Vaginal health products
View Patent ↗The invention provides compositions and methods for increasing the secretion of mucus within the reproductive tract of a female mammal.
1. A method of preventing or treating vaginal dryness in a mammal in need of such prevention or treatment comprising administering to the vaginal cavity an effective amount of a composition comprising a retinoid or a carotenoid, a nucleotide or a nucleoside, and a pharmaceutically acceptable excipient for use in the vaginal cavity area.
2. The method of claim 1 , wherein the retinoid or carotenoid is a compound of Formula IA or IB:
wherein:
X is CH, or N;
R is H or alkyl of 1 to 6 carbons;
m is an integer having the value of 0–5;
n is an integer having the value of 0–2;
r is an integer having the value 0–2;
L is —(C═Z)—NH— or —NH—(C═Z)— where Z is O or S;
Q is a phenyl, naphthyl, pyridyl, thienyl, furyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiazolyl, oxazolyl, imidazolyl or pyrrazolyl, wherein the phenyl, naphthyl pyridyl, thienyl, furyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiazolyl, oxazolyl, imidazolyl or pyrrazolyl group can be substituted with one or two R 1 groups;
W is F, Br, Cl, I, C 1-6 alkyl, fluoro-substituted C 1-6 alkyl, NO 2 , N 3 , OH, OCH 2 OCH 3 , O—C 1-10 alkyl, tetrazol, CN, SO 2 C 1-6 -alkyl, SO 2 C 1-6 -fluoro-substituted alkyl, SO—C 1-6 alkyl, CO—C 1-6 alkyl, COOR 8 , phenyl, phenyl itself substituted with a W group other than with phenyl or substituted phenyl, with the proviso that when X is CH and r is 0 then n is not 0 and at least one W group is not alkyl;
A is (CH 2 ) q where q is 0–5, lower branched chain alkyl having 3–6 carbons, cycloalkyl having 3–6 carbons, alkenyl having 2–6 carbons and 1 or 2 double bonds, alkynyl having 2–6 carbons and 1 or 2 triple bonds; and
B is COOH, COOR 8 , CONR 9 R 10 , CH 2 OH, CH 2 OR 11 , CH 2 OCOR 11 , CHO, CH(OR 12 ) 2 , CHOR 13 O, COR 7 , CR 7 (OR 12 ) 2 , CR 7 OR 13 O, where R 7 is an alkyl, cycloalkyl or alkenyl group containing 1 to 5 carbons, R 8 is an alkyl group of 1 to 10 carbons or trimethylsilylalkyl where the alkyl group has 1 to 10 carbons, or a cycloalkyl group of 5 to 10 carbons, or R 8 is phenyl or lower alkylphenyl, R 9 and R 10 independently are hydrogen, an alkyl group of 1 to 10 carbons, or a cycloalkyl group of 5–10 carbons, or phenyl or lower alkylphenyl, R 11 is lower alkyl, cycloalkyl, lower alkyl substituted cycloalkyl, phenyl or lower alkylphenyl, R 12 is lower alkyl, and R 13 is divalent alkyl radical of 2–5 carbons; or a pharmaceutically acceptable salt thereof.
3. The method of claim 1 , wherein the retinoid or carotenoid is a compound of Formula II:
wherein:
R 20 , R 21 and R 22 are each independently C 1-6 alkyl, fluoro-substituted C 1-6 alkyl, hydroxy-substituted C 1-6 alkyl, CH 2 OH, CH 2 OR 11 , CH 2 OCOR 11 , CHO, CH(OR 12 ) 2 , CHOR 13 O, COR 7 , CR 7 (OR 12 ) 2 , or CR 7 OR 13 O, where R 7 is an alkyl, cycloalkyl or alkenyl group containing 1 to 5 carbons, R 11 is lower alkyl, cycloalkyl, lower alkyl substituted cycloalkyl, phenyl or lower alkylphenyl, R 12 is lower alkyl, and R 13 is divalent alkyl radical of 2–5 carbons; or a pharmaceutically acceptable salt thereof.
4. The method of claim 1 , wherein the retinoid or carotenoid is vitamin A, beta-carotene, retinal, retinoic acid or retinol.
5. The method of claim 1 , wherein the nucleotide or nucleoside is a compound of Formula III:
wherein:
X 1 , X 2 and X 3 are each independently either O − or S − ;
R 1 is O, imido, methylene, or dihalomethylene; and
R 2 is H or Br; or
a pharmaceutically acceptable salt thereof.
