Methods and compositions for treating hyperhidrosis

• US 10,610,519 B2
• Filed: 05/03/2019
• Issued: 04/07/2020
• Est. Priority Date: 01/20/2016
• Status: Active Grant

• Current Assignee: TheraVida, Inc.
• Original Assignee: TheraVida, Inc.
• Inventors: McGraw, III, Benjamin F.
• Primary Examiner(s): Purdy, Kyle A
• Application Number:
  US16/403,115
• Publication Number:
  US 20190307727A1
• Time in Patent Office: 340 Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/216 of acids having aromatic rings, e.g. benactizyne, clofibrate
• CPC Class Codes: A61K 31/4178 not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/5047 Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: A61K 9/5084 Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs tablets containing such a mixture A61K9/2077
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Aspects of the disclosure include methods for treating hyperhidrosis in a subject with a composition including a muscarinic antagonist and a muscarinic agonist. In practicing methods according to certain embodiments, a therapeutically effective amount of a composition including a muscarinic antagonist or a pharmaceutically acceptable salt thereof and a muscarinic agonist or a pharmaceutically acceptable salt thereof is administered to a subject and is sufficient to reduce hyperhidrosis in the subject and to reduce a dry mouth side effect of the muscarinic antagonist. Compositions for practicing the subject methods are also described as well as dose units containing one or more of the subject compositions.

Claims

1. A method of treating hyperhidrosis in a subject in need thereof, the method comprising:

orally administering to the subject once per day or twice per day a single unit dose of a therapeutically effective amount of a composition comprising

an immediate release formulation of about 1 mg to 10 mg of oxybutynin, or a pharmaceutically acceptable salt thereof, and

a delayed-immediate release formulation of about 1 mg to 10 mg of pilocarpine, or a pharmaceutically acceptable salt thereof.

2. The method according to claim 1, wherein the delayed-immediate release formulation of pilocarpine, or a pharmaceutically acceptable salt thereof, comprises a plurality of delayed-immediate release pilocarpine beads, wherein each pilocarpine bead comprises:

a core;

a first layer comprising pilocarpine, or a pharmaceutically acceptable salt thereof, positioned over the core; and

a second layer comprising at least one polymer positioned over the first layer.

3. The method according to claim 1, wherein the composition is administered once per day.

4. The method according to claim 1, wherein the subject is diagnosed as having one or more condition selected from the group consisting of primary focal axillary hyperhidrosis, primary focal palmar hyperhidrosis, primary focal plantar hyperhidrosis, craniofacial hyperhidrosis, generalized hyperhidrosis, and compensatory sweating post-surgery.

5. The method according to claim 1, wherein the composition administered contains about 4 mg of the oxybutynin, or pharmaceutically acceptable salt thereof, and pilocarpine, or a pharmaceutically acceptable salt thereof, in an amount selected from the group consisting of about 4 mg, about 6 mg, and about 9 mg.

6. The method according to claim 1, wherein the composition administered contains about 6 mg of the oxybutynin, or pharmaceutically acceptable salt thereof, and pilocarpine, or a pharmaceutically acceptable salt thereof, in an amount selected from the group consisting of about 4 mg, about 6 mg, and about 9 mg.

7. The method according to claim 1, wherein the composition administered contains about 9 mg of the oxybutynin, or pharmaceutically acceptable salt thereof, and pilocarpine, or a pharmaceutically acceptable salt thereof, in an amount selected from the group consisting of about 4 mg, about 6 mg, and about 9 mg.

8. The method according to claim 1, wherein the composition comprises oxybutynin hydrochloride (HCl) and pilocarpine hydrochloride (HCl).

9. The method according to claim 1, wherein the composition is formulated such that the peak plasma concentration of the oxybutynin, or a pharmaceutically acceptable salt thereof, and the peak plasma concentration of the pilocarpine, or a pharmaceutically acceptable salt thereof, occurs at approximately the same time.

10. The method according to claim 2, wherein the first layer comprises a polymer selected from the group consisting of cellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, maltodextrin, sucrose, modified starch, a salt of alginic acid, soluble gums, carrageenan, polyvinylpyrrolidone (PVP) or polyvinylpolypyrrolidone (PVPP), ethylcellulose, cellulose acetate phthalate, hydroxypropylmethylcellulose phthalate, insoluble gums, polymethacrylate, a polyvinyl alcohol, shellac, and polyvinyl acetate phthalate.

11. The method according to claim 10, wherein the first layer comprises hydroxypropylmethylcellulose.

12. The method according to claim 2, wherein the second layer comprises one or more polymers selected from the group consisting of cellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, maltodextrin, sucrose, modified starch, a salt of alginic acid, soluble gums, carrageenan, polyvinylpyrrolidone (PVP) or polyvinylpolypyrrolidone (PVPP), ethylcellulose, cellulose acetate phthalate, hydroxypropylmethylcellulose phthalate, insoluble gums, polymethacrylate, a polyvinyl alcohol, shellac, and polyvinyl acetate phthalate.

13. The method according to claim 12, wherein the second layer comprises ethylcellulose and hydroxypropylcellulose.

14. The method according to claim 13, wherein the ratio of hydroxypropylcellulose to ethylcellulose is from about 5:

1 to about 1;

5 by weight.

15. The method according to claim 14, wherein the ratio of hydroxypropylcellulose to ethylcellulose is about 1:

1 by weight.

16. The method according to claim 2, wherein the core is about 15% to about 40% of the total weight of the bead,

the first layer is about 5% to about 30% of the total weight of the bead, and

the second layer is about 40% to about 70% of the total weight of the bead.

17. The method according to claim 2, wherein the core is a microcrystalline core that is about 20% of the total weight of the bead;

the first layer comprises the pilocarpine, or a pharmaceutically acceptable salt thereof, in an amount that is about 8% of the total weight of the bead, hydroxypropyl methylcellulose in an amount that is about 8% of the total weight of the bead, and talc in an amount that is about 4% of the total weight of the bead; and

the second layer comprises ethylcellulose in an amount that is about 26% of the total weight of the bead, hydroxypropylcellulose in an amount that is about 26% of the total weight of the bead, and dibutyl sebacate in an amount that is about 5% of the total weight of the bead.

18. The method according to claim 2, wherein the plurality of delayed-immediate release pilocarpine beads are formulated such that 20% or less of pilocarpine, or a pharmaceutically acceptable salt thereof, is released approximately 20 minutes after administering to the subject, and about 75% or more of pilocarpine, or a pharmaceutically acceptable salt thereof, is released approximately 30 minutes thereafter.