|
1 kits (10 Vials)
| Yawan: | |
|---|---|
▎ Tsarin Tirzepatid
Source: PubChem |
Jeri: Tyr-{Aib}-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-{Aib}-Leu-Asp-Lys-Ile-Ala-Gln-{diacid-C20-gamm a-Glu-(AEEA)2-Lys}-Ala-Phe-Val-Gln-Trp-Leu-Ile-Ala-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2 Tsarin kwayoyin halitta: C 225H 348N 48O68 Nauyin Kwayoyin: 4813 g/mol Lambar CAS: 2023788-19-2 Kamfanin CID na PubChem: 163285897 Synonyms: Zepbound; Munjaro |
▎ Binciken Tirzepatid
Menene asalin binciken Tirzepatid?
Tirzepatid maganin polypeptide na roba ne. Ci gabanta ya samo asali ne daga zurfin fahimtar iyakokin GLP-1 masu karɓar agonists na yanzu a cikin jiyya na nau'in ciwon sukari na 2 (T2DM) da kiba. Ko da yake GLP-1 agonists masu karɓa sun nuna kyakkyawan aiki a cikin sarrafa glucose na jini da asarar nauyi, masana kimiyya sun gano cewa kunna su na mai karɓar GIP yana da rauni sosai, wanda ke iyakance tasirin maganin kwayoyi. Don haka, ƙungiyar bincike da haɓaka ta himmatu don haɓaka sabon nau'in magani wanda zai iya kunna duka GIPR da GLP-1R a lokaci guda, da nufin cimma cikakkiyar ingantaccen sarrafa glucose na jini da sarrafa nauyi [1].
A yayin aiwatar da bincike da ci gaba, masana kimiyya sun gudanar da babban adadin bincike na bincike da gwaji na asibiti. A cikin matakin bincike na farko, an kimanta kaddarorin magunguna na Tirzepatid sosai ta hanyar gwaje-gwajen dabba, yana tabbatar da yuwuwar sa a cikin sarrafa glucose na jini da asarar nauyi. Sakamakon ya nuna cewa zai iya rage yawan matakan glucose na jini a cikin nau'ikan dabbobi kuma ya nuna kyakkyawan aiki a cikin sarrafa nauyi, yana kafa harsashin gwaji na asibiti na gaba.
Bayan haka, matakin gwajin asibiti ya haɗa da gwaji na Phase I, II, da III. Gwajin Mataki na I ya fi kimanta aminci, juriya, da kaddarorin magunguna na maganin. Sakamakon ya nuna cewa Tirzepatid yana da kyakkyawan aminci da haƙuri. Gwajin Mataki na II ya kara bincika inganci da amincin allurai daban-daban na Tirzepatid a cikin marasa lafiya tare da T2DM, da farko yana ƙayyade iyakar adadin sa. Mafi mahimmancin gwaji na asibiti na Mataki na III, kamar su jerin binciken SURPASS, sun haɗa da adadi mai yawa na marasa lafiya tare da T2DM. Sakamakon ya nuna cewa Tirzepatid ya fi girma fiye da masu karɓar masu karɓa na GLP-1 na yanzu, irin su semaglutide, don rage yawan glucose na jini da nauyi, yana ba da shaida mai ƙarfi don aikace-aikacen tallan Tirzepatid [1].
Menene tsarin aikin Tirzepatid?
Tirzepatid yana rage glucose na jini ta hanyoyi da yawa da ke aiki tare. Lokacin kunna mai karɓar GLP-1, Tirzepatid yana ɗaure ga mai karɓar GLP-1 akan ƙwayoyin β-pancreatic, yana kwaikwayon aikin GLP-1 na halitta. GLP-1 hormone ne da aka samar a cikin hanji kuma yana da mahimmanci don kiyaye glucose homeostasis. Yana iya haɓaka haɓakar insulin, ɓoyewa, da fahimtar glucose, rage ƙwayar glucagon don haɓaka satiety, kuma yana hana ci.
Wannan kunnawa na iya haɓaka ƙwayar insulin. Insulin shine babban hormone hypoglycemic a cikin jiki, wanda zai iya ƙara haɓakawa da kuma amfani da glucose ta sel, ta haka ne rage matakan glucose na jini. A cikin marasa lafiya tare da T2DM, ɓoyewar insulin bai isa ba ko kuma hankalin sel ga insulin ya ragu, yana haifar da haɓakar glucose na jini. Ta hanyar kunna mai karɓar GLP-1, Tirzepatid yana ƙara haɓakar insulin, wanda ke taimakawa haɓaka sarrafa glucose na jini.
