WO2017069793A1 - Compositions de gel vaginal et leurs procédés d'utilisation - Google Patents

Compositions de gel vaginal et leurs procédés d'utilisation Download PDF

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Publication number
WO2017069793A1
WO2017069793A1 PCT/US2016/016163 US2016016163W WO2017069793A1 WO 2017069793 A1 WO2017069793 A1 WO 2017069793A1 US 2016016163 W US2016016163 W US 2016016163W WO 2017069793 A1 WO2017069793 A1 WO 2017069793A1
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Prior art keywords
water soluble
viscous
pharmaceutical composition
soluble gel
vaginal
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PCT/US2016/016163
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English (en)
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Maureen MCGRATH
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Enertopia Corporation
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives

Definitions

  • the invention relates to the fields of pharmacology and medicine, and provides vaginal gel compositions and methods of use thereof.
  • Vaginal dryness is a frequent condition at menopausal age and is brought on by hypoestrogenism. Vaginal dryness is less common but equally unpleasant when it affects patients of childbearing age, where causes can include the use of low-dose combined estrogen- progesterone contraceptives, tampons, and stress.
  • the vaginal mucosa is normally moistened by fluid, visible on inspection as a clear secretion consisting of plasma transudate, cervical mucus, and vestibular gland secretions. Bartolini's and Skene's glands normally produce mucus as a lubricating fluid that is useful for normal performance of sexual intercourse, but with vaginal dryness this production does not take place.
  • the symptoms of vaginal dryness include pain, stinging, and itching, particularly during sexual intercourse.
  • Vaginal lubricants generally comprise mixtures of various moisturizers and
  • vaginal lubricating compositions to date have been that they are less than optimum for providing effective relief of vaginal dryness.
  • Another problem exists with compositions that are not formulated to maintain normal physiological conditions of the vagina Under normal physiological conditions, the vagina is a dynamic balance of vaginal microflora modulated by closely interdependent factors such as hormone levels, pH, and immune response. The cells of the vaginal wall play an important role in maintaining this balance, particularly the surface and intermediate layers of the epithelium, whose proliferation and maturity' is hormone- related.
  • vaginal lubricating compositions particularly vaginal lubricant compositions presented in a gel formulation similar to physiological vaginal secretions that help restore and maintain the balance of the vaginal ecosystem.
  • a viscous vaginal pharmaceutical composition comprising a water soluble gel
  • the water soluble gel comprises Niacin and/or L-Arginine
  • the water soluble gel has a pH of between about 3.8 and about 4.5.
  • the water soluble gel has a pH of about 4.0.
  • the water soluble gel comprises less than about 0.15% by weight of Niacin, particularly about 0.14% by weight of Niacin.
  • the water soluble gel comprises about 1% to about 3% by weight of L-Arginine, particularly about 2% by weight of L-Arginine.
  • the water soluble gel further comprises about 5% to about 15% by weight of Glycerin, particularly about 10% by weight of Glycerin. In another aspect, the water soluble gel further comprises about 1% to about 3% by weight of Lactic acid, particularly about 2% by weight of Lactic acid. In another aspect, the water soluble gel further comprises about 1% to about 2% by weight of Hydroxyethylcellulose, particularly about 1.5% by weight of Hydroxyethylcellulose. In another aspect, the water soluble gel further comprises about 0.01% to about 0.5% by weight of Tocopheryl Acetate, particularly about 0.1% of Tocopheryl Acetate.
  • the water soluble gel further comprises about 0.1% to about 1% by weight of Potassium Sorbate, particularly about 0.5% of Potassium Sorbate. In another aspect, the water soluble gel further comprises about 0.1% to about 1% Cremophor RH-40 (PEG-40
  • the water soluble gel further comprises about 70% to about 90% by weight of purified water, particularly about 80% by weight of purified water.
  • the water soluble gel further comprises one or more water soluble vitamins selected from the group consisting of vitamin Bl (thiamine) and vitamin C.
  • the water soluble gel further comprises one or more fat soluble vitamins selected from the group consisting of vitamins A, D, E, K, and F.