6. The method of claim 1 , wherein the nucleotide or nucleoside is dATP, ATP, dGTP, GTP, dCTP, CTP, dTTP, TTP, dUTP or UTP.
7. The method of claim 1 , wherein the effective amount comprises about 0.01 milligrams to about 1 milligrams retinoid or carotenoid.
8. The method of claim 1 , wherein the effective amount comprises about 0.1 micromolar to about 100 micromolar retinoid or carotenoid.
9. The method of claim 1 , wherein the composition comprises a lotion, cream gel, spray, foam or vaginal insert.
10. A composition for increasing mucus secretion in the female reproductive tract comprising an effective amount of a retinoid or a carotenoid, an effective amount of a nucleotide or nucleoside, and a pharmaceutically acceptable excipient for use in the vaginal cavity area.
11. The composition of claim 10 , wherein the retinoid or the carotenoid is a compound of Formula IA or IB:
wherein:
X is CH, or N;
R is H or alkyl of 1 to 6 carbons;
m is an integer having the value of 0–5;
n is an integer having the value of 0–2;
r is an integer having the value 0–2;
L is —(C═Z)—NH— or —NH—(C═Z)— where Z is O or S;
Q is a phenyl, naphthyl, pyridyl, thienyl, furyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiazolyl, oxazolyl, imidazolyl or pyrrazolyl, wherein the phenyl, naphthyl pyridyl, thienyl, furyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiazolyl, oxazolyl, imidazolyl or pyrrazolyl group can be substituted with one or two R 1 groups;
W is F, Br, Cl, I, C 1-6 alkyl, fluoro-substituted C 1-6 alkyl, NO 2 , N 3 , OH, OCH 2 OCH 3 , O—C 1-10 alkyl, tetrazol, CN, SO 2 C 1-6 -alkyl, SO 2 C 1-6 -fluoro-substituted alkyl, SO—C 1-6 alkyl, CO—C 1-6 alkyl, COOR 8 , phenyl, phenyl itself substituted with a W group other than with phenyl or substituted phenyl, with the proviso that when X is CH and r is 0 then n is not 0 and at least one W group is not alkyl;
A is (CH 2 ) q where q is 0–5, lower branched chain alkyl having 3–6 carbons, cycloalkyl having 3–6 carbons, alkenyl having 2–6 carbons and 1 or 2 double bonds, alkynyl having 2–6 carbons and 1 or 2 triple bonds; and
B is COOH, COOR 8 , CONR 9 R 10 , CH 2 OH, CH 2 OR 11 , CH 2 OCOR 11 , CHO, CH(OR 12 ) 2 , CHOR 13 O, COR 7 , CR 7 (OR 12 ) 2 , CR 7 OR 13 O, where R 7 is an alkyl, cycloalkyl or alkenyl group containing 1 to 5 carbons, R 8 is an alkyl group of 1 to 10 carbons or trimethylsilylalkyl where the alkyl group has 1 to 10 carbons, or a cycloalkyl group of 5 to 10 carbons, or R 8 is phenyl or lower alkylphenyl, R 9 and R 10 independently are hydrogen, an alkyl group of 1 to 10 carbons, or a cycloalkyl group of 5–10 carbons, or phenyl or lower alkylphenyl, R 11 is lower alkyl, cycloalkyl, lower alkyl substituted cycloalkyl, phenyl or lower alkylphenyl, R 12 is lower alkyl, and R 13 is divalent alkyl radical of 2–5 carbons; or a pharmaceutically acceptable salt thereof.
12. The composition of claim 10 , wherein the retinoid or the carotenoid is a compound of wherein the retinoid or carotenoid is vitamin A, beta-carotene, retinal, retinoic acid or retinol.
13. The composition of claim 10 , wherein the nucleotide or nucleoside is a compound of Formula III:
wherein:
X 1 , X 2 and X 3 are each independently either O − or S − ;
R 1 is O, imido, methylene, or dihalomethylene; and
R 2 is H or Br; or
a pharmaceutically acceptable salt thereof.
14. The composition of claim 10 , wherein the nucleotide or nucleoside is dATP, ATP, dGTP, GTP, dCTP, CTP, dTTP, TTP, dUTP or UTP.
15. The composition of claim 10 , wherein the effective amount comprises about 0.01 milligrams to about 1 milligrams retinoid or carotenoid.
16. The composition of claim 10 , wherein the effective amount comprises about 0.1 micromolar to about 100 micromolar retinoid or carotenoid.
17. The composition of claim 10 , the composition comprises a lotion, cream gel, spray, or foam.
18. The composition of claim 10 , wherein the composition comprises a vaginal insert.