EP2194978A1 - Utilisation de gestagènes en combinaison avec du (6s)-5-méthyltétrahydrofolate pour le traitement de l'endométriose avec réduction simultanée d'effets secondaires du traitement et diminution du risque de malformations congénitales en début de grossesse - Google Patents

Utilisation de gestagènes en combinaison avec du (6s)-5-méthyltétrahydrofolate pour le traitement de l'endométriose avec réduction simultanée d'effets secondaires du traitement et diminution du risque de malformations congénitales en début de grossesse

Info

Publication number
EP2194978A1
EP2194978A1 EP08785200A EP08785200A EP2194978A1 EP 2194978 A1 EP2194978 A1 EP 2194978A1 EP 08785200 A EP08785200 A EP 08785200A EP 08785200 A EP08785200 A EP 08785200A EP 2194978 A1 EP2194978 A1 EP 2194978A1
Authority
EP
European Patent Office
Prior art keywords
methyltetrahydrofolate
risk
therapy
pregnancy
daily dose
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Withdrawn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
EP08785200A
Other languages
German (de)
English (en)
Inventor
Christian Seitz
Annemarie Wasserfall
Konstanze Diefenbach
Kristina King
Holger Zimmermann
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.)
Bayer Pharma AG
Original Assignee
Bayer Schering Pharma AG
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=38846909&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=EP2194978(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Bayer Schering Pharma AG filed Critical Bayer Schering Pharma AG
Priority to EP08785200A priority Critical patent/EP2194978A1/fr
Publication of EP2194978A1 publication Critical patent/EP2194978A1/fr
Withdrawn legal-status Critical Current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
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • 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
    • 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
    • A61K31/56—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
    • 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
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • 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
    • 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
    • A61P15/02—Drugs for genital or sexual disorders; Contraceptives for disorders of the vagina
    • 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
    • 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
    • A61P15/18—Feminine contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/02—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • A61P5/34—Gestagens

