# US 2019/0167696 A1 · Method of treating hypertension

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2019/0167696 A1
- Document ID: US20190167696A1
- Status: Published application
- Kind: A1
- Application number: 16/207,597
- Filed: 2018-12-03
- Published: 2019-06-06
- Earliest claimed: 2017-12-03
- Assignees: Cipla Limited
- Applicants: Cipla Limited
- Inventors: Geena Malhotra; Kalpana Joshi; Jeevan Ghosalkar
- Web page: https://patentgrep.com/patent/US20190167696A1

## CPC

- A61K 31/5585: having five-membered rings containing oxygen as the only ring hetero atom, e.g. prostacyclin
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/08: Solutions {(composition of solutions A61K47/00)}
- A61K 9/10: Dispersions; Emulsions
- A61K 9/2018: {Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates}
- A61K 9/4866: {Organic macromolecular compounds}
- A61K 31/513: having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
- A61K 31/522: having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
- A61K 31/5575: having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
- A61K 31/5578: having a pentalene ring system, e.g. carbacyclin, iloprost
- A61K 47/12: Carboxylic acids; Salts or anhydrides thereof
- A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- A61P 9/12: Antihypertensives
- C07D 487/04: Ortho-condensed systems
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

Disclosed herein are methods of treating pulmonary hypertension, including pulmonary arterial hypertension, by administering to a patient in need thereof an effective amount of temozolomide, optionally in conjunction with one or more additional therapeutic agents. Compositions and kits including temozolomide for use in treating pulmonary hypertension, including pulmonary arterial hypertension, are also disclosed.

## Claims

### Claim 1

A method of treating pulmonary hypertension in a patient in need thereof, comprising administering to the patient a composition comprising an effective amount of temozolomide or a pharmaceutically acceptable salt or ester thereof.

### Claim 2 (depends on 1)

The method of claim 1, wherein the pulmonary hypertension is pulmonary arterial hypertension.

### Claim 3 (depends on 1)

The method of claim 1, wherein the patient has a resting pulmonary arterial pressure greater than 14 mm Hg.

### Claim 4 (depends on 1)

The method of claim 1, wherein the patient has a resting pulmonary arterial pressure greater than 40 mm Hg.

### Claim 5 (depends on 1)

The method of claim 1, wherein temozolomide is administered in an amount effective to lower resting pulmonary arterial blood pressure to a level no greater than 18 mm Hg.

### Claim 6 (depends on 1)

The method of claim 1, wherein temozolomide is administered in an amount effective to lower resting pulmonary arterial blood pressure at least 5% relative to the resting pulmonary arterial blood pressure prior to commencing treatment.

### Claim 7 (depends on 1)

The method of claim 1, wherein temozolomide is administered in a dose from 0.1 to 50 mg.

### Claim 8 (depends on 1)

The method of claim 1, wherein the composition comprises temozolomide hydrochloride.

### Claim 9 (depends on 8)

The method of claim 8, wherein the composition is administered orally, by injection, parenterally, buccally, transdermally, or by inhalation.

### Claim 10 (depends on 8)

The method of claim 8, wherein the composition is administered orally.

### Claim 11 (depends on 8)

The method of claim 8, wherein the composition is administered parenterally.

### Claim 12 (depends on 1)

The method of claim 1, further comprising administering at least one additional agent effective to treat pulmonary hypertension.

### Claim 13 (depends on 12)

The method of claim 12, wherein the at least one additional agent comprises one or more of phosphodiesterase inhibitors, calcium channel blockers, endothelin receptor antagonists, inotropic agents, prostacyclin pathway agonists, anti-coagulants, guanylate cyclase stimulators, PDE-5 inhibitors, or a combination thereof.

### Claim 14 (depends on 12)

The method of claim 12, wherein the at least one additional agent comprises one or more of avanafil, lodenafil, mirodenafil, sildenafil, tadalafil, vardenafil, udenafil, zaprinast, icariin, amlodipine, nifefipine, diltiazem, bosentan, ambrisentan, sitaxsentan, macitentan, riociguat, toprimate, fusadil, warfarin, digoxin, epoprostenol, treprostinil sodium, iloprost, selexipag, or a combination thereof.

### Claim 15

A pharmaceutical composition comprising temozolomide or a pharmaceutically acceptable salt or ester thereof, and at least one additional agent effective to treat pulmonary hypertension.

### Claim 16 (depends on 15)

The pharmaceutical composition of claim 15, wherein the at least one additional agent comprises one or more of phosphodiesterase inhibitors, calcium channel blockers, endothelin receptor antagonists, inotropic agents, prostacyclin pathway agonists, anti-coagulants, guanylate cyclase stimulators, PDE-5 inhibitors, or a combination thereof.

### Claim 17 (depends on 15)

The pharmaceutical composition of claim 15, wherein the at least one additional agent comprises one or more of avanafil, lodenafil, mirodenafil, sildenafil, tadalafil, vardenafil, udenafil, zaprinast, icariin, amlodipine, nifefipine, diltiazem, bosentan, ambrisentan, sitaxsentan, macitentan, riociguat, toprimate, fusadil, warfarin, digoxin, epoprostenol, treprostinil sodium, iloprost, selexipag, or a combination thereof.

### Claim 18

A kit comprising temozolomide or a pharmaceutically acceptable salt or ester thereof, in an amount effective to treat pulmonary hypertension, and at least one additional agent effective to treat pulmonary hypertension.

### Claim 19 (depends on 18)

The kit of claim 18, wherein the at least one additional agent comprises one or more of phosphodiesterase inhibitors, calcium channel blockers, endothelin receptor antagonists, inotropic agents, prostacyclin pathway agonists, anti-coagulants, guanylate cyclase stimulators, PDE-5 inhibitors, or a combination thereof.

### Claim 20 (depends on 18)

The kit of claim 18, wherein the at least one additional agent comprises one or more of avanafil, lodenafil, mirodenafil, sildenafil, tadalafil, vardenafil, udenafil, zaprinast, icariin, amlodipine, nifefipine, diltiazem, bosentan, ambrisentan, sitaxsentan, macitentan, riociguat, toprimate, fusadil, warfarin, digoxin, epoprostenol, treprostinil sodium, iloprost, selexipag, or a combination thereof.

### Claim 21 (depends on 18)

The kit according to claim 18, comprising a first composition comprising temozolomide or pharmaceutically acceptable salt or ester thereof, and a second composition comprising the at least one additional agent effective to treat pulmonary hypertension.