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WO2025222268A1 - Compositions topiques et méthodes de traitement de la vaginite atrophique - Google Patents

Compositions topiques et méthodes de traitement de la vaginite atrophique

Info

Publication number
WO2025222268A1
WO2025222268A1 PCT/CA2024/050527 CA2024050527W WO2025222268A1 WO 2025222268 A1 WO2025222268 A1 WO 2025222268A1 CA 2024050527 W CA2024050527 W CA 2024050527W WO 2025222268 A1 WO2025222268 A1 WO 2025222268A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
dose
buffer
oxytocin
buffering agent
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/CA2024/050527
Other languages
English (en)
Inventor
Alvin PETTLE
Joshi Laxminarayan
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Jastlabs Corp
Original Assignee
Jastlabs Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Jastlabs Corp filed Critical Jastlabs Corp
Priority to PCT/CA2024/050527 priority Critical patent/WO2025222268A1/fr
Priority to PCT/CA2025/050571 priority patent/WO2025222280A1/fr
Publication of WO2025222268A1 publication Critical patent/WO2025222268A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • A61P15/02—Drugs for genital or sexual disorders; Contraceptives for disorders of the vagina
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/08—Peptides having 5 to 11 amino acids
    • A61K38/095—Oxytocins; Vasopressins; Related peptides
    • 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
    • A61K47/02—Inorganic compounds
    • 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
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides 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
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • 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
    • A61K9/10—Dispersions; Emulsions
    • 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
    • A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems

Definitions

  • the present disclosure relates generally to medicated topical compositions and topical compositions for treating atrophic vaginitis in particular.
  • Atrophic vaginitis is inflammation of the vagina as a result of tissue thinning due to insufficient Sildenafil citrate and Oxytocin and is a common condition in menopausal women. Atrophic vaginitis can lead to dyspareunia in women.
  • Prior art formulations, particularly if they include synthetic hormones, for treating atrophic vaginitis increase the risk of adverse side effects for the patient.
  • a composition to treat atrophic vaginitis that minimizes adverse side effects is desired.
  • the present disclosure relates to a composition for treating astrophic vaginitis including a cream base including sildenafil citrate and oxytocin.
  • a cream base including sildenafil citrate and oxytocin.
  • the composition of claim 1 wherein the sildenafil citrate is in a dosage in the range of 25 mg/dose to 100 mg/dose, and oxytocin is in a dosage in the range of 40 lU/dose to 400 lU/dose.
  • the composition further includes a buffering agent.
  • the buffering agent is L- arginine.
  • the buffering agent is sodium phosphate monobasic.
  • the composition can include a stabilizer, and in another aspect, the stabilizer is boron citrate and/or chlorobutanol. In another aspect, the stabilizer is a suitable stabilizer that can keep oxytocin stable.
  • the stabilizer is boron citrate and/or chlorobutanol. In another aspect, the stabilizer is a suitable stabilizer that can keep oxytocin stable.
  • a base cream useful in compositions of the present disclosure can be an anhydrous vaginal base.
  • the anhydrous vaginal base can be the anhydrous vaginal base marketed under the trademark ELLAGETM.
  • a base cream useful in compositions of the present disclosure can include dimethicone, chlorocresol, chlorobutanol, butylated hydroxy toluene, Ceto stearyl alcohol, Ceto macrogol 1000, disodium EDTA, light liquid paraffin, polyethylene glycol 40 hydrogenated castor oil, propylene glycol, white soft paraffin, citric acid, sodium dihydrogen phosphate, Tocobiol-vitamin E- rosemary extract and purified water.
  • a base cream useful in compositions of the present disclosure can include petrolatum, cetyl alcohol, stearyl alcohol, butylated hydroxy toluene, mineral oil, polysorbate 80, disodium EDTA, methylchloroisothaizoline, methylisothiazoline, chlorobutanol, Tocobiol and rosemary extract, and purified water.
