Fluoroalkyl hydrocarbons for administering water insoluble or unstable drugs

• US 5,874,469 A
• Filed: 01/05/1996
• Issued: 02/23/1999
• Est. Priority Date: 01/05/1996
• Status: Expired due to Fees

• Current Assignee: Alcon Research Limited (Nestle SA)
• Original Assignee: Alcon Laboratories Incorporated (Alcon Incorporated)
• Inventors: Maniar, Manoj L., Lang, John C.
• Primary Examiner(s): SPIVACK, PHYLLIS G
• Application Number:
  US08/583,381
• Time in Patent Office: 1,145 Days
• Field of Search: 514/550, 514/546, 514/557, 514/558, 514/675, 514/722, 514/724
• US Class Current: 514/550
• CPC Class Codes: A61K 9/0026 Blood substitute; Oxygen transporting formulations; Plasma extender
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears

Abstract

Fluoroalkyl hydrocarbons as vehicles for pharmaceutical drugs are disclosed. These vehicles are particularly well-suited for delivering drugs which are insoluble in water or chemically unstable in aqueous media. Pharmaceutical solution compositions based on these vehicles have long shelf lives and provide improved drug bioavailability. In addition, the pharmaceutical compositions of the present invention are nonaqueous, and therefore do not require preservatives or tonicity agents. The invention is particularly useful in the field of ophthalmology.

Claims

1. A pharmaceutical solution composition which comprises a therapeutically effective amount of a drug and a non-aqueous liquid vehicle for the drug, said vehicle comprising a fluoroalkyl hydrocarbon selected from the group consisting of:

F(CF₂)_n CH₂ CH₂ OH

wherein n is 1 to 16;

##STR2## wherein n is 3 to 16;

F(CF₂)₇ COOH;

CF₃ CF₂ CF₂ OCF(CF₃)COOH;

CF₃ CF₂ CH₂ OH;

HF₂ CCF₂ OC₄ H₉ ;

F₃ C(CH₃)CHOOCCH₃ ;

F₃ CCH₂ OOCCH₃ ;

F₃ CCOCH₂ COC(CH₃)₃ ;

F CF(CF₃)CF₂ O!₂ CF(CF₃)COOCH₃ ; and

(CF₃)₂ CHOH.

2. A phannaceutical composition according to claim 1, wherein the fluoroalkyl hydrocarbon is selected from the group consisting of n-butyl-1,1,2,2-tetrafluoroethyl ether;

1,1,1-trifluoroisopropyl acetate;

2,2,2-trifluoroethyl acetate;

1,1,1-trifluoro-5,5-dimethyl-2,4-hexanedione;

1H,1H,2H,2H-perfluorooctanol;

perfluoro-n-octanoic acid;

perfluoro-2,5-dimethyl-3,6-dioxanonanoic acid, methyl ester;

1H,1H,2H,2H-perfluorodecanol;

methyl undecafluoro-2-methyl-3-oxahexanoate;

hexafluoroisopropanol;

dodecafluoro-2-methyl-3-oxahexanoic acid; and

1H,1H-pentafluoropropanol-1.

3. A pharmaceutical solution composition according to claim 2, wherein the fluoroalkyl hydrocarbon comprises methyl undecafluoro-2-methyl-3-oxahexanoate.

4. A pharmaceutical solution composition according to claim 2, wherein the fluoroalkyl hydrocarbon comprises 1H,1H,2H,2H-perfluorooctanol.

5. A pharmaceutical solution composition according to claim 2, wherein the fluoroalkyl hydrocarbon comprises a mixture of methyl undecafluoro-2-methyl-3-oxahexanoate and 1H,1H,2H,2H-perfluorooctanol.

6. A pharmaceutical solution composition according to claim 1, wherein the fluoroalkyl hydrocarbon has the formula:

space="preserve" listing-type="equation">F(CF.sub.2).sub.n CH.sub.2 CH.sub.2 OH

wherein n is 1 to 16.

7. A pharmaceutical solution composition according to claim 1, wherein the fluoroalkyl hydrocarbon has the formula:

##STR3## wherein n is 3 to 16.

8. A pharmaceutical solution composition according to claim 1, wherein the drug is hydrolytically unstable.

9. A pharmaceutical solution composition according to claim 1, wherein the drug is substantially insoluble in water.

10. A method of formulating a pharmaceutical solution composition containing a drug which is unstable or substantially insoluble in water, which comprises dissolving the drug in a fluoroalkyl hydrocarbon, whereby the drug is uniformly dispersed in the composition and is chemically stable, wherein the composition is a non-aqueous composition and the fluoroalkyl hydrocarbon is selected from the group consisting of:

F(CF₂)_n CH₂ CH₂ OH

wherein n is 1 to 16;

##STR4## Wherein n is 3 to 16;

F(CF₂)₇ COOH;

CF₃ CF₂ CF₂ OCF(CF₃)COOH;

CF₃ CF₂ CH₂ OH;

HF₂ CCF₂ OC₄ H₉ ;

F₃ (CH₃)CHOOCCH₃ ;

F₃ CCH₂ OOCCH₃ ;

F₃ CCOCH₂ COC(CH₃)₃ ;

F CF(CF₃)CF₂ O!₂ CF(CF₃ COOCH₃ ; and

(CF₃)₂ CHOH.

11. A method according to claim 10, wherein the fluoroalkyl hydrocarbon is selected from the group consisting of n-butyl-1,1,2,2-tetrafluoroethyl ether;

1,1,1-trifluoroisopropyl acetate;

2,2,2-trifluoroethyl acetate;

1,1,1-trifluoro-5,5-dimethyl-2,4-hexanedione;

1H,1H,2H,2H-perfluorooctanol;

perfluoro-n-octanoic acid;

perfluoro-2,5-dimethyl-3,6-dioxanonanoic acid methyl ester;

1H,1H,2H,2H-perfluorodecanol;

methyl undecafluoro-2-methyl-3-oxahexanoate;

hexafluoroisopropanol;

dodecafluoro-2-methyl-3-oxahexanoic acid; and

1H,1H-pentafluoropropanol-1.

12. A method according to claim 11, wherein the fluoroalkyl hydrocarbon comprises methyl undecafluoro-2-methyl-3-oxahexanoate.

13. A method according to claim 11, wherein the fluoroalkyl hydrocarbon comprises 1H,1H,2H,2H-perfluorooctanol.

14. A method according to claim 11, wherein the fluoroalkyl hydrocarbon comprises a mixture of methyl undecafluoro-2-methyl-3-oxahexanoate and 1H,1H,2H,2H-perfluorooctanol.

15. A method according to claim 10, wherein the fluoroalkyl hydrocarbon has the formula:

space="preserve" listing-type="equation">F(CF.sub.2).sub.n CH.sub.2 CH.sub.2 OH

wherein n is 1 to 16.

16. A method according to claim 10, wherein the fluoroalkyl hydrocarbon has the formula:

##STR5## wherein n is 3 to 16.