CJC 1295 hamwe na DAC 5mg

▎ CJC1295 Hamwe na DAC Imiterere

▎ CJC1295 Hamwe n'ubushakashatsi bwa DAC

Ni ubuhe bushakashatsi bwakozwe na CJC1295 Hamwe na DAC?

Gukoresha imisemburo gakondo ikura imisemburo irekura (GHRH) mukuvura bigarukira kubikorwa byigihe gito. Ibi byatumye abashakashatsi bashakisha uburyo bwogukora imisemburo ikura igihe kirekire igereranya imisemburo ya hormone kugirango barusheho kuvura no korohereza. Hamwe nabantu bakurikirana ubuzima nubwiza, imiti rusange ya farumasi yabaturage itanga imbaraga zo kwihuta kugirango imitsi igabanuke, igabanuka ryamavuta, nuruhu rwubusore. Kuruhande rwinyuma, imisemburo ikura ya hormone igereranya nka CJC1295 Hamwe na DAC yakwegereye ibitekerezo. Ubushakashatsi bwerekana ko abakoresha ihuriro bagaragaza ubuhanga nuburambe mugukoresha intego nyinshi, kandi intego yo guhitamo gukoresha ibintu nkibi harimo kugabanya ibiro, kongera imitsi, kuvugurura uruhu, gusinzira neza, no gukira ibikomere, nibindi ^[1] . Nkumwanya muremure ukora imisemburo ikura imisemburo igereranya, iterambere rya CJC1295 Hamwe na DAC rishingiye kumyumvire yimbitse yuburyo bugenga imisemburo ikura. Nubwo abana benshi bafite imisemburo ikura (GH) bafite ikibazo cyo gukura neza kuri GHRH, igice cya kabiri cyubuzima bwa GHRH ni kigufi cyane, bikagabanya ingaruka zo kuvura. Kugira ngo iki kibazo gikemuke, abashakashatsi bakoze CJC1295 Hamwe na DAC, igereranya rya GHRH rimaze igihe kinini. Ubushakashatsi bwerekanye ko bugizwe nitsinda rya menimide rikora kuri C-terminus, rikemerera guhuza hamwe na poroteyine za plasma nka serumu albumin, bityo bikongera ubuzima bwacyo bwa kabiri kandi bikabasha kongera imisemburo ikura mu bantu mu gihe kirenze iminsi itandatu nyuma y’ubuyobozi bumwe ^[2]

Nubuhe buryo bwo gukora bwa CJC1295 Hamwe na DAC mukuvura indwara zihariye?

Gukangura imisemburo ikura: 

CJC1295 Hamwe na DAC ni imiti ishingiye kuri peptide ishobora gutera imbaraga zo gukora imisemburo ikura (GH) ikomoka muri glande ya pitoito ^{[2, 3]} Ihuza itsinda rya menimide ikora kuri C-terminus, ikayemerera guhuza hamwe na poroteyine za plasma nka serumu albumin. Uku guhambira guha CJC1295-proteine ​​conjugate igihe kirekire cyane cyubuzima kandi ikayifasha kuzamura umusaruro wa GH mubantu muminsi irenga itandatu nyuma yubuyobozi bumwe. Ubushakashatsi bwerekanye ko inshinge ziterwa na CJC1295 Hamwe na DAC zishobora gutuma habaho kwiyongera ku buryo burambye, bushingiye ku bipimo byiyongera mu rwego rwa GH hamwe na insuline imeze nk’ikura rya I (IGF-I) ku bantu bakuze bafite ubuzima bwiza ^{[2, 3]} Nyuma yo gutera inshinge imwe ya CJC1295 Hamwe na DAC, impuzandengo ya plasma GH yiyongereyeho inshuro 2-10 kandi ikomeza iminsi 6 cyangwa irenga, hamwe na plasma IGF-I. Ikigereranyo cya kimwe cya kabiri cyubuzima bwa CJC1295 Hamwe na DAC ni iminsi 5.8-8.1. Nyuma yubuyobozi bwinshi, impuzandengo ya IGF-I yagumye hejuru yurwego rwibanze kugeza kuminsi 28.

