.

Pharmaceutical Business Intelligence

  • Anticipate P&T budget requirements
  • Evaluate market entry opportunities
  • Find generic sources and suppliers
  • Predict branded drug patent expiration

► Plans and Pricing

Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

DrugPatentWatch Database Preview

Claims for Patent: 6,504,030

« Back to Dashboard

Claims for Patent: 6,504,030

Title: Polymorphic form of clopidogrel hydrogen sulphate
Abstract:Novel orthorombic polymorph of clopidogrel hydrogen sulfate or hydrogen sulfate of methyl (+)-(S)-.alpha.-(2-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-5 -acetate and a process for its preparation
Inventor(s): Bousquet; Andre (Sisteron, FR), Castro; Bertrand (Kremlin-Bicetre, FR), Saint-Germain; Jean (Sisteron, FR)
Assignee: Sanofi-Synthelabo (Paris, FR)
Application Number:10/177,092
Patent Claims: 1. A process for the preparation of (+)-(S) clopidogrel hydrogen sulfate polymorph Form 2, the x-ray powder diffractogram of which shows characteristic peaks expressed as interplanar distance at approximately 4.11, 6.86, 3.60, 5.01, 3.74, 6.49, and 5.66 .ANG., which comprises allowing the acetone mother liquors of crystallization of (+)-(S) clopidogrel hydrogen sulfate polymorph Form 1 to stand for a period of 3 to 6 months to yield crystals of (+)-(S) clopidogrel hydrogen sulfate polymorph Form 2.

2. A process according to claim 1 wherein said mother liquors are obtained by reacting an acetone solution of (+)-(S) clopidogrel with 80% sulfuric acid and removing the crystallized (+)-(S) clopidogrel hydrogen sulfate polymorph Form 1.

3. A process for the preparation of (+)-(S) clopidogrel hydrogen sulfate polymorph Form 2, the infrared spectrum of which exhibits characteristic absorptions, expressed in cm.sup.-1 at 2251, 1497, 1189, and 1029 with respective transmittance percentages of approximately 43, 63.7, 18, and 33.2, which comprises allowing the acetone mother liquors of crystallization of (+)-(S) clopidogrel hydrogen sulfate polymorph Form 1 to stand for a period of 3 to 6 months to yield crystals of (+)-(S) clopidogrel hydrogen sulfate polymorph Form 2.

4. A process according to claim 3 wherein the mother liquors resulting from the crystallization of the polymorph Form 1 of (+)-(S) clopidogrel hydrogen sulfate contain from 0.3 to 1% water.

5. A process according to claim 3 wherein the mother liquors resulting from the crystallization of the polymorph Form 1 of (+)-(S) clopidogrel hydrogen sulfate contain up to about 10% of clopidogrel hydrogen sulfate, this amount being calculated on the basis of the amount of methyl (+)-(S)-.alpha.-(2-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-5 -acetate camphorsulfonate used for the preparation of the hydrogen sulfate.

6. A process according to claim 3 wherein the mother liquors resulting from the crystallization of the polymorph Form 1 of (+)-(S) clopidogrel hydrogen sulfate are allowed to stand for a period of 3 to 6 months at a temperature below 40.degree. C., to yield clopidogrel hydrogen sulfate Form 2.

7. A process according to claim 3 wherein said mother liquors are obtained by reacting an acetone solution of (+)-(S) clopidogrel with 80% sulfuric acid and removing the crystallized (+)-(S) clopidogrel hydrogen sulfate polymorph Form 1.

8. A process for the preparation of (+)-(S) clopidogrel hydrogen sulfate polymorph Form 2, having a melting point of 176.+-.3.degree. C., which comprises allowing the acetone mother liquors of crystallization of (+)-(S) clopidogrel hydrogen sulfate polymorph Form 1 to stand for a period of 3 to 6 months to yield crystals of (+)-(S) clopidogrel hydrogen sulfate polymorph Form 2.

9. A process according to claim 8 wherein the mother liquors resulting from the crystallization of the polymorph Form 1 of (+)-(S) clopidogrel hydrogen sulfate contain from 0.3 to 1% water.

