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1 kits (10 Vials)
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▎ Tsarin Semaglutid
Source: Pub Chem |
Jerin: His-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-lys (Aeea-Aeea-γ-glu-octadecanedioic)-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-OH Tsarin kwayoyin halitta: C 187H 291N 45O59 Nauyin Kwayoyin: 4114 g/mol Lambar CAS 910463-68-2 Farashin 56843331 Ma'ana: Rybelsus; Ozempic ; Wegovy |
▎ Binciken Semaglutid
Menene asalin bincike na Semaglutid?
Semaglutid analog ne na ɗan adam glucagon-kamar peptide-1 (GLP-1), wanda aka keɓance shi azaman agonist mai karɓa na GLP-1. GLP-1 hormone ne na halitta wanda ƙwayoyin hanji ke ɓoye bayan cin abinci. Yana taka rawa wajen haɓaka siginar insulin da hana fitar glucagon, ta haka ne ke daidaita matakan glucose na jini. Ci gaban Semaglutid ya samo asali ne daga zurfin bincike na ayyukan ilimin lissafin jiki na GLP-1. Duk da haka, GLP-1 yana da ɗan gajeren rabin rayuwa a cikin jiki, yana da kusan minti 1 zuwa 2 kawai, wanda aka danganta ga rashin lafiyarsa ga lalacewa ta hanyar dipeptidyl peptidase-4 (DPP-4) enzymes a cikin jiki. Don shawo kan wannan ƙayyadaddun, masana kimiyya sun gyara tsarin GLP-1 ta hanyar maye gurbin amino acid na musamman da ƙari na ƙungiyoyi masu kariya, yana haɓaka juriya ga enzymes DPP-4 kuma ta haka yana tsawaita lokacin aikinsa [1] . A cikin tsarin Semaglutid, alanine a matsayi na 8 ya maye gurbin α-aminoisobutyric acid (Aib). Wannan canjin ba kawai yana inganta kwanciyar hankali na miyagun ƙwayoyi ba har ma yana ƙarfafa ɗaurin sa ga mai karɓar GLP-1 (Ma H, 2020). Bugu da ƙari, sarkar gefen fatty acid na musamman da aka haɗa da C-terminus, wanda aka haɗa ta hanyar γ-glutamine zuwa ragowar lysine, yana ƙara tsawon rabin rayuwa, yana ba da damar yin allura sau ɗaya a mako ko kuma gudanar da baki na yau da kullum [1] . Da farko dangane da bincike da gyare-gyare na GLP-1 na halitta, Semaglutid yana nufin samar da zaɓuɓɓukan magani mafi inganci ga marasa lafiya tare da nau'in 2 metabolism [1,2] . Bayan inganta tsarin, yana riƙe da aikin ilimin lissafin jiki na GLP-1 yayin da yake haɓaka kaddarorin sa na harhada magunguna, yana zama muhimmin agonist mai karɓa na GLP-1 mai tsayi. Binciken da ci gaba na Semaglutid yana da matukar muhimmanci ga maganin nau'in nau'in nau'in nau'in 2, yana ba da sabon zaɓi ga marasa lafiya. Ta hanyar inganta tsarin, yana shawo kan matsalar gajeriyar rabin rayuwar GLP-1 na halitta, yana haɓaka kwanciyar hankali na miyagun ƙwayoyi da tsawon lokacin aiki.
Menene tsarin aikin Semaglutid?
