|
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 magani ne na polypeptide na roba, kuma ci gabansa ya samo asali ne daga zurfin fahimtar iyakokin GLP-1 masu karɓar agonists na yanzu a cikin kula da nau'in 2 na metabolism metabolism da kiba. Kodayake GLP-1 agonists masu karɓa sun riga sun nuna kyakkyawan aiki a cikin sarrafa glucose na jini da asarar nauyi, masana kimiyya sun gano cewa yayin da suke kunna mai karɓar GLP-1, tasirin su akan mai karɓar GIP yana da rauni sosai, wanda zuwa wani lokaci yana iyakance tasirin warkewa na magungunan. Don haka, ƙungiyar bincike da haɓakawa ta himmatu wajen haɓaka sabon nau'in magani wanda zai iya kunna duka GIPR da GLP-1R a lokaci guda, a cikin bege na samun ƙarin ingantaccen kuma 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. Da farko, a cikin matakin bincike na farko, an kimanta halayen magunguna na Tirzepatid sosai ta hanyar gwaje-gwajen dabba, kuma an tabbatar da yuwuwar sa a cikin sarrafa glucose na jini da asarar nauyi. Sakamakon ya nuna cewa Tirzepatid na iya rage matakin glucose na jini sosai a cikin samfuran dabbobi kuma yana da kyau a sarrafa nauyi. Waɗannan tabbataccen binciken sun kafa tushe mai ƙarfi don gwaje-gwajen asibiti na gaba.
Daga bisani, Tirzepatid ya shiga matakin gwaji na asibiti, ciki har da gwaji na I, II, da III. A cikin gwaji na lokaci na, aminci, haƙuri, da halayen magunguna na miyagun ƙwayoyi an yi la'akari da su musamman, kuma sakamakon ya nuna cewa Tirzepatid yana da aminci mai kyau da haƙuri. Gwajin kashi na II ya kara bincika inganci da amincin allurai daban-daban na Tirzepatid a cikin marasa lafiya da ke da nau'in 2 na metabolism, kuma da farko an ƙaddara iyakar adadin sa. Mafi mahimmancin gwaji na asibiti na III, kamar su jerin binciken SURPASS, sun rufe adadi mai yawa na marasa lafiya tare da nau'in ciwon sukari na 2. Sakamakon ya nuna cewa Tirzepatid ya fi agonists masu karɓa na GLP-1 da ke wanzu, kamar semaglutide, wajen rage glucose na jini da nauyi. Wannan sakamakon ci gaba ya ba da goyan bayan shaida mai ƙarfi don aikace-aikacen tallan Tirzepatid [1].
Tirzepatid polypeptide ne wanda ya ƙunshi amino acid guda 39, wanda a cikinsa aka gyara kowane amino acid ɗin don inganta kwanciyar hankali da ingancinsa. Wannan tsari na musamman na musamman yana ba Tirzepatid damar haɗa tasirin hormones na incretin guda biyu, GIP da GLP-1, cikin kwayoyin halitta guda ɗaya, kuma yana kunna masu karɓar hormone da ke cikin sarrafa glucose na jini ta hanyar tsarin aiki biyu. Musamman, Tirzepatid na iya yin aiki akan duka pancreas da tsarin juyayi na tsakiya. A gefe guda, yana haɓaka ƙwayar insulin kuma yana hana sakin glucagon, ta yadda ya kamata ya rage glucose na jini yadda ya kamata; a daya bangaren kuma, ta hanyar jinkirta zubar da ciki da kuma kara yawan koshi, yana rage sha'awa da cin abinci, don haka yana samun nasarar sarrafa nauyi. Wannan tsarin aikin dual yana ba Tirzepatid fa'idodi na musamman a cikin kula da nau'in 2 na metabolism metabolism da kiba, yana ba marasa lafiya ƙarin zaɓi na jiyya [1].
Menene tsarin aikin Tirzepatid?
Tirzepatid yana rage yawan glucose na jini ta hanyar hanyoyin aiki tare da yawa, kamar haka: Kunna mai karɓar GLP-1: Tirzepatid yana ɗaure ga mai karɓar GLP-1 akan ƙwayoyin β pancreatic, yana kwaikwayon tasirin GLP-1 na halitta. GLP-1 wani hormone ne da aka samar a cikin hanji kuma yana da mahimmanci don kiyaye glucose homeostasis 2. Yana iya inganta haɓakar insulin, ƙwayar insulin, da fahimtar glucose, da kuma rage ƙwayar glucagon don inganta satiety da hana ci 2.
