Derivatives of cyclodextrins, process for their preparation and their use in particular for solubilizing pharmacologically active substances

• US 8,440,814 B2
• Filed: 05/19/2009
• Issued: 05/14/2013
• Est. Priority Date: 03/28/2003
• Status: Expired due to Fees

• Current Assignee: Centre National De La Recherche Scientifique, Consejo Superior de Investigaciones Científicas,, Universidad de Sevilla, Universite Joseph Fourier
• Original Assignee: Centre National De La Recherche Scientifique, Consejo Superior de Investigaciones Científicas,, Universidad de Sevilla, Universite Joseph Fourier
• Inventors: Defaye, Jacques, Ortiz-Mellet, Carmen, Garcia-Fernandez, Jose Manuel, Gomez-Garcia, Maria, Chmurski, Kazimierz, Yu, Jian-Xin
• Primary Examiner(s): BLAND, LAYLA D
• Application Number:
  US12/468,356
• Publication Number:
  US 20090264540A1
• Time in Patent Office: 1,456 Days
• Field of Search: None
• US Class Current: 536/103
• CPC Class Codes: A61K 47/6951 using cyclodextrin cyclodextrins used as simple excipients A61K47/40
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C08B 37/0012 Cyclodextrin [CD], e.g. cycle with 6 units (alpha), with 7 units (beta) and with 8 units (gamma), large-ring cyclodextrin or cycloamylose with 9 units or more; Derivatives thereof
• CPC Class Codes: C08B 37/0015 Inclusion compounds, i.e. host-guest compounds, e.g. polyrotaxanes

Abstract

The invention relates to a compound corresponding to general formula (I) wherein n is a whole number from 1-6, m is a whole number equal to 5, 6 or 7, R¹ is an OH group, all R¹ s are identical, Z is an NHX group, X is a hydrogen atom, and R is a hydrogen atom or a bioidentification element, with the proviso that the compound wherein n=1, m=6, Z=NH₂ and R₁=OH is excluded.

Claims

1. A compound of the following general formula:

2. The compound of claim 1, wherein R¹ represents OH, and having the following general formula:

3. The compound of claim 1, wherein R¹ represents OH, and wherein Z represents an NHX group, X being a hydrogen atom.

4. The compound of claim 1, wherein R¹ represents an —

S—

CH₂—

(CH₂)_n—

Z group, and having the following general formula;

5. The compound of claim 1, wherein R¹ represents an —

S—

CH₂—

(CH₂)_n—

Z group, and having the following formula;

6. The compound of claim 5, wherein X represents a hydrogen atom and in that n is equal to 1, and having the following formula:

7. The compound of claim 4, corresponding to the following formula:

8. The compound of claim 1, wherein at least one of the NHX groups as defined in formula (I) is protonated and associated with a monovalent anion chosen from chloride, bromide or iodide.

9. The compound of claim 4, wherein n is equal to 1 and the Z group represents the quaternary ammonium ⁺NX₃ group, and in that the Z group can be associated with a monovalent anion chosen from chloride, bromide or iodide, and having the following formula:

10. The compound of claim 1, wherein m is equal to 6.

11. An inclusion complex of a compound according to claim 1 with a pharmacologically active molecule, a molar ratio between the compound and the pharmacologically active molecule being approximately 50:

1 to approximately 1;

1.

12. An inclusion complex of a compound according to claim 1 with a pharmacologically active molecule, a molar ratio between the compound the pharmacologically active molecule being approximately 50:

1 to approximately 1;

1, wherein the pharmacologically active molecule is an antineoplastic agent, belonging to the taxol family.

13. A pharmaceutical composition comprising a compound according to claim 1 with a pharmacologically acceptable vehicle.

14. A pharmaceutical composition comprising an inclusion complex of a compound according to claim 1, with a pharmacologically active molecule, a molar ratio between the compound and the pharmacologically active molecule being approximately 50:

1 to approximately 1;

1, in association with a pharmacologically acceptable vehicle.

15. A pharmaceutical composition comprising a compound according to claim 1 with a pharmacologically acceptable vehicle, in the form of an aqueous solution.

16. A pharmaceutical composition comprising an inclusion complex of a compound according to claim 1 with a pharmacologically active molecule, a molar ratio between the compound and the pharmacologically active molecule being approximately 50:

1 to approximately 1;

1, in association with a pharmacologically acceptable vehicle, the pharmaceutical composition being in the form of an aqueous solution.

17. A pharmaceutical composition comprising a compound according to claim 1 with a pharmacologically acceptable vehicle, wherein the composition contains per single dose approximately 50 mg to approximately 500 mg of one of the compound.

18. A pharmaceutical composition comprising an inclusion complex of a compound according to claim 1 with a pharmacologically active molecule, a molar ratio between the compound and the pharmacologically active molecule being approximately 50:

1 to approximately 1;

1, in association with a pharmacologically acceptable vehicle, wherein the composition contains per single dose approximately 100 mg to approximately 750 mg of one of said complex.