Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
1991-09-12
2001-02-13
Achutamurthy, Ponnathapu (Department: 1652)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
C514S089000, C514S091000, C514S092000, C514S094000, C514S171000, C514S212010, C514S218000, C514S312000, C514S338000, C514S249000, C514S255030, C514S278000, C514S318000, C514S343000, C514S409000, C514S422000, C514S423000, C514S616000, C548S413000
Reexamination Certificate
active
06187752
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a method for treating schizophrenia in mammalian species by administering an ACE inhibitor, such as captopril, ceronapril, zofenopril or fosinopril, alone or in combination with a neuroleptic or antipsychotic drug.
BACKGROUND OF THE INVENTION
U.S. Pat. Nos. 4,046,889 and 4,105,776 to Ondetti et al disclose proline derivatives which are angiotensin converting enzyme (ACE) inhibitors including captopril.
U.S. Pat. No. 4,168,267 to Petrillo discloses phosphinylalkanoyl prolines which are ACE inhibitors.
U.S. Pat. No. 4,337,201 to Petrillo discloses phosphinylalkanoyl substituted proline ACE inhibitors which includes fosinopril.
The Petrillo patent covers fosinopril.
U.S. Pat. No, 4,432,971 to Karanewsky et al discloses phosphonamidate substituted amino or imino acids which are angiotensin converting enzyme inhibitors.
U.S. Pat. No. 4,374,829 discloses carboxyalkyl dipeptide derivatives which are said to be angiotensin converting enzyme-inhibitors which includes enalapril.
U.S. Pat. No. 4,452,790 to Karanewsky et al is directed to phosphonate substituted amino or imino acids and salts thereof which are ACE inhibitors which includes (S)-1-[6-amino-2-[[hydroxy(4-phenylbutyl)phosphinyl]oxy]-1-oxohexyl]-L-proline or ceronapril.
U.S. Pat. No. 4,316,906 to Ondetti et al discloses ether and thioether mercaptoacyl prolines which are ACE inhibitors which includes zofenopril.
Sudilovsky, A., et al., “Attenuation of Apomorphine Induced Stereotypy by Captopril Pretreatment,” presented at the 13th Annual Meeting of the Society for Neuroscience, Nov. 6 to 11, 1983, Boston, Mass., Abstracts, Vol. 9, Part 1, page 132, disclose that captopril appears to attenuate apomorphine-induced stereotypy in rats which effect may be explained by captopril-induced alterations in endogenous modulators or antagonists of the dopamine receptor.
DESCRIPTION OF THE INVENTION
In accordance with the present invention, a method is provided for treating schizophrenia in mammalian species wherein an angiotensin converting enzyme inhibitor is systemically, such as orally or parenterally, administered in an amount effective to prevent or treat schizophrenia. The angiotensin converting enzyme inhibitor may be administered alone or in combination with a neuroleptic or anti-psychotic drug to treat schizophrenia (whether acute episodes or recurrence thereof).
Where the angiotensin converting enzyme (ACE) inhibitor is employed in combination with a neuroleptic or antipsychotic drug, the ACE inhibitor will be employed in a weight ratio to the neuroleptic or antipsychotic drug of within the range of from about 0.0001:1 to about 1000:1 and preferably from about 0.001:1 to about 25:1.
The angiotensin converting enzyme inhibitor which may be employed herein includes substituted proline derivatives, such as any of those disclosed in U.S. Pat. No. 4,046,889 to Ondetti et al mentioned above, with captopril, that is, 1-[(2S)-3-mercapto-2-methylpropionyl]-L-proline, being preferred, carboxyalkyl dipeptide derivatives, such as any of those disclosed in European Patent Application 0 012 401 mentioned above, with N-(1-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-L-proline, that is, enalapril, being preferred.
Other examples of angiotensin converting enzyme inhibitors suitable for use herein include any of the phosphonate substituted amino or imino acids or salts disclosed in U.S. Pat. No. 4,452,790 with (S)-1-[6-amino-2-[[hydroxy-(4-phenylbutyl)phosphinyl]oxy]-1-oxohexyl]-L-proline (ceronopril) being preferred, phosphinylalkanoyl prolines disclosed in U.S. Pat. No. 4,168,267 mentioned above, mercaptoacyl derivatives of substituted prolines disclosed in U.S. Pat. No. 4,316,906 with zofenopril being preferred, any of the phosphinylalkanoyl substituted prolines disclosed in U.S. Pat. No. 4,337,201 discussed above, with fosinopril being preferred, and the phosphonamidates disclosed in U.S. Pat. No. 4,432,971 discussed above.