  • compositions of the present disclosure can be formulated by taking a base cream useful for compositions of the present disclosure and blending non-cream ingredients disclosed herein into the cream.
  • standard compounding methods can be used for the blending.
  • the pH of the composition after blending is adjusted to be acidic.
  • the pH of the composition after blending is adjusted to a pH in the range of pH 3.5-4.5.
  • compositions according to aspects of the present disclosure can be dispensed using a pump.
  • the pump can dispense 0.5 g of the composition with each dispensation.
  • the present disclosure relates to a method of treating atrophic vaginitis including topically applying a composition according to an aspect of the present disclosure to a patient in need thereof.
  • the topical application is to the area around the entrance to the vagina.
  • the topical application is to the clitoris.
  • the topical application is to the anterior vaginal wall.
  • the location of topical application on the anterior vaginal wall is the area of the vaginal erogenous zone (commonly referred to as the ‘G-spot’ or Grafenberg spot).
  • Figure 1 is a process flowchart of a process for the manufacture of compositions according to embodiments of the present invention.
  • the composition can include a stabilizer, and in another aspect, the stabilizer is boron citrate and/or chlorobutanol. In another embodiment, the stabilizer is a suitable stabilizer that can keep oxytocin stable.
  • oxytocin API raw USP having the formula C43H66N12O12S2 in the amount of 40 III
  • hyaluronic acid having the formula (Ci4H2iNOn) n in an amount of 2 mg/dose at a concentration of 0.2%-0.5%
  • boron citrate in the amount of 1.5 mg and 0.5% chlorobutanol
  • a cream base in the amount of 726 mg.
  • compositions of the present invention can be formulated by taking a base cream useful for embodiments of the present invention and blending non-cream ingredients disclosed herein into the cream.
  • standard compounding methods can be used for blending.
  • the pH of the composition is adjusted to be acidic.
  • the pH of the composition is adjusted to a pH in the range of pH 3.5-4.5.
  • the stability of oxytocin is pH dependent, and it degrades faster at pH 1.2 and slowest at pH 3.5. Therefore, in one embodiment, the composition is maintained at a preferred pH of 3.5 by the inclusion of citric acid, Boric acid or boron citrate.
  • compositions of the present invention are formulated by including functional excipients selected from the group consisting of cetostearyl alcohol, Octyldodecanol, Cetyl Ester, Polysorbate 60 and Sorbitan Monostearate the cream base.
  • functional excipients selected from the group consisting of cetostearyl alcohol, Octyldodecanol, Cetyl Ester, Polysorbate 60 and Sorbitan Monostearate the cream base.
  • various components selected from the group consisting of buffering agents, pH adjuster, antioxidant and stabilizer are added to the composition.
  • Cream bases according to embodiments of the present invention were characterized by performing various studies including homogeneity, colour, odour, and feel to touch.
  • the chemical properties of a cream base govern how a cream acts as a drug delivery system to deliver a therapeutic dose to a patient to achieve desired therapeutic effectiveness.
  • Chemical properties which affect the stability of a cream composition and its use as a drug delivery system include pH and buffering capacity, osmolality, firmness and adhesiveness, bioadhesion, and viscosity.
  • the amount or level of various components in the composition were set according to the chemical properties achieved after testing.
  • vaginal creams plays a crucial role in maintaining the pH balance of the vaginal environment. Without being bound by theory, this can be achieved through the following: [0020] pH Regulation: The vagina naturally maintains an acidic pH, typically between 3.8 and 4.5, which helps prevent the growth of harmful bacteria and yeast. Vaginal creams often contain buffers, such as lactate or acetate, which help to regulate and maintain this acidic pH environment.
  • Protective Barrier Buffering agents in vaginal creams help to maintain the stability of the pH level despite changes caused by menstrual cycles, sexual activity, or the use of certain medications. This stability creates a protective barrier against infections and other imbalances.
  • vaginal creams with adequate buffer capacity can help prevent the overgrowth of harmful microorganisms like yeast (such as Candida) and bacteria (such as Gardnerella vaginalis), which can lead to infections like bacterial vaginosis or yeast infections.
