Crystalline modifications of N-α-(2,4,6-triisopropyl-phenylsulfonyl)-3-hydroxyamidino-(L)- phenylalanine 4-ethoxycarbonylpiperazide and/or salts thereof
View Patent ↗The present invention relates to novel crystalline modifications of N-α-(2,4,6-triisopropylphenylsulfonyl)-3-hydroxyamidino-(L)-phenylalanine 4-ethoxycarbonylpiperazide and/or salts thereof, which can be used as pharmaceutical agents, and to pharmaceutical compositions and pharmaceutical uses comprising these novel crystalline modifications.
1. A crystalline form of N-α-(2,4,6-triisopropylphenylsulfonyl)-3-hydroxyamido-(L)-phenylalanine 4-ethoxycarbonylpiperazide and/or a salt thereof.
2. The crystalline form as claimed in claim 1 , characterized in that it consists of a crystalline form of N-α-(2,4,6-triisopropylphenylsulfonyl)-3-hydroxyamido-(L)-phenylalanine 4-ethoxycarbonylpiperazide sulfate.
3. The crystalline form of N-α-(2,4,6-triisopropylphenylsulfonyl)-3-hydroxyamido-(L)-phenylalanine 4-ethoxycarbonylpiperazide sulfate as claimed in claim 2 , characterized in that it essentially contains the following peaks according to an X-ray diffractometry analysis:
3.7
10.3
12.1
13.8
16.4
19.2
22.2.
4. The crystalline form as claimed in claim 1 , characterized in that it comprises a crystalline form of N-α-(2,4,6-triisopropylphenylsulfonyl)-3-hydroxyamido-(L)-phenylalanine 4-ethoxycarbonylpiperazide hydrogen sulfate.
5. The crystalline form of claim 1 , wherein said salt of N-α-(2,4,6-triisopropylphenylsulfonyl)-3-hydroxyamido-(L)-phenylalanine 4-ethoxycarbonylpiperazide is a hydrogen sulfate and wherein said hydrogen sulfate is characterized in that it essentially contains the following peaks according to an X-ray diffractometry analysis:
4.3
10.1
20.2
21.4
24.0.
6. The crystalline form of N-α-(2,4,6-triisopropylphenylsulfonyl)-3-hydroxyamido-(L)-phenylalanine 4-ethoxycarbonylpiperazide hydrogensulfate as claimed in claim 5 , characterized in that it shows a decomposition from a temperature of 175° C.-195° C. (DSC, heating rate 2 Kmin-l).
7. The crystalline form as claimed in claim 1 , characterized in that it comprises a crystalline modification of N-α-(2,4,6-triisopropylphenylsulfonyl)-3-hydroxyamido-(L)-phenylalanine 4-ethoxycarbonylpiperazide as a free base.
8. The crystalline form as claimed in claim 7 , characterized in that it comprises a crystalline modification of N-α-(2,4,6-triisopropylphenylsulfonyl)-3-hydroxyamido-(L)-phenylalanine 4-ethoxycarbonylpiperazide as a free base as a single crystal.
9. The crystalline form of N-α-(2,4,6-triisopropylphenylsulfonyl)-3-hydroxyamido-(L)-phenylalanine 4-ethoxycarbonylpiperazide as a free base as claimed in claim 7 , characterized in that it essentially contains the following peaks according to an X-ray diffractometry analysis:
3.2
6.4
10.2
19.7.
10. The crystalline form as claimed in claim 1 , characterized in that it contains N-α-(2,4,6-triisopropylphenylsulfonyl)-3-hydroxyamido-(L)-phenylalanine 4-ethoxycarbonylpiperazide and sulfate anions in a molar ratio of 1.5-2.5:1.
11. The crystalline form as claimed in claim 1 , characterized in that it contains N-α-(2,4,6-triisopropylphenylsulfonyl)-3-hydroxyamido-(L)-phenylalanine 4-ethoxycarbonylpiperazide and hydrogensulfate anions in a molar ratio of 0.5 to 1.5:1.
12. The crystalline form as claimed in claim 1 , characterized in that it comprises units of in each case two molecules of N-α-(2,4,6-triisopropylphenylsulfonyl)-3-hydroxyamido-(L)-phenylalanine 4-ethoxycarbonylpiperazide and a sulfate anion in different conformations.
13. The crystalline form as claimed in claim 1 , characterized in that it contains between 2.5 and 3.5 moles of water per mole of salt.
14. A medicament comprising as active compound a crystalline form
as claimed in claim 1 , optionally together with a pharmaceutically tolerable carrier or/and excipient, said medicament is an orally, nasally, inhalatively, rectally or/and parenterally administrable agent.
15. The crystalline form as claimed in claim 10 , wherein said molar ratio is 2:1.
16. The crystalline form as claimed in claim 11 , wherein said molar ratio is 1:1.
17. The crystalline form of claim 1 , wherein two molecules of N-α-(2,4,6-triisopropylphenylsulfonyl)-3-hydroxyamido-(L)-phenylalanine 4-ethoxycarbonylpiperazide and a sulfate anion are present in one unit cell in different conformations.
18. The crystalline form of claim 2 , wherein said N-α-(2,4,6-triisopropylphenylsulfonyl)-3-hydroxyamido-(L)-phenylalanine 4-ethoxycarbonylpiperazide sulfate is a single crystal.
19. The crystalline form of claim 4 , wherein said N-α-(2,4,6-triisopropylphenylsulfonyl)-3-hydroxyamido-(L)-phenylalanine 4-ethoxycarbonylpiperazide hydrogen sulfate is a single crystal.