WO2012127500A2 - Composition pour la spermatogenèse - Google Patents

Composition pour la spermatogenèse Download PDF

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Publication number
WO2012127500A2
WO2012127500A2 PCT/IN2012/000165 IN2012000165W WO2012127500A2 WO 2012127500 A2 WO2012127500 A2 WO 2012127500A2 IN 2012000165 W IN2012000165 W IN 2012000165W WO 2012127500 A2 WO2012127500 A2 WO 2012127500A2
Authority
WO
WIPO (PCT)
Prior art keywords
highly purified
composition
spermatogenesis
hcg
fsh
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/IN2012/000165
Other languages
English (en)
Other versions
WO2012127500A3 (fr
Inventor
K. V. S. Prasad
Jay L. SOMAN
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.)
SANZYME Ltd
Original Assignee
SANZYME Ltd
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 SANZYME Ltd filed Critical SANZYME Ltd
Publication of WO2012127500A2 publication Critical patent/WO2012127500A2/fr
Publication of WO2012127500A3 publication Critical patent/WO2012127500A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/24—Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g. HCG; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]

Definitions

  • the present invention relates to a pharmaceutical composition for spermatogenesis. More particularly the present invention relates to a pharmaceutical composition comprising combination of Gonadotropins for promoting spermatogenesis in males.
  • the etiology of male infertility may be primary or secondary in nature.
  • Spermatogenesis in humans is complex and current knowledge has its limitations. The process of sperm manufacture requires, 74 days, regardless of number of sperm produced. Potential sperms are never produced because of cell death, especially during the meiosis-1 and during meiosis-2. Many sperm released from the seminiferous epithelium are abnormal. Spermatogenesis can be deficient in quantity of sperm produced, quality of sperm produced, or both.
  • testosterone human chorionic gonadotropin (hCG) in high doses alone, Clomiphene citrate, Aromatase inhibitors, and Bromocriptine have not been shown to be effective in men with idiopathic oligo/azoospermia.
  • Testosterone therapy can further suppress spermatogenesis.
  • the present invention provides a composition comprising combination of gonadotropins for promoting spermatogenesis in males.
  • the present invention provides a composition for promoting spermatogenesis in males comprising a mixture of gonadotropins selected from but not limited to group consisting of Follicle-stimulating hormone (FSH), Luteinizing hormone (LH) and Human chorionic gonadotropin (hCG).
  • FSH Follicle-stimulating hormone
  • LH Luteinizing hormone
  • hCG Human chorionic gonadotropin
  • the present invention provides a composition for promoting spermatogenesis in males comprising a combination of FSH and LH at low dose and micro-dose of hCG.
  • the present invention is directed towards providing compositions comprising combination of gonadotropins for promoting spermatogenesis in males.
  • the present invention provides a composition comprising a mixture of gonadotropins selected from but not limited to group consisting of Follicle-stimulating hormone (FSH), Luteinizing hormone (LH) and Human chorionic gonadotropin (hCG).
  • FSH Follicle-stimulating hormone
  • LH Luteinizing hormone
  • hCG Human chorionic gonadotropin
  • the composition may be presented as a single unit.
  • the composition comprises the combination of gonadotropins in optimum therapeutic concentrations.
  • the composition of the present invention comprises all three gonadotropins that is FSH, LH and HCG in quantities which can offer physiological rhythm of gonadotropin release, ease of administration, compliance of the subfertile subject with respect to the reduced number of administrations.
  • the present invention provides a composition for promoting spermatogenesis in males comprising a combination of FSH and LH at low dose and micro-dose of hCG.
  • the LH component of the composition may range from 10 IU to 300 IU.
  • the FSH component of the composition may range from 10 IU to 200 IU.
  • the HCG component of the composition may range from 50 IU to 750 IU.
  • the invention also provides a composition for promoting spermatogenesis in males comprising combination of 10 IU to 200 IU of highly purified FSH, 10 IU to 300 IU of highly purified LH and 50 IU to 750 IU of highly purified hCG having reduced endotoxin level of less than 0.03 EU/IU, preferably less than 0.01EU/IU per dosage.
  • composition of the present invention in addition to the combination of gonadotropins may comprise of pharmaceutical acceptable excipient(s) and /or carriers.
  • the invention also provides pharmaceutical formulations comprising composition of the present invention for promoting spermatogenesis in males comprising combination of 10 IU to 200 IU of highly purified FSH, 10 IU to 300 IU of highly purified LH and 50 IU to 750 IU of highly purified hCG.
  • composition of the present invention may be formulated in dosage form suitable for oral or any other form of administration appropriate to promote spermatogenesis.
  • the pharmaceutical formulations of the invention may be formulated for administration by any convenient route, often in association with a pharmaceutically and/or veterinarily acceptable carrier.
  • the present invention composition may be formulated in an injectable preparation.
  • the pharmaceutical formulations for parenteral administration will usually be sterile.
  • Pharmaceutical formulations adapted for parenteral administration include aqueous and non-aqueous sterile injection solutions which may contain antioxidants, buffers, bacteriostats and solutes which render the formulation isotonic with the blood of the intended recipient; aqueous and non-aqueous sterile suspensions which may include suspending agents and thickening agents are also within the scope of the invention.
  • the formulations may be presented in unit- dose or multi-dose containers, for example sealed ampoules and vials, and may be stored in a freeze-dried (lyophilised) condition requiring only the addition of the sterile liquid carrier, for example water for injections, immediately prior to use.
  • Extemporaneous injection solutions and suspensions may be prepared from sterile powders, granules and tablets.
  • the formulations can be administered through a prefilled syringe, an auto-injector or a multidose auto-injector.
  • the present invention provides a pharmaceutical formulation comprising composition of the present invention for promoting spermatogenesis in males comprising combination of 10 IU to 200 IU of highly purified FSH, 10 IU to 300 IU of highly purified LH and 50 IU to 750 IU of highly purified hCG, and pharmaceutically acceptable suitable excipients such as Lactose, Sucrose etc. which may aid in the stabilization of the lyophilized product.
  • Such formulation is filled into glass ampoules.
  • the present invention provides pharmaceutical formulation comprising the composition of the present invention for promoting spermatogenesis in males comprising combination of 10 IU to 200 IU of highly purified FSH, 10 IU to 300 IU of highly purified LH and 50 IU to 750 IU of highly purified hCG, formulated as a unit dosage in the form of a solid ready for dissolution to form a sterile injectable solution for intramuscular or for subcutaneous use.
  • the solid usually results from lyophilisation.
  • Typical excipients and carriers include sucrose, lactose, sodium chloride, buffering agents like sodium phosphate monobasic and sodium phosphate dibasic.
  • the solution may be prepared by diluting with water for injection immediately prior to use.
  • Oral and other pharmaceutical formulations may be presented in unit- or multi- dose form.
  • Oral pharmaceutical formulations may be in the form of solids, such as powders, granules, tablets, capsules (for example hard or soft gelatin capsules) or lozenges, or liquids, such as syrups or elixirs.
  • Fillers and/or carriers may be present as appropriate, and those skilled in the art of pharmaceutical formulation will be able to provide such additional or alternative excipients as may be necessary or desirable; flavouring agents are one example.
  • Any pharmaceutical formulation intended for oral administration may be formulated for enteric resistance, so as to assist delivery to the small intestine by avoiding or mitigating any digestion of the compound(s) as may occur in the stomach or the proximal part of the small intestine.
  • Tablets or capsules may be enteric coated, for example by conventional procedures.
  • Liquid pharmaceutical formulations may be effectively rendered enteric resistant by including or being co-administered with a suitable agent such as medium-chain triglycerides.
  • the present invention provides a kit for promoting spermatogenesis in males comprising of dose of 10 1U to 200 IU of highly purified FSH, 10 IU to 300 IU of highly purified LH and 50 IU to 750 IU of highly purified hCG for once a week or twice a week administration.
  • composition comprising for promoting spermatogenesis in males comprising combination of 10 IU to 200 IU of highly purified FSH, 10 IU to 300 IU of highly purified LH and 50 IU to 750 IU of highly purified hCG, or pharmaceutical formulation comprising the same may be administered once a week or twice a week, preferably twice weekly.
  • the composition comprising combinations of gonadotropins thus reduces the injections to be given to the subject in the need thereof by 10-60% of the total conventional consumption for the established treatment protocols, still ensure the desired clinical outcomes, by an independent, interdependent or complementary role for spermatogenesis.
  • compositions of the present invention can be given in a variety of conditions related to male sterility.
  • the composition of the present invention may be suitable In conditions of disrupted hypothalamic axis such as IHH or in all the conditions such as Kallman's syndrome and Hypogonadotropic Hypogonadism but not just limited to these, the combination is aimed to be superior to conventionally available single gonadotropin formulations, in that the invention has a role to meet simultaneous requirement of all three gonadotropins.
  • the no of animals used in the study were 18 male rabbits and each group was administered the drug as follows:
  • T-Sperm/hr Total number of sperm per ejaculate
  • T Sperm/h T Sperm per hour of abstinence

