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WO2017017511A1 - Formulation à libération modifiée pour le traitement de l'éjaculation précoce - Google Patents

Formulation à libération modifiée pour le traitement de l'éjaculation précoce Download PDF

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Publication number
WO2017017511A1
WO2017017511A1 PCT/IB2016/000223 IB2016000223W WO2017017511A1 WO 2017017511 A1 WO2017017511 A1 WO 2017017511A1 IB 2016000223 W IB2016000223 W IB 2016000223W WO 2017017511 A1 WO2017017511 A1 WO 2017017511A1
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WO
WIPO (PCT)
Prior art keywords
release
tramadol
ejaculation
minutes
composition
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.)
Ceased
Application number
PCT/IB2016/000223
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English (en)
Inventor
Selim KAMEEL
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Individual
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Individual
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Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of WO2017017511A1 publication Critical patent/WO2017017511A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • 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
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives

Definitions

  • the present invention generally relates to the treatment of premature ejaculation, more specifically relates to a pharmaceutical composition formulated for timed release of therapeutically effective amounts of active compounds which delay the onset of ejaculation in male patients.
  • PME Premature ejaculation
  • PME is not just a medical condition, but also a psychological condition. Both men and women consider it as failure as their mutual needs are unfulfilled, especially causing a huge embarrassment for men.
  • the above condition of PME may jeopardize relationships, resulting in loss of spouse, causes shame in social or family circle, instils fear of failure and even earns bad reputation for men.
  • the condition will also affect their ability to work to their fullest potential or failing completely due to loss of self-esteem, self-confidence as well as their ability to focus and concentrate on their work related tasks. Due to the above reasons, there is a very strong need for more effective and reliable treatment for PME.
  • Existing treatment options for PME includes drug therapy, behavioral therapy, psychological counseling and mechanical devices. All of these methods may have significant drawbacks. For example, use of topical local anesthetics such as lidocaine may result in loss of erection, and decrease the sensitivity of tissues. Use of antidepressants can cause side effects like nausea, dizziness and unwanted mood alterations. The improvements brought about by behavioral or psychological therapy is short lived and have a moderate success rate. Mechanical devices are relatively unpopular due to factors-like embarrassment to use and physical discomfort. [5] With the option of drug therapy, most of the existing medications for PME may result in little improvement in delaying the onset of ejaculation, especially when compared to placebo time.for example, improvement of 2-3 times than the placebo time.
  • the time delay in ejaculation induced by existing drug formulations highly depend on non-medicated time delay of a patient. For example, if non- medicated time delay for PME patient is 56 seconds, then the time delay for ejaculation can be increased only up to 96 seconds using existing medication. Any drug used for the treatment of PME should be reliable, providing a minimum time delay of 20 minutes before onset of ejaculation and 20 folds increase in time delay when compared to placebo time delay and should not depend on non-medicated time delay of patient.
  • the present invention relates to a modified release pharmaceutical composition for treating premature ejaculation.
  • the composition is formulated for timed release of therapeutically effective amounts of active compounds essentially comprises of tramadol, rabeprazole, cetirizine, sildenafil in their pharmaceutically acceptable salts thereof.
  • the composition further comprises pharmaceutically acceptable carriers thereof.
  • the timed release formulation of the present invention refers to modified and immediate release of the prescribed doses at the specified time.
  • the pharmaceutical composition of the present invention comprises a timed release formulation, comprising tramadol, rabeprazole, cetirizine hydrochloride at a pharmacologically active concentration of SO mg, 20mg and lOmg respectively formulated for immediate release, and sildenafil at active concentration of lOOmg is formulated for timed release after 4 hours.
  • the above composition is formulated for delaying the onset of ejaculation by approximately 20 minutes.
  • the pharmaceutical composition of the present invention comprises a timed release formulation comprising tramadol, rabeprazole, cetirizine hydrochloride at an active concentration 50mg, 20mg and lOmg respectively, formulated for immediate release and further tramadol SOmg formulated for timed release at 20 minutes, and sildenafil lOOmg formulated for timed release at 4 hours.
