HRP20040611A2 - Composition of estrogen and other hormones with ascorbate, lysine, proline and other substances - Google Patents

Composition of estrogen and other hormones with ascorbate, lysine, proline and other substances Download PDF

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Publication number
HRP20040611A2
HRP20040611A2 HR20040611A HRP20040611A HRP20040611A2 HR P20040611 A2 HRP20040611 A2 HR P20040611A2 HR 20040611 A HR20040611 A HR 20040611A HR P20040611 A HRP20040611 A HR P20040611A HR P20040611 A2 HRP20040611 A2 HR P20040611A2
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Croatia
Prior art keywords
salts
pharmaceutical composition
accordance
estrogen
proline
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HR20040611A
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English (en)
Inventor
Rath Matthias
Niedzwiecki Aleksandra
Netke Shrirang
Ivanov Vadim
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Rath Matthias
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Application filed by Rath Matthias filed Critical Rath Matthias
Priority to HR20040611A priority Critical patent/HRP20040611B1/hr
Publication of HRP20040611A2 publication Critical patent/HRP20040611A2/hr
Publication of HRP20040611B1 publication Critical patent/HRP20040611B1/hr

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/04Sulfur, selenium or tellurium; Compounds thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365Lactones
    • A61K31/375Ascorbic acid, i.e. vitamin C; Salts thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/401Proline; Derivatives thereof, e.g. captopril
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/56Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/565Compounds 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/726Glycosaminoglycans, i.e. mucopolysaccharides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/737Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/24Heavy metals; Compounds thereof
    • A61K33/26Iron; Compounds thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/24Heavy metals; Compounds thereof
    • A61K33/34Copper; Compounds thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00Drugs for genital or sexual disorders; Contraceptives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/08Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/24Drugs for disorders of the endocrine system of the sex hormones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/24Drugs for disorders of the endocrine system of the sex hormones
    • A61P5/30Oestrogens
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Endocrinology (AREA)
  • Molecular Biology (AREA)
  • Diabetes (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Inorganic Chemistry (AREA)
  • Dermatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Rheumatology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Reproductive Health (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Steroid Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Plant Substances (AREA)

Description

Ovaj se izum tiče sastava estrogena i srodnih hormona u kombinaciji s askorbatom, lizinom, prolinom i drugim supstancama koje djeluju na vezivna tkiva, njihove sposobnosti i njihove uporabe u kontracepciji, hormonskoj nadomjesnoj terapiji za vrijeme menopauze, te drugog korištenja u medicini, fiziologiji, farmakologiji, ljekarničkoj i kozmetičkoj primjeni.
Estrogeni i srodni hormoni se široko koriste u medicini. Njihove primarne primjene su kontracepcijska i hormonska nadomjesna terapija za vrijeme menopauze i druge.
Dugotrajna uporaba estrogena i srodnih hormona, ima međutim značajne i česte nuspojave, uključujući rak, posebno rak dojke, uterusa i drugih zloćudnosti u organima reproduktivnog sustava, srčane bolesti i druge koje su povezane s degeneracijom ekstracelularnog matriksa. U skladu s nekim izvorima (Pschyrembel, Klinisches Wörterbuch, 259 edition) liječenje s estrogenima se smatra kontraindiciranim u slučajevima tumora koji zavise o estrogenu, akutnih ili kroničnih bolesti jetre, trombo-embolije i hipertenzije. U slučaju trombo-embolijskih i ishemičkih bolesti, hipertenzije, estrogensko liječenje bi trebalo trenutačno zaustaviti.
Estrogeni i srodni hormoni pospješuju širenje raka i pogoršanje drugih bolesti slabljenjem ekstracelularnog matriksa. Učinak estrogena je posredovan aktiviranjem degradacije enzima vezivnog tkiva uključujući plazmin, kolagenaze i drugim izravnim ili neizravnim mehanizmima koji destabiliziraju vezivno tkivo.
Iz Europske patentne prijave 00115643.9 objavljene 17. siječnja 2001. je poznato, da su farmaceutski sastavi koji sadrže askorbat ili sastavi koji sadrže askorbat i inhibitore fibrinolize kao lizin i prolin kombinirane s drugim supstancama kao tokoferolom, koratinom, silenijem, pro-vitaminima i tragovima elemenata, prikladni farmaceutski sastavi za prevenciju i liječenje bolesti patoloških stanja povezanih s degradacijom ekstracelularnog matriksa, uključujući degenerativne bolesti, osobito arteriosklerozu, rak i druge srodne bolesti.
Postoji jasna potreba za razvojem terapeutskih strategija da se minimiziraju nuspojave liječenja estrogenom od inače blagotvornih hormonskih terapija.
Pretpostavljalo se, da kada se estrogen daje u kombinaciji s askorbatom, lizinom, prolinom i drugim supstancama, djelovanje svakog od ovih sastava bi ukidalo jedan drugog. Estrogensko liječenje dovodi do degradacije ekstracelularnog matriksa, dok poznati sastavi askorbinske kiseline, osobito u kombinaciji s lizinom i prolinom, smanjuju ili inhibiraju takvu degradaciju, čime bi estrogensko liječenje postalo beskorisno. Međutim, iznenađujuće, to barem djelomično nije slučaj zbog sinergijskog učinka takvih sastava askorbinske kiseline, osobito kombiniranih s lizinom i prolinom, koji s jedne strane sprječavaju ili inhibiraju degeneraciju ekstracelularnog matriksa, s druge strane međutim pojačavaju sintezu kolagena, osobito s askorbinskom kiselinom, koja stvara i podupire ekstracelularni matriks.
Spojevi koji se koriste u ovom izumu za kombiniranu uporabu ili terapeutsku primjenu s estrogenima i srodnim hormonima, su odabrani da suzbijaju slabljenje vezivnog tkiva ovim hormonima. Askorbat je poznat da stimulira sintezu kolagena, elastina i drugih makromolekula vezivnog tkiva od fibroblasta i srodnih stanica. Aminokiseline lizin i prolin su predominantne aminokiseline potrebne za sintezu molekula vezivnog tkiva. Željezo i bakar su tragovi elemenata koji kataliziraju produkciju ovih makromolekula.
Za vrijeme fizioloških stanja kao ovulacije i trudnoće, degradacija vezivnog tkiva estrogenom se suzbija reguliranim sistemom prirodnih mehanizama za sprječavanje degradacije kolagena. Pod patološkim stanjima uzrokovanim nuspojavama blagotvornih hormonskih terapija, prirodni mehanizmi koji više nisu aktivni za vrijeme i poslije menopauze, mogu se nadomjestiti terapeutskom uporabom kombinacija u skladu s ovim izumom. One su korisne da minimiziraju ili sprječavaju nuspojave dugotrajnih hormonskih terapija, uključujući rak i druga ozbiljna zdravstvena stanja, sve dok dopuštaju željeni medicinski ili terapeutski efekt estrogena i srodnih hormona.
Različiti spojevi za koje se traži pravo zaštite u ovoj prijavi mogu se koristiti zajedno u obliku kovalentno vezanih spojeva ili kao fizikalna smjesa ili u bilo kojoj drugoj kombinaciji.