Definitions

  • progestins in combination with (6S) -5-methyltetrahydrofolate for the treatment of endometriosis with concomitant reduction of therapy side effects as well as the reduction of the risk of congenital malformations at onset of pregnancy
  • the invention relates to the use of progestogens in combination with (6S) -5-methyltetrahydrofolate, wherein the daily dose of the gestagen corresponds at most to twice the Ovulationshemmdosis, for the preparation of pharmaceutical preparations for the treatment of endometriosis with simultaneous reduction of therapy side effects, such as the negative Influence on bone density / bone metabolism and risk of osteoporosis, as well as, if pregnancy occurs, the risk of congenital malformations, such as neural tube defects, cleft lip and palate, and pregnancy complications such as placental detachment and prematurity ,
  • the invention is suitable for long-term use. State of the art
  • Endometriosis is a chronic, gynecological disease that occurs primarily in 5-20% of women of childbearing age.
  • endometriosis is defined as the presence of endometrial or endometrial-like tissue outside the uterine cavity.
  • Typical symptoms of endometriosis are dysmenorrhea, dyspareunia and pain in bowel movements.
  • Endometriosis patients often complain of pelvic pain. Abdominal pain, which occurs in the second half of the cycle, followed by a painful menstrual period and subsequent freedom from symptoms until the middle of the following cycle is often thought to endometriosis, but permanent pain is not uncommon. However, about 30-40% of those suffering from endometriosis have no complaints. The disease is then only discovered by chance in conjunction with other diagnostic measures. In about 50-60%, the diagnosis "disease of endometriosis" as a random diagnosis in the clarification of sterility.
  • US 6,569,845 discloses the treatment of angiogenic diseases with dienogest in a daily dose of 0.5 to 10 mg.
  • exemplified pharmaceutical compositions which could also be widely used for the treatment of endometriosis, have a dienogest content of 400 mg to 2 g.
  • Osteoporosis is shown in the literature as irreversible bone loss with increased bone fragility. More than 5 million people in Germany suffer from osteoporosis. Women are affected more often than men. Osteoporosis is a painless, creeping process that not only reduces the amount of bone, but also changes the bone's 'architecture' to such an extent that it can no longer withstand normal stress. A common osteoporotic episode is the femoral neck fracture or extremely painful vertebral body fractures. Despite treatment, the risk of further fractures is very high. The main medication for osteoporosis is the combination of calcium with vitamin D. The first choice for osteoporosis therapy is the bisphosphonates alendronate and risedronate and the selective estrogen receptor modulator raloxifene.
  • BR ⁇ LL, H. et al explains in "Consensus statement: Therapy of postmenopausal osteoporosis, J. Min. 1/2007, 45-48, that as termination reasons of a therapy with oral bisphosphonates, the side effects come first.
  • Side effects of the indicated bisphosphonates include abdominal pain, flu-like syndrome, constipation, peripheral edema, tinnitus, and bronchitis.
  • Another disadvantage is that because of the risk of mucosal inflammation bisphosphonates are strictly according to prescription; In the morning sober while standing with a large glass of water. After taking it you should not lie down for at least half an hour.
  • the disadvantages of raloxifene are described in the literature with possible hot flashes, calf cramps and edema.
  • Estrogen-containing preparations are used in hormone replacement therapy to maintain bone mass. Estrogen-containing therapy is also associated with certain risks. It should be used to prevent uterine cancer only in women with intact uterus.
  • endometriosis is associated with subfertility and is often diagnosed during the evaluation of an unfulfilled desire to have a baby. A therapeutic goal in endometriosis is therefore often to increase the likelihood of pregnancy.
  • congenital malformations such as congenital heart defects, congenital malformations of the urinary tract, acute lymphoblastic leukemia, cleft lip and palate, or central nervous system malformations such as neural tube effects (spina bifida or anencephaly). being able to lead.
  • the German Society for Nutrition therefore recommends 400 ⁇ g folic acid as a daily dose, 600 ⁇ g for pregnant women and 600 ⁇ g for nursing mothers. This is a global statement. Lack of vitamin B 12 and folate deficiency show identical changes in the blood picture. By folate / folic acid folate deficiency can be compensated, but the lack of vitamin B 12 is not indicated. There is thus the danger of a masked vitamin B 12 deficiency.
  • Folic acid also pteroyl-mono-glutamic acid, N- (4 - (((2-amino-1,4-dihydro-4-oxo-6-pteridinyl) methyl) -amino) benzoyl) glutamic acid (empirical formula: Ci 9 H 19 N 7 ) O 6 ), called folinic acid, is a heat- and light-sensitive, water-soluble vitamin from the vitamin B complex (vitamin B 9 ).
  • folates predominantly exist in the diet as pteroyl polyglutamates. These are hydrolyzed after ingestion first in the mucosa cells to pteroyl monoglutamates, then mainly absorbed in the intestine by active transport.
  • the predominantly unmethylated folates are converted into methylated folates and are mainly bound to the cells as 5-methyltetrahydrofolate (5-MTHF) bound to albumin and ⁇ -macroglobulin transported, taken there, demethylated and converted into the polyglutamate form.
  • 5-MTHF 5-methyltetrahydrofolate
  • Demethylation involves the amino acid homocysteine and an enzyme that requires vitamin B 12 as a coenzyme. Furthermore, it is known that losses can occur in the folate content of food by the preparation (cooking) and storage. It is also known that intense UV radiation striking the human skin reduces folic acid in the body. Fair-skinned people are particularly affected. Inadequate supply of folate and / or vitamin B 12 is the
  • homocysteine in the blood rise The concentration of homocysteine in the blood can therefore be used as an indicator of the folate content.
  • hyperhomocysteinemia is reported by Malinow, MR et al, Homocyst (e) ine, diet, and cardiovascular disease, Statement for healthcare professionals from the Nutrition Committee, American Heart Association. Circulation 99, 178-182, 1999, defined by the following concentration in plasma: 16 - 30 ⁇ mol / L (moderate); 31-100 ⁇ mol / L (medium); > 100 ⁇ mol / l (heavy). A concentration above 10 ⁇ mol / l is considered critical and from 12 ⁇ mol / l there is need for action.
  • EP 0 898 965 claims the use of 5-methyl- (6S) -tetrahydrofolic acid or its pharmaceutically acceptable salts for the prevention of neural tube defects.
  • EP 1 044 975 discloses crystalline salts of 5-methyl- (6R 1 S) -, - (6S) -and- (6R) -tetrahydrofolic acid and use as a food supplement ingredient. Presentation of the invention
  • the object of the invention is to find a way to protect endometriosis patients from osteoporosis risk, to reduce endometriosis and to achieve the goal of endometriosis reduction, namely the onset of pregnancy, without realizing side effects.
  • progestogens in combination with (6S) -5-methyl-tetrahydrofolate (metafolin), wherein the daily dose of the gestagen corresponds at most twice and at least the Ovulationshemmdosis, together or separately with one or more pharmaceutically acceptable excipients / carriers for the manufacture of pharmaceutical preparations.
  • the daily dose of the gestagens may be up to twice the Ovulationshemmdosis.
  • the daily dose of dienogest is 1 mg up to a maximum of 2 mg.
  • Cyproterone acetate or chlormadinone acetate are used according to the invention in a daily dosage up to twice the Ovulationshemmdosis.
  • the ovulation inhibition dose of cyproterone acetate is 1 mg, that of chlormadinone acetate 1 .7 mg.
  • the object is also preferred according to the invention by the use of 0.1 to 10 mg (6S) -5-methyltetrahydrofolate as the daily dosage unit 0.4 to 1 mg of (6S) -5-methyltetrahydrofolate, more preferably 451 ⁇ g
  • the use according to the invention also realizes the production of pharmaceutical preparations with continuous administration of the dosage form for a period of at least 169 days or 25 weeks to several years, preferably more than 2 years, and is therefore surprisingly suitable for long-term application.
  • Tablets, capsules, dragees, wafers, transdermal therapy systems, ampoules, suppositories, gels, ointments, implants, vaginal rings or nasal sprays can be used for the use according to the invention.
  • the daily gestagen dose delivered by the non-oral forms of the pharmaceutical preparation is equivalent to one to two times the Ovulationshemmdosis amount daily in the oral Forms or maximally equivalent to the efficacy of 2 mg dienogest.
  • the object is achieved by a method for producing a pharmaceutical preparation for endometriosis therapy with simultaneous reduction of therapy side effects, such as the negative impact on bone density / bone metabolism and osteoporosis risk, and, if a pregnancy occurs, the reduction the risk of congenital malformations and pregnancy complications such as neural tube defects, cleft lip and palate, placental detachment and prematurity, containing a combination of progestins with (6S) -5-
  • Methyltetrahydrofolate and, together or separately, one or more pharmaceutically acceptable excipients / carriers, wherein the daily dose of progestin corresponds to at least the ovulation inhibitory dose to a maximum of twice the ovulation inhibitory dose.
  • Further embodiments of the pharmaceutical preparation produced by the method according to the invention correspond to claims 1 1, 1 2, 1 3, 14, 15, 16, 17 and 18. Exemplary embodiments Example 1
  • Example 2 All substances are suitably mixed, tabletted and optionally film-coated.
  • Example 2 All substances are suitably mixed, tabletted and optionally film-coated.
  • Tablets having the following composition are prepared: dienogest, micronized 2,000 mg min, 99% ⁇ 20 ⁇ m, 100% ⁇ 30 ⁇ m lactose monohydrate 62,800 mg microcrystalline cellulose 18,000 mg
  • Dienogest is used micronized with a mean particle size of 20 microns and mixed with lactose monohydrate, microcrystalline cellulose and potato starch.
  • the povidone K 25 is sprayed during granulation. After drying and mixing of talc, crospovidone and magnesium stearate, the mixture of the substances is pressed into tablets with a diameter of 7 mm and a mass of 135 mg.

