WO2025106494A1 - Compositions et méthodes de traitement d'une dysfonction érectile et d'un hypogonadisme masculin - Google Patents

Compositions et méthodes de traitement d'une dysfonction érectile et d'un hypogonadisme masculin Download PDF

Info

Publication number
WO2025106494A1
WO2025106494A1 PCT/US2024/055651 US2024055651W WO2025106494A1 WO 2025106494 A1 WO2025106494 A1 WO 2025106494A1 US 2024055651 W US2024055651 W US 2024055651W WO 2025106494 A1 WO2025106494 A1 WO 2025106494A1
Authority
WO
WIPO (PCT)
Prior art keywords
effective amount
therapeutically effective
cabergoline
pharmaceutically acceptable
sildenafil
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/US2024/055651
Other languages
English (en)
Inventor
Yanping Kong
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.)
Individual
Original Assignee
Individual
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 Individual filed Critical Individual
Publication of WO2025106494A1 publication Critical patent/WO2025106494A1/fr
Anticipated expiration legal-status Critical
Pending legal-status Critical Current

Links

Classifications

    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/48—Ergoline derivatives, e.g. lysergic acid, ergotamine
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
    • A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone

Definitions

  • the invention generally relates to novel therapeutic methods and pharmaceutical compositions for treating erectile dysfunction and male hypogonadism. More particularly, the invention relates to pharmaceutical compositions comprising sildenafil and cabergoline and uses thereof for treating erectile dysfunction and/or male hypogonadism.
  • Erectile dysfunction refers to an inability to achieve and/or maintain an erection satisfactory for the completion of sexual activity.
  • ED is a highly prevalent condition and may affect 30% to 50% of men aged 40 to 70 years. The risk of ED increases with age and as the population continues to grow and age and it is estimated that there will be approximately 332 million men worldwide with ED by the year 2025.
  • a normal level of libido, or sexual desire, is an important component of an individual’s health and well-being.
  • the primary naturally occurring hormone responsible for libido is testosterone.
  • Male hypogonadism refers to diminished functional activity of the testicles that may result in diminished production of sex hormones.
  • ED and male hypogonadism are common in elderly men and can lead to erection dysfunction, low libido and low energy. Increased longevity and population aging will increase the number of men with late onset ED and hypogonadism. As common conditions, they often are underdiagnosed and undertreated, merely considered a normal part of aging.
  • the invention is based in part on the unexpected discovery of therapeutic methods and pharmaceutical compositions, as demonstrated herein, that can be used to treat ED and/or male hypogonadism.
  • a method using sildenafil and cabergoline together in specifically selected dosages in treatment and/or prevention of ED and/or male hypogonadism is disclosed herein.
  • the invention generally relates to a method for treating erectile dysfunction, or a related disease or condition, comprising administering to a male subject in need thereof (a) a therapeutically effective amount of sildenafil, or a pharmaceutically acceptable form thereof, and (b) a therapeutically effective amount of cabergoline, or a therapeutically acceptable form thereof.
  • the invention generally relates to a method for treating male hypogonadism, or a related disease or condition, comprising administering to a male subject in need thereof (a) a therapeutically effective amount of sildenafil, or a pharmaceutically acceptable form thereof, and (b) a therapeutically effective amount of cabergoline, or a therapeutically acceptable form thereof.
  • the invention generally relates to a method for treating erectile dysfunction and male hypogonadism, or a related disease or condition, comprising administering to a male subject in need thereof (a) a therapeutically effective amount of sildenafil, or a pharmaceutically acceptable form thereof, and (b) a therapeutically effective amount of cabergoline, or a therapeutically acceptable form thereof.
  • the invention generally relates to a pharmaceutical composition
  • a pharmaceutical composition comprising (a) a therapeutically effective amount of sildenafil, or a pharmaceutically acceptable form thereof, and (b) a therapeutically effective amount of cabergoline, or a therapeutically acceptable form thereof, and a pharmaceutically acceptable excipient, carrier, or diluent.
  • the invention generally relates to a unit dosage form comprising a pharmaceutical composition according to invention.
  • the invention generally relates to a kit comprising a unit dosage form of the invention and optionally a unit form of a further therapeutic agent and instructions for administration thereof.
  • the invention generally relates to use of (a) a therapeutically effective amount of sildenafil, or a pharmaceutically acceptable form thereof, and (b) a therapeutically effective amount of cabergoline, or a therapeutically acceptable form thereof, for the manufacture of a medicament for the treatment of erectile dysfunction and/or male hypogonadism, or a related disease or condition.
