IP Library Patent Application 17460772
Patent Application
App. No. 17/460,772

Pharmaceutical Compositions And Methods

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Patent No.
US None
App. No.
17/460,772
Abstract

Pharmaceutical compositions and kits including a tyrosine hydroxylase inhibitor; melanin, a melanin promoter, or a combination thereof; a p450 3A4 promoter; and a leucine aminopeptidase inhibitor are provided. Also provided are methods of treating cancer in a subject, comprising administering an effective amount of a tyrosine hydroxylase inhibitor, a melanin promoter, a p450 3A4 promoter, and a leucine aminopeptidase inhibitor to the subject in need thereof. Also provided are methods of reducing cell proliferation in a subject comprising administering an effective amount of a tyrosine hydroxylase inhibitor, a melanin promoter, a p450 3A4 promoter, and a leucine aminopeptidase inhibitor to the subject in need thereof.

Claims (40)

1 . A method of treating a cancer in a subject, wherein said cancer is stomach cancer, brain cancer, liver cancer, testicular cancer, leukemia, or lymphoma, comprising administering an effective amount of a tyrosine hydroxylase inhibitor; a melanin promoter; a p450 3A4 promoter; and a leucine aminopeptidase inhibitor to the subject in need thereof, wherein:

the melanin promoter is methoxsalen or melanotan II;

the p450 3A4 promoter is 5, 5-diphenylhydantoin, valproic acid, or carbamazepine; and

the leucine aminopeptidase inhibitor is N-[(2S,3R)-3-amino-2-hydroxy-4-phenylbutyryl]-L-leucine or rapamycin.

2 . The method of claim 1 further comprising administering a growth hormone inhibitor.

3 . The method of claim 1 wherein at least two of the promoters and inhibitors are administered simultaneously.

4 . The method of claim 1 wherein at least three of the promoters and inhibitors are administered simultaneously.

5 . The method of claim 1 wherein each of the promoters and inhibitors is administered simultaneously.

6 . The method of claim 1 wherein the promoters and inhibitors are administered orally, subcutaneously, intravenously, transdermally, vaginally, rectally or in any combination thereof.

7 . The method of claim 6 wherein the transdermal administration is done with oleic acid, 1-methyl-2-pyrrolidone, or dodecylnonaoxyethylene glycol monoether.

8 . The method of claim 1 wherein the promoters and inhibitors are administered during a cycle consisting of five to seven days of administering the promoters and inhibitors and one to two days of not administering the promoters and inhibitors.

9 . The method of claim 8 wherein the promoters and inhibitors are administered over the course of at least six of said cycles.

10 . The method of claim 1 wherein the tyrosine hydroxylase inhibitor is a tyrosine derivative.

11 . The method of claim 10 wherein the tyrosine derivative is one or more of methyl (2R)-2-amino-3-(2-chloro-4 hydroxyphenyl) propanoate, D-tyrosine ethyl ester hydrochloride, methyl (2R)-2-amino-3-(2,6-dichloro-3,4-dimethoxyphenyl) propanoate H-D-Tyr(TBU)-allyl ester HCl, methyl (2R)-2-amino-3-(3-chloro-4,5-dimethoxyphenyl) propanoate, methyl (2R)-2-amino-3-(2-chloro-3-hydroxy-4-methoxyphenyl) propanoate, methyl (2R)-2-amino-3-(4-[(2-chloro-6-fluorophenyl) methoxy] phenyl) propanoate, methyl (2R)-2-amino-3-(2-chloro-3,4-dimethoxyphenyl) propanoate, methyl (2R)-2-amino-3-(3-chloro-5-fluoro-4-hydroxyphenyl) propanoate, diethyl 2-(acetylamino)-2-(4-[(2-chloro-6-fluorobenzyl) oxy] benzyl malonate, methyl (2R)-2-amino-3-(3-chloro-4-methoxyphenyl) propanoate, methyl (2R)-2-amino-3-(3-chloro-4-hydroxy-5-methoxyphenyl) propanoate, methyl (2R)-2-amino-3-(2,6-dichloro-3-hydroxy-4-methoxyphenyl) propanoate, methyl (2R)-2-amino-3-(3-chloro-4-hydroxyphenyl) propanoate, H-DL-tyr-OMe HCl, H-3,5-diiodo-tyr-OMe HCl, H-D-3,5-diiodo-tyr-OME HCl, H-D-tyr-OMe HCl, D-tyrosine methyl ester hydrochloride, D-tyrosine-ome HCl, methyl D-tyrosinate hydrochloride, HD-tyr-OMe.HCl, D-tyrosine methyl ester HCl, H-D-Tyr-OMe-HCl, (2R)-2-amino-3-(4-hydroxyphenyl) propionic acid, (2R)-2-amino-3-(4-hydroxyphenyl) methyl ester hydrochloride, methyl (2R)-2-amino-3-(4-hydroxyphenyl) propanoate hydrochloride, methyl (2R)-2-azanyl-3-(4-hydroxyphenyl) propanoate hydrochloride, 3-chloro-L-tyrosine, 3-nitro-L-tyrosine, 3-nitro-L-tyrosine ethyl ester hydrochloride, DL-m-tyrosine, DL-o-tyrosine, Boc-Tyr (3,5-I 2 )—OSu, Fmoc-tyr(3-NO 2 )—OH, and α-methyl-DL-tyrosine.