  • the water soluble gel further comprises one or more plant-derived minerals selected from the group consisting of iron, calcium, copper, cobalt, magnesium, potassium, manganese, zinc, chromium, molybdenum, vanadium, selenium, boron, iodine, and nickel, or salts or complexes thereof
  • the water soluble gel further comprises one or more plant extracts derived from a plant selected from the group consisting of wild yam (Dioscorea villosa), Ginseng (Panax quinquefolius), red raspberry (Rubus idaeus). Aloe vera, grape seed (e.g., grape seed oil), hemp (e.g., hemp oil), and Stevia rebaudiana (e.g., Stevia rebaudiana leaf powder).
  • wild yam Dioscorea villosa
  • Ginseng Panax quinquefolius
  • red raspberry Red raspberry
  • Aloe vera grape seed (e.g., grape seed oil), hemp (e.g., hemp oil), and Stevia rebaudiana (e.g., Stevia rebaudiana leaf powder).
  • the water soluble gel provides enhanced bioavailability of the one or more water soluble vitamins, the one or more fat soluble vitamins, the one or more plant-derived minerals, and/or the one or more plant extracts as compared to the bioavailability of these agents in the subject when administered orally.
  • the bioavailability of the one or more water soluble vitamins, the one or more fat soluble vitamins, the one or more plant-derived minerals, and/or the one or more plant extracts in a subject is at least about 1.5 times, 2 times, S times, or 10 times greater than the bioavailability of these agents in the subject when administered orally.
  • the bioavailability' of the one or more water soluble vitamins, the one or more fat soluble vitamins, the one or more plant-derived minerals, and/or the one or more plant extracts in a subject is greater than 20%.
  • any of the viscous vaginal pharmaceutical compositions comprising a water soluble gel described herein are provided, the method comprising the steps of: a) dissolving Niacin and/or L-Arginine in purified water to produce a water phase mixture; b) combining Glycerin and Hydroxyethylcellulose to produce a
  • Glycerin Hydroxyethylcellulose mixture c) adding the Glycerin/Hydroxyethylcellulose mixture to the water phase mixture; and d) adding Tocopheryl Acetate, Potassium Sorbate, and
  • Cremophor RH-40 to the water phase mixture; thereby producing the viscous vaginal pharmaceutical composition comprising a water soluble gel.
  • the methods further comprise adding a water soluble vitamin, fat soluble vitamin, a plant-derived mineral, and/or a plant extract to the water phase mixture.
  • a method for treating vaginal dryness in a subject in need thereof comprising vaginal administration to the subject of a therapeutically effective amount of any of the viscous vaginal pharmaceutical compositions comprising a water soluble gel described herein.
  • Vaginal dryness is a common condition that may affect women of all ages. The most common cause of vaginal dryness is decreased estrogen levels, which leads to thinning and drying of the vaginal wall. However, other factors such as stress, depression, and anxiety may also contribute to vaginal dryness. Vaginal dryness may make some daily activities uncomfortable, and it can also create quality of life issues for women and their partners.
  • vaginal compositions that provide or restore normal lubrication and hydration functions. These compositions are in the forms of creams, gels, films, liquids, solids, and foams. However, most existing compositions suffer from problems such as inconvenience, messiness, irritation, and poor lasting quality. Another problem exists with compositions that are not formulated to maintain normal physiological conditions of the vagina
  • the presently disclosed subject matter is directed to viscous vaginal pharmaceutical compositions comprising a water soluble gel, methods of making such compositions, and methods of using such compositions to treat vaginal dryness in a subject in need thereof.
  • the presently disclosed subject matter is directed to viscous vaginal pharmaceutical compositions comprising a water soluble gel, wherein the water soluble gel comprises L-Arginine, Niacin, Glycerin, Lactic acid, Hydroxyethylcellulose, Tocopheryl acetate, Potassium Sorbate, and Cremophor RH-40.
  • L-Arginine is an amino acid; one of the "building blocks" of proteins.