Semaglutid wani agonist mai karɓa ne na glucagon-kamar peptide-1 (GLP-1), kuma tsarin aikinsa shine kamar haka:
Tsarin Glucose na Jini: A matsayin sabon glucagon-kamar peptide-1 agonist mai karɓa (GLP-1RA), Semaglutid yafi rage sha'awar abinci ga marasa lafiya kuma yana rage fifikon abinci mai kitse ta hanyar hana ci. Yana daidaita cibiyar ciyarwa a cikin hypothalamus, rage cin abinci, ƙara yawan gamsuwa, hana zubar da ciki, da rage motsin ciki, don haka cimma burin asarar nauyi. Rashin nauyi yana taimakawa haɓaka juriya na insulin kuma yana ƙara daidaita matakan glucose na jini [3] (Kim HS, 2021). Semaglutid yana haifar da asarar nauyi a cikin rodents ta hanyar hanyoyin jijiyoyi da aka rarraba. Nazarin ya nuna cewa Semaglutid yana aiki kai tsaye a kan yankunan kamar kwakwalwar kwakwalwa, tsakiya na septal, da hypothalamus. Ko da yake ba ta ketare shingen kwakwalwar jini-kwakwalwa, tana mu'amala da kwakwalwa ta hanyar gabobin dawafi da wasu yankuna da ke kusa da ventricles. Yana haifar da kunnawar c-Fos na tsakiya a cikin yankuna na kwakwalwa na 10, ciki har da yankuna na baya-bayan nan kai tsaye da Semaglutid da yankuna na sakandare suka yi niyya ba tare da hulɗar GLP-1R kai tsaye ba, irin su tsakiya na parabrachial tsakiya. Bincike ta atomatik yana nuna cewa kunnawa na iya kasancewa yana da alaƙa da ƙarewar abinci ta hanyar neurons a cikin tsakiya na parabrachial na gefe, don haka daidaita matakan glucose na jini [4].
Tsarin Gastrointestinal: Semaglutid yana aiki akan masu karɓar GLP-1 a cikin sashin gastrointestinal. Ta hanyar hanyar jijiyar jijiyar ƙwayar cuta, yana aiki akan wuraren da ke cikin kwakwalwa irin su tsakiya na sashin jiki da kuma dorsal motor tsakiya na jijiyar vagus don daidaita motsin ciki. Yana iya hana ƙanƙarar antrum na ciki, haɓaka tashin hankali na pyloric sphincter, tsawaita lokacin zama na abinci a cikin ciki, da jinkirta shigarsa cikin duodenum, yana hana saurin haɓakar glucose na jini na jini da kuma sanya glucose jini ya canza mafi kwanciyar hankali [5] (Katsurada K, 2016). Bugu da ƙari, Semaglutid yana aiki akan masu karɓa na GLP-1 a cikin tsarin kulawa na tsakiya, musamman a cikin yankunan da ke cikin arcuate nucleus da paraventricular nucleus na hypothalamus. Yana hana sakin abubuwan da ke motsa sha'awa irin su neuropeptide Y (NPY) da furotin da ke da alaƙa da agouti (AgRP), kuma a lokaci guda yana kunna pro-opiomelanocortin (POMC) neurons, yana haɓaka ɓoyewar α-melanocyte-stimulating hormone (α-MSH) [5] . Wadannan tasirin suna haifar da jin daɗi, rage yunwa, da rage cin abinci, a kaikaice suna da tasiri mai kyau akan sarrafa glucose na jini.
Kariya na zuciya da jijiyoyin jini: Semaglutid na iya inganta sel endothelial na jijiyoyin jini don saki abubuwan vasodilator kamar su nitric oxide (NO), haɓaka ƙarfin haɓakar jijiyoyin jini da haɓaka haɓakar jini. A lokaci guda, yana hana amsawar kumburi da damuwa na oxidative, yana rage lalacewa ga sel endothelial na jijiyoyin jini, kuma yana rage haɗarin atherosclerosis. Bugu da ƙari, ta hanyar rage ci da cin abinci, Semaglutid yana taimakawa tare da asarar nauyi, yana inganta rashin lafiyar lipid metabolism, yana rage matakan triglycerides da low-density lipoprotein cholesterol (LDL-C), kuma yana ƙara yawan ƙwayar lipoprotein cholesterol (HDL-C). Hakanan yana iya samun tasiri mai amfani akan cutar hawan jini ta hanyar daidaita aikin hemodynamics na renal da ayyukan neuroendocrine, rage haɗarin hauhawar jini da cututtukan cututtukan zuciya [6].
Semaglutid da ka'idojin rubutu na WAT zuwa fassarar BAT da kunna BAT.
Source: PubMed [12]
Menene mabuɗin gwaji da karatu?
