Claims
- 1. A method for treating a female sexual dysfunction in a patient in need thereof comprising topically administering to the vagina or vulvar area of the patient a therapeutically effective amount of a composition comprising at least one S-nitrosothiol compound or a pharmaceutically acceptable salt thereof; at least one glyceride; and a pharmaceutically acceptable carrier.
- 2. The method of claim 1, wherein the S-nitrosothiol compound is S-nitroso-N-acetylcysteine, S-nitroso-captopril, S-nitroso-N-acetylpenicillamine, S-nitro-homocysteine, S-nitroso-cysteine, S-nitroso-glutathione or S-nitroso-cysteinyl-glycine.
- 3. The method of claim 2, wherein the S-nitrosothiol compound is S-nitroso-glutathione.
- 4. The method of claim 1, wherein the S-nitrosothiol compound is:(i) HS(C(Re)(Rf))mSNO; (ii) ONS(C(Re)(Rf))mRe; or (iii) H2N—CH(CO2H)—(CH2)m—C(O)NH—CH(CH2SNO)—C(O)NH—CH2—CO2H; wherein m is an integer from 2 to 20; Re and Rf are each independently a hydrogen, an alkyl, a cycloalkoxy, a halogen, a hydroxy, an hydroxyalkyl, an alkoxyalkyl, an arylheterocyclic ring, an alkylaryl, a cycloalkylalkyl, a heterocyclicalkyl, an alkoxy, a haloalkoxy, an amino, an alkylamino, a dialkylamino, an arylamino, a diarylanilno, an alkylarylamino, an alkoxyhaloalkyl, a haloalkoxy, a sulfonic acid, a sulfonic ester, an alkylsulfonic acid, an arylsulfonic acid, an arylalkoxy, an alkylthio, an arylthio, a cycloalkylthio, a cycloalkenyl, a cyano, an aminoalkyl, an aminoaryl, an aryl, an arylalkyl, an alkylaryl, a carboxamido, a alkylcarboxamido, an arylcarboxamido, an amidyl, a carboxyl, a carbamoyl, a carbamate, an alkylcarboxylic acid, an arylcarboxylic acid, an alkylcarbonyl, an arylcarbonyl, an ester, a carboxylic ester, an alkylcarboxylic ester, an arylcarboxylic ester, a haloalkoxy, a sulfonamido, an alkylsulfonamido, an arylsulfonamido, a sulfonic ester, a urea, a phosphoryl, a nitro, —T—Q , or —(C(Re)(Rf))k—T—Q, or Re and Rf taken together with the carbons to which they are attached form a carbonyl, a methanthial, a heterocyclic ring, a cycloalkyl group or a bridged cycloalkyl group; Q is —NO or —NO2; and T is independently a covalent bond, a carbonyl, an oxygen, —S(O)o— or N(Ra)Ri—, wherein o is an integer from 0 to 2, Ra is a lone pair of electrons, a hydrogen or an alkyl group; Ri is a hydrogen, an alkyl, an aryl, an alkylcarboxylic acid, an aryl carboxylic acid, an alkylcarboxylic ester, an arylcarboxylic ester, an alkylcarboxamido, an arylcarboxamido, an alkylaryl, an alkylsulfinyl, an alkylsulfonyl, an arylsulfinyl, an arylsulfonyl, a sulfonanildo, a carboxamido, a carboxylic ester, an amino alkyl, an amino aryl, —CH2—C(T—Q)(Re)(Rf), or —(N2O2—)·M+, wherein M+ is an organic or inorganic cation; with the proviso that when Ri is —CH2—C(T—Q)(Re)(Rf) or —(N2O2—)·M; then “—T—Q” can be a hydrogen, an alkyl group, an alkoxyalkyl group, an aminoalkyl group, a hydroxy group or an aryl group.
- 5. The method of claim 1, wherein the glyceride is a mono glyceride, a diglyceride, a triglyceride, a polyglycolyzed glyceride, or a mixture thereof.
- 6. The method of claim 1, wherein the glyceride is a mixture of caprylic triglycerides and capric triglycerides, a decanoly triglyceride, an octanoyl triglyceride, a C8-C12 triglyceride, a saturated polyglycolyzed glyceride, a glyceryl caprylate/caprate and PEG-8 (polyethylene glycol) caprylate/caprate complex, a unsaturated polyglycolyzed glyceride, an apricot kernel oil PEG-6 complex, an almond oil PEG-6 complex, a peanut oil PEG-6 complex, an olive oil PEG-6 complex, a corn oil PEG-6 complex, an ethoxylated glyceride, a glyceryl caprylate/caprate PEG-4 complex, or a mixture thereof.
- 7. The method of claim 1, wherein the composition is in the form of a cream, a spray, a lotion, a gel, an ointment, an emulsion, a foam, a coating for a condom, or a liposome composition.