  • L- Arginine has a chemical name of (2S)-2-Amino-5-guanidinopentanoic Acid and molecular formula C 6 H 14 N 4 O 2 .
  • L-Arginine is classified as a semi essential or conditionally essential amino acid because the ability of the body to synthesize sufficient quantities to meet its needs varies according to developmental age or the physical condition of the person. It is one of the more metabolically versatile amino acids, giving rise to nitric oxide (NO), urea, ornithine, citrulline, creatine, agmatine, glutamate, proline and polyamines. It can also be made synthetically in a laboratory and it is these man made versions that are usually found in medications.
  • NO nitric oxide
  • L-Arginine Because of L-Arginine's ability to reduce anxiety and promote sexual responsiveness, it is sometimes used as a libido-enhancing ingredient in personal lubricant products. L-Arginine is generally considered a safe lubricant ingredient, but in large amounts it can worsen the symptoms of asthma and other inflammatory lung conditions. L-Arginine is also known to be a vasodilator, which increases blood flow to the area to which the product is applied. L-Arginine dilates blood vessels by causing the body to produce nitric oxide. Nitric oxide is a molecule that signals smooth muscle surrounding blood vessels (including those in the penis) to relax, which dilates blood vessels and increases blood flow - a necessity for maintaining erections. L- Arginine should be avoided by individuals who have herpes as the vasodilator has been known to cause outbreaks.
  • Niacin is a water-soluble vitamin of the B complex (B3) occurring in various animal and plant tissues. Niacin is required by the body for the formation of coenzymes NAD and NADP. It has PELLAGRA-curative, vasodilating, and antilipemic properties. Niacin, also known as Nicotinic acid, has a molecular formula of C 6 H 5 NO 2 .
  • Niacin causes the blood vessels to dilate or open up near the skin, which results in a hot, tingling sensation accompanied by a red flushing of the skin.
  • Lactic Acid is a normal intermediate in the fermentation (oxidation, metabolism) of sugar. Lactic acid has a molecular formula of C 3 H 6 O 3 . Lactic acid is an acidic compound produced in muscular areas of the human body. The vaginal canal naturally produces some lactic acid.
  • Lactic acid affects the acidity (pH) of the vagina, which can in turn affect the growth of vaginal flora
  • pH acidity
  • lactic acid can promote growth of lactobacilli, and that a healthy amount of lactic acid can reduce the risk of yeast infections.
  • Production of lactic acid by Lactobacillus acid ifies the vaginal environment and forms a natural protective layer that acts as a defense against bacteria that can cause infection.
  • the vaginal pH fluctuates between 3.8 to 4.5 in a healthy vagina.
  • Glycerin is an organic compound known more formally as glycerol. Its common sources are animal fat and vegetable oil. Glycerin has the molecular formula
  • glycerin introduced in 1811 by French chemist Michel-Eugene Chevrul, is ordinarily applied to commercial materials containing more than 95% glycerol. Though Chevrul gave glycerin its name, the substance was first isolated in 1783 by German Swedish chemist Carl Willem Scheele, who described it as the "sweet principle of fat.”
  • Vegetable glycerin or glycerol
  • plant oils typically palm oil, soy, or coconut. Palm and coconut oils are natural triglyceride mixtures; each triglyceride is composed of three fatty acids esterified with glycerin. Vegetable glycerin has a number of valuable applications that include cosmetic products, foods and as a
  • Vegetable glycerin is produced using an extraction process called hydrolysis. During hydrolysis, oils are placed under the combined force of pressure, temperature, and water. The ester bond breaks and causes the glycerin to split from fatty acids and be absorbed by water; at which point the resultant is further isolated by distillation to increase purity. Purified vegetable glycerin has a texture similar to an oil or syrup due to its organic molecular makeup, specifically, three hydroxyl groups.
  • Vegetable glycerin used in food applications is USP grade or over 99% pure and has a sweet taste. It also metabolizes differently than sugar and is used in low carbohydrate foods for sweetness and moisture.
  • glycerin a substance that attracts moisture to the skin.
  • a humectant a substance that attracts moisture to the skin.
