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EP1404336A1 - Compositions comprenant un inhibiteur de cgmp pde5 pour administration transdermique au tissu erectile du penis - Google Patents

Compositions comprenant un inhibiteur de cgmp pde5 pour administration transdermique au tissu erectile du penis

Info

Publication number
EP1404336A1
EP1404336A1 EP01274318A EP01274318A EP1404336A1 EP 1404336 A1 EP1404336 A1 EP 1404336A1 EP 01274318 A EP01274318 A EP 01274318A EP 01274318 A EP01274318 A EP 01274318A EP 1404336 A1 EP1404336 A1 EP 1404336A1
Authority
EP
European Patent Office
Prior art keywords
penis
transdermal delivery
pharmaceutical composition
pharmaceutically acceptable
inhibitor
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.)
Withdrawn
Application number
EP01274318A
Other languages
German (de)
English (en)
Inventor
Sampad Bhattacharya
Kiran Kumar Tumbalam
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
Priority claimed from IN551MU2001 external-priority patent/IN190569B/en
Priority claimed from IN552MU2001 external-priority patent/IN190495B/en
Application filed by Individual filed Critical Individual
Publication of EP1404336A1 publication Critical patent/EP1404336A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • 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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • 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
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence

Definitions

  • the invention relates to a pharmaceutical composition
  • a pharmaceutical composition comprising cyclic guanosine monophosphate phosphodiesterase type 5 (cGMP PDE5) inhibitor, sildenafil citrate, pharmaceutically acceptable solubilisers and penetration enhancers, along with thickening agents, buffers, emulsifiers and / surfactants and preservatives, for transdermal delivery to the erectile tissue of the penis, a process of preparing the said composition and method for treatment of erectile dysfunction / vasculogenic impotence by direct/topical application of the transdermal composition to the tissues covering the corpus cavernosum and to the glans penis.
  • the transdermal delivery vehicle for topical application of the composition according to this invention may be in various forms such as gels, ointments, creams, lotions, emulsions and sprays.
  • erectile dysfunction there is a consistent inability to achieve or sustain an erection of sufficient rigidity for sexual intercourse, which may be manifested in many ways, and the causes can be vasculogenic, neurogenic, endocrinoiogic and psychogenic.
  • Vasculogenic impotence is thought to be the frequent cause of impotence.
  • blood flow in the vasculature of the penis is insufficient to obtain and / or maintain an erect state.
  • cGMP PDE5 inhibitors block the action of endogenous cGMP PDE5 which causes increased levels of cGMP in the corpus cavernosum tissue of penis resulting in smooth muscle relaxation and inflow of blood to the corpus cavernosum and subsequent erection.
  • compositions comprising sildenafil citrate are known wherein the dosage forms used for administration of active ingredients in patients are tablets for oral administration, nasal spray, buccal delivery, and rectal delivery.
  • the very route of administration limits the amount of the active ingredient, which can be made available to render any pharmacological effect.
  • the anatomy of the nose does not permit for administration of compositions upwards of 150 microlitres.
  • the intended effect is achieved by the drug entering the systemic circulation at a site which is far form the site of action, which necessitates increasing amounts of drug to be administered which is likely to cause the same side effects associated with oral drug therapy as only very potent drugs are normally effectively administered via the Nasal route for any systemic effect.
  • the amount of active ingredient that can be made available is not limited as in case of Nasal spray, but since therapeutic levels of drug in the blood achieve the intended effect, the associated side effects will manifest in a similar fashion as in case of Oral therapy.
  • compositions comprising cGMP PDE5 inhibitors sildenafil citrate by oral, buccal, sublingual or nasal methods have different drawbacks.
  • the main object of this invention is to provide a new different method and pharmaceutical composition comprising cGMP PDE5 inhibitor in combination with transdermal delivery vehicles for treating erectile dysfunction in patients by topical application directly to the tissues covering the corpus cavernosum and to the glans penis so that even a small amount of active ingredient that penetrates through the tissue layers covering the corpus cavernosum is enough to elicit the required pharmacological response and there is a scope for almost nil or very negligible amounts of the active ingredient to reach the systemic circulation, thus avoiding all " possible side effects.
  • Another object of this invention is to provide a new and different method and composition for treating of erectile dysfunction, which addresses the need of different patients more particularly in patients with cardiac, and stroke risks.
  • Further object of this invention is to provide a new and different method and composition for treatment of erectile dysfunction which improves the quality of life in patients who might suffer from side effects like colour vision or headache.
  • Further object of this invention is to provide a new and different method and composition for treatment of erectile dysfunction, which permits rapid response and eliminates the waiting period i.e. is associated with oral and any other therapy know in the prior art.
  • the present invention relates to pharmaceutical compositions which include a therapeutically effective amount of sildenafil citrate solubilised or dispersed in pharmaceutically acceptable solubilisers and penetration enhancers, along with the thickening agents, buffers, emulsifiers and pharmaceutically acceptable surfactants and preservatives as will be appreciated by those skilled in the art of drug formulation, preparation and delivery, to provide a method for safely and conveniently administering cGMP PDE5 inhibitor sildenafil citrate in patients for treatment of erectile dysfunction.
  • the method comprises direct administration of an effective amount of sildenafil citrate to the penis to produce an erection sufficient to permit intercourse.
  • the invention provides a method of treating erectile dysfunction.
  • This method includes administering to the tissues covering the corpus cavernosum and to the glans penis a therapeutically effective dosage of cGMP PDE5 inhibitor sildenafil citrate in combination with a transdermal delivery vehicle that includes solubilisers, penetration enhancers, thickening agents, surfactants and preservatives.