  • the above composition is formulated for delaying the onset of ejaculation by approximately 40 minutes.
  • the pharmaceutical composition of the present invention comprises a timed release formulation, comprising tramadol at lOOmg, rabeprazoleat 20mg, cetirizine hydrochloride at . lOmg formulated Tor immediate release and the composition further comprises tramadol SOmg formulated for timed release at 20 minutes and , sildenafil citrate lOOmg are formulated for timed release at 4 hours.
  • the above composition is formulated for delaying the onset of ejaculation by approximately 60 minutes.
  • the pharmaceutical composition of the present invention comprise a timed release formulation for delaying the onset of ejaculation irrespective of non- medicated time delay of a patient.
  • FIG. 1 shows a chart illustrating timed release of different doses of Zyrtec, Tramal, Pariet and sildenafil.
  • FIG. 2 shows a chart illustrating the minutes of delay in onset of ejaculation caused by timed release formulation of the present invention compared with other drug products at different dosage strengths.
  • compositions comprising a plurality of dosage amounts, each comprising, together with pharmaceutical excipients suitable for oral administration, a therapeutically effective dosage amounts of tramadol, rabeprazole, cetirizine, and sildenafil in their pharmaceutically acceptable salts thereof for the treatment of premature ejaculation in male individuals.
  • active agent drug
  • active compound active compound
  • pharmacologically active agent refers to a chemical material or compound which, when administered to human, induces a desired pharmacologic effect. Included are derivatives and analogs of those compounds or classes of compounds specifically mentioned which also induce the desired pharmacologic effect.
  • Premature ejaculation refers to persistent or recurring ejaculation with minimal stimulation before or during sexual intercourse. The term includes both "congenital” or “lifelong” premature ejaculation and “primary” or “acquired” premature ejaculation.
  • “Pharmaceutically acceptable salt” refers to a salt of a compound, which possesses the desired pharmacological activity of the parent compound.
  • Such salts include: acid addition salts, formed with inorganic acids; acid addition salts formed with organic acids; or salts formed when an acidic proton present in the parent compound is replaced by a metal ion, e.g., an alkali metal ion, aluminum ion; or coordinates with an organic base such as ethanolamine, and the like.
  • compositions are composed of materials that are present in pharmaceutical formulation other than the active ingredient. Carriers are considered safe and effective and may be administered to an individual without causing undesirable biological side effects.
  • carrier includes, but is not limited to, diluents, binders, lubricants, disintegrators, fillers, and coating compositions.
  • “Therapeutically effective amount” refers to the amount of an active compound that, when administered to a male patient for treating premature ejaculation, is sufficient to effect such treatment.
  • the “therapeutically effective amount” may vary depending on the active compound, the disease and its' severity and the age, weight, etc., of the patient to be treated.
  • timed release refers to total release of the prescribed doses of active compounds at the specified time.
  • the present invention relates to a modified release pharmaceutical composition for treating premature ejaculation.
  • the composition is formulated for timed release of therapeutically effective amounts of active compounds essentially comprising of tramadol, rabeprazole, cetirizine, and sildenafil in their pharmaceutically acceptable salts thereof in their pharmaceutically acceptable forms thereof.
  • active compounds essentially comprising of tramadol, rabeprazole, cetirizine, and sildenafil in their pharmaceutically acceptable salts thereof in their pharmaceutically acceptable forms thereof.
  • One or. more of the active compounds are formulated to comprise an immediate release profile, a timed release profile and its combination.
  • Timed release formulations are created by coating a solid dosage form with a film of polymer which is insoluble in the acid environment of the stomach, and soluble in the neutral environment of small intestines.
  • the timed release dosage units can be prepared, for example, by coating a drug or a drug-containing composition with a selected coating material.
  • the drug-containing composition may be, e.g., a tablet or a tablet for incorporation into a capsule, a tablet for use as an inner core in a "coated core" dosage form, or a plurality of drug-containing beads, particles or granules, for incorporation into either a tablet or capsule.
  • the pharmaceutical composition of the present invention comprises a timed release formulation, which can include pharmacologically active concentration of tramadol, rabeprazole, cetirizine hydrochloride formulated for immediate release.
  • the composition comprises a combination of sildenafil at an active concentration formulated for timed release after 4 hours. The above composition is formulated for delaying the onset of ejaculation by approximately 20 minutes.