- 8. The method of claim 1, further comprising administering to the patient a therapeutically effective amount of at least one vasoactive agent.
- 9. The method of claim 8, wherein the vasoactive agent is a potassium channel activator, a calcium channel blocker, an α-adrenergic receptor antagonist, a β-blocker, a phosphodiesterase inhibitor, adenosine, an ergot alkaloid, a vasoactive intestinal peptide, a prostaglandin, a dopamine agonist, an opioid antagonist, an endothelin antagonist, a thromboxane inhibitor or a mixture thereof.
- 10. The method of claim 1, further comprising administering to the patient at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase.
- 11. The method of claim 10, wherein the at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase is:(i) a compound that comprises at least one ON—O—, ON—N— or ON—C— group; (ii) a compound that comprises at least one O2N—O—, O2N—N—, O2N—S— or O2N—C— group; (iii) a N-oxo-N-nitrosoamine having the formula: R1R2—N(O—M+)—NO, wherein R1 and R2 are each independently a polypeptide, an amino acid, a sugar, an oligonucleotide, a straight or branched, saturated or unsaturated, aliphatic or aromatic, substituted or unsubstituted hydrocarbon, or a heterocyclic group, and M+ is an organic or inorganic cation.
- 12. The method of claim 11, wherein the compound comprising at least one ON—O—, ON—N— or ON—C— group is an ON—O-polypeptide, an ON—N-polypepetide, an ON—C— polypeptide, an ON—O-amino acid, an ON—N-amino acid, an ON—C-amino acid, an ON—O-sugar, an ON—N-sugar, an ON—C-sugar, an ON—O-oligonucleotide, an ON—N-oligonucleotide, an ON—C— oligonucleotide, a straight or branched, saturated or unsaturated, substituted or unsubstituted, aliphatic or aromatic ON—O-hydrocarbon, a straight or branched, saturated or unsaturated, substituted or unsubstituted, aliphatic or aromatic ON—N-hydrocarbon, a straight or branched, saturated or unsaturated, substituted or unsubstituted, aliphatic or aromatic ON—C-hydrocarbon, an ON—O-heterocyclic compound, an ON—N-heterocyclic compound or a ON—C-heterocyclic compound.
- 13. The method of claim 11, wherein compound comprising at least one O2N—O—, O2N—N—, O2N—S— or O2N—C— group is an O2N—O-polypeptide, an O2N—N-polypeptide, an O2N—S-polypeptide, an O2N—C-polypeptide, an O2N—O-amino acid, O2N—N-amino acid, O2N—S—amino acid, an O2N—C-amino acid, an O2N—O-sugar, an O2N—N-sugar, O2N—S-sugar, an O2N—C-sugar, an O2N—O-oligonucleotide, an O2N—N-oligonucleotide, an O2N—S-oligonucleotide, an O2N—C-oligonucleotide, a straight or branched, saturated or unsaturated, aliphatic or aromatic, substituted or unsubstituted O2N—O-hydrocarbon, a straight or branched, saturated or unsaturated, aliphatic or aromatic, substituted or unsubstituted O2N—N-hydrocarbon, a straight or branched, saturated or unsaturated, aliphatic or aromatic, substituted or unsubstituted O2N—S-hydrocarbon, a straight or branched, saturated or unsaturated, aliphatic or aromatic, substituted or unsubstituted O2N—C-hydrocarbon, an O2N—O-heterocyclic compound, an O2N—N-heterocyclic compound, an O2N—S-heterocyclic compound or an O2N—C-heterocyclic compound.
- 14. The method of claim 10, wherein the at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase is L-arginine, L-homoarginine, N-hydroxy-L-arginine, nitrosated L-arginine, nitrosylated L-arginine, nitrosated N-hydroxy-L-arginine, nitrosylated N-hydroxy-L-arginine, citrulline, ornithine, glutamine, lysine, a polypeptide comprising at least one of these amino acids or an inhibitor of the enzyme arginase.
- 15. The method of claim 10, wherein the at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase is a NONOate.
RELATED APPLICATIONS
This application claims priority to U.S. Provisional Application No. 60/202,935 filed May 9, 2000.
US Referenced Citations (34)
Foreign Referenced Citations (3)
| Number |
Date |
Country |
| WO9910731 |
Mar 1999 |
WO |
| WO9920266 |
Apr 1999 |
WO |
| WO9960630 |
Nov 1999 |
WO |
Non-Patent Literature Citations (1)
| Entry |
| Seeley et al., Archives of Sexual Behavior; 9 (2): 77-85 (1980). |
Provisional Applications (1)
|
Number |
Date |
Country |
|
60/202935 |
May 2000 |
US |
Patent Grant
6762202