A lokaci guda, kunna mai karɓar GLP-1 shima yana hana sakin glucagon. Glucagon yawanci yana haɓaka glycogenolysis da gluconeogenesis yayin azumi, yana haɓaka samar da glucose na jini. Ta hanyar hana aikin glucagon, Tirzepatid yana ƙara rage tushen glucose na jini, yana ba da gudummawa ga sarrafa glucose na jini [2]..
Lokacin kunna mai karɓar GIP, Tirzepatid yana aiki akan mai karɓar GIP a lokaci guda. Bayan kunnawa, yana iya haɓaka ji na insulin da ɓoyewa. Mai karɓar GIP yana samuwa a cikin kyallen takarda kamar ƙwayoyin β-pancreatic. Bayan kunnawa, ta hanyar watsa hanyoyin siginar siginar ciki, ƙwayar insulin yana ƙaruwa, kuma ana samun ingantaccen amsawar kwayar halitta ga insulin, don haka mafi inganci rage glucose na jini.
Tirzepatid shine na farko-in-aji dual glucagon-kamar peptide-1 da glucose-dogara insulinotropic polypeptide (GIP) analog, wanda aka amince da shi don kula da tsofaffi marasa lafiya tare da T2DM a matsayin haɗin gwiwa ga abinci da motsa jiki. Tirzepatid shine tsarin sinadarai na roba wanda ya dogara da jerin GIP, wanda ya ƙunshi peptide 39-amino acid. Yana kara samar da insulin, yana rage sakin glucagon ta hanyar dogaro da glucose, yana rage azumi da matakan glucose na jini, yana inganta wadatuwa, yana rage nauyin jiki, yana jinkirta fitar da ciki. Wannan tasirin agonist mai karɓa na dual yana sa Tirzepatid ya fi tasiri fiye da GLP-1 agonists masu karɓa guda ɗaya a cikin haɓaka ƙwayar insulin da hana sakin glucagon [2].
Tirzepatid kuma na iya jinkirta zubar da ciki da kuma kara yawan gamsuwa. Yana iya jinkirta zubar da ciki, yana tsawaita lokacin zama na abinci a cikin ciki da rage yawan sha na abubuwan gina jiki, don haka guje wa hauhawar glucose na jini bayan cin abinci. A cikin binciken da ba na asibiti da na asibiti ba, tasirin Tirzepatid akan zubar da ciki yana kama da na GLP-1 agonists mai karɓa. A cikin berayen da ke haifar da abinci, ƙimar jinkirin zubar da ciki ta hanyar Tirzepatid yayi kama da na semaglutide, amma waɗannan mummunan tasirin hanawa suna ɓacewa bayan makonni 2 na jiyya.
A cikin mahalarta tare da kuma ba tare da T2DM ba, Tirzepatid sau ɗaya-mako-mako (≥5 MG da ≥4.5 MG, bi da bi) ya jinkirta zubar da ciki bayan kashi ɗaya. A cikin mahalarta masu lafiya, an rage tasirin sakamako bayan yawancin allurai na Tirzepatid ko dulaglutide (Urva S, 2020). A lokaci guda kuma, yana iya yin aiki akan tsarin juyayi na tsakiya, ƙara yawan satiety, rage ci, da cin abinci. Ta hanyar sarrafa abin da ake ci, yana taimakawa a kaikaice don sarrafa matakan glucose na jini, musamman dacewa da matsalar kiba sau da yawa tare da marasa lafiya tare da T2DM, kuma yana taimakawa haɓaka juriya na insulin da yanayin rayuwa gaba ɗaya [2].
An gano Tirzepatid don haɓaka matakin adiponectin, adipocytokine mai alaƙa da hankalin insulin. Ƙara yawan matakan adiponectin yana taimakawa wajen inganta haɓakar insulin, yana sa sel su zama masu amsawa ga insulin, don haka mafi inganci da amfani da glucose da rage glucose na jini [2] . Bugu da ƙari, Tirzepatid kuma zai iya inganta bayanin martabar lipid kuma yana da tasirin kariya ga lafiyar zuciya. An tabbatar da cewa Tirzepatid zai iya inganta hawan jini, rage ƙananan ƙwayar lipoprotein (LDL) cholesterol da triglycerides [3] , yana kara tallafawa cikakkiyar fa'idodinsa a cikin sarrafa glucose na jini.
