(12) United States Patent (10) Patent No.: US 6,406,706 B1 Haque Et Al
Total Page：16
File Type：pdf, Size：1020Kb
USOO6406706B1 (12) United States Patent (10) Patent No.: US 6,406,706 B1 Haque et al. (45) Date of Patent: *Jun. 18, 2002 (54) USE OF C-AND B-SANTALOLS MAJOR Textbook of Pediatric Infectious Diseases, Edition 4, vol. 1, CONSTITUENTS OF SANDAL WOOD OIL Viral and Fungal Skin Infections, W.B. Saunders Company, IN THE TREATMENT OF WARTS, SKIN 1998, pp. 759–763. BLEMISHES AND OTHERWIRAL-INDUCED TUMIORS WPI Abstracts, Section Ch, Week 1997 10, Derwent Publi cations Ltd., Class B05, An 1997-103645, XP 00 2131419 (75) Inventors: Malika H. Haque, Azeez U. Haque, both of Columbus, OH (US) & JP 0833752OA, Tanaka, T. 1996. Database CAPLUS on STN, AN 1996:226082, abstract of JP (73) Assignee: Haque, Inc., Columbus, OH (US) 08026980, 1996. (*) Notice: Subject to any disclaimer, the term of this Database Medline on CAS, European Journal of Cancer patent is extended or adjusted under 35 Prevention, Dwivedi et al., “Chemopreventive effects of U.S.C. 154(b) by 0 days. sandalwood oil on skin papillomas in mice", 6(4):399-401, This patent is Subject to a terminal dis Aug., 1996. claimer. Dwivedl; Voss et al., Chemopreventive Effects of C-Santalol on Skin Tumor Development in Mice, College of Pharmacy, (21) Appl. No.: 09/637,290 South Dakota State University, Brookings, SD 57007, 1 (22) Filed: Aug. 11, 2000 paragraph abstract from the Proceedings of the American ASSociation for Cancer Research, Vol. 40, Mar. 1999. Related U.S. Application Data (63) Continuation-in-part of application No. 09/145,121, filed on Primary Examiner Diana Dudash Sep. 2, 1998, now Pat. No. 6,132,756, which is a continu ation-in-part of application No. 08/960,303, filed on Oct. 29, Assistant Examiner Alysia Berman 1997, now Pat. No. 5,945,116. (74) Attorney, Agent, or Firm-Standley & Gilcrest LLP (60) Provisional application No. 60/030,307, filed on Nov. 5, 1996. (57) ABSTRACT (51) Int. Cl." .................................................. A61K 9/02 (52) U.S. Cl. ................. ... 424/400; 514/729 The present invention provides a method for the treatment of (58) Field of Search ................................. 424/400, 430; Viral-induced tumors in mammals, more specifically, human 514/729 warts. The method uses C- and B-Santalols, or mixtures or derivatives thereof, to prepare medicaments for the treat (56) References Cited ment of Viral-induced tumors i.e., warts caused by the U.S. PATENT DOCUMENTS human papillomavirus (HPV) in humans. The method of the invention comprises the topical administration of C- and 4,908.355 A 3/1990 Gettings et al. 5.532.215 A 7/1996 Lexdey et al. ................. 514/8 B-Santalols, or mixtures or derivatives thereof, in a compo 5,541,058 A 7/1996 Kreider et al. ................. 435/5 Sition derived therefrom, to the human epidermis, as needed. 5,562900 A 10/1996 Boyer et al. ................ 424/115 The present invention is also concerned with a unique 5,693,327 A 12/1997 Shah antiviral composition useful for topical application. The 5,916,573 A 6/1999 Spiers et al. antiviral composition according to this invention is also FOREIGN PATENT DOCUMENTS effective against other DNA viruses such as the DNA pox CH 688 787 A 3/1998 Virus that causes Molluscum contagiosum and may be effec DE 26 54743 A 6/1978 tive against other DNA viruses such as AIDS virus and RNA OTHER PUBLICATIONS Viruses. The C- and B-Santalols composition, or mixtures or derivatives thereof, may also be effective in the treatment of Printed advertisement for Occlusal-HP, www.genderm.co, genital warts and HPV of the genital tract and in the GenDerm Corporation, 1996. treatment of cancer of the Skin and cervix. The C- and Copy of label and instructions for DuoFilm, Schering B-Santalols, or mixtures or derivatives thereof, may also be Plough HealthCare Products, 1995. effective in the prevention of dryness of the skin, rashes and Brochure for DuoFilm, Schering-Plough HealthCare Prod ucts, Inc., 1996. flakineSS associated with Seborrheic dermatitis, psoriasis and Principles and Practice of Pediatrics, Second Edition, J.B. allergic or eczematous rashes of the Skin. The C- and Lippincott Company, 1994, Chapter 35, p. 903. B-Santalols, or mixtures or derivatives thereof, may also be Atlas of Pediatric Dermatology, Lumps and Bumps, Wolfe, effective in the treatment of acne lesions of the face and the 1993, pp 5.5–5.7. body and in the eradication of pustular acne lesions caused Color Textbook of Pediatric Dermatology, Second Edition, by Staphylococcal acne and Streptococcal bacterial infec Viral Infections, Mosby, 1996, pp. 121-127. tions. Rudolph's Pediatrics, 20th Edition, Viral Infections, Simon & Shuster Company, 1996, p. 937–938. 