  • the invention generally relates to use of (a) a therapeutically effective amount of sildenafil, or a pharmaceutically acceptable form thereof, and (b) a therapeutically effective amount of cabergoline, or a therapeutically acceptable form thereof, for treating erectile dysfunction and male hypogonadism.
  • the trade name includes the product formulation, the generic drug, and the active pharmaceutical ingredient(s) of the trade name product, unless otherwise indicated by context.
  • Ranges provided herein are understood to be shorthand for all values within the range.
  • a range of 1 to 14 is understood to include any number, combination of numbers, or sub-range from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14.
  • the singular forms "a,” “an,” and “the” include plural reference, unless the context clearly dictates otherwise.
  • the term “about” is understood as within a range of normal tolerance in the art, for example within 2 standard deviations of the mean.
  • compositions and methods are intended to mean that the compositions and methods include the recited elements, but do not exclude other elements.
  • “consisting essentially of’ refers to administration of the pharmacologically active agents expressly recited and excludes pharmacologically active agents not expressly recited.
  • consisting essentially of does not exclude pharmacologically inactive or inert agents, e.g., pharmaceutically acceptable excipients, carriers or diluents.
  • disease As used herein, the terms “disease”, “disorder” or “condition” are used interchangeably herein to refer to a pathological condition, for example, one that can be identified by symptoms or other identifying factors as diverging from a healthy or a normal state.
  • the term “disease” includes disorders, syndromes, conditions, and injuries. Diseases include, but are not limited to, proliferative, inflammatory, immune, metabolic, infectious, and ischemic diseases.
  • a "pharmaceutically acceptable form” of a disclosed compound includes, but is not limited to, pharmaceutically acceptable salts, esters, hydrates, solvates, isomers, prodrugs, and isotopically labeled derivatives of disclosed compounds.
  • a "pharmaceutically acceptable form” includes, but is not limited to, pharmaceutically acceptable salts, esters, isomers, prodrugs and isotopically labeled derivatives of disclosed compounds.
  • a "pharmaceutically acceptable form” includes, but is not limited to, pharmaceutically acceptable salts and isotopically labeled derivatives of disclosed compounds.
  • the pharmaceutically acceptable form is a pharmaceutically acceptable salt.
  • pharmaceutically acceptable salt refers to those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of subjects without undue toxicity, irritation, allergic response and the like, and are commensurate with a reasonable benefit/risk ratio.
  • Pharmaceutically acceptable salts are well known in the art. For example, Berge et al. describes pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences (1977) 66: 1-19.
  • Pharmaceutically acceptable salts of the compounds provided herein include those derived from suitable inorganic and organic acids and bases.
  • Examples of pharmaceutically acceptable, nontoxic acid addition salts are salts of an amino group formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid or with organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid or malonic acid or by using other methods used in the art such as ion exchange.
  • inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid
  • organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid or malonic acid or by using other methods used in the art such as ion exchange.
  • salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, besylate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecyl sulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2- naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamo
  • organic acids from which salts can be derived include, for example, acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, lactic acid, trifluoracetic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like.
  • the salts can be prepared in situ during the isolation and purification of the disclosed compounds, or separately, such as by reacting the free base or free acid of a parent compound with a suitable base or acid, respectively.
  • the pharmaceutically acceptable form is a "solvate" (e.g., a hydrate).
  • solvate refers to compounds that further include a stoichiometric or non-stoichiometric amount of solvent bound by non-covalent intermolecular forces.
  • the solvate can be of a disclosed compound or a pharmaceutically acceptable salt thereof. Where the solvent is water, the solvate is a "hydrate".
  • solvates and hydrates are complexes that, for example, can include 1 to about 100, or 1 to about 10, or 1 to about 2, about 3 or about 4, solvent or water molecules. It will be understood that the term "compound” as used herein encompasses the compound and solvates of the compound, as well as mixtures thereof.
  • the pharmaceutically acceptable form is a prodrug.
  • prodrug refers to compounds that are transformed in vivo to yield a disclosed compound or a pharmaceutically acceptable form of the compound.
