US 200901 24584A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2009/0124584A1 Lyle (43) Pub. Date: May 14, 2009 (54) REGENERATION OF VAGINAL TISSUE WITH Related U.S. Application Data NON-SYSTEMIC VAGINAL ADMINISTRATION OF ESTROGEN (60) Provisional application No. 60/751,104, filed on Dec. 16, 2005. (75) Inventor: John W. Lyle, Vero Beach, FL (US) Correspondence Address: Publication Classification DILWORTH & BARRESE, LLP (51) Int. Cl. 333 EARLE OVINGTON BLVD., SUITE 702 A6II 3/565 (2006.01) UNIONDALE, NY 11553 (US) A6II 3/56 (2006.01) CI2O 1/02 (2006.01) (73) Assignee: LYLE CORPORATE DEVELOPMENT, INC., (52) U.S. Cl. ............................ 514/170; 514/182; 435/29 Farmingdale, NJ (US) (21) Appl. No.: 11/660,711 (57) ABSTRACT (22) PCT Fled: Jan. 20, 2006 Methods and formulations for the regeneration of vaginal tissue and vaginal cell health resulting from vaginal cell (86) PCT NO.: PCT/US2O06/OO2145 hypoxia in a human female. A pharmaceutical composition for topical non-systemic administration is formulated con S371 (c)(1), taining a hormonal agent administered to the vagina, Vulvar (2), (4) Date: Jan. 15, 2009 area of the individual undergoing treatment. US 2009/01 24584 A1 May 14, 2009 REGENERATION OF VAGINAL TISSUE WITH vides an acid level adequate to protect against Vaginal infec NON-SYSTEMIC VAGINAL tions in women past menopause. ADMINISTRATION OF ESTROGEN 0008 ERT does pose risks for some women. When hor mone replacement therapy (i.e. estrogen and/or progestin to replace the hormones lost at menopause) is administered 0001. This application claims priority to U.S. provisional systemically to relieve hot flashes, night Sweats, and vaginal application No. 60/751,104, filed on Dec. 16, 2005, the con dryness and to improve women's health, increased risk in tents of which are incorporated by reference herein. breast cancer, heart attacks, strokes, and blood clots have been reported. The associated systemic administration of BACKGROUND OF THE INVENTION progesterone and/or testosterone may produce side effects Such as, masculinisation with acne and excess body hair, 0002 This invention relates to compositions that are use Scalp hair loss, fluid retention, deepening of the Voice, ful for the revitalization of devitalized vaginal tissue. More enlargement of the clitoris and adverse effects on blood cho particularly, this invention relates to the non-systemic admin lesterol. istration of an estrogen and/orandrogen to the vaginal, Vulvar 0009 Women undergoing chemotherapy or radiotherapy and/orurethral area of a female patient, for the regeneration of for malignant diseases such as leukemia often experience vaginal tissue and vaginal cell health. vaginal dryness as a result of treatment. Many disease states, 0003. The etiology of vaginal pathologies may include Such as systemic sclerosis and other systemic autoimmune vascular/endothelial disease Such as hypertension and diabe disorders, Ehlers-Danlos syndrome, diabetes mellitus, and tes, neurological disorders, hormonal disorders, such as Sjogren's syndrome have decreased vaginal hydration and decreased levels of estrogen and/or testosterone, medical lubrication problems as significant disease-associated Symp therapies, such as, chemotherapy and radiation. For example, tOmS. the commonly reported sexual problem in women with dia 0010 Vaginal tissue cells may become hypoxic because of betes mellitus is lack of vaginal lubrication. It has been pos limited diffusion of oxygen from blood vessels, or they can be tulated that reduced vaginal lubrication in diabetic women acutely or transiently hypoxic because of intermittent blood may result from the structural changes of the vagina and flow. Vaginal tissue cells exposed to radiation and/or chemo vaginal tissue cells. therapy will experience detrimental effects and like all cells 0004. The vasculature and microvasculature of the vagina deprived of oxygen and nutrients they ultimately die. Because are innervated by nerves containing neuropeptides and other of the interdependence of all cells and their vasculature, pro neurotransmitters, and upon stimulation vaginal engorge longed ischemia secondary to blood vessel function will ment enables transudation to occur and this process is respon result in cell necrosis. sible for increased vaginal lubrication. Transudation allows a 0011. The present invention is advantageous as it provides flow of plasma through the epithelium and onto the vaginal a means for regenerating vaginal tissue-namely increased surface, the driving force for which is increased blood flow in genital blood flow leading to vaginal, clitoral and labial the vaginal capillary bed during the aroused state. In order for engorgement through the improvement of the overall health transudation