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  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Diabetes (AREA)
  • Gynecology & Obstetrics (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

L'invention concerne des gestagènes anti-androgènes en unité posologique quotidienne correspondant au maximum au double de la dose inhibant l'ovulation qui sont utilisés en combinaison avec du (6S)-5-méthyltétrahydrofolate pour la production de préparations pharmaceutiques servant au traitement de l'endométriose avec réduction simultanée d'effets secondaires du traitement, tels que l'influence négative sur la densité osseuse/le métabolisme osseux et le risque d'ostéoporose, ainsi qu'avec diminution du risque de malformations congénitales en début de grossesse, telles que les anomalies du tube neural et les fentes labio-maxillo-palatines, et de complications de grossesse, telles que le décollement du placenta et la prématurité. L'invention convient à une utilisation de longue durée.
EP08785200A 2007-08-24 2008-07-30 Utilisation de gestagènes en combinaison avec du (6s)-5-méthyltétrahydrofolate pour le traitement de l'endométriose avec réduction simultanée d'effets secondaires du traitement et diminution du risque de malformations congénitales en début de grossesse Withdrawn EP2194978A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP08785200A EP2194978A1 (fr) 2007-08-24 2008-07-30 Utilisation de gestagènes en combinaison avec du (6s)-5-méthyltétrahydrofolate pour le traitement de l'endométriose avec réduction simultanée d'effets secondaires du traitement et diminution du risque de malformations congénitales en début de grossesse

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP07016642A EP2027855A1 (fr) 2007-08-24 2007-08-24 Utilisation de gestagènes conjointement à du (6S)5-méthyltetrahydrofolate pour le traitement de l'endométriose avec une diminution simultanée des effets secondaires du traitement tout comme diminution du risque de malformations congénitale lors de l'introduction d'une gravidité
EP08785200A EP2194978A1 (fr) 2007-08-24 2008-07-30 Utilisation de gestagènes en combinaison avec du (6s)-5-méthyltétrahydrofolate pour le traitement de l'endométriose avec réduction simultanée d'effets secondaires du traitement et diminution du risque de malformations congénitales en début de grossesse
PCT/EP2008/006253 WO2009027003A1 (fr) 2007-08-24 2008-07-30 Utilisation de gestagènes en combinaison avec du (6s)-5-méthyltétrahydrofolate pour le traitement de l'endométriose avec réduction simultanée d'effets secondaires du traitement et diminution du risque de malformations congénitales en début de grossesse

