WO2008007993A1 - Utilisation d'une hormone chorionique ou lutéinisante destinée à la prévention ou au traitement de l'hypogonadisme lié à l'âge - Google Patents

Utilisation d'une hormone chorionique ou lutéinisante destinée à la prévention ou au traitement de l'hypogonadisme lié à l'âge Download PDF

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Publication number
WO2008007993A1
WO2008007993A1 PCT/RU2006/000365 RU2006000365W WO2008007993A1 WO 2008007993 A1 WO2008007993 A1 WO 2008007993A1 RU 2006000365 W RU2006000365 W RU 2006000365W WO 2008007993 A1 WO2008007993 A1 WO 2008007993A1
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WO
WIPO (PCT)
Prior art keywords
age
chorionic
disorders
hypogonadism
treatment
Prior art date
Application number
PCT/RU2006/000365
Other languages
English (en)
Russian (ru)
Inventor
Svetlana Yurievna Kalinchenko
Original Assignee
Koval, Anton Alexandrovich
Kulakova, Elena Vladimirovna
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 Koval, Anton Alexandrovich, Kulakova, Elena Vladimirovna filed Critical Koval, Anton Alexandrovich
Priority to EA200802426A priority Critical patent/EA200802426A1/ru
Priority to PCT/RU2006/000365 priority patent/WO2008007993A1/fr
Publication of WO2008007993A1 publication Critical patent/WO2008007993A1/fr

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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]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders

Definitions

  • chorionic or luteinizing hormone for the prevention or treatment of age
  • the present invention relates to the use of chorionic or luteinizing hormone, each of which belongs to the class of gonadotropic hormones, for the prevention and treatment of mature hypogonadism in men of mature and old age, as well as age-related disorders associated with androgen deficiency, which include sexual dysfunctions, such as erectile dysfunction, a decrease or absence of libido and a violation of ejaculation, a metabolic syndrome characterized by obesity, especially abdominal obesity m, dyslipidemia, arterial hypertension, and an increase in glucose levels above 5.6 nmol / L, osteoporosis, depression, muscle hypotrophy, anemia, skin changes such as dryness, sagging and loss of skin turgor, and urination disorders.
  • the invention also relates to a method for the prevention and treatment of age-related hypogonadism using chorionic or luteinizing hormone of urinary or recombinant origin.
  • the term “andropause” is used to describe age-related hormonal changes in men by analogy with a similar condition in women.
  • the term “andropause” comes from the Greek. "upro” (man) and “rasis” (stop, stop).
  • PADAM syndrome from the English “ratal aprogef deficiepf agile male”, partial androgen deficiency in older men, proposed in 1994 at the workshop of the Austrian Urological Society, was the most common.
  • the term “age-related hypogonadism” is most commonly used.
  • the first of them is characterized by a decrease in secretion, leading to a drop in testosterone levels below normal levels of testosterone in the blood, i.e. below 12 nmol / l (for total testosterone).
  • the second condition is characterized by a decrease in testosterone levels compared to previous years, however, it does not go beyond the normal range.
  • Age-related androgen deficiency leads to structural and functional changes in many organs and systems of the body.
  • target tissues such as the genitourinary system, central nervous system, musculoskeletal system, adipose tissue (Tepovever JL, Malé Lürmocher rélésepté regards terépu "Aprorause", Eppocripol. Am. p. 969).
  • the clinical picture of androgen deficiency is more pronounced, the earlier androgen deficiency develops in ontogenesis.
  • mature or middle age of men is meant the age of 35 years and older, although in accordance with the classification of the World Health Organization (WHO), the gerontological gradation of the age of men is distributed as follows: up to 44 years old - young age, 45-59 years - average age, 60-74 years -
  • WHO World Health Organization
  • SUBSTITUTE SHEET (RULE 26) old age, 75 years and older - senile age, older than 90 years - long-livers. According to foreign (US Vureau of Sepsus, 1996) and Russian (Goskomstat of Russia, 1998) studies, it is expected that in Russia the percentage of people aged 60 years and older will be 22.9% in 2025. Based on this, it becomes clear the relevance of issues related to health, as well as the quality of life of the elderly.
  • Human chorionic gonadotropin belongs to the family of hormones of the glycoprotein structure, which also includes follicle-stimulating hormone (FSH) and luteinizing hormone (LH). These hormones ensure the normal functioning of the male and female reproductive systems.
  • chorionic gonadotropin Human chorionic gonadotropin is secreted in large quantities by the cells of the trophoectoderm of the blastocyst - chorionic villi, in connection with which this hormone is called "chorionic gonadotropin". After implantation, the chorionic hormone is produced in the placenta.
  • the hCG molecule is a glycoprotein dimer consisting of two non-covalently bound protein subunits. Human luteinizing hormone is secreted by gonadotropic pituitary cells. Significant structural homology of hCG and LH molecules was noted with the exception of two amino acid residues. Therefore, hCG and LH have equal biological capabilities for recognition and activation of the same receptors.
  • the menopausal chorionic gonadotropin (hCG) was first isolated and purified, which was called “Profazi” (Latin name "Rofasi”) and was used to induce ovulation and to treat male
  • Urinary hCG (or hCG of urinary origin) is a relatively coarse hormonal extract from the urine of pregnant women.
  • the hormonal component of each vial of the extract is conventionally brought to the standard value by the method of biological samples (500 International Units (ME), 1000 ME, 1500 ME, 2000 ME or 5000 ME).
  • Recombinant gonadotropic hormones significantly increase the quality and safety of the use of drugs based on them.
  • the technology of recombinant deoxyribonucleic acids (DNA) allows you to fully control the production process. This also eliminates the complex problems associated with the availability and inconsistency of the composition of urine used as a raw material for obtaining gonadotropic hormones based on it, and the possibility of bacterial and viral infection of the drug is completely eliminated.
  • hCG stimulates the function of the corpus luteum, which consists in the production of progesterone, promotes gestation (has an inhibitory effect on the production of FSH), and in men it is involved in the activation of the hormonal function of Leydig cells (testosterone production) in the testis both during intrauterine development and subsequently.
  • LH enhances the development of intrasecretory elements in the testes and ovaries, thereby stimulating the formation of sex hormones, in women determines ovulation in the ovary and the formation of a burst graaf in the ovary
  • SUBSTITUTE SHEET (RULE 26) the corpus luteum of the corpus luteum and progesterone production, and also increases the release of LH in women during implantation of the fertilized egg (the hypothalamic-pituitary system is reflexively stimulated), preventing the corpus luteum from scarring, while the progesterone secretion in the corpus luteum increases, which prevents the uterine myometrium from contracting and pregnancy preservation.
  • chorionic gonadotropin preparations are used in the protocol for inducing multiple follicular maturation (superovulation) for assisted reproductive technologies (BPT), including in vitro fertilization (IVF), with the aim of inducing the final follicular maturation and luteinization after stimulation with gonadotropins, and also with anovulatory or oligovulatory infertility for the induction of ovulation and luteinization at the end of follicular growth stimulation and the use of luteinizing drugs gonadotropin for the treatment of infertility due to hypothalamic-pituitary disorders, leading to a decrease in the level of luteinizing and follicle-stimulating hormones in the body.
  • the invention proposes the use of chorionic (CG) or luteinizing (LH) hormone for the prevention and treatment of age-related hypogonadism, as well as related disorders.
  • CG chorionic
  • LH luteinizing