  • Vaginal creams with appropriate buffer capacity can also provide relief from symptoms such as itching, burning, or irritation, which may occur due to pH imbalances.
  • vaginal creams contain active ingredients such as antifungals or antibiotics. Optimal pH conditions, facilitated by buffer capacity, can enhance the efficacy of these active ingredients, making the treatment more effective.
  • Certain embodiments of the present composition include buffering agents composed of L-arginine and monobasic sodium phosphate.
  • the presence and level of the buffering agent maintains the desired buffering capacity of vaginal cream compositions according to embodiments of the present invention to achieve a well balanced in composition.
  • Levels of the buffering agent is balanced and pH adjusted with another pH adjusting component such as boric acid which is an acidifier as well as having antifungal properties.
  • compositions of the present invention are made by blending one or more non-cream ingredients disclosed herein into a cream base.
  • standard compounding methods can be used for blending.
  • the pH of the composition is adjusted to be acidic.
  • the pH of the composition is adjusted to a pH in the range of pH 3.5-4.5.
  • the stability of oxytocin is pH dependent, and it degrades faster at pH 1.2 and slowest at pH 3.5. Therefore, in one embodiment, the composition is maintained at a preferred pH of 3.5 by the inclusion of citric acid, boric acid, or boron citrate.
  • compositions according to embodiments of the present invention can be dispensed using a pump.
  • the pump can dispense 0.5 g of the composition with each dispensation.
  • the present invention relates to a method of treating atrophic vaginitis including topically administering a composition according to an embodiment of the present disclosure to a patient in need thereof.
  • the topical application is to the area around the entrance to the vagina.
  • the topical application is to the clitoris.
  • the topical application is to the anterior vaginal wall.
  • the location of topical application on the anterior vaginal wall is the area of the vaginal erogenous zone (commonly referred to as the ‘G-spot’ or Grafenberg spot).
  • stabilizers can be used in the present invention.
  • the term “stabilizer” refers to any substance that keeps Sildenafil citrate and Oxytocin chemically stable.
  • the term “stabilizer” refers to any substance that slows or retards the degradation or alteration of Sildenafil citrate and Oxytocin.
  • a stabilizer can protect Sildenafil citrate and Oxytocin from instability caused by light, moisture, heat, or oxidation.
  • the stabilizer is lipophilic.
  • the stabilizer is hydrophilic.
  • the stabilizer can prevent or retard the oxidation of the oil.
  • the stabilizer can be, but is not limited to, butylated hydroxy anisole (BHA), butylated hydroxytoluene (BHT), ascorbic acid and its esters, vitamin E and its esters, e.g., vitamin E acetate, sodium bisulfite, sodium metabisulfite, 3-dehydroshikimic acid (DHS), tocopherols and their esters, alkyl gallates, chelating agents, EDTA (ethylenediaminetetraacetic acid; edetate disodium), citric acid, benzyl alcohol, or combinations thereof.
  • the stabilizer can be edetate disodium, butylated hydroxy anisole, butylated hydroxytoluene, or combinations thereof.
  • the composition of the present invention further includes a pharmaceutically acceptable excipient.
  • excipient refers to a substance, or mixture of substances, that is used in the formulation of vaginal cream compositions to give desirable physical characteristics to the formulation.
  • pharmaceutically acceptable refers to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem complications commensurate with a reasonable benefit/risk ratio.
  • pharmaceutically acceptable means approved by a regulatory agency of the Federal or a state government or listed in the U.S.
  • Various pharmaceutically acceptable excipients can be used.
  • the pharmaceutically acceptable excipient can be, but is not limited to, a stiffening agent, an oil, a solvent, an emulsifier, a humectant, a buffering agent, a filler, an emollient, a stabilizer, or combinations thereof.
  • compositions of the present invention further include a "stiffing agent".
  • the term “stiffening agent” refers to a substance, or mixture of substances, added to make a vaginal cream composition more viscous at room temperature.
