2008033935A2 (en) * | 2006-09-12 | 2008-03-20 | Amr Technology, Inc. | Vinorelbine derivatives |
| FR2912406B1 (en) * | 2007-02-13 | 2009-05-08 | Pierre Fabre Medicament Sa | VINFLUNIN ANHYDROUS CRYSTAL SALTS, PROCESS FOR THEIR PREPARATION AND USE AS MEDICAMENT AND MEANS FOR PURIFYING VINFLUNIN. |
-
2009
- 2009-04-08 CN CNA2009101318379A patent/CN101607968A/en active Pending
- 2009-05-13 WO PCT/CN2009/071778 patent/WO2009152712A1/en active Application Filing
Cited By (4)
| 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 |
| CN102188394A (en) * | 2010-03-05 | 2011-09-21 | 石药集团中奇制药技术（石家庄）有限公司 | Vinflunine freeze-drying medicinal composition |
| 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 |
| CN103788117A (en) * | 2012-10-30 | 2014-05-14 | 何小解 | Technology for continuously synthesizing Dehydrate Catharanthine, vinorelbine and Vinflunine |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2009152712A1 (en) | 2009-12-23 |
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