  • a humectant can increase the solubility of the active ingredient, making it more easily absorbed by the skin.
  • glycerin within the presently disclosed viscous vaginal pharmaceutical compositions comprising a water soluble gel, vegetable glycerin may be used that is USP grade, non-GMO, and Kosher certified. Within the presently disclosed viscous vaginal pharmaceutical compositions and methods, glycerin acts as a humectant, which helps retain moisture.
  • Potassium Sorbate Potassium Sorbate is a very common food preservative used in foods like cheese, wine, meats and dried fruits. Potassium Sorbate works by helping inhibit the growth of yeast and mold, thus extending shelf life. Potassium Sorbate is said to have a toxicity level similar to table salt and is generally considered safe for consumption.
  • Candida Albicians is yeast normally found in small amounts in the vagina When the natural pH of the vagina is upset, this yeast can multiply and irritate the vaginal walls. This then causes vaginal yeast infection, marked by a burning sensation when urinating, pain during sexual intercourse, itching around the vagina, and a white and odorless discharge that looks similar to cottage cheese.
  • Potassium Sorbate acts as the preservative to extend product shelf life.
  • Tocophervl acetate is a form of vitamin E; a natural skin- conditioning agent and antioxidant. It is the ester of acetic acid and tocopherol and is often used as an alternative to pure tocopherol (or undiluted vitamin E) because it is considered more stable and less acidic.
  • Tocopheryl acetate is a fat-soluble vitamin that can be isolated from vegetable oils. It is also found in dairy products, meat, eggs, cereals, nuts and leafy green and yellow vegetables. Its substantiated benefits include enhancing the efficacy of active sunscreen ingredients, reducing the formation of free radicals from exposure to UV rays, promoting the healing process, strengthening the skin's barrier function, protecting the skin barrier's lipid balance and reducing trans epidermal water loss. Attributed with antioxidant, an anti-aging, moisturizing, antiinflammatory, and enhanced SPF property, tocopherol acetate is valued both as a dietary supplement and skincare active. It is used in a variety of cosmetic and personal care products.
  • Vitamin E is one of the most well researched antioxidants. It is available in eight different forms, which can be extracted from nature or synthetically produced. Though all members of the vitamin E family are fat-soluble, tocopherol is the most bioavailable, and thus the most readily absorbed by the body.
  • vitamin E The strong moisturizing properties of vitamin E might help relieve symptoms of vaginal dryness.
  • a fat-soluble antioxidant, vitamin E helps to protect the body from environmental free radicals and maintain the immune system
  • Vitamin E is a common component of commercial moisturizers because of its effectiveness in helping to repair damaged skin cells and in promoting skin cell moisture.
  • Hvdroxvetfavlcellulose Hydroxyethylcellulose (HEC), a non-ionic water-soluble polymer, is a white, free-flowing granular powder. It is insoluble in organic solvents, yet it is easily dispersed in cold and hot water to give solutions of varying viscosities. Chemically, it is cellulose that has been etherified with Hydroxyethyl groups to give the desired properties. It is used as a thickener, protective colloid, binder, stabilizer and suspending agent, particularly in application where non-ionic material is desired.
  • Hydroxyethylcellulose form films exhibit pseudo plastic solution behaviour, tolerate salts and retain water.
  • Hydroxyethylcellulose is used as a thickener to achieve a gel form product that is easy to apply.
  • Cremophor RH-40 is a non-ionic solubilizer and emulsifying agent obtained by reacting hydrogenated castor oil with ethylene oxide. Cremophor RH-40 is used to solubilize vitamins and hydrophobic active substances in aqueous solutions.
  • a viscous vaginal pharmaceutical composition comprising a water soluble gel
  • the water soluble gel comprises Niacin and/or L-Arginine
  • the water soluble gel has a pH of between about 3.8 and about 4.5.
  • the water soluble gel has a pH of about 4.0.
  • the water soluble gel comprises less than about 0.15% by weight of Niacin, particularly about 0.14% by weight of Niacin.
  • the water soluble gel comprises about 1% to about 3% by weight of L-Arginine, particularly about 2% by weight of L-Arginine.