Zane da Inganta Tsarin Sinadarai: Lokacin zayyana Semaglutid, an karɓi hanyar da za a iya jujjuyawa ga albumin don tsawaita tsawon lokacin aikin. Ta hanyar ƙayyade mafi kyawun haɗin fatty acids da masu haɗin gwiwa, yayin kiyaye ingancin mai karɓar GLP-1 (GLP-1R), ƙarfin ɗaure ga albumin ya haɓaka [7].
Aikace-aikacen Drug: Semaglutid shine glucagon-kamar peptide-1 agonist mai karɓa (GLP-1 RA) tare da ƙarancin kawar da rabin rayuwa, yana ba da izinin allurar subcutaneous sau ɗaya-mako. A cikin marasa lafiya tare da nau'in 2 metabolism (T2DM), tasirin asarar nauyi na allurar subcutaneous na Semaglutid sau ɗaya-mako ya fi na sauran GLP-1RAs sau ɗaya-mako-mako. A cikin gwajin bincike na kashi na II na marasa lafiya masu kiba ba tare da T2DM ba, allurar subcutaneous na Semaglutid sau ɗaya a rana ya nuna mafi kyawun asarar nauyi fiye da placebo kuma sau ɗaya a rana 3.0 MG liraglutide. Matsayin asarar nauyi da Semaglutid ya haifar a cikin wannan binciken ya zarce ka'idodin magungunan asarar nauyi da Hukumar Kula da Magunguna ta Turai (EMA) da Hukumar Kula da Abinci da Magunguna ta Amurka (FDA) suka kafa, kuma yana da lafiya, yana nuna cewa allurar subcutaneous sau ɗaya a rana na Semaglutid yana da yuwuwar zama magani na asarar nauyi na gaba [8].
Jiyya na cututtukan zuciya da jijiyoyin jini ta hanyar inganta aikin zuciya: Sakamakon gwajin gwaji na STEP-HFpEF ya nuna cewa babban maganin antidiabetic glucagon-like peptide 1 agonist Semaglutid ya inganta ingantaccen bayyanar cututtuka da ke da alaƙa da rashin ciwon zuciya tare da raguwar fitarwa (HFpEF) da aka kiyaye da kuma rage matakin N-terminal natype-NTP-BNP. Gwaje-gwajen bincike sun gano cewa babban jiyya tare da Semaglutid na iya ƙara yawan tashin hankali na trabeculae na ɗan adam fiye da sau uku a cikin hanyar dogaro da kashi, ba tare da haɓakar haɓakar arrhythmia ba. Wannan tasiri na iya zama saboda karuwa a cikin ɗaukar Ca2+ ta hanyar sarcoplasmic reticulum. Jiyya tare da babban adadin Semaglutid a cikin marasa lafiya tare da gazawar zuciya na iya inganta aikin atrial, ta haka yana kawar da alamun cutar [9].
Semaglutid yana ƙarƙashin bincike don maganin steatohepatitis maras barasa (NASH): Tsarin ma'ana na Semaglutid ya ba da gudummawa mai yawa don inganta tsarin glucose na jini, nauyin jiki, hawan jini, lipids na jini, aikin β-cell, da tsarin zuciya na zuciya a cikin marasa lafiya tare da nau'in 2 metabolism. Bugu da ƙari, haɓakar ƙirar baka na Semaglutid na iya ba da ƙarin fa'ida dangane da yarda da jiyya na marasa lafiya [7].
Menene bambance-bambance a cikin tasirin asarar nauyi na Semaglutid tsakanin al'ummomi daban-daban?
