Use of isothiocyanates compounds in treating prostatic diseases and skin cancer

• US 8,039,511 B2
• Filed: 11/14/2006
• Issued: 10/18/2011
• Est. Priority Date: 11/15/2005
• Status: Active Grant

• Current Assignee: WUXI JC Pharmaceutical Technology Company Limited
• Original Assignee: WUXI JC Pharmaceutical Technology Company Limited
• Inventors: Jin, Haiya, Zhong, Chengjuan, Chiao, Jenwei, Cheng, Jingcai
• Primary Examiner(s): ANDERSON, JAMES D
• Application Number:
  US12/093,829
• Publication Number:
  US 20090005438A1
• Time in Patent Office: 1,799 Days
• Field of Search: 514/514, 514/649, 514/665
• US Class Current: 514/514
• CPC Class Codes: A61K 31/26 Cyanate or isocyanate esters; Thiocyanate or isothiocyanate esters
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

A method for preventing and treating prostatic diseases and skin cancer using naturally or artificially synthesized isothiocyanates compounds or the derivatives or metabolites thereof.

Claims

1. A method for the treatment of benign prostatic hyperplasia in a subject, comprising:

administrating, to the subject, a composition comprising an effective amount of at least one compound of isothiocyanates, their derivatives, or metabolites,

wherein the isothiocyanates are selected from the group consisting of benzyl isothiocyanate (BITC), phenethyl isothiocyanate (PEITC), and allyl isothiocyanate (AITC),which have the following formulas (1), (2), and (3), respectively, or the combination thereof;

2. The method of claim 1, wherein the effective amount is an amount effective for inducing the expression of glutathione S-transferase (GSTP1) gene in prostate cells.

3. The method of claim 1, wherein the effective amount is an amount effective for inhibiting the expressions of (i) androgen receptor (AR), (ii) transcription factor Sp1, the upstream gene of androgen receptor (AR), and (iii) prostate specific antigen (PSA), the downstream gene of AR.

4. The method of claim 1, wherein the isothiocyanates, their derivatives, or metabolites are used alone or used as a formulation with excipients.

5. The method of claim 4, wherein the formulation is selected from the group consisting of a pharmaceutical product, dietary supplement, food, cosmetic product, or the combination thereof.

6. The method of claim 1, wherein the composition contains the following ingredients:

(a) active pharmaceutical ingredients (API) wherein said API is selected from the group consisting of phenethyl isothiocyanate (PEITC), benzyl isothiocyanate (BITC), and allyl isothiocyanate (AITC), or the combination thereof and the derivatives or metabolites thereof which are selected from the group consisting of N-acetylcysteine-conjugate of benzyl isothiocyanate (BITC-NAC), N-acetylcysteine conjugate of phenethyl isothiocyanate (PEITC-NAC), and N-acetylcysteine conjugate of allyl isothiocyanate (AITC-NAC), or the combination thereof, and

(b) pharmaceutically acceptable carrier for API, which include;

(b1) surfactants or solubilizing agents, wherein the surfactants are selected from the group consisting of polyoxyethylene lauryl ether, polyoxyethylene glycol monostearate, vitamin E polyethylene glycol succinate, polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, poloxamer, polysorbates or the combination thereof;

or the solubilizing agents are selected from the group consisting of polyvinylpyrrolidone K17, K25, K30, or K90;

polyethylene glycol 400, 4000, or 6000, or the combination thereof;

(b2) oil ingredients which are selected from the group consisting of fatty acids or triglyceride, monoglyceride or diglyceride, soybean oil, corn oil, peanut oil, stearic acid, palmitic acid, palm oil, sunflower oil, olive oil, coconut oil, sesame oil, cottonseed oil, canola oil, oleic acid, linoleic acid, medium-chain triglycerides, glyceryl monooctadecanoate, glyceryl monoacetate, glyceryl diacetate, glyceryl triacetate or the combination thereof;

(b3) antioxidants , which are water-soluble antioxidants or fat-soluble antioxidants, being selected from the group consisting of vitamin C, vitamin C palmitate, propyl gallate, tocopherol, tert-butylated-p-hydroxyanisole, 2,6-di-tert-butyl-p-methylphenol or the combination thereof;

or

(b4) combinations of the (b1), (b2), or (b3).

7. The method of claim 6, wherein the composition is selected from the group consisting of a tablet, a capsule, a pill, a powder for injection, an injection, a lyophilized powder, an ointment, a suppository, a cream, a film, an emulsion, a spray, an implant and a combination thereof.

8. The method of claim 6, wherein the composition is administered orally, intravenously, muscularly, subcutaneously, intracavitaryly, sublingually, anally, or topically.

9. The method of claim 6, wherein the composition is a pharmaceutical product or dietary supplement.

10. The method of claim 1, wherein the isothiocyanate is phenethyl isothiocyanate (PEITC).

11. The method of claim 1, wherein the derivative or metabolite of isothiocyanate is the N-acetylcysteine conjugate of phenethyl isothiocyanate (PEITC-NAC).

12. The method of claim 5, wherein the formulation is a pharmaceutical product.

13. The method of claim 1, wherein the composition is administered to the subject alone or in combined therapies.

14. The method of claim 13, wherein the combined therapies are selected from the group consisting of therapy with surgery, therapy with radiation, gene therapy and combinations thereof.