12 . The method of claim 11 wherein the tyrosine derivative is α-methyl-DL tyrosine.

13 . The method of claim 11 wherein 60 mg of the tyrosine derivative is administered orally and 0.25 mL of a 2 mg/mL suspension of the tyrosine derivative is administered subcutaneously.

14 . The method of claim 1 wherein the melanin promoter is methoxsalen.

15 . The method of claim 14 wherein 10 mg of the methoxsalen is administered orally and 0.25 mL of a 1 mg/mL suspension of the methoxsalen is administered subcutaneously.

16 . The method of claim 1 wherein the melanin promoter is melanotan II.

17 . The method of claim 1 wherein the p450 3A4 promoter is 5, 5-diphenylhydantoin.

18 . The method of claim 17 wherein 30 mg of the 5, 5-diphenylhydantoin is administered orally.

19 . The method of claim 1 wherein the p450 3A4 promoter is valproic acid or carbamazepine.

20 . The method of claim 1 wherein the leucine aminopeptidase inhibitor is N-[(2S,3R)-3-amino-2-hydroxy-4-phenylbutyryl]-L-leucine.

21 . The method of claim 20 wherein 20 mg of the N-[(2S,3R)-3-amino-2-hydroxy-4-phenylbutyryl]-L-leucine is administered orally.

22 . The method of claim 1 wherein the leucine aminopeptidase inhibitor is rapamycin.

23 . The method of claim 20 wherein the p450 3A4 promoter is 5,5-diphenylhydantoin.

24 . The method of claim 23 wherein the melanin promoter is melanotan II.

25 . The method of claim 1 further comprising administering an effective amount of D-leucine.

26 . The method of claim 24 wherein the tyrosine derivative is α-methyl-DL tyrosine.

27 . The method of claim 1 wherein the melanin promoter is melanotan II; the p450 3A4 promoter is 5, 5-diphenylhydantoin; and the tyrosine hydroxylase inhibitor is α-methyl-DL tyrosine.

28 . The method of claim 27 wherein the leucine aminopeptidase inhibitor is N-[(2S,3R)-3-amino-2-hydroxy-4-phenylbutyryl]-L-leucine.

29 . The method of claim 27 wherein the leucine aminopeptidase inhibitor is rapamycin.

30 . The method of claim 1 further comprising assessing progression of the cancer in said subject.

31 . The method of claim 2 further comprising assessing progression of the cancer in said subject.

32 . The method of claim 1 , wherein said cancer is stomach cancer.

33 . The method of claim 1 , wherein said cancer is brain cancer.

34 . The method of claim 1 , wherein said cancer is liver cancer.

35 . The method of claim 1 , wherein said cancer is testicular cancer.

36 . The method of claim 1 , wherein said cancer is leukemia.

37 . The method of claim 1 , wherein said cancer is lymphoma.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 11, 2022
From: HOFFMAN, STEVEN
To: TYME, INC.
Reel/Frame 059892/0917 →