  • Preferred formulations for transdermal use herein are gels, ointments, creams, lotions, emulsions and sprays. All these preparations contain solubilisers by which cGMP PDE5 inhibitor sildenafil citrate is in a solubilised or dispersed form and penetration enhancers, which will facilitate therapeutic drug concentrations at the site of action, the corpus cavernosum tissue of the penis.
  • a topical application dosage unit for transdermal delivery for treating erectile dysfunction in patients.
  • This dosage unit includes an effective amount of a cyclic guanosine monophosphate phosphodiesterase inhibitor in combination with a topical application formulation for transdermal delivery.
  • These formulations contain pharmaceutically acceptable solubilisers, penetration enhancers, thickening agents, buffers, emulsifiers, surfactants and preservatives.
  • solubilisers, penetration enhancers and surfactants are selected to facilitate effective concentration of sildenafil citrate at the site of action, the corpus cavernosum tissue of penis.
  • the present invention is directed to pharmaceutical compositions and methods for treating erectile dysfunction in patients.
  • the compositions include a cyclic guanosine monophosphate phosphodiesterase type 5 inhibitor in combination with a transdermal delivery vehicle.
  • erectile dysfunction is indicated to involve medically related symptoms resulting in the inability of a male to perform sexually including impotence.
  • impotence is used to indicate an inability to achieve or sustain an erection of sufficient rigidity for vaginal penetration and sexual intercourse.
  • phosphodiesterase inhibitor as used herein is intended to mean an agent that is capable of inhibiting or selectively reducing the activity of any one or more phosphodiesterases.
  • the phosphodiesterase inhibitor is sildenafil citrate also known as l-[[3-(6,7-dihydro-l-methyl-7-oxo-3-propyl-lH-pyrazolo [4,3-d] pyrimidin- 5-yl)-4-ethoxyphenyl] sulfonyl]-4-methylpiperazine citrate.
  • transdermal delivery includes both transdermal (percutaneous) and transmucosal administration i.e.
  • transdermal delivery is achieved by topical application of the pharmaceutical compositions in a sufficient quantity to the skin of the penis and by application to the tissues covering the corpus cavernosum and to the glans penis which are exposed when the foreskin of the penis is retracted and folded back.
  • penetration enhancers used herein relates to an increase in the permeability of the skin of the penis and the tissues covering the corpus cavernosum and the glans penis to the cGMP PDE5 inhibitor.
  • cGMP PDE5 inhibitor a sufficient amount of the cGMP PDE5 inhibitor to provide the desired effect i.e. treatment of erectile dysfunction.
  • delivery vehicle refers to carrier materials suitable for topical application for transdermal delivery.
  • Carriers or vehicles used herein include any such material known in the art which are nontoxic and do not interact with other components of the composition in a deleterious manner.
  • topical application is used to mean external application to the skin or mucosa of the composition to ultimately deliver transdermally cGMP PDE5 inhibitor to the site of action, the corpus cavernosum tissue of the penis.
  • transdermal delivery vehicles for topical application can take various forms including for example, gels, ointments, creams, lotions and sprays.
  • the various forms of the delivery vehicle are made by solubilising or dispersing Sildenafil Citrate in pharmaceutically acceptable solubilisers and can include pharmaceutically acceptable penetration enhancers, thickening agents, emulsifiers, surfactants and preservatives.
  • the solubilisers in the delivery vehicle of the present invention include for example diethyleneglycol monoethyl ether, polyoxyl 35 castor oil, polyoxyl 40 hydrogenated castor oil, dimethyl isosorbide, 2-pyrrolidone, N-methyI-2- pyrrolidone, propylene glycol, glycerin, and mixtures thereof.
  • concentration of the solutions will depend upon the type of delivery vehicle selected. Such agents will also be used as penetration enhancers in the delivery vehicle of the present invention.
  • the viscosity of the delivery vehicles of the present invention can be maintained at a desired level using pharmaceutically acceptable thickening agents.
  • Thickening agents that can be used in accordance with the present invention include carbomer, cetostearyl alcohol, stearic acid, polyethylene glycols, poloxamers, paraffins, stearyl alcohols, polyvinyl alcohol, polycarbophils, methyl hydroxy ethyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose sodium, microcrystalline wax, and mixtures thereof.
  • the concentration of the thickening agent will depend upon the type of delivery vehicle selected and the viscosity desired.
  • the emulsifiers, in the delivery vehicles of the present invention that can be used include polyoxyl-35 castor oil, cetomacrogol 1000, glyceryl stearate and polyethylene glycol 75 stearate, polyoxyl 40- hydrogenated castor oil, polyethylene glycol-6-32 stearate and glycol stearate, polysorbate 80 and mixtures thereof.
  • concentration of the emulsifiers will depend upon the type of delivery vehicle selected. Such agents can also be used as surfactants and may be present in a concentration ranging from about 0.001 to 30% by weight.
  • compositions may also be included into the transdermal delivery vehicle provided they do not interfere with the action or decrease the penetration of the inhibitor.
  • Such pharmaceutically acceptable excipients may be preservatives.
  • Preservatives that can be used with the present delivery vehicles include methyl paraben, propyl paraben, ethyl paraben, butyl paraben, sodium benzoate and combinations thereof.
  • the preservatives will be present in the present delivery vehicles in a concentration of upto about 0.6% by weight.
  • the composition, as described above are applied topically to the skin of the penis and to the tissues covering the corpus cavernosum and glans penis when the foreskin is retracted and folded, to treat erectile impotence.
  • “applied topically” or “topical application” is intended to mean that the cGMP PDE5 inhibitor is combined with a suitable delivery vehicle for transdermal delivery or absorption to the corpus cavernosum tissue of the penis.
  • compositions for transdermal delivery which may include a therapeutically, effective amount of cGMP PDE5 inhibitor solubilised or dispersed in a pharmaceutically acceptable solubilisers, thickening agents and pharmaceutically acceptable emulsifiers and surfactants.
