|
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 PubChem CID: 163285897 Synonyms: Zepbound; Munjaro |
▎ Binciken Tirzepatid
Menene asalin binciken Tirzepatid?
Tirzepatid maganin polypeptide na roba ne. Bincikensa da haɓakawa sun samo asali ne daga zurfin fahimtar iyakokin GLP-1 masu karɓar agonists na yanzu a cikin kula da nau'in metabolism na nau'in 2 da kiba a wancan lokacin. Kodayake GLP-1 agonists masu karɓa sun nuna kyakkyawan aiki a cikin sarrafa glucose na jini da asarar nauyi, masana kimiyya sun gano cewa kunna mai karɓar GIP yana da rauni sosai, wanda ke iyakance tasirin magungunan zuwa wani ɗan lokaci. Don haka, ƙungiyar bincike da haɓakawa ta himmatu wajen haɓaka sabon magani wanda zai iya kunna duka GIPR da GLP-1R lokaci guda don cimma cikakkiyar ingantaccen sarrafa glucose na jini da sarrafa nauyi [1].
A lokacin bincike da ci gaban tsarin Tirzepatid, masana kimiyya sun gudanar da babban adadin bincike na asali da gwaji na asibiti. A cikin matakin bincike na farko, an yi amfani da gwaje-gwajen dabba don kimanta abubuwan da ke cikin magunguna na Tirzepatid sosai. Sakamakon ya tabbatar da yuwuwar sa a cikin sarrafa glucose na jini da asarar nauyi, yana kafa harsashin gwaji na asibiti na gaba. Daga baya, Tirzepatid ya shiga matakin gwaji na asibiti, ciki har da matakan I, II, da III. Mataki na I yafi kimanta aminci, juriya, da kaddarorin magunguna na maganin, kuma sakamakon ya nuna kyakkyawan aminci da haƙuri. Mataki na II ya kara bincika inganci da amincin allurai daban-daban a cikin marasa lafiya tare da nau'in metabolism na nau'in 2, da farko yana ƙayyade kewayon tasiri mai tasiri. Mahimmin gwajin gwaji na asibiti na III, irin su jerin binciken SURPASS, sun haɗa da adadi mai yawa na marasa lafiya tare da nau'in metabolism na 2. Sakamakon ya nuna cewa Tirzepatid ya fi girma fiye da masu karɓar GLP-1 na yanzu, irin su Semaglutid, don rage yawan glucose na jini da nauyi, yana ba da shaida mai karfi don aikace-aikacen tallace-tallace [1].
Tirzepatid polypeptide ne wanda ya ƙunshi amino acid 39, kuma an gyara tsarinsa don inganta kwanciyar hankali da harhada magunguna. Tsarinsa na musamman yana ba shi damar haɗa tasirin incretins guda biyu, GIP da GLP-1, cikin kwayoyin halitta guda ɗaya, yana kunna masu karɓar hormone waɗanda ke cikin sarrafa glucose na jini ta hanyar tsarin dual. Musamman, a gefe guda, yana aiki akan pancreas don haɓaka haɓakar insulin da hana sakin glucagon don rage glucose na jini; a gefe guda kuma, yana aiki akan tsarin juyayi na tsakiya, jinkirta zubar da ciki, ƙara yawan gamsuwa, rage ci da cin abinci, da samun nasarar sarrafa nauyi. Wannan tsarin dual yana ba Tirzepatid fa'idodi na musamman a cikin kula da nau'in 2 metabolism da kiba, yana ba marasa lafiya ƙarin zaɓin jiyya [1].
Menene tsarin aikin Tirzepatid?