  • the water soluble gel further comprises about 5% to about 15% by weight of Glycerin, particularly about 10% by weight of Glycerin. In another aspect, the water soluble gel further comprises about 1% to about 3% by weight of Lactic acid, particularly about 2% by weight of Lactic acid. In another aspect, the water soluble gel further comprises about 1% to about 2% by weight of Hydroxyethylcellulose, particularly about 1.5% by weight of Hydroxyethylcellulose. In another aspect, the water soluble gel further comprises about 0.01% to about 0.5% by weight of Tocopheryl Acetate, particularly about 0.1% of Tocopheryl Acetate.
  • the water soluble gel further comprises about 0.1% to about 1% by weight of Potassium Sorbate, particularly about 0.5% of Potassium Sorbate. In another aspect, the water soluble gel further comprises about 0.1% to about 1% Cremophor RH-40 (PEG-40
  • the water soluble gel further comprises about 70% to about 90% by weight of purified water, particularly about 80% by weight of purified water.
  • the water soluble gel further comprises one or more water soluble vitamins selected from the group consisting of vitamin Bl (thiamine) and vitamin C.
  • the water soluble gel may comprise less man about 0.015% by weight of vitamin Bl, particularly about 0.011% by weight of vitamin B 1.
  • the water soluble gel may comprise less than about 0.08% by weight of vitamin C, particularly about 0.075% by weight of vitamin C.
  • the vitamin C may be provided in the form of Ascorbic Acid.
  • the water soluble gel further comprises one or more fat soluble vitamins selected from the group consisting of vitamins A, D, E, K, and F.
  • the water soluble gel may comprise less than about 0.015% by weight of vitamin A, particularly about 0.012% by weight of vitamin A.
  • the water soluble gel may comprise less than about 0.005% by weight of vitamin D, particularly about 0.003% or about 0.0025% by weight of vitamin D.
  • the water soluble gel may comprise less than about 0.15% by weight of vitamin E, particularly about 0.1% by weight of vitamin E.
  • the water soluble gel further comprises one or more plant-derived minerals selected from the group consisting of iron, calcium, copper, cobalt, magnesium, potassium, manganese, zinc, chromium, molybdenum, vanadium, selenium, boron, iodine, and nickel, or salts or complexes thereof.
  • iron may be in the form of ferric pyrophosphate, ferric chloride, ferrous sulfate, iron succinate, ferrous sodium succinate, etc.
  • calcium may be in the form of calcium chloride, calcium lactate, calcium gluconate, etc.
  • the water soluble gel further comprises one or more plant extracts derived from a plant selected from the group consisting of wild yam (Dioscorea villosa),
  • Ginseng Panax quinquefolius
  • red raspberry Rubus idaeus
  • Aloe vera grape seed (e.g., grape seed oil), hemp (e.g., hemp oil), and Stevia rebaudiana (e.g., Stevia rebaudiana leaf powder).
  • the water soluble gel further comprises wild yam extract
  • the water soluble gel may comprise less than about 2.0% by weight of wild yam extract, particularly about 1.0% by weight of wild yam extract.
  • the water soluble gel further comprises Ginseng extract
  • the water soluble gel may comprise less than about 2.0% by weight of Ginseng extract, particularly about 1.0% by weight of Ginseng extract.
  • the water soluble gel may comprise less than about 2.0% by weight of Red raspberry extract, particularly about 1.0% by weight of Red raspberry extract.
  • the water soluble gel further comprises Grape seed extract
  • the water soluble gel may comprise less than about 2.0% by weight of Grape seed extract, particularly about 1.0% by weight of Grape seed extract.
  • the water soluble gel further comprises Aloe vera extract
  • the water soluble gel may comprise less than about 2.0% by weight of Aloe vera extract, particularly about 1.0% by weight of Aloe vera extract.
  • the water soluble gel further comprises hemp oil
  • the water soluble gel may comprise less than about 0.1% by weight of hemp oil, particularly about 0.05% by weight of hemp oil.
