Combination of atovaquone with proguanil for the treatment of protozoal infections

• US 6,166,046 A
• Filed: 10/01/1999
• Issued: 12/26/2000
• Est. Priority Date: 11/26/1992
• Status: Expired due to Term

• Current Assignee: Smithkline Beecham Corporation (Smithkline Beecham PLC)
• Original Assignee: Glaxo Wellcome Incorporated (GlaxoSmithKline PLC)
• Inventors: Hutchinson, David Brian Ashton, Latter, Victoria Susan, Gutteridge, Winston Edward, Pudney, Mary
• Primary Examiner(s): Harrison, Robert H.
• Application Number:
  US09/409,871
• Time in Patent Office: 452 Days
• Field of Search: 514/565, 514/350, 514/682, 514/895, 552/298, 552/299, 564/234
• US Class Current: 514/350
• 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 31/12 Ketones
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 33/02 Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 33/06 Antimalarials
• CPC Class Codes: A61P 33/08 for Pneumocystis carinii
• 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

The invention relates to combinations of atovaquone and proguanil, their use in the treatment and prophylaxis of parasitic infections such as protozoal parasitic infections, e.g., malaria and toxoplasmosis, and infections caused by P. carinii and their use in the manufacture of medicaments for the treatment and/or prophylaxis of such infections. The combinations can conveniently be administered in a single pharmaceutical formulation. Preferably, atovaquone and proguanil are administered in a potentiating ratio so that they act in synergy.

Claims

1. A combinations of 2-[4-(4-chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthoquinone and 1-(4-chlorophenyl)-5-isopropylbiguianide hydrochloride wherein the 2-[-4-(4-chlorophenyl)cyclohexyl)-3-hydroxy-1,4-naphthoquinone and the 1-(4-chlorophenyl)-5-isopropylbiguanide hydrochloride are present in a ratio in the range of 1:

1 to 3;

1.

3. A combination according to claim 1 or claim 2 wherein the 2-[4(4-chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthoquinone is in the form of the trans isomer or a mixture of the cis and trans isomers in which the trans isomer predominates.

4. A pharmaceutical formulation comprising a combination according to claim 1 or claim 2 in association with one or pharmaceutically acceptable carriers thereof.

2. A combination of 2-8 4-(4-chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthoquinone and 1-(4-chlorophenyl-5-isopropylbiguanide hydrochloride wherein the ratio of 2-[4-(4-chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthoquinone to 1-(4-chlorophenyl-5-isopropylbiguanide hydrochloride if 5:

2.

5. A unit dose formulation comprising 50 mg to 3 mg each of 2-[4-(4-chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthoquinone and 1-(4-chlorophenyl)-5-isopropylbiguanide hydrochloride in a ratio in the range of 1:

1 to 3;

1.

6. A unit dose formulation according to claim 5 comprising 500 mg of 2-[4-(4-chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthoquinone and 200 mg of 1-(4-chlorophenyl)-5-isopropylbiguianide hydrochloride.