  • a prodrug can be inactive when administered to a subject, but is converted in vivo to an active compound, for example, by hydrolysis (e.g., hydrolysis in blood).
  • hydrolysis e.g., hydrolysis in blood
  • a prodrug has improved physical and/or delivery properties over the parent compound.
  • Prodrugs can increase the bioavailability of the compound when administered to a subject (e.g., by permitting enhanced absorption into the blood following oral administration) or which enhance delivery to a biological compartment of interest (e.g., the brain or lymphatic system) relative to the parent compound.
  • exemplary prodrugs include derivatives of a disclosed compound with enhanced aqueous solubility or active transport through the gut membrane, relative to the parent compound.
  • the prodrug compound often offers advantages of solubility, tissue compatibility or delayed release in a mammalian organism (see, e.g., Bundgard, H., Design of Prodrugs (1985), pp. 7- 9, 21-24 (Elsevier, Amsterdam).
  • a discussion of prodrugs is provided in Higuchi, T., et al., "Pro-drugs as Novel Delivery Systems," A.C.S. Symposium Series, Vol. 14, and in Bioreversible Carriers in Drug Design, ed. Edward B. Roche, American Pharmaceutical Association and Pergamon Press, 1987, both of which are incorporated in full by reference herein.
  • a prodrug can include, but are not limited to, its physical properties, such as enhanced water solubility for parenteral administration at physiological pH compared to the parent compound, or it can enhance absorption from the digestive tract, or it can enhance drug stability for long-term storage.
  • pharmaceutically acceptable excipient, carrier, or diluent refers to a pharmaceutically acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material, involved in carrying or transporting the subject pharmaceutical agent from one organ, or portion of the body, to another organ, or portion of the body.
  • Each carrier must be “acceptable” in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient.
  • materials which can serve as pharmaceutically-acceptable carriers include: sugars, such as lactose, glucose and sucrose; starches, such as corn starch and potato starch; cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients, such as cocoa butter and suppository waxes; oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; glycols, such as propylene glycol; polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; esters, such as ethyl oleate and ethyl laurate; agar; buffering agents, such as magnesium hydrox
  • wetting agents such as sodium lauryl sulfate, magnesium stearate, and polyethylene oxide-polypropylene oxide copolymer as well as coloring agents, release agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the compositions.
  • the terms “prevent”, “preventing”, or “prevention” refer to a method for precluding, delaying, averting, or stopping the onset, incidence, severity, or recurrence of a disease or condition.
  • a method is considered to be a prevention if there is a reduction or delay in onset, incidence, severity, or recurrence of a disease or condition or one or more symptoms thereof in a subject susceptible to the disease or condition as compared to a subject not receiving the method.
  • the disclosed method is also considered to be a prevention if there is a reduction or delay in onset, incidence, severity, or recurrence of one or more symptoms of a disease or condition in a subject susceptible to the disease or condition after receiving the method as compared to the subject's progression prior to receiving treatment.
  • the reduction or delay in onset, incidence, severity, or recurrence of cancer can be about a 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100%, or any amount of reduction in between.
  • Prevention and the like do not mean preventing a subject from ever getting the specific disease or disorder. Prevention may require the administration of multiple doses.
  • Prevention can include the prevention of a recurrence of a disease in a subject for whom all disease symptoms were eliminated, or prevention of recurrence in a relapsing-remitting disease.
  • the terms “subject” and “patient” are used interchangeably herein to refer to a living animal (human or non-human).
  • the subject may be a mammal.
  • the terms “mammal” or “mammalian” refer to any animal within the taxonomic classification mammalia.
  • a mammal may be a human or a non-human mammal, for example, dogs, cats, pigs, cows, sheep, goats, horses, rats, and mice.
  • the term "subject” does not preclude individuals that are entirely normal with respect to a disease or condition, or normal in all respects.
  • the term “therapeutically effective amount” refers to the dose of a therapeutic agent or agents sufficient to achieve the intended therapeutic effect with minimal or no undesirable side effects.
  • a therapeutically effective amount can be determined by a skilled physician, e.g., by first administering a low dose of the pharmacological agent(s) and then incrementally increasing the dose until the desired therapeutic effect is achieved with minimal or no undesirable side effects.
  • treatment refers to a method of reducing, delaying or ameliorating such a condition, or one or more symptoms of such disease or condition, before or after it has occurred. Treatment may be directed at one or more effects or symptoms of a disease and/or the underlying pathology.