  • the water soluble gel may comprise less than about 0.030% by weight of Stevia rebaudiana leaf powder, particularly about 0.020% by weight of Stevia rebaudiana leaf powder.
  • plant-derived As used herein, the terms "plant-derived”, “plant extract”, and '3 ⁇ 4erbal extract” are used interchangeably to refer to substances that are produced in plant tissues and that can be obtained from plants or herbs by isolating at least a part of the plant away from its natural state, such as by removing water ⁇ e.g. , extracting the juice and/or pulp), or by extracting one or more components chemically, mechanically, thermally, by size, or otherwise separating the components using polar, non-polar, mineral, petroleum or other solvents.
  • the isolation of the active agent from the plant will depend on the nature of the active agent, such as water solubility and the like, and sensitivity to decomposition (e.g., denaturation by heat, pH, oxygen, light, etc.).
  • Plant extracts also include dehydrated plant materials in which the bulk liquid is removed to concentrate the bioavailable solids in the plant or herb.
  • the water soluble gel provides enhanced bioavailability of the one or more water soluble vitamins, the one or more fat soluble vitamins, the one or more plant-derived minerals, and/or the one or more plant extracts as compared to the bioavailability of these agents in the subject when administered orally.
  • Bioavailability refers to the extent and rate at which the active moiety (drug or metabolite) enters systemic circulation, thereby accessing the site of action. Bioavailability for a given formulation provides an estimate of the relative fraction of the orally administered dose that is absorbed into the systemic circulation. Low bioavailability is most common with oral dosage forms of poorly water-soluble, slowly absorbed drugs.
  • Insufficient time for absorption in the gastrointestinal tract is a common cause of low bioavailability. If the drug does not dissolve readily or cannot penetrate the epithelial membrane (e.g., if it is highly ionized and polar), time at the absorption site may be insufficient. Orally administered drugs must pass through the intestinal wall and then the portal circulation to the liver, both of which are common sites of first-pass metabolism (metabolism that occurs before a drug reaches systemic circulation). Thus, many drugs may be metabolized before adequate plasma concentrations are reached.
  • Bioavailability is usually assessed by determining the area under the plasma
  • AUC concentration-time curve
  • the bioavailability of the one or more water soluble vitamins, the one or more fat soluble vitamins, the one or more plant-derived minerals, and/or the one or more plant extracts in a subject is at least about 1.5 times, 2 times, 2.5 times, 3 times, 3.5 times, 4 times, 4.5 times, 5 times, 5.5 times, 6 times, 6.5 times, 7 times, 7.5 times, 8 times, 8.5 times, 9 times, 9.5 times, or 10 times greater than the bioavailability of these agents in the subject when administered orally.
  • the bioavailability of the one or more water soluble vitamins, the one or more fat soluble vitamins, the one or more plant-derived minerals, and/or the one or more plant extracts in a subject is greater than 20% or at least about 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, or greater.
  • any of the viscous vaginal pharmaceutical compositions comprising a water soluble gel described herein are provided, the method comprising the steps of: a) dissolving Niacin and/or L-Arginine in purified water to produce a water phase mixture; b) combining Glycerin and Hydroxyethylcellulose to produce a
  • the methods further comprise adding a water soluble vitamin, a fat soluble vitamin, a plant-derived mineral, and/or a plant extract to the water phase mixture.
  • a method for treating vaginal dryness in a subj ect in need thereof comprising vaginal administration to the subject of a therapeutically effective amount of any of the viscous vaginal pharmaceutical compositions comprising a water soluble gel as described herein.
  • ''administering refers to contacting at least a cell with a viscous vaginal pharmaceutical composition comprising a water soluble gel as described herein.
  • a "subject” can include a human subject for medical purposes, such as for the treatment of an existing disease, disorder, condition or the prophylactic treatment for preventing the onset of a disease, disorder, or condition.
  • a “subject” can include a patient afflicted with or suspected of being afflicted with a disease, disorder, or condition.
  • the terms “subject” and “patient” are used interchangeably herein.
  • the subject is suffering from or susceptible to a disease, disorder, or condition associated with vaginal dryness.