  • tramadol constitutes an opioid pain reliever which acts by binding to opioid receptor and inhibiting reuptake of serotonin and norepinephrine.
  • Rabeprazole is selected from a class of proton pump inhibitors.
  • Cetirizine is an antihistamine which acts as racemic selective HI receptor antagonist.
  • Sildenafil acts by inhibiting cGMP-specific phosphodiesterase type S.
  • the pharmaceutical composition of the present invention comprises a timed release formulation which contains active concentration of tramadol, rabeprazole, cetirizine hydrochloride, all three active compounds formulated for immediate release.
  • the composition further comprises tramadol formulated for * timed release at 20 minutes, tramadol formulated for timed release at 40 minutes and sildenafil formulated for timed release at 4 hours.
  • the above composition is formulated for delaying the onset of ejaculation by approximately 40 minutes.
  • the pharmaceutical composition of the present invention comprises a timed release formulation, which can include tramadol, rabeprazole, cetirizine hydrochloride formulated for immediate release.
  • the composition further comprises tramadol formulated fpr timed release at 20 minutes.
  • sildenafil citrate and cetirizine hydrochloride are formulated for timed release at once after 4 hours of dosing.
  • the above composition is formulated for delaying the onset of ejaculation by approximately 60 minutes.
  • the present pharmaceutical composition acts by delaying the onset of ejaculation in male patients, wherein the drug induced time delay is independent of non-medicated time delay for ejaculation.
  • the time delay created by the present pharmaceutical composition is 20 times more than placebo induced time delay in patients with premature ejaculation.
  • the composition is formulated in a single tablet or capsule, configured to release therapeutically effective amounts of one or more active compounds in a timed sequence.
  • Timed release formulation of the present invention comprises full quantitative timely release (FQTR), which denotes full release of a certain dose at a specific point of time.
  • Existing oral medication options for treating the condition of PME generally doubles the non-medicated time delay for ejaculation. For example, if the non- medicated time delay is 2 minutes and medicine induced time delay would be approximately 4 minutes. Whereas the present pharmaceutical composition is formulated to provide a minimum time delay of at least 20 minutes irrespective of non-medicated time delay. Moreover, the present oral drug composition is formulated into different strengths as exemplified in the above embodiments, thus providing patients with different options to choose from, based on their needs.
  • the pharmaceutical composition of the present invention comprise a timed release formulation, hereinafter referred to as first or lower strength, including tramadol SOmg, rabeprazole 20mg, cetirizine hydrochloride lOmg formulated for immediate release.
  • the composition comprises a combination of sildenafil lOOmg formulated for timed release after 4 hours.
  • first or lower strength including tramadol SOmg, rabeprazole 20mg, cetirizine hydrochloride lOmg formulated for immediate release.
  • the composition comprises a combination of sildenafil lOOmg formulated for timed release after 4 hours.
  • the pharmaceutical composition of the present invention comprise a timed release formulation, hereinafter referred to as second or medium strength, including tramadol SOmg, rabeprazole 20mg, cetirizine hydrochloride lOmg, all three active compounds formulated for immediate release.
  • the composition further comprises tramadol SOmg formulated for timed release at 20 minutes, and sildenafil lOOmg formulated for timed release at 4 hours.
  • the above composition is formulated for resulting in,an ejaculation time delay of approximately 40 minutes.
  • the pharmaceutical composition of the present invention comprise a timed release formulation, hereinafter referred to as third strength, including tramadol lOOmg, rabeprazole 20mg, cetirizine hydrochloride lOmg formulated for immediate release.
  • the composition further comprises tramadol SOmg formulated for timed release at 20 minutes.
  • sildenafil citrate lOOmg is formulated for timed release at once after 4 hours of dosing.
  • the above composition is formulated for resulting in an ejaculation time delay of approximately 60 minutes.
  • FIG.l shows a chart illustrating different doses of Zyrtec, Tramal, Pariet and sildenafil formulated for timed release at 0 hours, 20 minutes and 4 hours after dosing.
  • Zyrtec lOmg, Tramal lOOmg and Pariet 20mg were formulated for immediate release at 0 minutes, Tramal SOmg formulated for timed release at 20 minutes after dosing, and Sildenafil lOOmg formulated for timed release at 4 hrs after dosing.
  • FIG. 2 shows a line chart illustrating the minutes of delay in onset of ejaculation, caused by the timed release formulation in different strengths (first, second and third strengths) as given in the above examples.
  • the chart also shows minutes of delay caused by other drug formulations.

