The treatment of purulent diseases of the female genital track of domestic animals by administration of an amount of a domestic animal luteolytic-uterine smooth muscle stimulating prostaglandin (DALUSMUS-PG) effective to cure said disease is disclosed.
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21. A method for treating a female domestic dog or cat suffering from a purulent genital tract disease which comprises:
administering to said dog or cat an amount of a domestic animal luteolytic-uterine smooth muscle stimulating prostaglandin (DALUSMUS-PG) effective to cure said disease.
1. A method for treating a female domestic animal suffering from a purulent genital tract disease which comprises:
administering to said animal an amount of a domestic animal luteolytic-uterine smooth muscle stimulating prostaglandin (DALUSMUS-PG) effective to cure said disease.
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concomitantly administering an amount of an antibiotic effective to treat or prevent an infection associated with said purulent genital tract
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A wide variety of genital tract diseases of female domestic animals are known to produce significant morbidity and mortality. The cervix, vagina, uterus are prime sites for the formation and development of numerous purulent genital tract diseases, such as pyometra, mucometra, metritis, endometritis, vaginitis, and cervicitis.
The diagnosis and treatment of each of the above named diseases is readily accomplished by a veterinarian ordinarily skilled in the treatment of domestic animals. Such a ,-2,2-Difluoro-PGE2, methyl ester;
16,16-Difluoro-13,14-dihydro-PGE2, methyl ester;
racemic-17-Phenyl-18,19,20-trinor-PGF1α ;
15-Methyl-PGF1α ;
racemic-15-methyl-17-phenyl-18,19,20-trinor-PGF1α ;
15-Methyl-PGF1α, methyl ester;
cis-4,5-Didehydro-PGF1α ;
5-oxa-PGF1α;
17-Phenyl-18,19,20-trinor-PGF1α ;
13,14-Dihydro-17-phenyl-18,19,20-trinor-PGF1α ;
15-Methyl-cis-4,5-didehydro-PGF1α, methyl ester;
cis-4,5-Didehydro-PGF1α, methyl ester;
16,16-Dimethyl-cis-4,5-didehydro-PGF1α, methyl ester;
5-oxa-16-(p-fluorophenoxy)-17,18,19,20-tetranor-PGF1α, methyl ester;
cis-4,5-Didehydro-16,16-dimethyl-PGF1α ;
15-Methyl-cis-4,5-didehydro-PGF1α ;
PGF2α ;
PGF2α, 1-lysine salt;
PGF2α, 1-arginine salt;
5,6-trans-PGF2α ;
15-Methyl-PGF2α ;
17-Phenyl-18,19,20-trinor-PGF2α, methyl ester;
17-Phenyl-18,19,20-trinor-PGF2α ;
20-Ethyl-PGF2α ;
15-Methyl-PGF2α, methyl ester;
17-Phenyl-18,19,20-trinor-PGF2α, 15-methyl ether;
20-Methyl-PGF2α ;
16,16-Dimethyl-PGF2α ;
16-Methyl-PGF2α ;
16-Methyl-16-phenoxy-18,19,20-trinor-PGF2α ;
15-Methyl-15-epi-PGF2α, methyl ester;
16,16-Dimethyl-17-phenyl-18,19,20-trinor-PGF2α ;
PGF2α, 15-methyl ether;
16-Phenoxy-17,18,19,20-tetranor-PGF2α ;
PGF2α, isopropyl ester;
15-methyl-17-phenyl-18,19,20-trinor-PGF2α, methyl ester;
16-Fluoro-PGF2α ;
13,14-Dihydro-PGF2α ;
17-p-chlorophenyl-18,19,20-trinor-PGF2α, ethyl ester;
16,16-Dimethyl-PGF2α, methyl ester;
16-Methyl-16-phenoxy-18,19,20-trinor-PGF2α, methyl ester;