  • the terms “treat,” treating,” “treatment,” and the like are meant to decrease, suppress, attenuate, diminish, arrest, the underlying cause of a disease, disorder, or condition, or to stabilize the development or progression of a disease, disorder, condition, and/or symptoms associated therewith.
  • the terms “treat,” “treating,” “treatment,” and the like, as used herein can refer to curative therapy, prophylactic therapy, and preventative therapy. Treatment according to the presently disclosed methods can result in complete relief or cure from a disease, disorder, or condition, or partial amelioration of one or more symptoms of the disease, disease, or condition, and can be temporary or permanent.
  • treatment also is intended to encompass prophylaxis, therapy and cure.
  • a viscous vaginal pharmaceutical composition comprising a water soluble gel as described herein can be administered
  • an agent refers to the amount of the agent necessary to elicit the desired biological response.
  • the effective amount of an agent may vary depending on such factors as the desired biological endpoint, the agent to be delivered, the composition of the pharmaceutical composition, the target tissue or cell, and the like.
  • the term "effective amount” refers to an amount sufficient to produce the desired effect, e.g., to reduce or ameliorate the severity, duration, progression, or onset of a disease, disorder, or condition, or one or more symptoms thereof; prevent the advancement of a disease, disorder, or condition, cause the regression of a disease, disorder, or condition; prevent the recurrence, development, onset or progression of a symptom associated with a disease, disorder, or condition, or enhance or improve the prophylactic or therapeutic effect(s) of another therapy.
  • composition comprising a water soluble gel as described herein can result in at least about a 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or even 100% decrease in one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8. 9, or 10) symptoms of a disease, disorder, or condition associated with vaginal dryness.
  • a water soluble gel as described herein can result in at least about a 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or even 100% decrease in one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8. 9, or 10) symptoms of a disease, disorder, or condition associated with vaginal dryness.
  • composition comprising a water soluble gel as described herein as described herein results in at least about a 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or even 100% decrease in the likelihood of developing a disease, disorder, or condition associated with vaginal dryness compared to a control population of subjects that are not administered a viscous vaginal pharmaceutical composition comprising a water soluble gel as described herein.
  • a viscous vaginal pharmaceutical composition comprising a water soluble gel as described herein results in at least about a 1.1-fold, 1.2-fold, 1.3-fold, 1.4-fold, 1.5-fold, 1.6-fold, 1.7-fold, 1.8-fold, 1.9-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8- fold, 9-fold, 10-fold, 15-fold, 20-fold, 25-fold, 30-fold, 35-fold, 40-fold, 45-fold, 50-fold, 55- fold, 60-fold, 65-fold, 70-fold, 75-fold, 80-fold, 85-fold, 90-fold, 95-fold, or 100-fold decrease in the likelihood of developing a disease, disorder, or condition associated with vaginal dryness compared to a control population of subj ects that are not administered a viscous vaginal pharmaceutical composition comprising a water soluble gel as described herein.
  • Actual dosage levels of the agents described herein can be varied so as to obtain an amount of the agent that is effective to achieve the desired therapeutic response for a particular subject, composition, route of administration, and disease, disorder, or condition without being toxic to the subject.
  • the selected dosage level will depend on a variety of factors including the activity of the particular agent employed, or salt thereof, the route of administration, the time of administration, the rate of excretion of the particular agent being employed, the duration of the treatment, other drugs, agents and/or materials used in combination with the particular agent employed, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well known in the medical arts.
  • Lubricants improve sexual intercourse by making genital tissues moist, which decreases friction and makes intimate contact more pleasurable. Friction can cause small tears in the fragile vaginal lining through which disease-causing microorganisms can enter. Using lubricant may prevent these tears from forming. Lubricant should be applied before sexual intercourse and can easily be integrated into foreplay. It can also be useful during sexual activity- after menopause. Estrogen levels dip quite a bit during menopause and a woman's natural lubrication may decrease.
  • Lubricants can help ease vaginal dryness and improve sexual intercourse.