Wannan kunnawa na iya haɓaka ƙwayar insulin. Insulin shine babban hormone mai rage glucose na jini a cikin jiki, wanda zai iya ƙara yawan ɗauka da kuma amfani da glucose ta sel, ta haka ne rage matakan glucose na jini. A cikin marasa lafiya da ke da nau'in metabolism na nau'in 2, ƙwayar insulin ba ta isa ba ko kuma hankalin sel ga insulin ya ragu, wanda ke haifar da haɓakar glucose na jini. Tirzepatid yana ƙara haɓakar insulin ta hanyar kunna mai karɓar GLP-1, wanda ke taimakawa haɓaka sarrafa glucose na jini. A lokaci guda, kunna mai karɓar GLP-1 na iya hana sakin glucagon. Glucagon yawanci yana haɓaka glycogenolysis da gluconeogenesis a cikin yanayin azumi, yana haɓaka samar da glucose na jini. Ta hanyar hana tasirin glucagon, Tirzepatid yana ƙara rage tushen glucose na jini, wanda ke taimakawa wajen sarrafa glucose na jini [2] (Anonymous, 2023).
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 na pancreatic. Bayan kunnawa, ta hanyar tafiyar da siginar siginar intracellular, haɓakar insulin yana ƙaruwa, kuma ana haɓaka amsawar sel zuwa insulin, ta haka ne ya fi dacewa da rage yawan glucose na jini. motsa jiki 2. Tirzepatid shine tsarin sinadarai na roba wanda ya dogara da jerin GIP, wanda ya ƙunshi peptide 39-amino acid. Yana kara fitar da sinadarin insulin, yana rage sakin glucagon ta hanyar dogaro da glucose, yana rage azumi da matakan glucose na jini, yana inganta wadatuwa, yana rage nauyi, yana jinkirta fitar da ciki.
Wannan tasirin agonist mai karɓar mai karɓa na biyu yana sa Tirzepatid ya fi tasiri wajen haɓaka ƙwayar insulin da hana sakin glucagon fiye da masu karɓar mai karɓar GLP-1 guda ɗaya [2]..
Jinkirta zubar da ciki da karuwar satiety: Tirzepatid na iya jinkirta zubar da ciki, yana tsawaita lokacin zama na abinci a cikin ciki, rage yawan sha na gina jiki, don haka guje wa karuwa mai yawa a cikin glucose na jini bayan cin abinci. A cikin bincike na asali da na asibiti, 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 nau'in ciwon sukari na 2 ba, Tirzepatid sau ɗaya-mako-mako (≥5 da ≥4.5mg, bi da bi) yana jinkirta zubar da ciki bayan kashi ɗaya. A cikin mahalarta masu lafiya, an rage wannan tasirin bayan yawancin allurai na Tirzepatid ko dulaglutide [3] .
A lokaci guda kuma, yana iya yin aiki akan tsarin juyayi na tsakiya, ƙara yawan gamsuwa, da rage ci da abinci. Ta hanyar sarrafa cin abinci, a kaikaice yana taimakawa wajen sarrafa matakan glucose na jini, musamman dacewa da matsalar kiba sau da yawa tare da marasa lafiya tare da nau'in ciwon sukari na 2, kuma yana taimakawa haɓaka juriya na insulin da yanayin rayuwa gaba ɗaya [2]..
Haɓaka haɓakar insulin da ƙwayar lipid: An gano Tirzepatid don haɓaka matakin adiponectin, wanda shine adipocytokine mai alaƙa da haɓakar insulin. Ƙara yawan adadin adiponectin yana taimakawa wajen inganta haɓakar insulin, yana sa sel su zama masu kula da insulin, don haka mafi inganci da amfani da glucose, yana rage glucose na jini [2]..
Bugu da ƙari, Tirzepatid kuma zai iya inganta bayanin martabar lipid kuma yana da tasirin kariya ga lafiyar zuciya da jijiyoyin jini. An tabbatar da cewa Tirzepatid zai iya inganta hawan jini, rage ƙananan ƙwayar lipoprotein (LDL) cholesterol da triglycerides [4] .Wannan yana ƙara goyan bayan fa'idodin fa'ida a cikin sarrafa glucose na jini.