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Endocrinology (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Reproductive Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Zoology (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention concerne des compositions comprenant une combinaison de gonadotrophines pour promouvoir la spermatogenèse chez les hommes. L'invention concerne en particulier une composition comprenant un mélange de gonadotrophines choisies, de façon non limitative, dans le groupe comprenant l'hormone folliculostimulante (FSH), l'hormone lutéinisante (LH) et la gonadotrophine chorionique humaine (hCG), ainsi que des formulations pharmaceutiques comprenant cette composition.
PCT/IN2012/000165 2011-03-11 2012-03-12 Composition pour la spermatogenèse Ceased WO2012127500A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN692MU2011 2011-03-11
IN692/MUM/2011 2011-03-11

Publications (2)

Publication Number Publication Date
WO2012127500A2 true WO2012127500A2 (fr) 2012-09-27
WO2012127500A3 WO2012127500A3 (fr) 2013-03-14

Family

ID=46879829

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2012/000165 Ceased WO2012127500A2 (fr) 2011-03-11 2012-03-12 Composition pour la spermatogenèse

Country Status (1)

Country Link
WO (1) WO2012127500A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110787286A (zh) * 2019-11-21 2020-02-14 重庆市畜牧科学院 Fsh和hcg在制备促进睾丸细胞功能恢复的药物中的应用

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5508261A (en) * 1991-06-18 1996-04-16 University Of Medicine & Dentistry Of New Jersey Analogs of glycoprotein hormones having altered receptor binding specificity and activity and methods for preparing and using same
TW518235B (en) * 1997-01-15 2003-01-21 Akzo Nobel Nv A gonadotropin-containing pharmaceutical composition with improved stability on prolong storage
WO2004087213A1 (fr) * 2003-04-02 2004-10-14 Ares Trading S.A. Formulations pharmaceutiques fsh et lh
US20040248784A1 (en) * 2003-06-03 2004-12-09 Marco Filicori Unitary combinations of FSH and hCG

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110787286A (zh) * 2019-11-21 2020-02-14 重庆市畜牧科学院 Fsh和hcg在制备促进睾丸细胞功能恢复的药物中的应用

Also Published As

Publication number Publication date
WO2012127500A3 (fr) 2013-03-14

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