  • the treatment can be any reduction and can be, but is not limited to, the complete ablation of the disease or the symptoms of the disease. As compared with an equivalent untreated control, such reduction or degree of prevention is at least 5%, 10%, 20%, 40%, 50%, 60%, 80%, 90%, 95%, or 100% as measured by any standard technique.
  • compositions or methods disclosed herein can be combined with one or more of any of the other compositions and methods provided herein.
  • Isotopically-labeled compounds are also within the scope of the present disclosure.
  • an "isotopically-labeled compound” refers to a presently disclosed compound including pharmaceutical salts thereof, each as described herein, in which one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number usually found in nature.
  • isotopes that can be incorporated into compounds presently disclosed include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, fluorine and chlorine, such as 2 H, 3 H, 13 C, 14 C, 15 N, 18 O, 17 0, 31 P, 32 P, 35 S, 18 F, and 36 C1, respectively.
  • the compounds may be useful in drug and/or substrate tissue distribution assays.
  • Tritiated ( 3 H) and carbon- 14 ( 14 C) labeled compounds are particularly preferred for their ease of preparation and detectability.
  • substitution with heavier isotopes such as deuterium ( 2 H) can afford certain therapeutic advantages resulting from greater metabolic stability, for example increased in vivo half-life or reduced dosage requirements and, hence, may be preferred in some circumstances.
  • Isotopically labeled compounds presently disclosed, including pharmaceutical salts, esters, and prodrugs thereof, can be prepared by any means known in the art.
  • substitution of normally abundant hydrogen ( 1 H) with heavier isotopes such as deuterium can afford certain therapeutic advantages, e.g., resulting from improved absorption, distribution, metabolism and/or excretion (ADME) properties, creating drugs with improved efficacy, safety, and/or tolerability. Benefits may also be obtained from replacement of normally abundant 12 C with 13 C. (See, WO 2007/005643, WO 2007/005644, WO 2007/016361, and WO 2007/016431.)
  • Compounds of the present invention are, subsequent to their preparation, preferably isolated and purified to obtain a composition containing an amount by weight equal to or greater than 95% (“substantially pure”), which is then used or formulated as described herein. In certain embodiments, the compounds of the present invention are more than 99% pure.
  • Solvates and polymorphs of the compounds of the invention are also contemplated herein.
  • Solvates of the compounds of the present invention include, for example, hydrates.
  • Any appropriate route of administration can be employed, for example, parenteral, intravenous, subcutaneous, intramuscular, intraventricular, intracorporeal, intraperitoneal, rectal, or oral administration. Most suitable means of administration for a particular patient will depend on the nature and severity of the disease or condition being treated or the nature of the therapy being used and on the nature of the active compound.
  • Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules.
  • the compounds described herein or derivatives thereof are admixed with at least one inert customary excipient (or carrier) such as sodium citrate or dicalcium phosphate or
  • fillers or extenders as for example, starches, lactose, sucrose, glucose, mannitol, and silicic acid
  • binders as for example, carboxymethylcellulose, alignates, gelatin, polyvinylpyrrolidone, sucrose, and acacia
  • humectants as for example, glycerol
  • disintegrating agents as for example, agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain complex silicates, and sodium carbonate
  • solution retarders as for example, paraffin
  • absorption accelerators as for example,
  • the dosage forms may also comprise buffering agents.
  • Solid compositions of a similar type may also be employed as fillers in soft and hard- filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethyleneglycols, and the like.
  • Solid dosage forms such as tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells, such as enteric coatings and others known in the art.
  • Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, and elixirs.
  • the liquid dosage forms may contain inert diluents commonly used in the art, such as water or other solvents, solubilizing agents, and emulsifiers, such as for example, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propyleneglycol, 1,3- butyleneglycol, dimethylformamide, oils, in particular, cottonseed oil, groundnut oil, corn germ oil, olive oil, castor oil, sesame oil, glycerol, tetrahydrofurfuryl alcohol, polyethyleneglycols, and fatty acid esters of sorbitan, or mixtures of these substances, and the like.
  • the composition can also benzoate, propyleneglycol, 1,3- butylenegly
  • the invention provides a novel approach to treatment of ED and/or male hypogonadism.
  • the therapeutic methods and pharmaceutical compositions disclosed herein can benefit patients in terms of additional treatment options, improved treatment outcome, and/or fewer or less severe side effects.