  • a stiffening agent is any substance that promotes formation of a formulation having a semisolid consistency.
  • the stiffening agent can be hydrophilic (e.g., CARBOPOL, carboxymethylcellulose, hydroxypropyl methylcellulose, alginate, polyethylene glycol).
  • the stiffening agent has low hydrophilic-lipophilic balance (HLB). In some embodiments, the hydrophilic-lipophilic (HLB) value is less than 7.
  • the HLB value is less than 5. In some embodiments, the HLB value is about 4.
  • suitable stiffening agents include, but are not limited to, hydrogenated vegetable oil, cetyl alcohol, cetyl esters wax, microcrystalline wax, paraffin, stearyl alcohol, lauryl alcohol, myristal alcohol, cetostearyl alcohol, white wax, yellow wax, beeswax, candelilla wax, cotton wax, carnauba wax, bayberry wax, rice-bran wax, and combinations thereof.
  • the stiffening agent is a mixture of cetyl esters wax, cetyl alcohol, and beeswax.
  • compositions of the present invention further include an "oil".
  • oil refers to any pharmaceutically acceptable hydrophobic liquid.
  • an oil is an ester of glycerol (1 ,2,3-propanetriol) and fatty acids.
  • the fatty acid hydrocarbon chains each contain greater than 8 carbons.
  • each hydrocarbon chain can contain from about 12 to about 36 carbon atoms.
  • the hydrocarbon chains can contain a variety of functional groups.
  • the hydrocarbon chain can be branched.
  • the hydrocarbon chains are unsaturated or polyunsaturated.
  • the hydrocarbon chains are saturated.
  • the degree of saturation can affect the physical state, for example viscosity, of the oil.
  • the oil can be, but is not limited to, vegetable, nut, and seed oils (e.g., almond oil, castor oil, coconut oil, corn oil, cotton seed oil, jojoba oil, linseed oil, grape seed oil, rape seed oil, mustard oil, olive oil, palm and palm kernel oil, peanut oil, safflower oil, sesame oil, soybean oil, sunflower-seed oil, crambe oil, wheat germ oil, and cocoa butter), hydrocarbon and petroleum oils (e.g., petrolatum, mineral oil, and liquid paraffin).
  • vegetable, nut, and seed oils e.g., almond oil, castor oil, coconut oil, corn oil, cotton seed oil, jojoba oil, linseed oil, grape seed oil, rape seed oil, mustard oil, olive oil, palm and palm kernel oil, peanut oil, safflower oil, sesame oil, soybean oil, sunflower-seed oil,
  • the term “oil” refers to higher fatty acids (e.g., lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, 12-hydroxystearic acid, undecylenic acid, tall acid, lanolin fatty acid, isostearic acid, linoleic acid, and linolenic acid) and combinations thereof.
  • the oil is not an ester of glycerol, e.g., mineral oil and silicone oil.
  • compositions of the present invention further include a "solvent".
  • solvent refers to any substance capable of dissolving or dispersing one or more of the conjugated Sildenafil citrate and Oxytocin or the excipients of the present invention.
  • the solvent can be aqueous or non-aqueous.
  • the solvent is hydrophilic, and is 10% to 75% by weight, or 20% to 60% by weight, of the total composition.
  • the solvent is lipophilic, and is 20% to 60% by weight, or 25% to 50% by weight, of the total composition.
  • the solvent is water, a polyol (e.g., glycerol) or combinations thereof.
  • the solvent is an oil as described above.
  • compositions of the present invention further include an "emulsifier".
  • emulsifier refers to any substance that promotes formation and stabilization of an emulsion or suspension.
  • the emulsifier includes, but is not limited to, sodium lauryl sulfate, propylene glycol monostearate, methyl stearate, glyceryl monostearate, Cetyl Ester, Ceto Stearyl Alcohol and combinations thereof.
  • compositions of the present invention further include a "humectant".