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

Abstract

L'invention concerne une composition pharmaceutique à libération modifiée pour le traitement de l'éjaculation précoce. La composition ci-dessus présente une libération quantitativement totale au moment opportun (FQTR) de quantités thérapeutiquement efficaces de composés actifs comprenant le tramadol, le rabéprazole, la cétirizine, le sildénafil, ou les sels pharmaceutiquement acceptables correspondants. La libération quantitativement totale au moment opportun de la composition pharmaceutique consiste en la libération complète et immédiate des doses prescrites au moment spécifié et en une seule fois, permettant de retarder la survenue de l'éjaculation d'au moins 20 minutes quel que soit le délai du temps sans médication.
PCT/IB2016/000223 2015-07-28 2016-02-25 Formulation à libération modifiée pour le traitement de l'éjaculation précoce Ceased WO2017017511A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201514811093A 2015-07-28 2015-07-28
US14/811,093 2015-07-28

Publications (1)

Publication Number Publication Date
WO2017017511A1 true WO2017017511A1 (fr) 2017-02-02

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PCT/IB2016/000223 Ceased WO2017017511A1 (fr) 2015-07-28 2016-02-25 Formulation à libération modifiée pour le traitement de l'éjaculation précoce

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090215810A1 (en) * 2005-12-13 2009-08-27 Trinity Laboratories, Inc. Method to Treat Premature Ejaculation in Humans
US20100047343A1 (en) * 2006-07-12 2010-02-25 The University Of Kansas Multiparticulate formulation having tramadol in immediate and controlled release form
US8158147B2 (en) * 2002-02-21 2012-04-17 Valeant International (Barbados) Srl Modified release formulations of at least one form of tramadol
KR20130032316A (ko) * 2010-07-06 2013-04-01 주식회사 네비팜 다폭세틴을 포함하는 시간차 서방출 경구투여형 약학적 조성물

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8158147B2 (en) * 2002-02-21 2012-04-17 Valeant International (Barbados) Srl Modified release formulations of at least one form of tramadol
US20090215810A1 (en) * 2005-12-13 2009-08-27 Trinity Laboratories, Inc. Method to Treat Premature Ejaculation in Humans
US20100047343A1 (en) * 2006-07-12 2010-02-25 The University Of Kansas Multiparticulate formulation having tramadol in immediate and controlled release form
KR20130032316A (ko) * 2010-07-06 2013-04-01 주식회사 네비팜 다폭세틴을 포함하는 시간차 서방출 경구투여형 약학적 조성물

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
MARTYN-ST JAMES, M. ET AL.: "Tramadol for premature ejaculation: a systematic review and meta-analysis", BMC UROLOGY, vol. 15, no. 6, 30 January 2015 (2015-01-30), pages 1 - 11, XP021211053 *

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