LT5239B - 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 PDFInfo
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- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 title claims abstract description 20
- 229940011871 estrogen Drugs 0.000 title claims abstract description 19
- 239000000262 estrogen Substances 0.000 title claims abstract description 19
- 235000010323 ascorbic acid Nutrition 0.000 title claims abstract description 11
- 229940088597 hormone Drugs 0.000 title claims abstract description 11
- 239000005556 hormone Substances 0.000 title claims abstract description 11
- 239000011668 ascorbic acid Substances 0.000 title claims abstract description 10
- 239000004472 Lysine Substances 0.000 title claims abstract description 9
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 title claims abstract description 9
- 239000000203 mixture Substances 0.000 title claims abstract description 9
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 title claims abstract description 8
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 title claims abstract description 6
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 title claims abstract description 5
- 229940072107 ascorbate Drugs 0.000 title abstract description 7
- 239000000126 substance Substances 0.000 title abstract description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 claims description 8
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 claims description 8
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- 238000011282 treatment Methods 0.000 claims description 6
- 230000009245 menopause Effects 0.000 claims description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 4
- 229960005070 ascorbic acid Drugs 0.000 claims description 3
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- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims description 2
- 239000010949 copper Substances 0.000 claims description 2
- 229910052802 copper Inorganic materials 0.000 claims description 2
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- 229910052742 iron Inorganic materials 0.000 claims description 2
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- 239000011669 selenium Substances 0.000 claims description 2
- 229910052711 selenium Inorganic materials 0.000 claims description 2
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 claims 2
- YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 claims 2
- PROQIPRRNZUXQM-UHFFFAOYSA-N (16alpha,17betaOH)-Estra-1,3,5(10)-triene-3,16,17-triol Natural products OC1=CC=C2C3CCC(C)(C(C(O)C4)O)C4C3CCC2=C1 PROQIPRRNZUXQM-UHFFFAOYSA-N 0.000 claims 1
- BFPYWIDHMRZLRN-UHFFFAOYSA-N 17alpha-ethynyl estradiol Natural products OC1=CC=C2C3CCC(C)(C(CC4)(O)C#C)C4C3CCC2=C1 BFPYWIDHMRZLRN-UHFFFAOYSA-N 0.000 claims 1
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 claims 1
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 claims 1
- 208000024172 Cardiovascular disease Diseases 0.000 claims 1
- 229920001287 Chondroitin sulfate Polymers 0.000 claims 1
- BFPYWIDHMRZLRN-SLHNCBLASA-N Ethinyl estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 BFPYWIDHMRZLRN-SLHNCBLASA-N 0.000 claims 1
- 102000003886 Glycoproteins Human genes 0.000 claims 1
- 108090000288 Glycoproteins Proteins 0.000 claims 1
- 229920002683 Glycosaminoglycan Polymers 0.000 claims 1
- LCWXJXMHJVIJFK-UHFFFAOYSA-N Hydroxylysine Natural products NCC(O)CC(N)CC(O)=O LCWXJXMHJVIJFK-UHFFFAOYSA-N 0.000 claims 1
- YNVGQYHLRCDXFQ-XGXHKTLJSA-N Lynestrenol Chemical compound C1CC[C@@H]2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 YNVGQYHLRCDXFQ-XGXHKTLJSA-N 0.000 claims 1
- 208000001132 Osteoporosis Diseases 0.000 claims 1
- 102000016611 Proteoglycans Human genes 0.000 claims 1
- 108010067787 Proteoglycans Proteins 0.000 claims 1
- 125000003289 ascorbyl group Chemical class [H]O[C@@]([H])(C([H])([H])O*)[C@@]1([H])OC(=O)C(O*)=C1O* 0.000 claims 1
- 239000002775 capsule Substances 0.000 claims 1
- 229940059329 chondroitin sulfate Drugs 0.000 claims 1
- 150000001879 copper Chemical class 0.000 claims 1
- YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 claims 1
- 230000029087 digestion Effects 0.000 claims 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 claims 1
- 229930182833 estradiol Natural products 0.000 claims 1
- 229960005309 estradiol Drugs 0.000 claims 1