  • “Therapeutically significant” amount as used herein means a unit dosage of the present vehicle to be applied to the skin of the penis and the tissues covering the corpus cavernosum of the penis in patients to render the intended physiological effect i.e. to allow an erection in impotent patients.
  • the cGMP PDE5 inhibitor is desirably l-[[3-(6,7-dihydro-l-methyl-7-oxo-3-propyl- lH-pyrazolo [4,3-d] pyrimidin-5-yl)-4-ethoxyphenyl] sulfonyl]-4-methylpiperazine citrate.
  • a method for treating impotence includes topical application to the penis for transdermal delivery through the tissues covering the corpus cavernosum and glans penis a therapeutically effective dosage of cGMP PDE5 inhibitor in combination with a transdermal delivery vehicle.
  • the inhibitor used herein is sildenafil citrate.
  • a further embodiment of the present invention include a transdermal delivery dosage unit by topical application for treating impotency in patients.
  • This transdermal delivery dosage unit includes an effective amount of cGMP PDE5 inhibitor, sildenafil citrate in combination with pharmaceutically acceptable delivery vehicle.
  • This delivery vehicle includes solubilisers, penetration enhancers, thickening agents and pharmaceutically acceptable surfactants and preservatives.
  • the pH of the delivery vehicle is selected so as to facilitate cGMP PDE5 inhibitor permeation through the tissue covering the corpus cavernosum and the glans penis, and is adjusted between 4 to 8 by selecting the concentration of the buffers and mixtures thereof.
  • Buffers that may be suitable for use in the present invention include for example phosphate, acetate, citrate, citrophosphate and tris buffers.
  • Suitable dosage forms developed with the present cGMP PDE5 inhibitor, sildenafil citrate are found in Remingtons pharmaceutical sciences 19 th edition, which is incorporated by reference, and include gels, ointments, creams, lotions and sprays.
  • Process of preparing the composition according to this invention comprises the following steps: i. Sildenafil Citrate is solubilised or dispersed in a mixture of solvents, co- solvents and/or penetration enhancers as herein described, the preservatives as herein described are further dissolved in the same; ii. The thickening agent as herein described are melted by heating or dispersed in Purified Water as the case may be; iii. The solution of step 1 is mixed with the thickening agent as herein described properly to obtain a homogenous mixture; iv. Adequate buffering agents and/or pH adjusting agent as herein described are added slowly to the above and mixed properly; v. Where necessary the congealed mass of Ointment or Cream may be homogenised or passed through a Colloidal mill and again mixed properly; vi. The finished product is then filled in different dosage units.
  • a preferred embodiment was prepared by solubilising the cGMP PDE5 inhibitor, Sildenafil Citrate 2.8 g in a mixture of 2-pyrrolidone 30 g, N-methyl 2-pyrrolidone 5 g, Polyoxyl 40 Hydrogenated Castor Oil 2g. Added Methyl Paraben 0.1 g, Propyl Paraben 0.01 g to the above mixture and stirred to dissolve. Added Poloxamer to Purified Water and stirred to dissolve and mixed the above solution under stirring to form a Gel. The gel was filled in tubes and jars.
  • Solubilised cGMP PDE5 inhibitor Sildenafil Citrate 2.8 g in a mixture of N-methyl 2- pyrrolidone 25 g, Propylene Glycol 3 g, Added Methyl Paraben 0.1 g, Propyl Paraben 0.01 g to the above and stirred to dissolve, Added Purified Water to the above and heated to 60 degree centigrade, Heated a mixture of Cetostearyl Alcohol 5.6 g, Cetomacrogol-1000, 1.5 g, White Soft Paraffin 5 g and Liquid Paraffin 5 g to 65 degree centigrade, Mixed both the aqueous and oily phases and stirred continuously till the mixture cooled and formed the Cream.
  • Solubilised Sildenafil Citrate 2.8 g in a mixture of 2-pyrrolidone 30 g, Diethylene Glycol Monoethyl Ether 10 g, Glycerin lOg and added Methyl Paraben 0.1 g and Propyl Paraben 0.01 g and stirred to dissolve, Dispersed Carbomer 980 0.4 g, in Purified Water and to it added the above solution and stirred well, Added Triethanolamine 0.2 g drop by drop under continuous stirring and mixed properly. The Lotion was filled in containers.
  • Example : 6 A preferred embodiment was prepared by solubilising the cGMP PDE5 inhibitor, Sildenafil Citrate 2.8 g in a mixture of 2-pyrrolidone 30 g, N-methyl 2-pyrrolidone 5 g, Polyoxyl 40 Hydrogenated Castor Oil 2 g. Added Methyl Paraben 0.1 g, Propyl Paraben 0.01 g to the above mixture and stirred to dissolve. Added Poloxamer to Purified Water and stirred to dissolve. Added 20 ml of Acetate Buffer pH 4 to the drug solution and mixed. Mixed the drug solution containing buffer with dispersion of Poloxamer under stirring to form a Gel. The gel was filled in tubes and jars.
  • Topicically applied delivery vehicles comprising sildenafil citrate for transdermal delivery to the erectile tissue of the penis
  • Topicically applied delivery vehicles comprising sildenafil citrate for transdermal delivery to the erectile tissue of the penis
  • the invention relates to a new and different method and compositions for treatment of erectile dysfunction which addresses the needs of different patients more particularly in patients with cardiac, and stroke risks where oral or other types of administration pose enormous risk and also helps improve the quality of life in patients who might suffer from side effects like Colour vision or Headache.
  • the invention allows direct application of the transdermal preparation to the tissues covering the corpus cavernosum and to the glans penis.
  • the preparation contains penetration enhancers, which will facilitate effective concentrations of Sildenafil Citrate at the site of action i.e. the corpus cavernosum.
  • sildenafil Citrate for erectile dysfunction is the corpus cavernosum in the penis.
  • the amount of active ingredient that normally permeates across the dermal and subdermal tissues is one-tenth to two tenths of the amount applied.
  • the composition is applied directly to the intended site of action, even a small amount of active ingredient that permeates through the tissue layers that cover the corpus cavernosum, is enough to elicit the required pharmacological response. Also there is scope for almost nil or very negligible amounts of the active ingredient to reach the systemic circulation, thus avoiding all possible side effects
  • Sildenafil Citrate has been classified broadly as a drug that has changed the life style of various patients, suffering from vassculogenic impotence the method of administration permits rapid response and eliminates the waiting period that is associated with oral and any other therapy.