Bincike mai alaƙa
Inganci akan sarrafa nauyi a cikin marasa lafiya tare da kiba da nau'in 2 metabolism:
Yawancin bincike na asibiti sun tabbatar da tasirin asarar nauyi: A cikin binciken mai suna 'SURMOUNT-2', wannan gwaji shine lokaci 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 mafi girma kuma glycated haemoglobin (HbA₁c) na 7 - 10% an ba da izini don karɓar allurar subcutaneous na Tirzepatid sau ɗaya a mako-mako (10mg ko 15mg) ko placebo na makonni 72. Sakamakon ya nuna cewa a cikin mako 72, yawan asarar nauyi a cikin Tirzepatid 10mg da 15mg kungiyoyin shine -12.8% da -14.7%, bi da bi, yayin da a cikin rukunin placebo shine -3.2%. Matsakaicin bambance-bambancen jiyya na Tirzepatid 10mg da 15mg idan aka kwatanta da placebo sune -9.6 kashi da maki -11.6, bi da bi, duka biyun suna da mahimmancin ƙididdiga (p＜0.0001). Bugu da ƙari, ƙarin marasa lafiya da aka yi wa magani tare da Tirzepatid sun kai iyakar asarar nauyi na 5% ko fiye (79 - 83% vs 32%) [5] (Garvey WT, 2023). 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 nauyi ba ne kawai amma kuma ya taka rawa mai kyau a cikin sarrafa glucose na jini [5].
Tasirin haɓakawa akan neuropathy masu alaƙa da metabolism:
Wasu nazarin sun nuna cewa glucagon-like peptide 1 agonists (GLP1-RAs) na iya rage haɗarin lalata a cikin marasa lafiya tare da nau'in ciwon sukari na 2 ta hanyar inganta ƙwaƙwalwar ajiya, koyo, da kuma shawo kan rashin fahimta. A matsayin dual glucose-dependent insulin polypeptide agonist agonist (GIP-RA) / GLP-1RA, Tirzepatid an yi nazari don tasirinsa akan alamomin ci gaban neuronal (CREB da BDNF), apoptosis (BAX / Bcl2 rabo), bambance-bambance (pAkt, MAP2, GAP43, da AGBL4), da insulin juriya (GLUT, 1 GLUUT, GLUUT, 1, GLUUT, 1, GLUUT, da BDNF). Neuroblastoma cell line (SHSY5Y). Sakamakon a karon farko ya jaddada rawar da Tirzepatid ke takawa wajen kunna hanyar pAkt/CREB/BDNF da siginar sigina na ƙasa, da kuma tasirin sa a cikin neuroprotection. Hakanan ya nuna cewa Tirzepatid zai iya 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 game da haɓakar cututtukan da ke da alaƙa da metabolism [6]. .
Ci gaban bincike a cikin jiyya na nau'in 2 metabolism:
Wasu nazarin sun nuna cewa Tirzepatid, a matsayin sabon nau'in maganin hypoglycemic, ya zama agonist na GIP / GLP-1R na farko da aka amince da shi don maganin metabolism a cikin Amurka. An tabbatar da cewa yana da tasiri mai mahimmanci na raguwar glucose na jini da asarar nauyi a cikin manyan gwaje-gwaje na asibiti da yawa, kuma akwai shaida 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 fagen cututtukan hanta maras barasa (NAFLD), renal da neuroprotection, da dai sauransu [7]..
Sakamakon dogon lokaci na T irzepatide 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 [8] . Binciken ya gano cewa a tsakanin manya na Amurka da suka cancanci maganin Tirzepatid, bayan jiyya tare da 15mg na Tirzepatid, an kiyasta cewa 70.6% da 56.7% na manya suna da asarar nauyi na ≥15% kuma wanda ke nufin adadin kiba ya ragu da ≥15%, wanda ke nufin adadin kiba 20. 58.8%. A cikin mutanen da ba tare da cututtukan zuciya ba, kimanin shekaru 10 na hadarin cututtukan zuciya ya ragu daga 10.1% kafin magani zuwa 7.7% bayan jiyya, 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 kuma yana da mahimmanci a cikin jiyya na nau'in ciwon sukari na 2 da kiba. Zai iya inganta haɓakar ƙwayar insulin yadda ya kamata, yana hana ƙwayar glucagon, daidaita glucose na jini daidai, rage haɗarin rikitarwa, haɓaka aikin ƙwayoyin β pancreatic, da jinkirta ci gaban metabolism. 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, yana nuna yuwuwar a cikin maganin cututtukan cututtukan da ke da alaƙa da haɓakar rayuwa irin su steatohepatitis maras-giya, cututtukan 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 gudanar da allurar sa sau ɗaya a mako ya dace don amfani kuma yana iya haɓaka ƙa'idodin kulawar marasa lafiya. Ta hanyar sarrafa glucose na jini yadda ya kamata da kuma rage haɗarin rikice-rikice, yanayin jiki na marasa lafiya na iya inganta sosai, za a iya haɓaka iya ayyukansu na yau da kullun da ingancin rayuwarsu, za a iya ƙara amincewarsu kan shawo kan cututtuka, za a iya sauke nauyin tunaninsu, kuma za a iya inganta daidaita rayuwarsu.
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. Iliminsa na ilimi da ƙwarewar sana'a ya ƙunshi nau'o'in fannoni daban-daban 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 [5].