Manya da cututtukan zuciya da suka rigaya, kiba ko kiba amma ba tare da metabolism ba: A cikin SELECT sakamakon sakamakon cututtukan zuciya, Semaglutid ya rage manyan cututtukan cututtukan zuciya da 20% a cikin manya na 17,604 tare da cututtukan cututtukan zuciya da suka rigaya, kiba ko kiba, kuma ba tare da metabolism ba [10] (Ryan DH, 2024). A cikin wannan bincike da aka ƙayyade, masu bincike sunyi nazarin sakamakon Semaglutid akan nauyin jiki, sakamakon anthropometric, aminci, da haƙuri bisa ga ma'auni na jiki (BMI). Marasa lafiya da ke karɓar Semaglutid sun sami ci gaba da raguwa a cikin nauyin jiki a cikin makonni 65, yana dawwama har zuwa shekaru 4. A cikin makonni 208, idan aka kwatanta da ƙungiyar placebo, Semaglutid ya haifar da raguwa mai yawa a cikin nauyin jiki (-10.2%), kewayen kugu (-7.7 cm), da kuma tsayi-da-tsawo rabo (-6.9%), yayin da ƙungiyar placebo ta rage (-1.5%, -1.3 cm, da -1.0%) bi da bi, kuma duk sun kasance masu mahimmanci tare da placebo. Rashin nauyi mai ma'ana na asibiti ya faru a cikin maza da mata, duk kabilanci, nau'ikan jiki, da yankuna. Semaglutid yana da alaƙa da ƙananan abubuwan da ba su da kyau. Ga kowane nau'in BMI (<30, 30 zuwa <35, 35 zuwa <40, da ≥40 kg / m²), abubuwan da suka faru na mummunan abubuwan da suka faru na Semaglutid (yawan abubuwan da aka lura a cikin shekaru 100 na mutum) ya kasance ƙasa (43.23, 43.54, 51.07, 6, 4, 51.07, 4, 51, 5, 4, 51.07, da Semaglutid). 49.66, 52.73, da 60.85 don placebo). Semaglutid yana da alaƙa da ƙarin ƙimar katsewar samfurin gwaji. Yayin da nau'in BMI ya ragu, adadin dakatarwa ya karu. A cikin gwajin SELECT, a cikin makonni 208, Semaglutid ya haifar da hasara mai mahimmanci na asibiti da kuma ingantawa a cikin ƙimar anthropometric idan aka kwatanta da placebo, kuma asarar nauyi ya ci gaba har tsawon shekaru 4.
Mutanen da ke da kiba ko kiba amma ba tare da metabolism ba: Binciken na yau da kullun ya kimanta inganci da amincin Semaglutid a cikin mutanen da ke da kiba ko kiba amma ba tare da metabolism ba [11] . Wannan bita ya haɗu da sakamakon gwaje-gwaje na asibiti da yawa, yana jaddada tasirin Semaglutid akan asarar nauyi, sigogi na rayuwa, da kuma sakamakon lafiyar gaba ɗaya. Sakamakon ya nuna cewa Semaglutid yana da alaƙa da asarar nauyi mai yawa da haɓakawa a cikin alamun kiwon lafiya masu alaƙa da kiba, kuma yana iya zama zaɓi mai mahimmanci na jiyya ga marasa lafiya masu kiba.
Marasa lafiya marasa ciwon sukari (shaida daga RCT da yawa): A cikin gwajin gwaji na 4 bazuwar, marasa lafiya da nauyin nauyi na 96 zuwa 105 kg sun sami allurar subcutaneous mako-mako na 2.4 MG na Semaglutid da kuma salon rayuwa (nasihar, abinci, da aikin jiki) don asarar nauyi. Ɗaya daga cikin gwaje-gwajen da aka bazu don marasa lafiya marasa ciwon sukari (N = 1961) ya nuna cewa bayan makonni 68, asarar nauyi shine 15% (15 kg), wanda ya bambanta da 2% (3 kg) a cikin rukunin placebo. Matsakaicin marasa lafiya tare da asarar nauyi na ≥5% shine 86% idan aka kwatanta da 32% a cikin rukunin placebo, kuma adadin da ake buƙata don magance (NNT) = 2; Matsakaicin marasa lafiya tare da asarar nauyi na ≥10% shine 69% idan aka kwatanta da 12% a cikin rukunin placebo, da NNT = 2. Rashin asarar nauyi ya tashi a kusan makonni 60. Abubuwan da suka faru na cututtukan cututtuka na gastrointestinal (AEs) sun kasance 74% idan aka kwatanta