  • humectant refers to any substance that promotes retention of moisture in the composition of the present invention.
  • the humectant includes, but is not limited to, polyethylene glycol, propylene glycol, glycerin, polyol, polyol derivatives, and combinations thereof.
  • compositions of the present invention further include a "buffering agent".
  • buffering agent refers to any substance capable of neutralizing both acids and bases and thereby maintaining the desired pH of the composition of the present invention.
  • the buffering agent affects the emulsifying properties.
  • different buffering agents can be provided to increase or decrease the emulsification of the conjugated Sildenafil citrate and Oxytocin or the excipients of the present invention.
  • the buffer can be, but is not limited to, Tris buffers (Tris EDTA (TE), Tris acetate (TAE), Tris phosphate (TPE), Tris glycine), phosphate buffers (e.g., monobasic sodium phosphate, potassium phosphate), bicarbonate buffers, acetate buffers (e.g., sodium acetate), ammonium buffers, citrate buffers, and derivatives, L arginine, L-arginine HCI and combinations thereof.
  • an organic acid buffer is used.
  • an acetate buffer, a phosphate buffer, or a citrate buffer can be used.
  • a zwitterionic buffer can be used.
  • the buffering agent is a phosphate buffer (e.g., sodium phosphate monobasic).
  • compositions of the invention can be physiologically compatible and/or sufficient to maintain stability of the composition.
  • the composition of the present invention can have a pH of 3.5 to 4.5.
  • compositions of the present invention further include an "emollient".
  • an “emollient” is a substance that moisturizes and increases the pliability of the vaginal epithelium.
  • the emollient can be, but is not limited to, lanolin, isopropyl myristate, palmitate, oleyl alcohol, beeswax, mineral oil, silicone oil, Octyldodecanol, Cetostearyl Alcohol or combinations thereof.
  • compositions of the present invention further include a "filler".
  • a “filler” is a substance used to give bulk to the composition without chemically reacting with the Sildenafil citrate and Oxytocin of the present invention. Fillers are known to those in the art, see e.g., Remington: The Science and Practice of Pharmacy, 20 th ed. (2000).
  • a vaginal cream is a semi-solid preparation suitable for application to the vaginal tract.
  • a vaginal cream can be a vaginal ointment, vaginal gel or vaginal emulsion.
  • vehicle bases can be used in the vaginal cream and are known to those in art.
  • suitable vehicle bases include, but are not limited to, hydrocarbon bases or oleaginous bases, absorption bases, water-removable bases and water-soluble bases (Remington: The Science and Practice of Pharmacy, 20 th ed. (2000)).
  • the vehicle base is non-irritating, non-staining, stable, non-pH dependent and/or compatible with the conjugated Sildenafil citrate and Oxytocin of the present invention.
  • the amount of active agent or agents in a dosage form can vary.
  • the exact dosage amount can be selected depending upon the needs of the female to which the active agent is being administered, as determined by a relevant person.
  • one of skill in the art can perform pharmacokinetic studies and use the results of the study to adjust the dosage amount for a female, or a group of females, to a suitable level.
  • one skill in the art can determine an appropriate dosage amount based on varying dosage amounts and comparing to symptomatic relief.
  • appropriate animal studies may be performed to determine an appropriate dosage amount.
  • a “relevant person” as used herein, includes, for example, a physician, physician assistant, nurse practitioner, pharmacist, and customer service representative.
  • compositions of the present invention can be present in a dosage form.
  • compositions of the present invention are in a dosage form, wherein the dosage form is in the range of 25 mg/dose to 100 mg/dose of Sildenafil citrate, and 40 1 ll/dose to 400 1 ll/dose of Oxytocin.
  • amounts of “Sildenafil citrate and Oxytocin” refer to a summation of the amounts of Sildenafil citrate equivalent to Sildenafil and Oxytocin.
  • the composition of the present invention is in a dosage form, wherein the dosage form is 25 mg/dose of Sildenafil citrate and 40 lll/dose of Oxytocin.