- PROQIPRRNZUXQM-ZXXIGWHRSA-N estriol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H]([C@H](O)C4)O)[C@@H]4[C@@H]3CCC2=C1 PROQIPRRNZUXQM-ZXXIGWHRSA-N 0.000 claims 1
- 229960001348 estriol Drugs 0.000 claims 1
- 229960002568 ethinylestradiol Drugs 0.000 claims 1
- QJHBJHUKURJDLG-UHFFFAOYSA-N hydroxy-L-lysine Natural products NCCCCC(NO)C(O)=O QJHBJHUKURJDLG-UHFFFAOYSA-N 0.000 claims 1
- 229960002591 hydroxyproline Drugs 0.000 claims 1
- 229910052500 inorganic mineral Inorganic materials 0.000 claims 1
- 238000007918 intramuscular administration Methods 0.000 claims 1
- 238000001990 intravenous administration Methods 0.000 claims 1
- 159000000014 iron salts Chemical class 0.000 claims 1
- 229960001910 lynestrenol Drugs 0.000 claims 1
- 239000011707 mineral Substances 0.000 claims 1
- 235000010755 mineral Nutrition 0.000 claims 1
- 229940053934 norethindrone Drugs 0.000 claims 1
- VIKNJXKGJWUCNN-XGXHKTLJSA-N norethisterone Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 VIKNJXKGJWUCNN-XGXHKTLJSA-N 0.000 claims 1
- 238000007911 parenteral administration Methods 0.000 claims 1
- 150000003147 proline derivatives Chemical class 0.000 claims 1
- 150000003342 selenium Chemical class 0.000 claims 1
- 238000007920 subcutaneous administration Methods 0.000 claims 1
- 208000024891 symptom Diseases 0.000 claims 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 claims 1
- 210000002808 connective tissue Anatomy 0.000 abstract description 8
- 239000003814 drug Substances 0.000 abstract description 3
- 239000002537 cosmetic Substances 0.000 abstract description 2
- 230000003054 hormonal effect Effects 0.000 abstract 1
- 230000035479 physiological effects, processes and functions Effects 0.000 abstract 1
- 238000009256 replacement therapy Methods 0.000 abstract 1
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- 238000001794 hormone therapy Methods 0.000 description 3
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- 238000003786 synthesis reaction Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 208000001435 Thromboembolism Diseases 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 208000030090 Acute Disease Diseases 0.000 description 1
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- 102000016942 Elastin Human genes 0.000 description 1
- 108010014258 Elastin Proteins 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 150000000996 L-ascorbic acids Chemical group 0.000 description 1
- UPYKUZBSLRQECL-UKMVMLAPSA-N Lycopene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1C(=C)CCCC1(C)C)C=CC=C(/C)C=CC2C(=C)CCCC2(C)C UPYKUZBSLRQECL-UKMVMLAPSA-N 0.000 description 1
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- 230000001154 acute effect Effects 0.000 description 1
- 150000001746 carotenes Chemical class 0.000 description 1
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- 230000011382 collagen catabolic process Effects 0.000 description 1
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
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- 235000010384 tocopherol Nutrition 0.000 description 1
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- NCYCYZXNIZJOKI-UHFFFAOYSA-N vitamin A aldehyde Natural products O=CC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-UHFFFAOYSA-N 0.000 description 1
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- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
Šis išradimas apima estrogeno ir giminingų hormonų kompozicijas derinyje su askorbatu, lizinu, prolinu ir kitomis medžiagomis, paveikiančiomis jungiamuosius audinius, jų gebėjimą ir jų panaudojimą kontracepcijoje, hormonų pakaitų terapijoje menopauzės metu, ir taikymą kitose medicinos, fiziologijos, farmakologijos, farmacijos ir kosmetikos srityse.The present invention includes compositions of estrogen and related hormones in combination with ascorbate, lysine, proline and other agents affecting connective tissues, their ability and their use in contraception, hormone replacement therapy during menopause, and applications in other medical, physiological, pharmacological, pharmaceutical and cosmetic applications.
Estrogenai ir giminingi hormonai yra plačiai panaudojami medicinoje. Jų svarbiausias pritaikymas yra kontracepcijoje ir hormonų pakaitų terapijoje menopauzės metu ir kitur.Estrogens and related hormones are widely used in medicine. Their most important applications are in contraception and hormone replacement therapy during menopause and elsewhere.