Other examples of ACE inhibitors that may be employed herein include Beecham's BRL 36,378 as disclosed in European patent Nos. 80822 and 60668; Chugai's MC-838 disclosed in CA. 102:72588v and Jap. J. Pharmacol. 40:373 (1986); Ciba-Geigy's CGS 14824 (3-([1-ethoxycarbonyl-3-phenyl-(1S)-propyl]-amino)-2,3,4,5-tetrahydro-2-oxo-1-(3S)-benzazepine-1 acetic acid HCl) disclosed in U.K. Patent No. 2103614 and CGS 16,617 (3(S)-[[(1S)-5-amino-1-carboxypentyl]amino]-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-ethanoic acid) disclosed in U.S. Pat. No. 4,473,575; cetapril (alacepril, Dainippon) disclosed in Eur. Therap. Res. 39:671 (1986); 40:543 (1986); ramipril (Hoechst) disclosed in Eur. Patent No. 79-022 and Curr. Ther. Res. 40:74 (1986); Ru 44570 (Hoechst) disclosed in Arzneimittelforschung 35:1254 (1985), cilazapril (Hoffman-LaRoche) disclosed in J. Cardiovasc. Pharmacol. 9:39 (1987); R
O
31-2201 (Hoffman-LaRoche) disclosed in FEBS Lett. 165:201 (1984); lisinopril (Merck) disclosed in Curr. Therap. Res. 37:342 (1985) and Eur. patent appl. No. 12-401, indalapril (delapril) disclosed in U.S. Pat. No. 4,385,051; rentiapril (fentiapril, Santen) disclosed in Clin. Exp. Pharmacol. Physiol. 10:131 (1983); indolapril (Schering) disclosed in J. Cardiovasc. Pharmacol. 5:643, 655 (1983); spirapril (Schering) disclosed in Acta. Pharmacol. Toxicol. 59 (Supp. 5):173 (1986); perindopril (Servier) disclosed in Eur. J. Clin. Pharmacol. 31:519 (1987); quinapril (Warner-Lambert) disclosed in U.S. Pat. No. 4,344,949 and CI 925 (Warner-Lambert) ([3S-[2[R(*)R(*)]]3R(*)]-2-[2-[[1-(ethoxy-carbonyl)-3-phenylpropyl]amino[-1-oxopropyl]-1,2,3,4-tetrahydro-6,7-dimethoxy-3-isoquinolinecarboxylic acid HCl) disclosed in Pharmacologist 26:243, 266 (1984), WY-44221 (Wyeth) disclosed in J. Med. Chem. 26:394 (1983).
The disclosure of the above-mentioned patents and other references are incorporated herein by reference.
Examples of neuroleptics or antipsychotic drugs suitable for use herein to be employed in combination with the ACE inhibitor include, but are not limited to fluphenazine hydrochloride, fluphenazine decanoate, haloperidol, prochlorperazine, loxapine succinate, loxapine hydro- chloride, thioridazine hydrochloride, molindone hydrochloride, thiothixene, thiothixene hydrochloride, trifluoperazine hydrochloride, chlorprothixene, chlorprothixene lactate and/or hydrochloride, chlorpromazine, perphenazine and/or amitriptyline hydrochloride, and/or cholecystokinin.
In carrying out the method of the invention, the angiotensin converting enzyme inhibitor alone or in combination with the neuroleptic or antipsychotic drug may be incorporated in a single conventional dosage form or each compound may be incorporated into a separate conventional dosage form to be taken at the same time. The dosage forms may comprise conventional oral forms, rectal forms or parenteral forms, such as tablets, capsules, suppositories, powders, ampoules, elixirs, suspensions, solutions, syrups, sustained release preparations and fluid injectable forms, such as sterile solutions. Oral dosage forms are preferred, although parenteral forms, such as intramuscular, intraperitoneal or intravenous forms are quite satisfactory as well.
The dose administered must be carefully adjusted according to age, weight and condition of the patient, as well as the route of administration, dosage form and regimen and the desired result.
Thus, for oral administration, a satisfactory result may be obtained employing the ACE inhibitor in an amount within the range of from about 0.01 mg/kg to about 100 mg/kg and preferably from about 0.1 mg/kg to about 25 mg/kg, and when employing ceronapril preferably from about 0.01 to about 10 mg/kg, alone or in combination with the neuroleptic or antipsychotic in an amount within the range of from about 0.01 mg/kg to about 100 mg/kg and preferably from about 0.1 mg/kg to about 25 mg/kg with the ACE inhibitor and neuroleptic or antipsychotic being employ
Feldon Joram
Rawlins John N. P.
Smith A. David
Sudilovsky Abraham
Weiner Ina
Achutamurthy Ponnathapu
Burton & Rodney
E.R. Squibb & Sons, Inc.
Moore William W.
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