da 48% a cikin rukunin placebo, da kuma adadin da ake bukata don cutar da su (NNH) = 3. Yawan marasa lafiya da ke dakatar da magani saboda abubuwan da ba su da kyau sun kasance 7% idan aka kwatanta da 3% a cikin rukunin placebo, da NNH = 25. A cikin wani nau'i na rashin daidaituwa na 6 a cikin gwagwarmayar gwagwarmayar rayuwa tare da 1 (N. Ƙungiyar Semaglutid ta kasance 16% (17 kg), wanda ya bambanta da 6% (6 kg) a cikin rukunin placebo. A cikin gwajin gwajin da aka bazu-bincike don masu ciwon sukari (N = 1210), an ba marasa lafiya 2.4 MG na Semaglutid mako-mako, 1.0 MG na Semaglutid mako-mako, ko placebo. Bayan makonni 68, matsakaicin asarar nauyi shine 10% (2.4 mg), 7% (1.0 mg), da 3% (placebo) bi da bi. Adadin marasa lafiya tare da asarar nauyi na ≥5% shine 69% (2.4 mg), 57% (1.0 MG) idan aka kwatanta da 29% a cikin rukunin placebo. Don 2.4 MG da 1.0 MG allurai, NNT = 9. Abubuwan da ba su da kyau sun kasance iri ɗaya a cikin nau'i-nau'i daban-daban. A cikin nauyin kulawa da bazuwar gwajin gwagwarmaya (N = 803), mahalarta marasa ciwon sukari sun sami magani na mako-mako tare da 2.4 MG na Semaglutid na makonni 20, sa'an nan kuma an raba su cikin rukuni na ci gaba da maganin Semaglutid ko ƙungiyar placebo. Bayan makonni 48, ƙungiyar da ke ci gaba da maganin Semaglutid sun rasa 8% na nauyin jikinsu, yayin da ƙungiyar placebo ta sami 7% na nauyin jikinsu.
A ƙarshe, Semaglutid shine GLP-1 agonist agonist mai karɓa tare da ƙimar aikace-aikacen a cikin filayen da yawa. A fagen jiyya na metabolism, yana sarrafa matakan glucose na jini yadda ya kamata ta hanyar ɗaure ga masu karɓar GLP-1, haɓaka haɓakar insulin, da hana sakin glucagon, yana ba da zaɓi mai mahimmanci na jiyya ga marasa lafiya tare da nau'in metabolism na nau'in 2. A cikin yanayin jiyya na kiba, Semaglutid yana rage yawan kuzari ta hanyar hanyoyin kamar hana ci abinci na tsakiya da jinkirta zubar da ciki, yana taimaka wa marasa lafiya masu kiba su rasa nauyi da inganta yanayin rayuwa. Bugu da ƙari, Semaglutid kuma yana nuna yiwuwar aikace-aikacen da ake bukata a cikin rigakafi da maganin cututtuka na zuciya da jijiyoyin jini. Ingantawarsa na abubuwan haɗari na zuciya da jijiyoyin jini yana ba da sabuwar hanya don rage abubuwan da ke faruwa na cututtukan zuciya.
Game da Marubuci
Abubuwan da aka ambata a sama duk bincike ne, gyara su kuma Cocer Peptides ne suka haɗa su.
Mawallafin Jaridar Kimiyya
Hegner P mai bincike ne a Jami'ar Regensburg. Ayyukansa sun haɗa da Chemistry, Tsarin zuciya, da Ilimin zuciya. A cikin Chemistry, yana bincika halayen da ke da alaƙa da lafiyar zuciya. A cikin nazarin tsarin zuciya na zuciya, yana bincikar zuciya da ayyuka na jirgin ruwa, yana neman fahimtar hanyoyin warkewa. Binciken ilimin zuciyarsa yana mai da hankali kan rigakafin cututtukan zuciya, ganowa, da magani.
Gudunmawar Hegner tana da mahimmanci. Bayanan sinadarai nasa sun haifar da sabon ci gaban magungunan cututtukan zuciya. Ayyukansa akan hanyoyin zuciya da na jirgin ruwa sun inganta fahimtar cututtukan zuciya. A asibiti, bincikensa ya inganta tsarin kula da cututtukan zuciya, yana haɓaka matakan kulawa da marasa lafiya. Gabaɗaya, tsarin koyarwa da yawa na Hegner yana wadatar da maganin cututtukan zuciya, yana ba da bege don rage nauyin cututtuka da ingantacciyar sakamako mai haƙuri. An jera Hegner P a cikin ambaton ambaton [9].