Tačiau ilgalaikis estrogeno ir giminingų hormonų naudojimas turi žymių ir įprastų pašalinių poveikių apimančių vėžį, ypatingai krūties vėžį, gimdą ir kitų reprodukcinės sistemos organų supiktybėjimus, širdies ligas ir kitas ligas, kurios susijusios su ekstraceliuliarinio matrikso degeneracija. Pagal vertinimus, rastus keliuose šaltiniuose (Pschyrembel, Klinisches VVoerterbuch, 259 leidinį), gydymas estrogenais prieštarauja tokiais atvejais, kai gydoma nuo estrogeno priklausančius auglius, ūmias ir chronines kepenų ligas, tromboemboliją ir padidėjusį kraujospūdį. Tromboembolinių ir išeminių ligų padidėjusio kraujopsūdžio atveju gydymas estrogenu turi būti nedelsiant nutrauktas.However, the long-term use of estrogen and related hormones has significant and common side effects including cancer, especially breast cancer, uterus and other reproductive system abnormalities, heart disease and other diseases associated with extracellular matrix degeneration. Estimates found in several sources (Pschyrembel, Klinisches Woerterbuch, Publication 259) suggest that estrogen treatment is at odds with estrogen-dependent tumors, acute and chronic liver disease, thromboembolism, and high blood pressure. In case of high blood pressure in thromboembolic and ischemic diseases, estrogen treatment should be discontinued immediately.
Estrogenai ir kiti giminingi hormonai pagerina vėžio išsisėjimą ir kitų ligų paūmėjimą silpnindami ekstraceliuliarinį matriksą. Šis estrogeno poveikis yra tarpininkaujamas jungiamojo audinio aktyvacijos skaldant fermentus, apimant plazminą kolagenazes, ir kitais tiesioginiais ir netiesioginiais mechanizmais, destabilizuojančiais jungiamąjį audinį.Estrogens and other related hormones improve cancer survival and other exacerbations by weakening the extracellular matrix. These effects of estrogen are mediated by the activation of connective tissue by cleavage of enzymes, including plasma collagenases, and other direct and indirect mechanisms that destabilize the connective tissue.
Iš Europos patento paraiškos Nr. 00115643.9, publikuotos 2001-01-17, žinoma, kad farmacinės kompozicijos, turinčios askorbato arba kompozicijos, turinčios askorbato ir fibrinolizės inhibitorius, tokius kaip lizinas ir prolinas, derinyje su kitomis medžiagomis, tokiomis kaip tokoferolis, karotinas, selenas, provitaminai ir mikroelementai, yra tinkamos farmacinės kompozicijos patologinių būsenų giminingų ekstraceliuliarinio matrikso degradacijai, apimant degeneracines ligas, ypatingai aterosklerozę, vėžį ir kitas giminingas ligas, profilaktikai ir gydymui.From European patent application no. 00115643.9, published January 17, 2001, pharmaceutical formulations containing ascorbate or compositions containing ascorbate and fibrinolysis inhibitors such as lysine and proline are known to be in combination with other substances such as tocopherol, carotene, selenium, provitamins and trace elements. suitable pharmaceutical compositions for the prophylaxis and treatment of extracellular matrix-related pathological conditions, including degenerative diseases, in particular atherosclerosis, cancer and other comorbidities.
Todėl egzistuoja aiškus poreikis vystyti gydymo strategijas, kad iki minimumo sumažėtų kitų naudingų hormonų terapijos gydymo estrogenu pašaliniai poveikiai.Therefore, there is a clear need to develop treatment strategies to minimize the side effects of other beneficial hormone therapy with estrogen therapy.