  • urinary or recombinant CG, urinary or recombinant LH, or a combination of FSH / LH of urinary origin are used as gonadotropic hormones for this purpose.
  • CG or LH recombinant human gonadotropins
  • CG or LH is administered subcutaneously or intramuscularly.
  • an automatic or semi-automatic injector in particular an injector such as a syringe pen, for example, a syringe pen used for insulin therapy and manufactured by Vetkop & Diksiksop, which allows you to maximize the regimen
  • SUBSTITUTE SHEET (RULE 26) administration of drugs to the profile of spontaneous secretion of endogenous gonadotropins, not to violate the regimen of drugs, and also provides maximum ease of use.
  • Another object of the invention is a method for the prevention and treatment of age-related hypogonadism, which consists in introducing into the body of a man in need of such therapy a chorionic or luteinizing hormone.
  • Another object of the invention is the use of HCG or LH for the preparation of a medicinal product intended for the prevention or treatment of age-related hypogonadism, as well as related disorders.
  • the present invention also provides a medicament containing chorionic or luteinizing hormone for the treatment or prevention of age-related hypogonadism, as well as related disorders.
  • the invention further relates to the use of a pharmaceutical composition containing chorionic or luteinizing hormone and adjuvants and diluents / diluents commonly used in conjunction with it, for the preparation of the aforementioned drug of the invention.
  • a pharmaceutical composition containing chorionic or luteinizing hormone and adjuvants and diluents / diluents commonly used in conjunction with it, for the preparation of the aforementioned drug of the invention.
  • the object of the study was male patients with clinical and biochemical manifestations of age-related androgen deficiency.
  • the criteria on the basis of which patients were included in the study were as follows: male gender, age 35 years and older, informed consent of patients for examination and treatment, presence of clinical and biochemical manifestations of age-related hypogonadism.
  • SUBSTITUTE SHEET (RULE 26) also diseases in which, according to modern views, the appointment of hormone replacement therapy is contraindicated and which include prostate cancer, breast cancer and benign prostatic hyperplasia with severe signs of infravesical obstruction.
  • AMS Update MaIe Status
  • I-PSS international system for the total assessment of symptoms in prostate diseases
  • TRUS transabdominal ultrasound
  • PRI digital rectal examination
  • SUBSTITUTE SHEET (RULE 26) manifestations, while the severity of symptoms progressed with age (see the graph in Fig. 1, where 27-36 points correspond to mild ones, 37-49 points correspond to moderate ones, and 50 and more points correspond to sharply expressed symptoms).
  • the decrease in testosterone concentration in the examined patients was not accompanied by an increase in the level of gonadotropins, which indicates a predominantly secondary genesis of age-related hypogonadism, which served as the basis for using the method of stimulating therapy with chorionic gonadotropins for the secretion of intrinsic endogenous testosterone.
  • all patients underwent a stimulating test with chorionic gonadotropin, which was administered intramuscularly at a dose of 2000 ME every other day, making a total of 3 injections. In all cases, the test results were positive.
  • the level of total testosterone in patients of group 1 after the test was 18.2 ⁇ 1.5 nmol / L, and in patients of group 2 it was 16.4 ⁇ 1.7 nmol / L.
  • Table 7 Effect of hCG therapy on the lipid profile of men with hepatitis B virus
  • SUBSTITUTE SHEET (RULE 26) a significant increase in HDL levels from 1.15 to 1.28 mmol / l (p ⁇ 0.045) when using hCG and from 1.0 to 1, 3 with the use of Ovitrel.
  • HG therapy (hCG and Ovitrel) has a significant beneficial effect on the waist circumference and BMI, allowing you to reduce the waist circumference by 7.27% and 9.87% (for hCG and Ovitrel, respectively) and reduce the BMI by 3.57% and 2.87% (testosterone is a fat-mobilizing hormone, and its decrease enhances the effect of fat-accumulating hormones such as insulin and cortisol).
  • chorionic gonadotropin therapy in patients with age-related hypogonadism has a clear positive effect and affects all aspects of the patient's psycho-emotional and physical-functional state, which in turn affects the patient’s health and quality of life .
  • the level of testosterone is within normal limits and there are no peaks of supraphysiological concentration that can adversely affect the patient's condition.
  • the greatest effectiveness of this therapy is observed in middle-aged men (35-59 years old) with clinical and laboratory signs of age-related hypogonadism. The effect of the treatment is maintained even after the drug is discontinued, which allows recommending course treatment in this category of patients.
  • chorionic gonadotropin therapy In elderly men (60-74 years), the effect of chorionic gonadotropin therapy is not prolonged, probably due to a decrease in the number of Leydig cells and the progression of apoptosis, which once again clearly reflects the need for the use of this therapy as early as possible. In order to obtain a positive effect in elderly patients, the selection of a dose of chorionic gonadotropin should be carried out individually, depending on the level of testosterone in the blood.
  • recombinant chorionic hormone has a number of advantages, consisting in the possibility of using the drug once a week, the possibility of subcutaneous administration and the absence of such
  • SUBSTITUTE SHEET (RULE 26) the introduction of urinary gonadotropins side effects like pyrogenic and allergic reactions, as well as an increase in the mammary glands.
  • compositions examples include compositions (dosage forms)
  • Release form bottle or ampoule complete with a solvent (1 ml of water for injection or 1 ml of water for injection plus benzyl alcohol (0.9-1.1%) or metacresol (0.3%)). Description: lyophilized powder or porous mass (lyophilisate) of white or almost white color.
  • Pharmacotherapeutic group luteinizing agent.
  • Lyophilized powder is obtained in the usual way. Immediately before use, the lyophilisate is diluted with an appropriate solvent in the amount required for 1 injection (1 ml).
  • composition per 1 ampoule Composition per 1 ampoule:
  • SUBSTITUTE SHEET (RULE 26) Components Amount human chorionic gonadotropin 2000 ME lactose 10 mg potassium diphosphate 232 ⁇ g potassium monophosphate 181 ⁇ g sodium hydroxide qs acetic acid qs
  • Pharmacotherapeutic group gonadotropin hormone.
  • a similar composition have preparations with a human chorionic gonadotropin content of 500 ME, 1000 ME, 1500 ME and 5000 ME.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Endocrinology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Reproductive Health (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