Uruhare rwo kubura imisemburo ikura: 

Mubyitegererezo byinyamanswa bifite imisemburo ikura (GH), CJC1295 Hamwe na DAC yerekanye ingaruka nziza. Ku mbeba zifite gene ya GHRH, inyamaswa zakira dose ya buri munsi ya CJC1295 Hamwe na DAC yerekanaga uburemere bwumubiri nuburebure bwumubiri ^[4] Imbeba zavuwe buri masaha 48 na 72 zifite uburemere bwumubiri nuburebure bwumubiri kuruta inyamaswa zivurwa na platbo. Nubwo ubusanzwe bwuzuye bwo gukura butagerwaho, hari iterambere ryagaragaye. Mu matsinda yose yo kuvura, ubwinshi bwibinure hamwe nububyibushye bwibisanzwe byari bisanzwe. CJC1295 Hamwe na DAC nayo yatumye ubwiyongere bwa pitoito RNA na GH mRNA, byerekana imikurire ya selile somatotroph, igisubizo cyemejwe namashusho yubudahangarwa.

Nigute CJC1295 Hamwe na DAC igera ku ngaruka zirambye muburyo bw'imiterere?

Guhuza hamwe na serumu albumin: 

C. ^​ ​Bimaze guhambirwa kuri serumu albumin, CJC-1295 ikora ibintu bisa nkaho bihamye, bityo bikongerera igihe ibikorwa byayo mumubiri. Kurugero, iyo itsinda rya maleimide rya CJC-1295 rihuza guhuza umuhogo wubusa kuri serumu albumin, ubuzima bwayo bwamaraso bwiyongera cyane. Ubu buryo bwa conjugation burihariye muri peptide yongera imikorere kandi bushiraho urufatiro rwingaruka zirambye za CJC-1295 ^[5].

Kunoza umutekano: 

Ibikomoka kuri malimide bitatu byahujwe no guhindura imisemburo ikura ya muntu ikura (hGRF), muri yo CJC-1295 ni uburyo bwa tetra bwasimbuwe na hGRF (1-29), hamwe na Nε-3-maleimidopropionamide ikomoka kuri lysine yongerewe kuri C-terminus ^[6] . Mu isesengura ryimisemburo ya hormone ikura yimbeba yimbeba imbere ya pitoito, serumu yumuntu uko ari itatu ya conjugate yakoraga mubuzima. Iyo ibikomoka kuri malimide byatewe mu buryo bwihuse mu mbeba zisanzwe za Sprague Dawley, imisemburo ikura ikabije yagaragaye muri plasma. Muri byo, CJC-1295 yerekanye ubwiyongere bwikubye inshuro 4 ahantu munsi yimisemburo ikura ugereranije na hGRF (1-29) mumasaha 2. Byongeye kandi, isesengura ry’iburengerazuba ryakozwe kuri plasma yimbeba zatewe na CJC-1295 ryerekanye ko hari imiti ikingira indwara ya CJC-1295 mu itsinda rihuye na serumu albumin, yagaragaye nyuma yiminota 15 nyuma yo guterwa kandi ikomeza kuzenguruka amasaha arenga 24. Ibisubizo byerekana ko CJC-1295 ari igereranya rihamye kandi rikora HGRF (1-29) hamwe na plasma yaguye igice cya kabiri cyubuzima ^[6].

Ingaruka za CJC-1295 kumubiri wose wt (TBW; bisobanura ± SE). Igihe cyo kuvura 5-wk kirangiye, itsinda rya CJC / 24 h ryerekanye igituntu gisanzwe rwose. Amatsinda ya CJC / 48 h na CJC / 72 h yageze kuri TBW hejuru cyane ugereranije nitsinda rya GHRHKO / pbo, nubwo ryakomeje kuba rito ugereranije no mu itsinda rya HTZ / pbo.