  • V-LoveTM Gel is a water-based personal lubricant. It is formulated with ingredients that will not cause latex to deteriorate and rinses off easily in plain water.
  • V-LoveTM Gel is a water-based personal lubricant that contains L-Arginine, Niacin, Glycerin, Lactic acid, Hydroxyethylcellulose, Tocopheryl acetate and Potassium Sorbate.
  • V-LoveTM Gel contains the following ingredients and quantities in weight percent:
  • V-LoveTM Gel contains L-Arginine, Niacin, Glycerin, Lactic acid, Hydroxyethylcellulose, Tocopheryl acetate, Potassium Sorbate, and Cremophor RH-40, along with various vitamins, plant-derived minerals, and/or plant extracts.
  • mis alternative formulation for V-LoveTM Gel contains the following ingredients and quantities in weight percent:
  • V- LoveTM Gel is pH balanced for women (pH of between about 3.8 and about 4.5, particularly 4.0).
  • V-LoveTM Gel provides a moisturizing feeling for vaginal dryness as well as a lubricant effect that enhances sexual pleasure with a partner or for individual intimate moments.
  • V- LoveTM Gel can be used daily, is silky smooth, is fragrance free, and is free of DEA, gluten, parebens, and sorbitol.
  • V-LoveTM Gel is water based and latex condom friendly.
  • V-LoveTM Gel as described in Example 1 may be made as follows. Into a mixing tank, add the purified water and dissolve L-arginine and niacin. Glycerin and Hydroxyethylcellulose are mixed together and added into the water phase mixture. Potassium Sorbate and Tocopherol acetate are then added and mixed. The end product is a translucent gel.

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  • Life Sciences & Earth Sciences (AREA)
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  • Urology & Nephrology (AREA)
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Abstract

La présente invention concerne des compositions pharmaceutiques vaginales visqueuses comprenant un gel soluble dans l'eau, des procédés de fabrication de telles compositions, et des procédés d'utilisation de telles compositions pour traiter la sécheresse vaginale chez une patiente qui en a besoin.
PCT/US2016/016163 2015-10-22 2016-02-02 Compositions de gel vaginal et leurs procédés d'utilisation WO2017069793A1 (fr)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020055278A1 (fr) 2018-09-14 2020-03-19 Amira Fazlagic Composition contre le vieillissement de la peau dans la zone intime
WO2021228816A1 (fr) 2020-05-12 2021-11-18 Janssen Vaccines & Prevention B.V. Administration de vecteurs adénoviraux homologues
CN114762652A (zh) * 2021-05-10 2022-07-19 山东华中生物科技有限公司 一种阴道凝胶及其制备方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009016350A2 (fr) * 2007-08-01 2009-02-05 Lrc Products Ltd. Gel stimulant
WO2010057117A2 (fr) * 2008-11-14 2010-05-20 Helm Pharmaceuticals, Inc. Composition pour la délivrance transdermique de médicaments topiques
US20110229446A1 (en) * 2010-03-02 2011-09-22 Roman Stephen B Method and composition to relieve sexual discomfort and improve vaginal health

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009016350A2 (fr) * 2007-08-01 2009-02-05 Lrc Products Ltd. Gel stimulant
WO2010057117A2 (fr) * 2008-11-14 2010-05-20 Helm Pharmaceuticals, Inc. Composition pour la délivrance transdermique de médicaments topiques
US20110229446A1 (en) * 2010-03-02 2011-09-22 Roman Stephen B Method and composition to relieve sexual discomfort and improve vaginal health

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020055278A1 (fr) 2018-09-14 2020-03-19 Amira Fazlagic Composition contre le vieillissement de la peau dans la zone intime
WO2021228816A1 (fr) 2020-05-12 2021-11-18 Janssen Vaccines & Prevention B.V. Administration de vecteurs adénoviraux homologues
CN114762652A (zh) * 2021-05-10 2022-07-19 山东华中生物科技有限公司 一种阴道凝胶及其制备方法
CN114762652B (zh) * 2021-05-10 2024-04-09 山东华中生物科技有限公司 一种阴道凝胶及其制备方法

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