Manoma, kad kai estrogeno skiriamas derinyje su askorbatu, lizinu, prolinu ir kitomis medžiagomis, poveikis kiekvienos iš tokių kompozicijų panaikintų vienas kitą. Gydymas estrogenu veda į ekstraceliuliarinio matrikso degradaciją, tuo tarpu žinomos kompozicijos iš askorbo rūgščių ypatingai derinyje su lizinu ir prolinu, sumažina arba stabdo tokias degradacijas, todėl gydymas estrogenu tampa nebenaudingas. Tačiau yra nuostabu, kad tai yra bent jau iš dalies negalima, nes dėl tokių askorbo rūgšties kompozicijų, ypatingai, kai yra derinyje su lizinu ir protinu, sinergistinio poveikio, kurios iš vienos pusės apsaugo arba slopina ekstraceliuliarinio matrikso degradaciją, o iš kitos pusės, vis dėl to pagerina kolageno sintezę, ypatingai su askorbo rūgštimi, kuri sukuria ir sustiprina ekstraceliuliarinį matriksą.When estrogen is administered in combination with ascorbate, lysine, proline and other substances, it is expected that the effects of each of these compositions would cancel each other out. Treatment with estrogen leads to degradation of the extracellular matrix, whereas known compositions of ascorbic acids, especially in combination with lysine and proline, reduce or prevent such degradation, rendering estrogen treatment useless. However, it is surprising that this is at least in part impossible because of the synergistic effects of such ascorbic acid compositions, particularly when combined with lysine and protin, which on the one hand prevent or inhibit extracellular matrix degradation and on the other as a result, it improves collagen synthesis, particularly with ascorbic acid, which creates and strengthens the extracellular matrix.
Junginiai, panaudoti šiame išradime, skirti panaudoti derinyje arba terapiniam taikymui su estrogenais ir giminingais hormonais, yra parenkami, kad neutralizuotų jungiamojo audinio susilpninimą tokiais hormonais. Žinoma, kad askorbatas stimuliuoja kolageno, elastino ir kitų jungiamojo audinio makromolekulių sintezę nuo fibroblasto ir giminingų ląstelių. Aminorūgštys lizinas ir prolinas yra vyraujančios aminorūgštys, reikalingos jungiamojo audinio molekulių sintezei. Geležis ir varis yra mikroelementai, kurie katalizuoja šių makromolekulių gamybą.The compounds used in the present invention for use in combination or for therapeutic use with estrogens and related hormones are selected to counteract connective tissue attenuation by such hormones. Ascorbate is known to stimulate the synthesis of collagen, elastin and other connective tissue macromolecules from fibroblast and related cells. The amino acids lysine and proline are the predominant amino acids required for the synthesis of connective tissue molecules. Iron and copper are trace elements that catalyze the production of these macromolecules.
Fiziologinių būsenų, tokių kaip ovuliacija arba nėštumas, metu jungiamojo audinio degradacija estrogenu yra neutralizuojama natūralių mechanizmų reguliavimo sistema, kad apsaugotų kolageno degradaciją. Esant patologinėms būsenoms, iššauktoms naudingos hormonų terapijos pašalinių poveikių, natūralus mechanizmas, kuris yra daugiau nebeaktyvus menopauzės metu arba po jos, gali būti pakeistas šio išradimo derinių terapiniu panaudojimu. Jie yra naudingi sumažinti arba apsaugoti nuo ilgai trunkančios hormonų terapijos pašalinių poveikių apimant vėžį ir kitas sunkias sveikatos būsenas, tuo tarpu leisdami pasireikšti estrogeno ir giminingų hormonų norimam medicininiam arba terapiniam efektui.During physiological conditions such as ovulation or pregnancy, estrogen degradation of connective tissue is a system that regulates natural mechanisms to prevent collagen degradation. In pathological states caused by the side effects of beneficial hormone therapy, the natural mechanism that is no longer active during or after menopause can be replaced by the therapeutic use of the combinations of the invention. They are useful in reducing or protecting against the side effects of long-term hormone therapy, including cancer and other serious health conditions, while allowing the desired medical or therapeutic effect of estrogen and related hormones.
Skirtingi junginiai, pareikšti šioje paraiškoje, gali būti vartojami kartu kovalentinės jungties junginių formoje arba kaip fiziniai mišiniai, arba bet kuriame kitame derinyje.The different compounds disclosed in this application may be used together in the form of covalent bond compounds, either as physical mixtures or in any other combination.
Claims (9)
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| EP1156439A1 (en) | 2000-05-16 | 2001-11-21 | Sony Corporation | Information providing apparatus, server apparatus and information processing method |
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| EP1156439A1 (en) | 2000-05-16 | 2001-11-21 | Sony Corporation | Information providing apparatus, server apparatus and information processing method |
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