Publications (1)

Publication Number Publication Date
EP2194978A1 true EP2194978A1 (fr) 2010-06-16

Family

ID=38846909

Family Applications (2)

Application Number Title Priority Date Filing Date
EP07016642A Withdrawn EP2027855A1 (fr) 2007-08-24 2007-08-24 Utilisation de gestagènes conjointement à du (6S)5-méthyltetrahydrofolate pour le traitement de l'endométriose avec une diminution simultanée des effets secondaires du traitement tout comme diminution du risque de malformations congénitale lors de l'introduction d'une gravidité
EP08785200A Withdrawn EP2194978A1 (fr) 2007-08-24 2008-07-30 Utilisation de gestagènes en combinaison avec du (6s)-5-méthyltétrahydrofolate pour le traitement de l'endométriose avec réduction simultanée d'effets secondaires du traitement et diminution du risque de malformations congénitales en début de grossesse

Family Applications Before (1)

Application Number Title Priority Date Filing Date
EP07016642A Withdrawn EP2027855A1 (fr) 2007-08-24 2007-08-24 Utilisation de gestagènes conjointement à du (6S)5-méthyltetrahydrofolate pour le traitement de l'endométriose avec une diminution simultanée des effets secondaires du traitement tout comme diminution du risque de malformations congénitale lors de l'introduction d'une gravidité

Country Status (17)

Country Link
EP (2) EP2027855A1 (fr)
JP (1) JP2010536808A (fr)
KR (1) KR20100047872A (fr)
CN (1) CN101784271A (fr)
AR (1) AR070023A1 (fr)
AU (1) AU2008291406A1 (fr)
BR (1) BRPI0815756A2 (fr)
CA (1) CA2696030A1 (fr)
CL (1) CL2008002485A1 (fr)
EA (1) EA201000338A1 (fr)
MX (1) MX2010002190A (fr)
PA (1) PA8793901A1 (fr)
PE (1) PE20090608A1 (fr)
TW (1) TW200930377A (fr)
UY (1) UY31306A1 (fr)
WO (1) WO2009027003A1 (fr)
ZA (1) ZA201002035B (fr)

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CN101874806A (zh) * 2009-04-29 2010-11-03 北京本草天源药物研究院 一种地诺孕素固体制剂
CN108379226B (zh) * 2018-05-28 2019-11-29 上海市计划生育科学研究所 氯地孕酮自微乳组合物、其制备方法及应用

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CH693255A5 (de) 1997-06-13 2003-05-15 Eprova Ag Verwendung von Tetrahydrofolaten in der natürlichenstereoisomeren Form zur Herstellung einer pharmazeutischenZubereitung geeignet zur Beeinflussung des Homocystein-Spiegels.
AU1690399A (en) 1997-12-26 1999-07-19 Mochida Pharmaceutical Co., Ltd. Neovascularization inhibitor containing dienogest as the active ingredient
CH693905A5 (de) 1999-04-15 2004-04-15 Eprova Ag Stabile kristalline Salze von 5-Methyltetrahydrofolsäure.
US20050032741A1 (en) * 2003-08-06 2005-02-10 Balaji Venkataraman Vitamin Compositions
DE102005034498A1 (de) * 2005-07-20 2007-01-25 Grünenthal GmbH Orale Kontrazeption mit Trimegeston
DE102005053771A1 (de) * 2005-11-09 2007-05-10 Grünenthal GmbH Darreichform zur hormonalen Kontrazeption

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AU2008291406A1 (en) 2009-03-05
ZA201002035B (en) 2012-09-26
CN101784271A (zh) 2010-07-21
UY31306A1 (es) 2008-11-28
PE20090608A1 (es) 2009-06-12
JP2010536808A (ja) 2010-12-02
CL2008002485A1 (es) 2009-11-20
AR070023A1 (es) 2010-03-10
KR20100047872A (ko) 2010-05-10
CA2696030A1 (fr) 2009-03-05
TW200930377A (en) 2009-07-16
BRPI0815756A2 (pt) 2015-02-18
PA8793901A1 (es) 2009-04-23
MX2010002190A (es) 2010-03-17
WO2009027003A1 (fr) 2009-03-05
EA201000338A1 (ru) 2010-08-30
EP2027855A1 (fr) 2009-02-25

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