17-Cyclohexyl-18,19,20-trinor-PGF2α ;
20-Ethyl-15-methyl-PGF2α, methyl ester,
17-(p-fluorophenyl)-18,19,20-trinor-PGF2α ;
15-epi-2,2-difluoro-15-methyl-PGF2α, methyl ester;
2,2-Difluoro-15-methyl-PGF2α, methyl ester;
15-Methyl-11β-PGF2α, methyl ester;
2,2-Difluoro-17-phenyl-18,19,20-trinor-PGF2α, methyl ester;
15-Methyl-13,14-dihydro-PGF2α, methyl ester;
15 -Methyl-PGF2α, methyl ester, 15-methyl ether;
13,14-Didehydro-15-epi-PGF2α, methyl ester;
15-epi-cis-13-16,16-Difluoro-PGF2α, methyl ester;
15-epi-16,16-Difluoro-PGF2α, methyl ester;
2-Decarboxy-2-hydroxymethyl-16,16-dimethyl-PGF2α ;
PGF2α, p-acetamidophenyl ester;
PGF2α, biphenyl ester;
PGF2α, p-benzaldehyde semicarbazone ester;
15-epi-15-Ethyl-PGF2α, methyl ester;
16,16,15-Trimethyl-PGF2α, methyl ester;
13,14-Didehydro-PGF2α, methyl ester;
(12E)-12,13-Didehydro-13,14-dihydro-15-methyl-PGF2α, methyl ester;
15-epi-cis-13-PGF2α, methyl ester;
13,14-Dihydro-17-phenyl-18,19,20-trinor-PGF2α ;
15-epi-cis-13-16-(p-fluorophenoxy)-17,18,19,20-tetranor-PGF2α, methyl ester;
15-epi-cis-13-PGF2α ;
16-(m-trifluoromethylphenoxy)-17,18,19,20-tetranor-PGF2α ;
15-Methyl-PGF2α, naphthyl ester;
15-Methyl-PGF2α, p-acetyl phenyl ester;
2-Decarboxy-2-aminomethyl-PGF2α ;
11β-16,16-Dimethyl-PGF2α, methyl ester;
15-Methyl-16-phenoxy-17,18,19,20-tetranor-PGF2α,methyl ester;
15-epi-15-Methyl-16-phenoxy-17,18,19,20-tetranor-PGF2α, methyl ester;
13,14-Dihydro-2,2-difluoro-PGF2α, methyl ester;
2a,2b-Dihomo-17,18,19,20-tetranor-16-phenoxy-PGF2α ;
2-Decarboxy-2-aminomethyl-16,16-dimethyl-PGF2α ;
2-Decarboxy-2-aminomethyl-15-methyl-PGF2α ;
2a,2b-Dihomo-15-methyl-17-phenyl-18,19,20-trinor-PGF2α, methyl ester;
13,14-Didehydro-PGF2α ;
11-Deoxy-16,16-difluoro-PGF2α, methyl ester;
2,2,16,16-Tetrafluoro-PGF2α, methyl ester;
16-(m-chlorophenoxy)-17,18,19,20-tetranor-PGF2α ;
15-epi-cis-13-2,2-Difluoro-PGF2α, methyl ester;
2,2-Difluoro-16-(m-trifluoromethylphenoxy)-17,18,19,20-tetranor-PGF2.a lpha., 15-methyl ether, methyl ester;
PGF2α, 2-methyl phenyl ester;
PGF2α, 2,6-dimethyl phenyl ester;
PGF2α, Phenyl ester;
16,16-Difluoro-13,14-dihydro-PGF2α, methyl ester;
13,14-Dihydro-15-epi-15-methyl-PGF2α ;
17-Phenyl-18,19,20-trinor-8β,12α-PGF2α, methyl ester; and
16-Phenoxy-17,18,19,20-tetranor-8β,12α-PGF2α, methyl ester.
The above DALUSMUS-PG's are all named essentially according to the system of nomenclature described by Nelson, J. Med. Chem. 17:911 (1974).
With regard to the above list of DALUSMUS-PG's, various known pharmacologically acceptable salts are used in place of the free acids or methyl esters enumerated above. Examples of such known salts are those with pharmaceutically acceptable metal cations, ammonium amine cations, quaternary ammonium cations, and basic amino acid cations.
Known among the pharmaceutically acceptable metal cations of prostaglandin salts are those derived from the alkali metals, e.g., lithium, sodium, and potassium, and from the alkaline earth metals, e.g., magnesium and calcium, and also the cationic forms of other metals, e.g., aluminum, zinc, and iron.