Source: PubMed [5]
Bincike mai alaƙa
Inganci akan sarrafa nauyi a cikin marasa lafiya tare da kiba da nau'in ciwon sukari na 2
Yawancin karatu na asibiti sun tabbatar da tasiri mai mahimmanci na Tirzepatid a cikin sarrafa nauyin jiki a cikin marasa lafiya da kiba da T2DM. A cikin wani bincike mai suna 'SURMOUNT-2', wanda shine mataki na 3, makafi biyu, bazuwar, gwajin sarrafa wuribo da aka gudanar a cikin ƙasashe bakwai. Manya (shekaru ≥18 shekaru) tare da ma'auni na jiki (BMI) na 27 kg / m² ko sama da matakin glycated haemoglobin (HbA₁c) na 7 - 10% an ba da izini don karɓar allurar subcutaneous na Tirzepatid sau ɗaya-mako (10 mg ko 15 mg) ko placebo na makonni 72.
Sakamakon ya nuna cewa a cikin mako 72, yawan asarar nauyi a cikin Tirzepatid 10 MG da 15 MG shine -12.8% da -14.7%, bi da bi, idan aka kwatanta da -3.2% a cikin rukunin placebo. Matsakaicin bambance-bambancen jiyya na Tirzepatid 10 MG da 15 MG idan aka kwatanta da placebo sune -9.6 kashi da maki -11.6, bi da bi, duka biyun sun kasance masu mahimmanci (p <0.0001). Bugu da ƙari, yawancin marasa lafiya da ke karɓar maganin Tirzepatid sun kai iyakar asarar nauyi na 5% ko fiye (79 - 83% vs 32%) [4].
A cikin binciken 'SURMOUNT-2', matsakaicin matsakaicin nauyi shine 100.7 kg, BMI shine 36.1 kg/m², kuma HbA₁c ya kasance 8.02%. Bayan makonni 72 na jiyya, Tirzepatid ba kawai rage nauyin jiki sosai ba amma yana da tasiri mai kyau akan sarrafa glucose na jini [4].
Tasirin haɓakawa akan neuropathy masu alaƙa da ciwon sukari
Nazarin ome sun nuna cewa GLP1-RAs na iya rage haɗarin lalata a cikin marasa lafiya tare da T2DM ta hanyar inganta ƙwaƙwalwar ajiya, koyo, da kuma shawo kan rashin fahimta. A matsayin dual GIP-RA / GLP-1RA, an yi nazarin Tirzepatid a cikin layin kwayoyin neuroblastoma (SHSY5Y) don tasirinsa akan alamun ci gaban neuronal (CREB da BDNF), apoptosis (BAX / Bcl2 rabo), bambanta (pAkt, MAP2, GAP43, da AGBL4), da insulin juriya (GBSLUT1), da kuma insulin juriya (GBSLUT1).
Sakamakon a karon farko ya jaddada rawar da Tirzepatid ke takawa wajen kunna hanyar pAkt/CREB/BDNF da ɓangarorin sigina na ƙasa, da kuma tasirin sa na neuroprotective. Hakanan ya nuna cewa Tirzepatid ya sami damar magance tasirin da ke da alaƙa da hyperglycemia da juriya na insulin a matakin neuronal. Sabili da haka, Tirzepatid na iya inganta haɓakar neurodegeneration da ke haifar da hyperglycemia kuma ya shawo kan juriya na insulin neuronal, yana ba da sabbin fahimta don haɓakar ciwon sukari da ke da alaƙa da neuropathy [5]..
Ci gaban bincike a cikin jiyya na nau'in ciwon sukari na 2
Wasu nazarin sun nuna cewa a matsayin sabon nau'in maganin hypoglycemic, Tirzepatid ya zama agonist na GIP/GLP-1R na farko da aka amince da shi don maganin ciwon sukari a Amurka. An tabbatar da cewa yana da tasiri mai mahimmanci akan rage yawan glucose na jini da kuma rage nauyin jiki a cikin gwaje-gwaje masu yawa na asibiti, kuma akwai shaidun da ke nuna cewa yana da babban tasiri a cikin kariya ta zuciya.
Bugu da ƙari, ra'ayin peptides na roba ya buɗe yawancin yiwuwar da ba a sani ba ga Tirzepatid. Gwaje-gwajen da ke gudana (NCT04166773) da shaidu sun nuna cewa ya zama magani mai ban sha'awa a cikin fagage irin su cututtukan hanta maras barasa (NAFLD), kariya ta koda, da kariya ta neuroprotection [6].