Tirzepatid yana rage yawan glucose na jini ta hanyoyi da yawa:
Kunna masu karɓar GLP-1: Tirzepatid yana ɗaure ga masu karɓar GLP-1 akan ƙwayoyin beta na pancreatic, yana kwaikwayon aikin GLP-1 na halitta. GLP-1 wani hormone ne da hanji ke samarwa wanda ke da mahimmanci don kiyaye glucose homeostasis. Yana iya inganta haɓakar insulin, ɓoyewa, da fahimtar glucose, da kuma rage ƙwayar glucagon don haɓaka satiety da kashe ci. A cikin marasa lafiya da ke da nau'in metabolism na nau'in 2, rashin isasshen ƙwayar insulin ko raguwar hankalin salula ga insulin yana haifar da haɓakar glucose na jini. Tirzepatid yana ƙara haɓakar insulin ta hanyar kunna masu karɓar GLP-1, inganta sarrafa glucose na jini. A lokaci guda, kunna masu karɓar GLP-1 na iya hana sakin glucagon, yana ƙara rage tushen glucose na jini da ba da gudummawa ga sarrafa glucose na jini [2]..
Kunna masu karɓar GIP: Tirzepatid yana aiki akan masu karɓar GIP, kuma kunna shi na iya haɓaka haɓakar insulin da ɓoyewa. Masu karɓar GIP galibi suna cikin kyallen takarda kamar ƙwayoyin beta na pancreatic. Bayan kunnawa, ta hanyar watsa siginar siginar ciki, ƙwayar insulin yana ƙaruwa, kuma ana haɓaka amsawar tantanin halitta ga insulin, yana rage glucose na jini sosai [2] . 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].
Jinkirta Korar Ciki da Ƙarfafa Satiety: Tirzepatid na iya jinkirta zubar da ciki, da tsawaita lokacin zama na abinci a cikin ciki, rage yawan sha na abinci, da hana haɓakar glucose na jini bayan cin abinci. Tasirinsa akan zubar da ciki yayi daidai da na GLP-1 agonists mai karɓa. A lokaci guda kuma, yana aiki akan tsarin juyayi na tsakiya, yana haɓaka koshi, rage ci da abinci, wanda ya dace musamman ga matsalar kiba sau da yawa tare da marasa lafiya tare da nau'in metabolism na 2, yana taimakawa haɓaka juriya na insulin da yanayin yanayin rayuwa gaba ɗaya [2].
Inganta Jijin Insulin da Lipid Metabolism: Tirzepatid na iya haɓaka matakin adiponectin, adipocytokine da ke da alaƙa da haɓakar insulin, yana taimakawa haɓaka haɓakar insulin, yana ba da damar sel su sami ƙarfi sosai da amfani da glucose, da rage glucose na jini (Anonymous, 2023). Bugu da ƙari, yana iya inganta bayanin martabar lipid, yana da tasirin kariya ga lafiyar zuciya. An tabbatar da cewa zai iya inganta hawan jini, rage LDL cholesterol da triglycerides [3].
Source: PubMed [5]
Menene karatun da ke da alaƙa?
Inganci akan Gudanar da Nauyi a cikin Marasa lafiya masu Kiba da Nau'in Metabolism Na 2
Yawancin karatu na asibiti sun tabbatar da cewa Tirzepatid yana da tasirin asarar nauyi. A cikin binciken 'SURMOUNT-2', an gudanar da wannan mataki na 3, makafi biyu, bazuwar, gwajin sarrafa wuribo a cikin ƙasashe bakwai. Manya (shekaru ≥ 18 shekaru) tare da BMI na 27 kg / m² ko sama da HbA₁c na 7 - 10% an yi rajista kuma an ba su bazuwar 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 kashi da -11.6 maki bi da bi, waɗanda ke da mahimmancin ƙididdiga (p <0.0001). Bugu da ƙari, ƙarin marasa lafiya da ke karɓar maganin Tirzepatid sun kai iyakar 5% ko asarar nauyi mafi girma (79 - 83% vs 32%) (Garvey WT, 2023). A cikin wannan binciken, matsakaicin nauyin tushe 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].