Claims (9)

1. Farmaceutski sastav estrogena i srodnih hormona u kombinaciji s farmaceutskim sastavima, naznačen time, da je za prevenciju i liječenje patoloških stanja povezanih s degeneracijom ekstracelularnog matriksa.
2. Farmaceutski sastav u skladu s patentnim zahtjevom 1, naznačen time, da sadrži askorbinsku kiselinu ili askorbatne soli.
3. Farmaceutski sastav u skladu s patentnim zahtjevom 1, naznačen time, da sadrži estrogen, estradiol, etinilestradiol, estriol, noretisteron, linestrenol i srodne hormone koji sadrže lizin ili soli lizina ili hidroksilizin ili soli hidroksilizina.
4. Farmaceutski sastav u skladu s prethodnim patentnim zahtjevima, naznačen time, da sadrži prolin ili soli prolina ili hidroksiprolin ili soli hidroksiprolina.
5. Farmaceutski sastav u skladu s prethodnim patentnim zahtjevima, naznačen time, da sadrži selen, ili soli selena, bakar ili soli bakra, željezo ili soli željeza i druge minerale ili tragove elemenata.
6. Farmaceutski sastav u skladu s prethodnim patentnim zahtjevima, naznačen time, da sadrži kondroitin sulfat, glikozaminoglikane ili druge proteoglikane ili glikoproteine poznate da su dio ekstracelularnog matriksa.
7. Uporaba farmaceutskih sastava u skladu s prethodnim patentnim zahtjevima, naznačena time, da je za kontrolu fertiliteta, hormonsku nadomjesnu terapiju za ublažavanje tipičnih simptoma povezanih s menopauzom.
8. Uporaba farmaceutskog sastava u skladu s patentnim zahtjevom od 1 do 6, naznačena time, da sprječava osteoporozu, kardiovaskularne bolesti i druge lakše bolesti za vrijeme menopauze.
9. Uporaba farmaceutskih sastava u skladu s prethodnim patentnim zahtjevima, naznačena time, da se daju u oralnim oblicima, kapsulama ili u bilo kojem drugom obliku prikladnom za probavu, za sublingvalnu, intravenoznu, supkutanu, intra-muskularnu, transdermalnu i bilo koju drugu parenteralnu primjenu.
HR20040611A 2001-12-14 2004-07-06 Sastav estrogena i drugih hormona s askorbatom, lizinom, prolinom i drugim supstancama HRP20040611B1 (hr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
HR20040611A HRP20040611B1 (hr) 2001-12-14 2004-07-06 Sastav estrogena i drugih hormona s askorbatom, lizinom, prolinom i drugim supstancama