Sakamakon dogon lokaci na tirzepatide akan lafiyar zuciya da jijiyoyin jini
Tirzepatid na iya rage haɗarin cututtukan zuciya ta hanyar haɓaka asarar nauyi. Wani binciken yayi nazarin tasirin Tirzepatid akan kiba da cututtukan cututtukan zuciya a cikin manya na Amurka (Wong ND, 2024). Binciken ya gano cewa a tsakanin manya na Amurka da suka cancanci maganin Tirzepatid, bayan jiyya tare da 15 MG na Tirzepatid, an kiyasta cewa 70.6% da 56.7% na manya suna da asarar nauyi na ≥15% da ≥20%, bi da bi, wanda ke nufin raguwar 58.8% na adadin masu kiba.
Daga cikin wadanda ba tare da cututtukan zuciya ba, kimanin shekaru 10 da aka kiyasta hadarin cututtukan zuciya na zuciya ya ragu daga 10.1% 'kafin jiyya' zuwa 7.7% 'bayan magani', yana nuna cikakkiyar raguwar haɗarin 2.4% da raguwar haɗarin dangi na 23.6%, wanda ke nufin cewa za'a iya hana 2 miliyan abubuwan cututtukan cututtukan zuciya a cikin shekaru 10.
A ƙarshe, Tirzepatid labari ne mai dual agonist na GIP da masu karɓar GLP-1, wanda ke da mahimmanci a cikin kula da T2DM da kiba. Yana iya inganta haɓakar ƙwayar insulin yadda ya kamata, hana ƙwayar glucagon, daidaita glucose na jini daidai, rage haɗarin rikitarwa, haɓaka aikin ƙwayoyin β-pancreatic, da jinkirta ci gaban ciwon sukari. Har ila yau, yana da tasiri mai kariya akan tsarin zuciya da jijiyoyin jini.
A wajen maganin kiba, yana iya rage cin abinci yadda ya kamata, rage sha’awa, kara koshi, taimaka wa masu fama da kiba su rage kiba, da rage hadarin da ke da alaka da kiba. Hakanan yana iya haɓaka juriya na insulin da metabolism na lipid. Bugu da ƙari, ya nuna yuwuwar a cikin maganin cututtukan da ke da alaƙa da rikice-rikice irin su steatohepatitis maras-giya, ciwon bacci na bacci, da gazawar zuciya. Yana iya inganta mahara na rayuwa Manuniya lokaci guda, samar da mafi m magani shirin.
Tsarin allurar sa na sati-sati ya dace don amfani kuma yana iya inganta yarda da jiyya na marasa lafiya.
Game da Marubuci
Abubuwan da aka ambata a sama duk bincike ne, gyara su kuma Cocer Peptides ne suka haɗa su.
Mawallafin Jaridar Kimiyya
Dokta William T. Garvey fitaccen malami ne kuma mai bincike da ke da alaƙa da manyan cibiyoyi masu daraja, ciki har da Jami'ar Alabama a Birmingham, Jami'ar Aston, da Cibiyar Kiwon Lafiyar Tsohon Soja ta Birmingham. Asalin iliminsa da ƙwarewar ƙwararrun ƙwararrun ƙwararrun ƙwararrun fannoni a cikin fannonin likitanci da kimiyya. Dokta Garvey ya ba da gudummawa mai mahimmanci ga fannonin ilimin endocrinology da metabolism, abinci mai gina jiki da abinci mai gina jiki, nazarin halittu da ilimin halittu, da kuma magani na gabaɗaya da na ciki, tare da mai da hankali musamman kan tsarin cututtukan zuciya da cututtukan zuciya. An san aikinsa sosai kuma an girmama shi sosai, musamman ana kiransa da Babban Mai Binciken Bincike a cikin Yankin Cross-Field na 2023 da 2024, yana nuna babban tasiri da tasirin bincikensa akan al'ummar kimiyya.
Dokta Garvey's bincike sha'awa da gwaninta ya fadada zuwa sassa daban-daban na cututtuka na rayuwa da sarrafa su. Ya kasance mai himma wajen nazarin ciwon sukari mellitus, kiba, da rikice-rikicen da ke tattare da su, da nufin buɗe sabbin dabarun warkewa da haɓaka sakamakon haƙuri. Ayyukansa sun ƙunshi bincike na kimiyya na asali, gwaje-gwaje na asibiti, da nazarin fassarar fassarar, ƙaddamar da rata tsakanin binciken dakin gwaje-gwaje da aikace-aikacen likita na ainihi. Ta hanyar bincike mai zurfi, Dokta Garvey ya ba da gudummawa ga zurfin fahimtar hanyoyin da ke tattare da rikice-rikice na rayuwa kuma ya taimaka wajen tsara ka'idodin asibiti da ka'idojin magani a fagen ilimin endocrinology da metabolism. Dr. William T. Garvey an jera shi a cikin ambaton ambaton [4].