Inganta Ciwon Cutar Neuropathy
Nazarin ya nuna cewa GLP1-RAs na iya rage haɗarin lalata a cikin marasa lafiya tare da nau'in 2 na metabolism ta hanyar inganta ƙwaƙwalwar ajiya, koyo, da kuma shawo kan rashin fahimta. A matsayin dual GIP-RA / GLP-1RA, a cikin layin kwayar cutar neuroblastoma (SHSY5Y), bincike ya gano cewa Tirzepatid yana da tasiri a kan alamun ci gaban neuronal (CREB da BDNF), apoptosis (RAX / Bcl2 rabo), bambancin (pAkt, MAP2, GAP43, da AGBL4), da insulin juriya (GLUT3), da insulin juriya (GLUT3). SORBS1). Sakamakon ya jaddada muhimmancin Tirzepatid a cikin kunna hanyar pAkt / CREB / BDNF da kuma siginar sigina na kasa da kuma tasirin neuroprotective, yana nuna cewa zai iya magance tasirin da ke hade da hyperglycemia da insulin juriya 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 game da haɓakar cututtukan cututtukan da ke da alaƙa da metabolism [5]..
Ci gaban Bincike a cikin Maganin Nau'in Metabolism Na 2
A matsayin sabon nau'in maganin hypoglycemic, Tirzepatid ya zama agonist na GIP/GLP-1R na farko da aka amince da shi don maganin metabolism a cikin Amurka. Yawancin gwaje-gwaje na asibiti da yawa sun tabbatar da raguwar glucose na jini mai mahimmanci da kuma asarar nauyi, kuma yana da yuwuwar kariya ta zuciya. Ma'anar peptides na roba ya buɗe yawancin yuwuwar da ba a san su ba don Tirzepatid. Gwaje-gwajen da ke gudana (NCT04166773) da shaidu sun nuna cewa magani ne mai ban sha'awa a cikin fagagen cututtukan hanta maras barasa (NAFLD), renal da neuroprotection [6] (Ma Z, 2023).
Tasirin Dogon Tirzepatid akan Lafiyar Zuciya
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 [7] . Binciken ya gano cewa a cikin manya na Amurka da suka cancanci maganin Tirzepatid, bayan jiyya tare da 15 MG na Tirzepatid, an kiyasta 70.6% da 56.7% na manya sun rasa ≥ 15% da ≥ 20% na nauyin jikinsu bi da bi, wanda ke nufin raguwar 58.8% na adadin mutane 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 magani' zuwa 7.7% 'bayan magani', tare da cikakken raguwar haɗari na 2.4% da raguwar haɗarin dangi na 23.6%, hana 2 miliyan abubuwan cututtukan zuciya.
A ƙarshe, Tirzepatid sabon nau'in agonist dual agonist na GIP da masu karɓar GLP-1, wanda ke da mahimmanci a cikin jiyya na nau'in 2 metabolism da kiba. Yana iya inganta haɓakar ƙwayar insulin yadda ya kamata, hana ƙwayar glucagon, daidaita glucose na jini daidai, rage haɗarin rikice-rikice, inganta aikin ƙwayoyin beta na pancreatic, jinkirta ci gaban metabolism, kuma yana da tasirin cardioprotective. A cikin maganin kiba, yana iya rage cin abinci yadda ya kamata, rage sha'awar abinci, ƙara koshi, taimakawa masu kiba su rage kiba, da rage haɗarin matsalolin da ke da alaƙa da kiba. Hakanan yana iya haɓaka juriya na insulin da metabolism na lipid. Bugu da ƙari, yana nuna yuwuwar a cikin maganin cututtukan cututtukan da ke da alaƙa na rayuwa irin su steatohepatitis mara-giya, ciwo na bacci na bacci, da gazawar zuciya, kuma yana iya haɓaka haɓakar alamomin rayuwa da yawa a lokaci guda, yana ba da cikakken tsarin kulawa. Hanyar allurar sa na sati-sati ya dace don amfani kuma yana iya inganta yarda da jiyya na marasa lafiya. Ta hanyar sarrafa glucose na jini yadda ya kamata da kuma rage haɗarin rikice-rikice, zai iya inganta yanayin jikin marasa lafiya da yawa, haɓaka ikon ayyukansu na yau da kullun da ingancin rayuwa, ƙara amincewa da kula da cututtuka, rage nauyin tunaninsu, da haɓaka daidaitawar zamantakewa.
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 sosai a cikin nazarin metabolism metabolism, 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 ].