to take place a sufficient number of healthy of female vaginal tissue. Thus, the present invention provides vaginal cells are necessary for a female sexual arousal a means to restore, or potentiate, the normal vaginal tissue response relating to genital (e.g. vaginal and clitoral) blood through improved vaginal cell health as determined by vagi flow. Inadequate genital response to sexual stimulation may nal tissue blood flow, regeneration of vaginal cells, and be due to lack of vagina and/or the clitoral engorgement that increasing the number of healthy vaginal cells present. results from illnesses, which cause damage to the vascular structures that Supply the vaginal tissues. Such illnesses are, SUMMARY OF THE INVENTION for example, diabetes, hypertension and atherosclerosis, or 0012. The present invention provides a method of treating the result of medical treatments, such as, radiation or chemo a human female exhibiting vaginal cell hypoxia and who is therapy, all of which affect the health and vitality of vaginal not currently receiving chronic hormonal therapy, the method tissue cells. comprising topically administering to the vaginal tissue of the 0005. In women, diabetes can lead to hardening of the female patient at least once in a seven day period a non blood vessels of the vaginal wall. Decreased blood flow due to systemic vaginal cell hypoxia treatment amount of a compo diabetes may cause the vagina to be too dry, both normally sition comprising at least one hormone selected from the and during arousal. It also may cause a woman to be at much group consisting of estrogen and androgen and/or pharma greater risk of getting recurring yeast infections. ceutically acceptable salt and ester thereof. 0006 Atrophic vaginitis is an inflammation of the vagina 0013. In another embodiment of the present invention, a due to thinning and shrinking tissues and decreased lubrica method of treating vaginal tissue in a human female under tion of the vaginal walls. It is caused by a lack of estrogen and going or having undergone, a therapy or treatment that a decrease in blood Supply and nutrients to the vaginal tissue, impairs the health of vaginal tissue cells and who is not and those two changes together can cause the vaginal wall to currently receiving chronic hormonal therapy, the method thin out. Low levels of estrogen in women will also cause the comprising topically administering to the vaginal tissue of the vagina to become less acidic which may cause changes to the female patient, at least once in a seven day period a non vaginal flora, so the vagina becomes more prone to trauma systemic vaginal cell hypoxia treatment amount of a compo and infection. sition comprising at least one hormone selected from the 0007 Current medical practices for the treatment of group consisting of estrogen and androgen and/or pharma menopausal, diabetic woman and atrophic vaginitis includes ceutically acceptable salt and ester thereof. estrogen replacement therapy (ERT), which is important in 0014. In yet another embodiment of the present invention, keeping blood flowing in vaginal tissues. Estrogen also pro a method of treating vaginal tissue in a human female exhib US 2009/01 24584 A1 May 14, 2009 iting clinical signs of a disease or condition that impairs the 0022 “Devitalized tissue' and “devitalized cells' as use health of vaginal tissue cells and who is not currently receiv herein describes vaginal tissue or cells that have lost their ing chronic hormonal therapy, the method comprising topi vitality or have been diminished or destroyed. Devitalized cally administering to the vaginal tissue of the female patient, tissue may also be called necrotic or dead tissue which exhib at least once a in a seven day period, a non-systemic vaginal its a characteristic gray appearance, due to a lack of oxygen cell hypoxia treatment amount of a composition comprising and nutrients. The cause of devitalized or necrotic cells or at least one hormone selected from the group consisting of tissues is through injury, illness, disease, especially in a local estrogen and androgen and/or pharmaceutically acceptable ized area of the body, chemotherapy and radiation therapy. salt and ester thereof. 0023 The term “disease' as used herein is an actual physi 0015. In describing and claiming the present invention, the cal, pathophysiological process that can cause an abnormal following terms and expressions shall be understood to have condition of the body or mind. A pathological condition of a the designated meanings. part, organ, or system of an organism resulting from various 0016 “Administration,” and “administering refer to the causes which include, but are not limited to infection, genetic manner in which a drug is presented to a subject.