# US 2012/0083447 A1 · Novel Therapeutic Treatments Using Centhaquin

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- Number: US 2012/0083447 A1
- Document ID: US20120083447A1
- Status: Published application
- Kind: A1
- Application number: 13/266,205
- Filed: 2010-04-29
- Published: 2012-04-05
- Earliest claimed: 2009-04-30
- Assignees: Midwestern University
- Inventors: Anil Gulati
- Web page: https://patentgrep.com/patent/US20120083447A1

## CPC

- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 31/4025: not condensed and containing further heterocyclic rings, e.g. cromakalim
- A61K 31/42: Oxazoles
- A61K 31/506: not condensed and containing further heterocyclic rings
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 7/04: Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/12: Antihypertensives
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61K 2300/00: Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
- 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

## Abstract

Methods of treating hypertension, pain, and resuscitative hemorrhagic shock using an adrenergic agent, like centhaquin, are disclosed. The methods treat mammals, including humans.

## Claims

### Claim 1

A method of treating hypertension comprising administering to a mammal in need thereof (a) a therapeutically effective amount of an adrenergic agent and (b) a therapeutically effective amount of an endothelin antagonist.

### Claim 2 (depends on 1)

The method of claim 1 wherein the adrenergic agent and the endothelin antagonist are administered simultaneously.

### Claim 3 (depends on 2)

The method of claim 2 wherein the adrenergic agent and the endothelin antagonist are administered from a single composition.

### Claim 4 (depends on 2)

The method of claim 2 wherein the adrenergic agent and the endothelin antagonist are administered from separate compositions.

### Claim 5 (depends on 1)

The method of claim 1 wherein the adrenergic agent and the endothelin antagonist are administered sequentially.

### Claim 6 (depends on 5)

The method of claim 5 wherein the adrenergic agent is administered prior to the endothelin antagonist.

### Claim 7 (depends on 5)

The method of claim 5 wherein the endothelin antagonist is administered prior to the adrenergic agent.

### Claim 8 (depends on 1)

The method of claim 1 wherein the adrenergic agent is selected from the group consisting of centhaquin, clonidine, guanfacine, guanabenz, guanoxbenz, methyldopa, prazosin, tamsulosin, doxazosin, terazosin, phentolamine, phenoxybenzamine, mirtazapine, and mixtures thereof.

### Claim 9 (depends on 1)

The method of claim 1 wherein the adrenergic agent comprises centhaquin, clonidine, or a mixture thereof.

### Claim 10 (depends on 1)

The method of claim 1 wherein the endothelin antagonist comprises an endothelin-A antagonist.

### Claim 11 (depends on 10)

The method of claim 10 wherein the endothelin-A antagonist comprises a specific endothelin-A antagonist.

### Claim 12 (depends on 10)

The method of claim 10 wherein the endothelin-A antagonist comprises a nonspecific endothelin-A antagonist.

### Claim 13 (depends on 1)

The method of claim 1 wherein the endothelin antagonist is selected from the group consisting of compounds 1 through 35 of Appendix A.

### Claim 14 (depends on 1)

The method of claim 1 wherein the endothelin antagonist is selected from the group consisting of compounds 46 through 67 of Appendix B.

### Claim 15 (depends on 1)

The method of claim 1 wherein the endothelin antagonist is selected from the group consisting of compounds 36 through 45 of Appendix C.

### Claim 16 (depends on 1)

The method of claim 1 wherein the endothelin antagonist is selected from the group consisting of compounds 68 through 109 of Appendix D.

### Claim 17 (depends on 1)

The method of claim 1 wherein the endothelin antagonist is selected from the group consisting of atrasentan, tezosentan, bosentan, darnsenten,sitaxsentan, enrasentan, BMS-207940, BMS-193884, BMS-182874, J-104132, VML 588/Ro 61-1790, T-0115, TAK-044, BQ-788, BQ123, YM-598, LU 135252, PD 145065, A-127722, ABT-627, A-192621, A-182086, TBC3711, BSF208075, S-0139, TBC2576, TBC3214, PD156707, PD180988, ABT-546, ABT-627, Z1611, RPR118031A, SB247083, SB217242, S-Lu302872, TPC10950, SB209670, and mixtures thereof.

### Claim 18 (depends on 1)

The method of claim 1 wherein the endothelin antagonist comprises BMS-182874.

### Claim 19 (depends on 1)

The method of claim 1 wherein the endothelin antagonist comprises an endothelin converting enzyme inhibitor.

### Claim 20 (depends on 19)

The method of claim 19 wherein the endothelin converting enzyme inhibitor is selected from the group consisting of N-((1-((2(S)-(acetylthio)-1-oxopentyl)-amino)-1-cyclopentyl)-carbonyl-S-4-phenylphenyl-alanine methyl ester), phosphoramidon, and mixtures thereof.

### Claim 21 (depends on 1)

The method of claim 1 wherein the mammal is a human.

### Claim 22

A composition comprising (a) adrenergic agent, (b) an endothelin antagonist, and (c) an optional excipient.

### Claim 23 (depends on 22)

The composition of claim 22 wherein the endothelin antagonist comprises an endothelin-A antagonist.

### Claim 24

A method of treating pain comprising administering to a mammal in need thereof a therapeutically effective amount of centhaquin.

### Claim 25 (depends on 24)

The method of claim 24 wherein the centhaquin is administered in a dose range from 10 μg to about 300 μg.

### Claim 26

A method of treating pain comprising administering to a mammal in need thereof a therapeutically effective amount of an opiate analgesic and a therapeutically effective amount of centhaquin.

### Claim 27 (depends on 26)

The method of claim 26 wherein the opiate analgesic is selected from the group consisting of opium, morphine, morphine sulfate, codeine, codeine phosphate, codeine sulfate, diacetylmorphine, morphine hydrochloride, morphine tartate, diacetylmorphine hydrochloride, dextromethorphan hydrobromide, hydrocodone bitartrate, hydromorphone, hydromorphone hydrochloride, levorphanol tartrate, oxymorphone hydrochloride, oxycodone hydrochloride, fentanyl, meperidine, methodone, propoxyphene, dextromethorphan, hydrocodone, hydromorphone, levorphanol, oxymorphone, oxycodone, levallorphan, salts thereof, and mixtures thereof.

### Claim 28 (depends on 24)

The method of claim 24 wherein the subject is a mammal.

### Claim 29 (depends on 29)

The method of claim 29 wherein the subject is human.

### Claim 30 (depends on 24)

The method of claim 24 wherein the pain is chronic pain.

### Claim 31 (depends on 24)

The method of claim 24 wherein the pain is acute pain.

### Claim 32

A method of treating resuscitative hemorraghic shock or shock due to circulatory failure comprising administering to a mammal in need thereof a therapeutically effective amount of centhaquin.

### Claim 33 (depends on 32)

The method of claim 32 wherein the centhaquin is administered with Ringer's lactate.