Pharmaceutical preparations and methods for their regional administration

• US 6,416,778 B1
• Filed: 07/23/1999
• Issued: 07/09/2002
• Est. Priority Date: 01/24/1997
• Status: Expired due to Term

• Current Assignee: FemmPharma, Inc.
• Original Assignee: FemmePharma Co.
• Inventors: Ragavan, Vanaja V., DiPiano, Gerianne M.
• Primary Examiner(s): Spear, James M.
• Application Number:
  US09/355,213
• Time in Patent Office: 1,082 Days
• Field of Search: 424/430, 424/464, 424/433, 424/489
• US Class Current: 424/430
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 9/0034 Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51

Abstract

Formulations have been developed for regional delivery of drugs, for example, into a cavity such as the pelvic region, peritoneal region, or directly on organs of interest. Regional delivery increases comfort and bioavailability of the drug, resulting in rapid and relatively high blood levels in the regions to be treated in the substantial absence of side effects due to the high levels required for efficacy following systemic delivery. In the preferred embodiment, these formulations consist of drug micro or nanoparticles, which may be formed of drug alone or in combination with an excipient or polymeric carrier. The excipient or polymer may be used to manipulate release rates and to increase adhesion to the affected region. The drug formulation can be applied as a dried powder, a liquid suspension or dispersion, or as a topical ointment, creme, lotion, foam or suppository.

Claims

1. A drug formulation comprising drug particles suitable for regional administration of an effective amount to provide relief from symptoms of a disease or disorder selected from the group consisting of endometriosis, endometrial bacterial infections, cancer, and endocrine conditions in a region in patients in need thereof, wherein the region is selected from the group consisting of the uterus, fallopian tubes, peritoneal space, pelvic cul-de-sac, ovaries, and urinogenital tract,

wherein the effective amount is a dosage which results in low serum drug levels and reduced side effects as compared to systemic administration of the drug, and

wherein the formulation is in a carrier promoting quick uptake of the drug into the blood stream, a carrier manipulating release of drug, or a carrier promoting adhesion of the drug selected from the group consisting of a liquid suspension or dispersion, a hydrogel suspension or dispersion, a topical ointment, a cream, a lotion, and a foam.

2. The formulation of claim 1 wherein the region is the female reproductive organs.

3. The formulation of claim 2 wherein the patients have a disorder located in the reproductive organs.

5. The formulation of claim 3 wherein the drug is for treatment of endometriosis and is selected from the group consisting progestins, estrogens, antiestrogens and antiprogestins.

6. The formulation of claim 1 wherein the drug is in the form of micro or nano particulates and wherein the particulates adhere to mucosal tissue.

7. The formulation of claim 1 wherein the drug is in the form of micro or nano particulates and wherein the particulates comprise polymer which alters the rates of drug absorption in the region to be treated.

8. The formulation of claim 1 which can be administered vaginally, intraperitoneally, or directly on the reproductive organs of interest.

9. The formulation of claim 8 wherein the drug is danazole and wherein the formulation is suitable for vaginal administration in patients in need thereof and is in a dosage effective for treatment of endometriosis.

10. The formulation of claim 1 wherein the drug is selected from the group consisting of an anticancer drug, a cytotherapeutic and an anti-proliferative drug in a dosage effective for treatment of cancer in the region of the patient where administered.

13. The formulation of claim 1 wherein the drug is an antibacterial agent effective for treatment of endometrial bacterial infections.

14. The formulation of claim 1 wherein the drug has steroidal activity suitable for treatment of endocrine conditions.

15. The formulation of claim 1 wherein the drug is effective for treatment of endocrine conditions selected from the group consisting of menopause, infertility, contraception, dysfunctional uterine bleeding, dysmenorrhea, adenomyosis, and assisted reproductive technologies.

23. The method of claim 1 wherein the drug is an antibacterial agent effective for treatment of endometrial bacterial infections.

4. A method of treating a patient having a disease or disorder selected from the group consisting of endometriosis, endometrial bacterial infections, cancer, and endocrine conditions comprising the step of topically administering to the patient a drug formulation suitable for regional administration comprising an effective amount of drug to provide relief from symptoms of the disease or disorder in a region in the patient in need thereof, wherein the region is selected from the group consisting of the uterus, fallopian tubes, peritoneal space, pelvic cul-de-sac, ovaries, and urinogenital tract,

wherein the effective amount of drug is a dosage which results in low serum drug levels with reduced side effects as compared to system administration of the drug, and

wherein the formulation is in a carrier promoting quick uptake of the drug into the blood stream, a carrier manipulating release of drug, or a carrier promoting adhesion of the drug selected from the group consisting of a liquid suspension or dispersion, a hydrogel suspension or dispersion, a topical ointment, a cream, a lotion, and a foam.

17. The method of claim 4 wherein the region is the female reproductive organs.

18. The method of claim 17 wherein the patient has a disorder located in the reproductive organs.

19. The method of claim 18 wherein the drug is for treatment of endometriosis and is selected from the group consisting progestins, estrogens, antiestrogens and antiprogestins and the patient has endometriosis.

20. The method of claim 17 wherein the step of administration is selected from the group consisting of vaginal administration, intraperiotoneal administration and direct administration.

21. The method of claim 4 wherein the drug is danazole and wherein the formulation is vaginally administered in the patient in need thereof in a dosage effective for treatment of endometriosis.

22. The method of claim 4 wherein the drug is selected from the group consisting of an anticancer drug, a cytotherapeutic and an anti-proliferative drug in a dosage effective for treatment of cancer in the region of the patient where administered.

24. The method of claim 4 wherein the drug has steroidal activity suitable for treatment of endocrine conditions.

11. A method for treating endometriosis comprising administering to the mucosal membranes of the female reproductive tract particulate danazole in a carrier promoting quick uptake of the drug into the blood stream, a carrier manipulating release of drug, or a carrier promoting adhesion of the drug, wherein the carrier is selected from the group consisting of a liquid suspension or dispersion, a hydrogel suspension or dispersion, a topical ointment, a cream, a lotion, and a foam, wherein the dosage of the danazole is effective to reduce the symptoms of endometriosis without causing blood levels of danazole achieved with systemic administration of the danazole.

26. The method of claim 11 wherein the danazole is in a form suitable for application to the uterus.

12. A composition for treating endometriosis comprising particulate danazole in a carrier promoting quick uptake of the drug into the blood stream, a carrier manipulating release of drug, or a carrier promoting adhesion of the drug, when applied to the mucosal membranes of the female reproductive tract, wherein the carrier is selected from the group consisting of a liquid suspension or dispersion, a hydrogel suspension or dispersion, a topical ointment, a cream, a lotion, and a foam wherein the dosage of the danazole is effective to reduce the symptoms of endometriosis without causing blood levels of danazole achieved with systemic administration of the danazole.

16. The composition of claim 12 wherein the danazole is in an effective dosage for treating endometriosis when applied to the uterus and causes reduced side effects.

25. The method of claim 16 wherein the drug is effective for treatment of endometrial bacterial infections selected from the group consisting of menopause, infertility, contraception, dysfunctional uterine bleeding, dysmenorrhea, adenomyosis, and assisted reproductive technologies.