USOO5837254A United States Patent (19) 11 Patent Number: 5,837,254 Chen (45) Date of Patent: Nov. 17, 1998 54 METHOD OF TREATING CANDIDA AND Kudo-Chemical Abstracts, vol. 114 (1991) abstract 114:254, CRYPTOCOCCUS FUNGAL INFECTIONS BY O21K. ADMINISTERING GENTIAN Song Chemical Abstracts, Vol. 106 (1987) abstract 106:60602d 76 Inventor: Yu Chen, 1520 Taylor Ave., Baltimore, Sadritdinov-Chemical Abstracts, vol. 78 (1973) abstract Md. 21234 79634b. Phytochemistry, vol. 41, No. 1, pp. 111-116 (1996) entitled 21 Appl. No.: 748,949 “Secoiridoids and Antifungal Aromatic Acids From Genti ana Algida'. 22 Filed: Nov. 14, 1996 Copies of pp. 81 and 82 of Materia Medica Chinese Herbal 51 Int. Cl. ............................ A61K 35/78; A61 K9/02; Medicine compiled and translated by Dan Bensky & Andrew A61 K9/20: A61 K9/48 Gamble. 52 U.S. Cl. ....................... 424/195.1; 424/430; 424/433; 424/451; 424/464; 514/967; 514/944 Primary Examiner-David M. Naff 58 Field of Search ................................. 424/195.1, 451, ASSistant Examiner-Janet M. Kerr 424/452, 465, 430, 433, 464; 514/967, Attorney, Agent, Or Firm-Breneman & Georges 944 57 ABSTRACT 56) References Cited A method and preparations for the treatment of vaginal yeast and other yeast infections is provided for the treatment of PUBLICATIONS infections caused by candida albicans and cryptococcuS The Merck Manual, vol. 1, General Medicine, 15th Edition, neoformans. The method and preparations of the invention Merck & Co., Inc., Rahway, NJ, pp. 106, 107,188, 189, and can also be used for other yeast and fungal infections 1372-1374, 1987. including Systemic, mucosal and cutaneous caused by can Copies of pp. 11-16 and 7-8 of Scientific American Medi dida and cryptococcuS. The vaginal antiyeast and antifungal cine (1980), vol. 2. preparations include, in addition to Suppositories and mouth Copies of pp. 144-149 of Topley and Wilson's Principles of washes, troches, lotions, creams, tablets and capsules con Bacteriology, Virology and Immunity, 8th ed. (1990), vol. 1. taining gentian preparations as an active ingredient obtained A copy of p. 135 of Lederberg (ed.) Encyclopedia of from the, plant Radix gentianae Longdancao other active Microbiology, (1992) vol. 1. ingredients which may also be present are American Radix Copies of pp. 337–338, 682–686, 1089, 1136–1139 and Ginseng, Radix Scutellariae Basica Lensis and FructuS 1142-1143 of Zinsser Microbiology, 20th ed. (1992). Gardeniae Jasminoidis. For Systemic fungal infections gen Copies of pp. 207-208 of Goodman & Gilman's The Phar tian preparations from the plant Radix gentianae Longdan macological Basis of Therapeutics, 9th ed. (1996). cao are taken orally in the form of lozenges, tablets, capsules Copies of pp. 1401-1411 of Principles of Pharmacology, or in Solution form for gargling or Swallowing. The novel Paul L. Munson (1995). gentian preparations also can be applied topically for cuta A copy of p. 627 of The Merck Index, 10th Ed. (1981). neous yeast infections and are administered in the form of Copies of pp. 262-269 of Novak's Textbook of Gynecology, Suppositories, lozenges and creams to treat mucosal yeast 10th Ed. (1980). infections. The gentian oral preparations of the invention are Copies of pp. 183–185 of The Healing Herbs, (1991). capable of passing through the blood brain barrier as dem A copy of page 145 of The Honest Herbal, 3rd Ed. (1993). onstrated by the cure of meningitis caused by cryptococcuS A copy of p. 186 of Chinese Medicinal Herbs, (1973). in AIDS patients. The treatment and novel compositions of A copy of p. 104 of Chinese Herbal Medicine, (1986). the invention are effective in controlling fungal and yeast Copies of pp. 255-277 of A Compilation of Chinese Litera infections in two days to two weeks and provide a non-toxic ture in the 1980s in Chinese with a certified translation. treatment of vaginal yeast and other fungal infections caused Copies of pp. 105-106,256, 644-645, 1131 and 1175 of The by cryptococcuS and candida. Chemical Constituents of Oriental Herbs, (1982). CRC Handbook of Medicinal Herbs, (1986). 