  • compositions for treating atrophic vaginitis include the ingredients as set out in Table 1.
  • Phase A (Aqueous Phase): Transfer calculated amount of purified water in a suitable container fitted with mechanical stirrer and add boric acid to dissolve under stirring conditions and the dispersed Sildenafil citrate under stirring conditions and continue mixing till ready to add to next phase.
  • Phase B (Aqueous Phase): Transfer calculated amount of purified water in a suitable container fitted with mechanical stirrer and heat water to 65°C and add L arginine and mix to dissolve under stirring conditions and continue mixing till ready to add to next phase.
  • Phase C (Oil Phase): Transfer calculated amount of Cetyl Ester (Crodamal SS) Ceto Stearyl Alcohol, Octyldodecanol (Kollicream OD), Polysorbate 60, Sorbitan Monostearate 60, Monobasic Sodium Phosphate and mix well in a jacketed tank of Homogenizer and heat to 65oC to melt and mix well. Add Hydroxytoluene and Chlorobutanol as Antioxidant and preservative and mix till earlier phase added.
  • Water Phase Transfer calculated amount of purified water in a suitable container and heated to 65oC temperature and maintain temperature till it is used.
  • Homogenization Start homogenizer after setting predetermined operating conditions and add phase A, B and Water phase and homogenized to cream base and add Oxytocin and finally check pH and adjust in case needed to 3.5 and allow the material to cool to room temperature and send sample for QC analysis.
  • compositions of Table 1 are in the dosage forms set out in Table 2.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Endocrinology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Reproductive Health (AREA)
  • Inorganic Chemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Dispersion Chemistry (AREA)
  • Gynecology & Obstetrics (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne une composition pour le traitement de la vaginite atrophique comprenant une base de crème contenant du citrate de sildénafil et de l'oxytocine. Selon la composition de la revendication 1, la posologie du citrate de sildénafil se situe dans la plage de 25 mg/dose à 100 mg/dose, et la posologie de l'oxytocine se situe dans la plage de 40 UI/dose à 400 UI/dose. Selon un autre aspect, la composition comprend en outre un agent tampon. Selon un autre aspect, l'agent tampon est la L-arginine. Selon un autre aspect, l'agent tampon est le phosphate de sodium monobasique.
PCT/CA2024/050527 2024-04-22 2024-04-22 Compositions topiques et méthodes de traitement de la vaginite atrophique Pending WO2025222268A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
PCT/CA2024/050527 WO2025222268A1 (fr) 2024-04-22 2024-04-22 Compositions topiques et méthodes de traitement de la vaginite atrophique
PCT/CA2025/050571 WO2025222280A1 (fr) 2024-04-22 2025-04-21 Compositions topiques stables pour le traitement de la vaginite atrophique

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CA2024/050527 WO2025222268A1 (fr) 2024-04-22 2024-04-22 Compositions topiques et méthodes de traitement de la vaginite atrophique

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20190105261A1 (en) * 2017-10-11 2019-04-11 Illustris Pharmaceuticals, Inc. Methods and compositions for topical delivery
US20190175640A1 (en) * 2014-10-06 2019-06-13 Algamed Therapeutics (A.M.T.) Ltd Compositions comprising sulfated polysaccharides and uses thereof
CA3021459A1 (fr) * 2018-10-19 2020-04-19 Springer, John S. Compositions comprenant du tetrahydrocannabinol (thc) pouvant etre utilise comme aphrodisiaque

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20190175640A1 (en) * 2014-10-06 2019-06-13 Algamed Therapeutics (A.M.T.) Ltd Compositions comprising sulfated polysaccharides and uses thereof
US20190105261A1 (en) * 2017-10-11 2019-04-11 Illustris Pharmaceuticals, Inc. Methods and compositions for topical delivery
CA3021459A1 (fr) * 2018-10-19 2020-04-19 Springer, John S. Compositions comprenant du tetrahydrocannabinol (thc) pouvant etre utilise comme aphrodisiaque

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