L'invention concerne l'utilisation d'une hormone chorionique ou lutéinisante destinée à la prévention ou au traitement de l'hypogonadisme lié à l'âge ainsi qu'aux troubles liés à l'âge et dus à une déficience en androgènes.
PCT/RU2006/000365 2006-07-11 2006-07-11 Utilisation d'une hormone chorionique ou lutéinisante destinée à la prévention ou au traitement de l'hypogonadisme lié à l'âge WO2008007993A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EA200802426A EA200802426A1 (ru) 2006-07-11 2006-07-11 Применение хорионического или лютеинизирующего гормона для профилактики или лечения возрастного гипогонадизма
PCT/RU2006/000365 WO2008007993A1 (fr) 2006-07-11 2006-07-11 Utilisation d'une hormone chorionique ou lutéinisante destinée à la prévention ou au traitement de l'hypogonadisme lié à l'âge

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/RU2006/000365 WO2008007993A1 (fr) 2006-07-11 2006-07-11 Utilisation d'une hormone chorionique ou lutéinisante destinée à la prévention ou au traitement de l'hypogonadisme lié à l'âge

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WO2008007993A1 true WO2008007993A1 (fr) 2008-01-17

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EA200200892A1 (ru) * 2000-02-22 2003-02-27 Апплайд Резеч Системз Арс Холдинг Н.В. СПОСОБ ОЧИСТКИ чХГ И РЕКОМБИНАТНЫЙ чХГ, ОЧИЩЕННЫЙ ЭТИМ СПОСОБОМ

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EA200200892A1 (ru) * 2000-02-22 2003-02-27 Апплайд Резеч Системз Арс Холдинг Н.В. СПОСОБ ОЧИСТКИ чХГ И РЕКОМБИНАТНЫЙ чХГ, ОЧИЩЕННЫЙ ЭТИМ СПОСОБОМ

Non-Patent Citations (7)

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Title
"Ovulyatsiya, ili vse samoe interesnoe o preparatakh, kotorye pomogajut etogo dobitsya", TEXTOVOI DOCUMENT, 12 May 2006 (2006-05-12), Retrieved from the Internet <URL:http://www.search.rambler.ru/cgi-bin/rambler_search?oe=125&words> *
INSULINOTERAPIYA: "Posobie dlya vrachei pod red. akad", RAN I RAMN I.I. DEDOVA. GL.. REZHIMY INSULINOTERAPII. M., 2004, Retrieved from the Internet <URL:http://www.hghltd.yandex.com> *
LUVERIC: "Annotatsiya", 2 June 2004 (2004-06-02), pages 1, Retrieved from the Internet <URL:http://www.hghltd.yandex.com> *
PERGORIN: "Annotatsiya", 27 February 1995 (1995-02-27), pages 1 - 2, Retrieved from the Internet <URL:http://www.hghltd.yandex.com> *
PROFASI: "Annotatsiya", VIDAL, 2000, pages 1 - 2, Retrieved from the Internet <URL:http://www.hghltd.yandex.com> *
S. JU KALINCHENKO: "Testosteron-korol gormonov, gormon korolei", ZHURNAL "SEX I ZHIZN", no. 1, 2004, pages 12 - 22, Retrieved from the Internet <URL:http://www.hghltd.yandex.com> *
SCHEPELEV PETR ANDREEVICH: "Erectilnaya disfunktsiya: sovremennoe sostoyanie problemy s tochki zreniya spetsialista-androloga", CONSILIUM PROVIOSURM, vol. 4, no. 2, 2004, Retrieved from the Internet <URL:http://www.hghltd.yandex.com> *

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