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  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Gynecology & Obstetrics (AREA)
  • Reproductive Health (AREA)
  • Engineering & Computer Science (AREA)
  • Urology & Nephrology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Endocrinology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Dermatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne une composition pharmaceutique comprenant un inhibiteur de la cGMP phosphodiestérase de type 5, du citrate de Sildenafil, des agents de solubilisation et améliorant la pénétration, acceptables sur le plan pharmaceutique, des agents épaississants, des tampons, des émulsifiants ainsi que des tensioactifs et des conservateurs, acceptables sur le plan pharmaceutique, cette composition étant destinée à âtre administrée par voie transdermique dans le tissu érectile du pénis. L'invention concerne aussi un procédé de préparation de cette composition ainsi qu'une méthode de traitement du dysfonctionnement érectile et de l'impuissance vasculogène par application directe/topique de la composition transdermique sur des tissus recouvrant le corps caverneux et sur la muqueuse du gland. Le support d'administration pour une application topique de la composition, selon l'invention, peut se trouver sous des formes variées, notamment de gel, d'onction, de crème, de lotion, d'émulsion et d'aérosol.
EP01274318A 2001-06-14 2001-11-27 Compositions comprenant un inhibiteur de cgmp pde5 pour administration transdermique au tissu erectile du penis Withdrawn EP1404336A1 (fr)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
INMU02001551 2001-06-14
IN551MU2001 IN190569B (fr) 2001-06-14 2001-06-14
IN552MU2001 IN190495B (fr) 2001-06-14 2001-06-14
INMU02001552 2001-06-14
PCT/IN2001/000210 WO2002102385A1 (fr) 2001-06-14 2001-11-27 Compositions comprenant un inhibiteur de cgmp pde5 pour administration transdermique au tissu erectile du penis