  • Sildenafil sold under the brand name Viagra® among others, is an agent used to treat erectile dysfunction and pulmonary arterial hypertension. Sildenafil acts by blocking phosphodiesterase 5 (PDE5), an enzyme that promotes breakdown of cGMP, which regulates blood flow in the penis.
  • PDE5 phosphodiesterase 5
  • Cabergoline sold under the brand name Dostinex® among others, is a dopaminergic agent used in the treatment of high prolactin levels, prolactinomas, Parkinson's disease, and other indications. Cabergoline is a potent dopamine D2 receptor agonist.
  • the invention generally relates to a method for treating erectile dysfunction, or a related disease or condition, comprising administering to a male subject in need thereof (a) a therapeutically effective amount of sildenafil, or a pharmaceutically acceptable form thereof, and (b) a therapeutically effective amount of cabergoline, or a therapeutically acceptable form thereof.
  • the invention generally relates to a method for treating male hypogonadism, or a related disease or condition, comprising administering to a male subject in need thereof (a) a therapeutically effective amount of sildenafil, or a pharmaceutically acceptable form thereof, and (b) a therapeutically effective amount of cabergoline, or a therapeutically acceptable form thereof.
  • the invention generally relates to a method for treating erectile dysfunction and male hypogonadism, or a related disease or condition, comprising administering to a male subject in need thereof (a) a therapeutically effective amount of sildenafil, or a pharmaceutically acceptable form thereof, and (b) a therapeutically effective amount of cabergoline, or a therapeutically acceptable form thereof.
  • sildenafil Any pharmaceutically acceptable sildenafil may be used.
  • (a) is sildenafil salt.
  • (a) is sildenafil citrate.
  • cabergoline Any pharmaceutically acceptable cabergoline may be used.
  • (b) is cabergoline in its free form.
  • the subject is administered a daily dose of about 25 mg to about 100 mg (e.g., about 25 mg to about 75 mg, about 50 mg to about 100 mg) of sildenafil, or a pharmaceutically acceptable form thereof, and about 0.125 mg to about 1 mg (c.g., about 0.125 mg to about 0.5 mg, about 0.5 mg to about 1 mg) of cabergoline, or a therapeutically acceptable form thereof.
  • the subject is administered a daily dose of about 50 mg of sildenafil and about 0.25 mg of cabergoline.
  • (a) and (b) are together in a single oral dosage form.
  • the single oral dosage form is a tablet.
  • the single oral dosage form is a capsule.
  • the single oral dosage form is a liquid solution or suspension.
  • (a) and (b) are in two separate oral dosage forms.
  • (a) and (b) are administered twice weekly for a time period of about 1 week to about 2 years (e.g., about 1 week to about 6 months, about 6 months to about 1 year).
  • the method further comprises administering to the subject a further therapy or a further therapeutic agent (e.g., testosterone or clomiphene).
  • a further therapeutic agent e.g., testosterone or clomiphene
  • the invention generally relates to a pharmaceutical composition
  • a pharmaceutical composition comprising (a) a therapeutically effective amount of sildenafil, or a pharmaceutically acceptable form thereof, and (b) a therapeutically effective amount of cabergoline, or a therapeutically acceptable form thereof, and a pharmaceutically acceptable excipient, carrier, or diluent.
  • (a) is sildenafil citrate salt.
  • (b) is cabergoline in its free form.
  • the invention generally relates to a unit dosage form comprising a pharmaceutical composition according to invention.
  • the pharmaceutical composition is suitable for oral administration.
  • the unit dosage form is a tablet or capsule.
  • the unit dosage form is a liquid solution or suspension.
  • the invention generally relates to a kit comprising a unit dosage form of the invention and optionally a unit form of a further therapeutic agent and instructions for administration thereof.
  • the invention generally relates to use of (a) a therapeutically effective amount of sildenafil, or a pharmaceutically acceptable form thereof, and (b) a therapeutically effective amount of cabergoline, or a therapeutically acceptable form thereof, for the manufacture of a medicament for the treatment of erectile dysfunction and/or male hypogonadism, or a related disease or condition.
  • the invention generally relates to use of (a) a therapeutically effective amount of sildenafil, or a pharmaceutically acceptable form thereof, and (b) a therapeutically effective amount of cabergoline, or a therapeutically acceptable form thereof, for treating erectile dysfunction and male hypogonadism.
  • Table 1 lists ingredients for an exemplary formulation according to the invention.
  • Table 2 shows exemplary analytical data from test of exemplary tables.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne une nouvelle composition pharmaceutique comprenant du sildénafil et de la cabergoline et sa méthode d'utilisation pour traiter une dysfonction érectile et/ou un hypogonadisme masculin.
PCT/US2024/055651 2023-11-15 2024-11-13 Compositions et méthodes de traitement d'une dysfonction érectile et d'un hypogonadisme masculin Pending WO2025106494A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202363599019P 2023-11-15 2023-11-15
US63/599,019 2023-11-15

