Postmenopausal (PM) women suffer from vaginal atrophy, with a loss of natural moisture and elasticity, as well as vaginal dysbiosis and increased vaginal pH, collectively known as the Genitourinary Syndrome of Menopause (GSM). Symptoms of GSM include vaginal dryness, burning, irritation and malodor, as well as sexual dysfunction. There are 66 million such women in the US and over 50% of these women have signs of GSM at menopause. Symptoms progress over time and require continual treatment. Current vaginal lubricants and moisturizers (VL&M) are first line therapies for GSM but they can cause vaginal mucosal damage and inhibit healthy lactobacillus growth, based on physiochemical properties and formula excipients. There is an unmet need for a VL&M that relieves symptoms of GSM while minimizing disruption to the vaginal ecosystem. The overall goal of this proposal is to develop a biome-friendly, moisturizing, lubricating and pH-balancing vaginal gel for improved GSM symptom relief in PM women. Fairhaven Health specializes in women's health, including an isotonic vaginal product line. A VL&M gel prototype has been developed (SAGE) to improve GSM symptom relief by reducing immune, mucosal, and biome toxicity, compared to existing products. SAGE's proprietary formula has been preliminarily found to cause less mucosal irritation and less disruption to healthy lactobacillus versus existing VL&M. A novel unit-dose applicator system has been designed to deliver the sterile, preservative-free SAGE. The following Phase 1 Aims will move SAGE towards commercialization. Aim 1) Finalize Formula & Compare Functional Properties (1A) Studies will define the final SAGE formula and mixing protocols to ensure physiochemical properties are retained during sterilization and stability testing. (1B) Studies will confirm key functional properties (for GSM symptom relief) of mucoadhesion, lubricity and buffering capacity of SAGE versus competitive products. Aim 2) Vaginal Biome Compatibility Testing Evaluation of SAGE in this Aim will be performed by the Laboratory of Genital Tract Biology at Brigham and Women's Hospital. (2A) Studies will evaluate the impact of SAGE and competitive products on valuable vaginal Lactobacillus species of the healthy human vagina. (2B) A human in-vitro model study will monitor markers of cell damage and immunotoxicity following contact of bacteria-colonized vaginal epithelia with SAGE versus competitive VL&M. A final SAGE formula will be acceptable for a Phase 2 SBIR if it is equivalent or superior to other VL&M in functional properties; and superior over competitors in epithelium-associated lactobacillus colony forming units; epithelial integrity; and/or markers of epithelial disruption and inflammatory activity. The team behind SAGE has combined expertise in clinical and experimental vaginal biology, vaginal product development, regulatory clearance, sterile manufacturing of gels and commercial sales in women's vaginal products.
Public Health Relevance Statement: An Isotonic Biome-Friendly Vaginal Moisturizer to Relieve Genitourinary Menopausal Symptoms NARRATIVE Postmenopausal women suffer from vaginal atrophy, with a loss of natural moisture and elasticity, as well as a rise in vaginal pH, causing the Genitourinary Syndrome of Menopause (GSM) with symptoms of vaginal dryness, burning, irritation and malodor, as well as sexual dysfunction. Current vaginal lubricants and moisturizers (VL&M) are first line therapies for GSM but they can cause vaginal mucosal damage and harm healthy lactobacillus (based on their formulas and chemistry). The goal of this proposal is to develop a biome-friendly, moisturizing, lubricating and pH-balancing vaginal gel for improved GSM symptom relief, using a state-of-the-art human in- vitro model to evaluate markers of cell damage and immunotoxicity, as well as lactobacillus growth for the new gel versus existing VL&M.
Project Terms: Adverse effects; aged; Area; Atrophic; Bacteria; base; Biology; biomaterial compatibility; Buffers; cell injury; Chemistry; Chronic; Clinical; Clinical Research; Colony-forming units; commercialization; cytotoxicity; Data; design; Development; Diagnosis; Discipline of obstetrics; Dose; Dryness; dysbiosis; Ecosystem; Elasticity; Ensure; Epithelial; Epithelium; Equilibrium; Evaluation; evaluation/testing; Excipients; experience; Future; Gel; Genitourinary system; Goals; Growth; Gynecology; Health; High Prevalence; Hospitals; Human; Hydrogels; Immune; immunotoxicity; improved; in vitro Model; Indigenous; Inflammation; Inflammatory; inflammatory marker; irritation; Isotonic Exercise; Laboratories; Lactic acid; Lactobacillus; Life Expectancy; Lubricants; Menopausal Symptom; Menopausal Syndrome; Menopause; Microbe; Modernization; Monitor; Mucous Membrane; new growth; novel; Odors; Outcome; Phase; phase 1 study; phase 2 study; Phase II Clinical Trials; Polymers; Postmenopause; product development; Production; professor; Property; Protocols documentation; prototype; Recommendation; reduce symptoms; reproductive; Reproductive Biology; reproductive tract; Research; Safety; Sales; Sexual Dysfunction; Small Business Innovation Research Grant; stability testing; Sterility; Sterilization; Study models; Symptoms; Syndrome; System; Time; Toxic effect; Vagina; Vaginal Gel; vaginal lactobacilli; vaginal microbiome; Woman; Women's Health; Xylose