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
PCT/EP2001/014726 WO2003051371A1 (en) 2001-12-14 2001-12-14 Composition of estrogen and other hormones with ascorbate, lysine, proline and other substances
HR20040611A HRP20040611B1 (hr) 2001-12-14 2004-07-06 Sastav estrogena i drugih hormona s askorbatom, lizinom, prolinom i drugim supstancama

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HRP20040611A2 true HRP20040611A2 (en) 2005-04-30
HRP20040611B1 HRP20040611B1 (hr) 2008-03-31

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HR20040611A HRP20040611B1 (hr) 2001-12-14 2004-07-06 Sastav estrogena i drugih hormona s askorbatom, lizinom, prolinom i drugim supstancama

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Country Link
EP (1) EP1453520B1 (hr)
JP (1) JP2005511768A (hr)
KR (1) KR20040063950A (hr)
CN (1) CN1582152A (hr)
AT (1) ATE338555T1 (hr)
AU (1) AU2002233257B2 (hr)
BR (1) BR0116856A (hr)
CA (1) CA2467964C (hr)
CZ (1) CZ2004809A3 (hr)
DE (1) DE60122943T2 (hr)
DK (1) DK1453520T3 (hr)
EE (1) EE200300310A (hr)
ES (1) ES2272555T3 (hr)
HR (1) HRP20040611B1 (hr)
HU (1) HUP0500896A3 (hr)
IL (1) IL162013A0 (hr)
MX (1) MXPA04005771A (hr)
NO (1) NO20033555L (hr)
NZ (1) NZ532976A (hr)
PT (1) PT1453520E (hr)
SI (1) SI21785A (hr)
WO (1) WO2003051371A1 (hr)

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Publication number Priority date Publication date Assignee Title
US20040253319A1 (en) * 2003-06-11 2004-12-16 Shrirang Netke Pharmaceutical compositions and method for alleviating side-effects of estrogen replacement therapy
CN101111222A (zh) * 2005-02-01 2008-01-23 伊玛吉恩有限公司 刺激胶原蛋白合成和/或kgf表达的方法
WO2008139314A1 (en) * 2007-05-11 2008-11-20 Horphag Research (Luxembourg) Holding Sa Compositions and methods for treating joint disorders
WO2010146078A2 (en) * 2009-06-16 2010-12-23 Bergen Teknologioverføring As Novel uses of hydroxyproline compositions
JP6018800B2 (ja) * 2012-05-25 2016-11-02 ライオン株式会社 経口投与組成物
JP6125899B2 (ja) * 2012-05-25 2017-05-10 ライオン株式会社 骨粗鬆症予防および/または改善剤
WO2013176054A1 (ja) * 2012-05-25 2013-11-28 ライオン株式会社 アスコルビン酸誘導体を含む剤およびその用途
CN113244227B (zh) * 2020-02-12 2022-09-02 浙江医药股份有限公司新昌制药厂 一种17β-雌二醇与维生素C的分子复合物及其制备方法及应用

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GB888631A (en) * 1959-02-24 1962-01-31 Upjohn Co Improvements in or relating to oral therapeutic compositions comprising steroids
US4980358A (en) * 1988-04-04 1990-12-25 George D. McAdory Method employing gonadal hormones and dopamine agonist intended for combined use in the improvement of lymphocyte function
CA2078804C (en) * 1991-10-01 2003-02-25 Takehiko Suzuki Manufacture and use of novel glycosides of catechol estrogens
EP1068868A3 (en) * 1997-07-08 2001-01-31 Rath, Matthias, Dr. med. Synergistic compositions comprising ascorbate and lysine for states related to extracellular matrix degeneration
DE29916231U1 (de) * 1999-09-15 2000-02-17 Renner, Jobst, Dr., 81479 München Multivitamin- und -mineralpräparat

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Publication number Publication date
DE60122943T2 (de) 2007-04-26
CN1582152A (zh) 2005-02-16
CA2467964A1 (en) 2003-06-26
KR20040063950A (ko) 2004-07-14
EE200300310A (et) 2003-10-15
NO20033555D0 (no) 2003-08-11
HUP0500896A3 (en) 2008-04-28
AU2002233257B2 (en) 2008-08-14
CZ2004809A3 (cs) 2004-12-15
DE60122943D1 (de) 2006-10-19
NO20033555L (no) 2003-10-02
NZ532976A (en) 2006-02-24
AU2002233257A1 (en) 2003-06-30
IL162013A0 (en) 2005-11-20
BR0116856A (pt) 2004-08-03
SI21785A (sl) 2005-12-31
CA2467964C (en) 2008-06-03
HRP20040611B1 (hr) 2008-03-31
DK1453520T3 (da) 2007-01-15
PT1453520E (pt) 2006-12-29
EP1453520A1 (en) 2004-09-08
ES2272555T3 (es) 2007-05-01
WO2003051371A1 (en) 2003-06-26
EP1453520B1 (en) 2006-09-06
MXPA04005771A (es) 2004-09-10
HUP0500896A2 (en) 2007-02-28
JP2005511768A (ja) 2005-04-28
ATE338555T1 (de) 2006-09-15

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