Dimethyl sulfoxide (DMSO) or DMSO and methylsulfonylmethane (MSM) formulations to treat infectious diseases

• US 9,855,212 B2
• Filed: 10/29/2010
• Issued: 01/02/2018
• Est. Priority Date: 10/30/2009
• Status: Active Grant

• Current Assignee: Abela Pharmaceuticals, Inc.
• Original Assignee: Abela Pharmaceuticals, Inc.
• Inventors: Cozean, Colette, Benjamin, Rodney, Keller, Anthony, Varelman, Jeff
• Primary Examiner(s): Haghighatian, Mina
• Application Number:
  US13/503,625
• Publication Number:
  US 20130045941A1
• Time in Patent Office: 2,622 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 31/10 Sulfides; Sulfoxides; Sulfones
• CPC Class Codes: A61K 31/133 having hydroxy groups, e.g. sphingosine
• CPC Class Codes: A61K 31/17 having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine isoureas, isothioureas A61K31/155; sulfonylureas A61K31/64
• CPC Class Codes: A61K 31/4409 only substituted in position 4, e.g. isoniazid, iproniazid
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/4965 Non-condensed pyrazines
• CPC Class Codes: A61K 31/7036 having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/06 for tuberculosis
• 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

Embodiments of the invention relate generally to formulations comprising dimethylsulfoxide (DMSO) alone or in combination with methylsulfonylmethane (MSM), and one or more therapeutic agents, and uses of such formulations to treat infectious diseases. In several embodiments, such formulations are effective in treating drug-resistant infectious diseases, for example, drug-resistant tuberculosis.

Claims

1. A method for treating drug-resistant tuberculosis in a human subject in need thereof, comprising:

pretreating the subject with intravenous administration of a pretreatment composition comprising about 50 mg to about 60 mg dimethylsulfoxide DMSO; and

administering to the pretreated subject a formulation comprising therapeutic agents dissolved in DMSO, via an inhalant device selected from the group consisting of;

an inhaler, a nebulizer and a ventilator,

wherein the therapeutic agents comprise three or more compounds selected from the group consisting of;

streptomycin, isoniazid, rifampicin, pyrazinamide, and ethambutol.

2. The method of claim 1, wherein the total formulation volume is about 3 ml.

3. The method of claim 1, wherein the formulation is administered to the subject at least three times daily.

4. The method of claim 1, wherein the formulation comprises a daily dose of:

rifampicin in an amount ranging from about 500 mg to about 700 mg,

isoniazid in an amount ranging from about 200 mg to about 400 mg,

pyrazinamide in an amount ranging from about 2.0 g to about 3.0 g, and

ethambutol in an amount ranging from about 1.0 g to about 2.0 g.

5. The method of claim 4, wherein the formulation comprises a daily dose of about 600 mg rifampicin, 300 mg isoniazid, 2.4 g pyrazinamide, and 1.2 g ethambutol.

6. The method of claim 1, wherein the inhalant device is configured to generate particles of the formulation that range in size from about 0.5 um to about 5 um.

7. The method of claim 1, wherein the formulation further comprises an odor reducing compound selected from the group consisting of urea and a sulfur binding compound.

8. The method of claim 7, wherein the odor reducing compound reduces the odor associated with DMSO.

9. The method of claim 1, wherein the formulation comprises a daily dose of streptomycin in an amount ranging from about 10 mg to about 200 g.

10. The method of claim 1, wherein the DMSO sensitizes the drug-resistant tuberculosis bacteria by increasing the permeability of the bacteria to the therapeutic agents.

11. A method for treating drug-resistant tuberculosis, comprising:

intravenously administering a pretreatment composition comprising about 50 mg to about 60 mg dimethylsulfoxide (DMSO) to a subject having drug-resistant tuberculosis, and then

administering a formulation comprising DMSO and therapeutic agents to the subject via an inhalant device,

wherein the inhalant device is configured to deliver the formulation to directly contact drug-resistant tuberculosis bacteria in the subject'"'"'s lung tissue, wherein the inhalant device is an inhaler, a nebulizer, or a ventilator;

wherein the therapeutic agents comprise a daily dose of;

rifampicin in an amount ranging from about 500 mg to about 700 mg,

isoniazid in an amount ranging from about 200 mg to about 400 mg,

pyrazinamide in an amount ranging from about 2.0 g to about 3.0 g, and

streptomycin in an amount ranging from about 10 mg to about 200 g per kg of body weight,

wherein the DMSO in the formulation sensitizes the drug-resistant tuberculosis bacteria to at least one of the isoniazid, rifampicin, pyrazinamide, and streptomycin, thereby generating sensitized tuberculosis bacteria, and

wherein at least one of isoniazid, rifampicin, pyrazinamide, and streptomycin lethally inhibits the sensitized tuberculosis bacteria, thereby treating the drug-resistant tuberculosis.

12. The method of claim 11, wherein the therapeutic agents further comprise ethambutol in an amount ranging from about 1.0 g to about 2.0 g.