Publications (1)

Publication Number Publication Date
WO2025106494A1 true WO2025106494A1 (fr) 2025-05-22

Family

ID=95743458

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2024/055651 Pending WO2025106494A1 (fr) 2023-11-15 2024-11-13 Compositions et méthodes de traitement d'une dysfonction érectile et d'un hypogonadisme masculin

Country Status (1)

Country Link
WO (1) WO2025106494A1 (fr)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110182997A1 (en) * 2008-02-01 2011-07-28 Vectura Limited Suspension formulations
US20150018324A1 (en) * 2010-12-10 2015-01-15 Basawaraj Chickmath Testosterone undecanoate compositions
US20210221793A1 (en) * 2014-09-17 2021-07-22 Cyclerion Therapeutics, Inc. Pyrazole derivatives as sgc stimulators
US20230285283A1 (en) * 2020-07-29 2023-09-14 Kydes Pharmaceuticals, Llc Pharmaceutical formulations comprising tadalafil

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110182997A1 (en) * 2008-02-01 2011-07-28 Vectura Limited Suspension formulations
US20150018324A1 (en) * 2010-12-10 2015-01-15 Basawaraj Chickmath Testosterone undecanoate compositions
US20210221793A1 (en) * 2014-09-17 2021-07-22 Cyclerion Therapeutics, Inc. Pyrazole derivatives as sgc stimulators
US20230285283A1 (en) * 2020-07-29 2023-09-14 Kydes Pharmaceuticals, Llc Pharmaceutical formulations comprising tadalafil

Similar Documents

Publication Publication Date Title
CA2762013C (fr) Granulation de pirfenidone et excipients pharmaceutiquement acceptables
EP3233809B1 (fr) Formulations de 2-(tert-butylamino)-4-((1r,3r,4r)-3-hydroxy-4-méthylcyclohexylamino)-pyrimidine-5-carboxamide
KR20110062943A (ko) 퀴나졸린 유도체를 유효성분으로 하는 전립선 비대증 예방 또는 치료제
EP3801534B1 (fr) Traitement de la phénylcétonurie par la sépiaptérine
US12291528B2 (en) Crystalline imidazo[4,5-b]pyridine compound, pharmaceutical compositions, and their use in treating medical conditions
JPH0761923A (ja) アルツハイマー病治療剤
KR100443891B1 (ko) 당뇨병성합병증의예방·치료제
WO2025106494A1 (fr) Compositions et méthodes de traitement d'une dysfonction érectile et d'un hypogonadisme masculin
JP2024513830A (ja) 微粉化ソラベグロンの組成物およびその使用方法
US20250025444A1 (en) Treatment of neurodegenerative diseases via administration of buntanetap and a phosphodiesterase inhibitor
EP3332779B1 (fr) Agent visant à remédier à l'hyperactivité du détrusor avec altération de la contractilité
KR102208221B1 (ko) 신경근육질환의 예방 또는 치료용 약학적 조성물
EP4585214A1 (fr) Agent prophylactique ou thérapeutique pour porphyria
AU2013201986B2 (en) Capsule Formulation Of Pirfenidone And Pharmaceutically Acceptable Excipients
TW202527911A (zh) 用於治療猝睡症的化合物
AU2014240300C1 (en) Capsule Formulation of Pirfenidone and Pharmaceutically Acceptable Excipients
HK40128459A (en) Prophylactic or therapeutic agent for porphyria
KR101086895B1 (ko) 시부트라민 및 티옥트산을 포함하는 약제학적 조성물
WO2021125313A1 (fr) Agent thérapeutique contenant un composé de pyrimidine en tant que principe actif
HK40062237A (en) A3 adenosine receptor ligand for use for achieving a fat loss effect
HK40051961B (en) Administration of sepiapterin without food for use in a method for increasing sepiapterin plasma exposure
HK40051961A (en) Administration of sepiapterin without food for use in a method for increasing sepiapterin plasma exposure
JP2002524508A (ja) 新規組成物
EP1706117A1 (fr) Methode de traitement des troubles de l'erection
HK1209342B (en) A3 adenosine receptor ligands for use in treatment of a sexual dysfunction

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 24892109

Country of ref document: EP

Kind code of ref document: A1