5 Claims, No Drawings 5,837,254 1 2 METHOD OF TREATING CANDIDA AND the utilization of capsules, lotions and liquids prepared in CRYPTOCOCCUS FUNGAL INFECTIONS BY accordance with the present invention. ADMINISTERING GENTIAN 2. Description of Related Prior Art A number of Species of the fungus candida albicans are BACKGROUND OF THE INVENTION capable of causing candidiasis. Candida albicans can Switch 1. Field of the Invention reversibly and at high frequency among at least Seven The present invention pertains to a method and novel different phenotypes defined by colony morphology. The compositions containing gentian from the gentianaceae fam changes in candida albicans are often associated with ily of plants for the treatment of vaginal yeast infections and changes in virulence which are related to the particular other fungal infections caused by various fungal and yeast balance of the flora composition in the particular organ as forms Such as candida and cryptococcuS. More particularly, well as immunological condition of the patient. Candida and the invention pertains to novel compositions and prepara cryptococcuS are ubiquitous in the environment and gener tions obtained from the root of the plant having the phar ally do not create problems, except where the immune maceutical name of Radix gentianae Longdancao for the System is weak or compromised or the normal floral balance treatment of vaginal yeast infections and other fungus and 15 of the skin, mucous membranes, gastrointestinal tract or yeast infections caused by candida albicans and cryptococ body is changed as a result of a variety of factorS Such as CS. StreSS, changes in pH, nutrition and changes in the immune The plant Radix gentianae Longdancao is also known by System of the patient. Candida albicans is part of the normal the botanical names Gentiana Scabra Bge, Gentiana triflora flora of the Skin, mucous membranes in the mouth, throat, Pall, Gentiana manshurica Kitag, Gentiana algida Pall, intestine and genital tract. Normally candida fungus lives in Gentiana regescens Fransh and Gentiana lutea which will a healthy balance with the other bacteria and yeasts in the be referred to collectively as Radix gentianae Longdancao. body as part of the normal flora. As a result infection is Radix gentianae Longdancao may be used to prepare novel always present and candida albicans is the most common antifungal preparations and novel medicaments in the form Systemic mycosis. of topical creams, liquids, lotions, capsules, lozenges and 25 A number of environmental Stimuli are known to trigger Suppositories. The novel preparations from Radix gentianae or to block the growth of candidiasis. Candida flora is Longdancao may be applied topically or transmucosally to generally kept in balance by killer toxins produced by other treat cutaneous and mucosal Syndromes caused by candida yeast and fungus in the normal flora of the body. Abnormal infection or taken internally in the form of lotions, liquids, physiological changes in the epithelium may be involved tablets and capsules for the treatment of Systemic candida together with a host of other factors, including genetics, and cryptococcuS infections. nutrition, StreSS and other factors that result in infections of The novel method of treatment of candida and crypto various organs of the body, particularly in immuno coccuS infection with novel preparations from Radix genti Suppressed individuals or in individuals that have had the anae Longdancao is effective in treating not only cutaneous 35 normal floral balance changed by the taking of wide Spec and mucosal candidiasis but also Systemic candidiasis trum antibiotics Such as tetracycline. The taking of Such involving the bloodstream and metastatic invasion of the wide spectrum antibiotics has in many cases eliminated meninges, bones, joints, peritonium and myocardium. The beneficial flora which keep candida albicans in check and novel Radix gentianae Longdancao preparations, when prevented candidiasis. taken internally, pass through the digestive System and enter 40 In addition to a great number of environmental factors a the blood Stream for the treatment of Systemic candida host of immunological conditions of the patient result in infections and pass the blood brain barrier to treat meningeal varying degrees of Susceptibility to candidiasis and crypto candidiasis and cryptococcuS meningitis in AIDS patients. coccuS infections. Cancer patients, organ transplant patients The novel preparations of the invention do not require and patients with immunologic disorders, chronic infections, injection or IV application for the treatment of fungal 45 leukemia, acquired immunodeficiency disorder diseases infections of candida albicans, candida tropicalis and other (AIDS), Hodgkin's disease, neutropenia and other hemato candida Species referred to collectively as candida and logic diseases and endocrinopathies including diabetes leave cryptococcuS neoformans and other cryptococcuS Species the patient particularly Susceptible to fungal infections by collectively referred to as cryptococcus. The novel Radix candida albicans and cryptococcuS. Such immunologically gentianae Longdancao preparations are advantageous over 50 compromised patients are at a risk of Systemic candidiasis, the prior art Since they are nontoxic to the patient and may cryptococcal meningitis and other infections resulting from be utilized in patients having weak or compromised immune