Publications (1)

Publication Number Publication Date
EP1404336A1 true EP1404336A1 (fr) 2004-04-07

Family

ID=26324905

Family Applications (1)

Application Number Title Priority Date Filing Date
EP01274318A Withdrawn EP1404336A1 (fr) 2001-06-14 2001-11-27 Compositions comprenant un inhibiteur de cgmp pde5 pour administration transdermique au tissu erectile du penis

Country Status (2)

Country Link
EP (1) EP1404336A1 (fr)
WO (1) WO2002102385A1 (fr)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010044094A2 (fr) * 2008-09-03 2010-04-22 Krishna Radharaman Agarwal Composition topique pour traiter un dysfonctionnement érectile
CN102740891B (zh) * 2010-02-05 2016-08-10 磷肌酸有限公司 载体组合物
WO2012058573A1 (fr) * 2010-10-29 2012-05-03 University Of Medicine And Dentistry Of New Jersey Utilisation d'un inhibiteur de la phosphodiestérase pour stimuler l'érection post-chirurgicale chez des hommes subissant une prostatectomie radicale
TWI422399B (zh) * 2011-01-21 2014-01-11 Tritech Biopharmaceuticals Co Ltd 促進第五型磷酸二酯酶抑制劑經皮吸收的醫藥組成物
ES2395801B1 (es) * 2011-06-23 2014-06-06 María Carmen PARDINA PALLEJÀ "pentoxifilina por vía transvaginal para el tratamiento de la infertilidad"
JP5872060B2 (ja) 2011-12-26 2016-03-01 トライテック バイオファーマシューティカルズ カンパニー リミテッドＴｒｉｔｅｃｈ Ｂｉｏｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｃｏ．， Ｌｔｄ． Ｐｄｅ−５インヒビターの経皮送達を増強するための方法および改良された医薬組成物
US20150099751A1 (en) * 2013-10-07 2015-04-09 King Abdulaziz University In situ gel loaded with phosphodiesterase type v inhibitors nanoemulsion

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SE463851B (sv) * 1988-09-02 1991-02-04 Amsu Ltd Komposition foer behandling av erektil dysfunktion via uretra
GB9301192D0 (en) * 1993-06-09 1993-06-09 Trott Francis W Flower shaped mechanised table
CA2291256A1 (fr) * 1997-05-29 1998-12-03 Mochida Pharmaceutical Co., Ltd. Agent therapeutique destine a traiter la dysfonction erectile
US6127363A (en) * 1997-10-28 2000-10-03 Vivus, Inc. Local administration of Type IV phosphodiesterase inhibitors for the treatment of erectile dysfunction
US6156753A (en) * 1997-10-28 2000-12-05 Vivus, Inc. Local administration of type III phosphodiesterase inhibitors for the treatment of erectile dysfunction
TW542719B (en) * 1998-02-23 2003-07-21 Pfizer Res & Dev Method of treating impotence due to spinal cord injury
DE19834505A1 (de) * 1998-07-31 2000-02-03 Hexal Ag Transdermales therapeutisches System zur Anwendung von Sildenafil
DE19834506A1 (de) * 1998-07-31 2000-02-03 Hexal Ag Transmucosales therapeutisches System zur Anwendung von Sildenafil

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Publication number Publication date
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