Known among the pharmaceutically acceptable amine cations are those derived from primary, secondary, or tertiary amines. Examples of suitable amines are methylamine, dimethylamine, trimethylamine, ethylamine, dibutylamine, triisopropylamine, N-methyl hexylamine, decylamine, dodecylamine, allylamine, crotylamine, cyclopentylamine, dicyclohexylamine, benzylamine, dibenzylamine, α-phenylethylamine, β-phenylethylamine, ethylenediamine, diethylenetriamine, and like aliphatic, cycloaliphatic, and araliphatic amines containing up to and including about 18 carbon atoms, as well as heterocyclic amines, e.g., piperidine, morpholine, pyrrolidine, piperazine, and lower-alkyl derivatives thereof, e.g., 1-methylpiperidine, 4-ethylmorpholine, 1-isopropylpyrrolidine, 2-methylpyrrolidine, 1,4-dimethylpiperazine, 2-methylpiperidine, amantadine and the like, as well as amines containing water-solubilizing or hydrophilic groups, e.g., mono-, di-, and triethanolamine, ethyldiethanolamine, N-butylethanolamine, 2-amino-1-butanol, 2-amino-2-ethyl-1,3-propanediol, 2-amino-2-methyl-1-propanol, tris(hydroxymethyl)aminomethane, N-phenylethanolamine, N-(p-tert-amylphenyl)-diethanolamine, galactamine, N-methylglucamine, N-methylglucosamine, ephedrine, phenylephrine, epinephrine, procaine, and the like.
Known among the pharmaceutically acceptable quaternary ammonium cations are tetramethylammonium, tetraethylammonium, benzyltrimethylammonium, phenyltriethylammonium, and the like.
Known among the basic amino acid cations are arginine and lysine.
The purulent genital tract diseases of female domestic animals are those described above, particularly in the Background of The Invention.
Finally, the present invention requires the use of an amount of DALUSMUS-PG which is effective to cure the purulent genital tract disease. For this purpose a wide variety of dosage schedules and routes of administration are employed. For convenience, however, the DALUSMUS-PG is preferably administered either one or twice daily. The treatment regiment is continued until the clinical manifestations of the disease begin to subside, ordinarily after 1 to 2 days of treatment. However, the treatment is repeated within 5 to 10 days after the initial administration if during this period the regression of the clinical symptoms of the disease is incomplete.
In situations where the animal is under veterinary care the preferred route of administration is parenteral, especially intermuscular and subcutaneous. In this case, the DALUSMUS-PG is conventially formulated for parenteral administration by known methods.
However, other routes of administration can be employed when the parenteral route is not convenient. Thus oral formulation (in liquids or tablets) or vaginal formulation (preferably as suppositories, although DALUSMUS-PG-impregnated silastic devices are also employed) are undertaken and administration is effected by these routes.
Effective dosage of the DALUSMUS-PG depends upon the potency of the DALUSMUS-PG relative to PGF2α, for which doses on the order to 1.0 mg./kg./day for subcutaneous or intramuscular administration are employed. However, for any animal the dosages are varied within a wide range when in the opinion of the attending veterinarian the animal is receiving too little PG (i.e., therapeutic progress is too slow or absent) or too much PG (i.e., side effects, notably diarrhea and vomiting, are too intense or too prolonged after administration). Thus for PGF2α doses in the range of 0.01-1.0 mg./kg./day are employed. Further employing oral or vaginal routes of administration require somewhat higher doses of DALUSMUS-PG than are required by parenteral administration, i.e. from two to 10 times the corresponding dose.
For DALUSMUS-PG's other than PGF2α, the dosage is readily determined by the attending veterinarian, employing known methods. Thus, for example, the veterinarian would initiate treatment at the low end of the dosage range for PGF2α, and thereafter rapidly adjust the dosage upward or downward, based on animal response, as described above. In any event for DALUSMUS-PG's other than PGF2α the parenteral dose should not exceed 10 times the maximum dose of PGF2α indicated above.
A further aspect of the present invention is the concomitant administration of antibiotic with the DALUSMUS-PG, in an amount effective to treat or prevent an infection associated with the purulent genital tract disease. Preferred antibiotics are a penicillin, a tetracycline, lincomycin, clindamycin, chloramphenicol, and streptomycin.
The use of the antibiotic is either therapeutic (i.e., in the amount known to be useful in treatment of an existing infectious condition) or prophylactic (i.e., in an amount effective to prevent or forestall the development of an infection associated with the purulent genital tract disease). When employed therapeutically, the preferred method of treatment requires a culture to be taken which will determine antibiotic sensitivity to the infecting organism and thus aid in a rational selection of the antibiotic.
As employed concomitantly, the antibiotic can be administered by the same or a different route as the DALUSMUS-PG, but in any case as is known in the art for antibiotics administration to animals.
| Patent | Priority | Assignee | Title |
| 6486207, | Dec 10 1998 | NEXMED HOLDINGS , INC | Compositions and methods for amelioration of human female sexual dysfunction |
| 6825234, | Dec 10 1998 | NEXMED HOLDINGS INC | Compositions and methods for amelioration of human female sexual dysfunction |
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