6 Claims, No Drawings US 6,406,706 B1 1 2 USE OF C-AND B-SANTALOLS MAJOR is a 17% Solution of Salicylic acid in a polyacrylic Vehicle. CONSTITUENTS OF SANDAL WOOD OIL The Shering-Plough Company of Memphis, Tenn. produces IN THE TREATMENT OF WARTS, SKIN and markets a product known as Duo FilmF) which is a patch BLEMISHES AND OTHERWIRAL-INDUCED containing Salicylic acid. The product literature recommends TUMIORS that the wart be washed and dried prior to the application of a medicated patch which contains 40% salicylic acid. This This application is a continuation-in-part of U.S. Ser. No. patch is then covered with an additional bandage and the 09/145,121 filed Sep. 2, 1998, now U.S. Pat. No. 6,132,756, procedure is repeated every 48 hours until the wart is gone, which itself is a continuation-in-part of U.S. Ser. No. 08/960, which Sometimes takes up to 12 weeks. 303 filed Oct. 29, 1997, now U.S. Pat. No. 5,945,116, which Recently, it has also been observed that individuals with claimed the benefit of U.S. Provisional Application No. depressed immune Systems, Such as Sufferers of Acquired 60/030,307 filed Nov. 5, 1996. Immune Deficiency Syndrome (AIDS), may be prone to HPV infections which may result in tumor growth over their TECHNICAL FIELD entire bodies, resulting in great mental and physical distreSS The present invention generally relates to therapeutic 15 to the afflicted individual. agents for the treatment of Viral-induced tumors, Such as Current modalities for the treatment of viral-induced warts. In one embodiment, the therapeutic agent is in the tumors involve the removal of the tumor by either: (1) form of Sandalwood oil or an isolate or isolates from the Surgical intervention (laser or operative); (2) the application Sandalwood oil described herein. Use of the oil or its of organic acids, Such as glacial acetic acid and/or Salicylic components as a topical agent for the treatment of Viral acid and lactic acid to “burn” the tumor away; (3) the induced tumors, Such as human papillomavirus-induced injection into the tumor of an anti-tumor vaccine prepared tumors, is disclosed. The therapeutic agents in Sandalwood from ground tumors; and to a lesser extent, (4) the use of a oil were found to be C- and B-Santalols. Use of C- and drug, Such as podophyllin, interferons and fluorouracil or B-Santalols in the treatment of Viral-induced tumors, Such as 5-FU; and (5) freezing. human papillomavirus-induced tumors, is disclosed. 25 While being useful for removing the viral-induced tumor, the current treatment modalities still Suffer from one or more BACKGROUND OF THE INVENTION of the following drawbacks: (1) they may result in the Viruses, which induce tumors in mammals, are wide destruction of healthy uninfected tissue; (2) they may result Spread. Indeed, there are over Sixty known types of human in Scarring and disfigurement; (3) they may result in dis papillomaviruses (HPV) which are DNA viruses. These comfort to the mammal being treated thereby; (4) they may Viruses may induce the production of tumors. Some of these result in necrosis of the tumor and the Surrounding tissue HPV's have been associated with benign tumors, such as may result in a Secondary infection which may require common warts, while others have been Strongly implicated treatment with an antibiotic; and (5) they do not always as etiologic agents in dysplasia and carcinomas in the oral result in the destruction of latent viral DNA which may be and genital mucosa of the infected mammal. 35 maintained in Surrounding tissues. Furthermore with these Warts are a very common skin lesion in humans and are conventional treatments, Subjects Suffer from Significant caused by various human papillomaviruses (DNA virus). local, and at times, Systemic Side effects, incomplete reso Each virus is related to a specific clinical presentation of the lution and frequent recurrences of the tumors, and of course, wart. Warts are infectious and may be autoinoculated and 40 the expense incurred. Spread to other individuals by direct contact. It is also known that phototherapy is used for removing Verrucae warts have a rough Surface, are lumpy and laryngeal papillomatosis tumors. While Such phototherapy typically flesh colored. Finger-like projections and Some reduces tumor growth by about 50%, it also results in a times dark Specks are present, which are the result of generalized Skin photoSensitivity for at least Six weeks, as thrombosed capillaries. Usually these warts are found on the 45 well as other minor reactions. Despite the apparent SucceSS face and Scalp. Plantar warts are found on the planter Surface of this technique, the presence of latent viral DNA is of the feet and may be deep and painful. These warts occur nonetheless still maintained in the Surrounding tissues. Singularly or in clusters and may be spread over a wide area. An article by B. M. Lawrence entitled “Progress in Flat warts are typically Small, flat-topped, flesh colored Essential Oils”, Perfumer & Flavorist, Vol.