10. A process according to claim 8 wherein the mother liquors resulting from the crystallization of the polymorph Form 1 of (+)-(S) clopidogrel hydrogen sulfate contain up to about 10% of clopidogrel hydrogen sulfate, this amount being calculated on the basis of the amount of methyl (+)-(S)-.alpha.-(2-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-5 -acetate camphorsulfonate used for the preparation of the hydrogen sulfate.

11. A process according to claim 8 wherein the mother liquors resulting from the crystallization of the polymorph Form 1 of (+)-(S) clopidogrel hydrogen sulfate are allowed to stand for a period of 3 to 6 months at a temperature below 40.degree. C., to yield clopidogrel hydrogen sulfate Form 2.

12. A process according to claim 8 wherein said mother liquors are obtained by reacting an acetone solution of (+)-(S) clopidogrel with 80% sulfuric acid and removing the crystallized (+)-(S) clopidogrel hydrogen sulfate polymorph Form 1.

13. A process for the preparation of clopidogrel hydrogen sulfate polymorph Form 2 which comprises reacting an acetone solution of (+)-(S) clopidogrel with 94-96% sulfuric acid and seeding the resulting solution with (+)-(S) clopidogrel hydrogen sulfate polymorph Form 2 to effect crystallization of (+)-(S) clopidogrel hydrogen sulfate polymorph Form 2.

14. A process according to claim 13 wherein the acetone solution of (+)-(S) clopidogrel is obtained by extracting a mixture of methyl (+)-(S)-.alpha.-(2-chlorophenyl)4,5,6,7-tetrahydrothieno[3,2-c]pyridine-5- acetate camphorsulfonate in an organic solvent with an aqueous solution of potassium carbonate, concentrating the organic phase and taking up the resulting residue in acetone.

15. A process for the preparation of (+)-(S) clopidogrel hydrogen sulfate polymorph Form 2 which comprises reacting an acetone solution of (+)-(S) clopidogrel with 80% sulfuric acid and heating the mixture at reflux to effect crystallization of (+)-(S) clopidogrel hydrogen sulfate polymorph Form 2.

16. A process according to claim 15 wherein the mixture is heated at reflux for about two hours.

17. (+)-(S) Clopidogrel hydrogen sulfate Form 2 prepared by the process of claim 1.

18. (+)-(S) Clopidogrel hydrogen sulfate Form 2 prepared by the process of claim 3.

19. (+)-(S) Clopidogrel hydrogen sulfate Form 2 prepared by the process of claim 8.

20. (+)-(S) Clopidogrel hydrogen sulfate Form 2 prepared by the process of claim 13.

21. (+)-(S) Clopidogrel hydrogen sulfate Form 2 prepared by the process of claim 15.

22. (+)-(S) Clopidogrel hydrogen sulfate Form 2, the x-ray powder diffraction pattern of which shows characteristic peaks, expressed in terms of interplanar distance, at approximately 4.11 and 6.86 .ANG. prepared by the process of claim 1.

23. (+)-(S) Clopidogrel hydrogen sulfate Form 2, the x-ray powder diffraction pattern of which shows characteristic peaks, expressed in terms of interplanar distance, at approximately 4.11 and 6.86 .ANG. prepared by the process of claim 13.

24. (+)-(S) Clopidogrel hydrogen sulfate Form 2, the x-ray powder diffraction pattern of which shows characteristic peaks, expressed in terms of interplanar distance, at approximately 4.11 and 6.86 .ANG. prepared by the process of claim 15.

25. A process according to claim 1 wherein the mother liquors resulting from the crystallization of the polymorph Form 1 of (+)-(S) clopidogrel hydrogen sulfate contain from 0.3 to 1% water.

26. A process according to claim 1 wherein the mother liquors resulting from the crystallization of the polymorph Form 1 of (+)-(S) clopidogrel hydrogen sulfate contain up to about 10% of clopidogrel hydrogen sulfate, this amount being calculated on the basis of the amount of methyl (+)-(S)-.alpha.-(2-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-5 -acetate camphorsulfonate used for the preparation of the hydrogen sulfate.

27. A process according to claim 1 wherein the mother liquors resulting from the crystallization of the polymorph Form 1 of (+)-(S) clopidogrel hydrogen sulfate are allowed to stand for a period of 3 to 6 months at a temperature below 40.degree. C., to yield clopidogrel hydrogen sulfate Form 2.
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

How are People Using DrugPatentWatch?

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

`abc