Inkomoko: PubMed ^[4]

Ni ubuhe buryo bwo kuvura bwa CJC1295 Hamwe na DAC?

CJC1295 Hamwe na DAC irashobora gutera imbaraga gusohora imisemburo ikura (GH). Ubushakashatsi bwinshi bwerekanye ko uyu muti ushobora kongera igipimo cya plasma GH ku bantu bakuze bafite ubuzima bwiza ku buryo buterwa na ^dose . Kurugero, mubushakashatsi bwibintu bizima, amasomo afite hagati yimyaka 21 na 61 bafite impuzandengo ya plasma GH yiyongereyeho inshuro 2-10 muminsi 6 cyangwa irenga nyuma yo guhabwa inshinge ziterwa na CJC1295 Hamwe na DAC. Izi ngaruka zo gutera imisemburo ikura imisemburo ikura ningirakamaro cyane kubarwayi bafite imisemburo ikura.

Ku bana bafite imisemburo ikura, nubwo abana benshi bafite imikurire myiza yimisemburo ikura ya hormone ikura (GHRH), igice gito cyubuzima bwa GHRH kigabanya ikoreshwa ryayo. Nkurugero rurerure rwa GHRH, CJC1295 Hamwe na DAC irashobora guhitamo guhuza guhuza alubumu ya endogenous, bityo ikongerera igice cyubuzima bwayo nigihe cyo gukora. Mu bushakashatsi bwakozwe ku mbeba za GHRH gene knockout (GHRHKO), byagaragaye ko ubuyobozi bwa buri munsi bwa CJC1295 Hamwe na DAC bushobora kugumana uburemere busanzwe bw’umubiri hamwe n’uburebure bw’imbeba, byerekana ko uyu muti ufite agaciro gakoreshwa mu kuvura imisemburo ikura y’abana bato ^[4] .

C. Kandi nyuma yubuyobozi bwinshi, impuzandengo ya IGF-I irashobora kuguma hejuru yumurongo mugihe cyiminsi 28 ^[4] . IGF-I ifite imirimo itandukanye yingenzi yumubiri mumubiri wumuntu, harimo guteza imbere ikwirakwizwa ryingirabuzimafatizo, gutandukana, no kubaho, no kugenzura metabolism, nibindi. Kubwibyo, kongera urwego rwa IGF-I bishobora kugira ingaruka nziza mukuvura indwara zitandukanye.

Ni ubuhe buryo bushoboka bwa CJC1295 Hamwe na DAC mubice byubuvuzi nibindi bijyanye?

Gukura imisemburo ya hormone: 

CJC1295 Hamwe na DAC irashobora gukomeza gukangura glande ya pitoito kugirango isohore imisemburo ikura. Ku barwayi bafite imisemburo ikura idahagije bitewe nimpamvu zitandukanye, cyane cyane abana ningimbi, irashobora kunoza neza imiterere yimikurire niterambere ridindiza kandi bigatera imbere gukura. Mu kuvura kubura imisemburo ikura, imiti gakondo yo gusimbuza imisemburo yo gukura yageze ku bisubizo bimwe, ariko CJC1295 Hamwe na DAC ifite ibyiza byihariye. Irashobora guhuza alubumu ya endogenous, bityo ikongerera igice cyigihe cyigihe nigihe cyo gukora ^[4] . Kurugero, mubushakashatsi bwakozwe nimbeba za GHRH gene knockout, byagaragaye ko ubuyobozi bwa buri munsi bwo kuvura CJC-1295 bushobora kugumana imiterere isanzwe yumubiri no gukura kwimbeba za GHRHKO, harimo uburemere bwumubiri usanzwe, uburebure bwumubiri, ubwinshi bwibinure, hamwe nubwinshi bwibinure byamavuta, kandi mugihe kimwe bishobora no gutuma ubwiyongere bwa pitoito RNA na GH mRNA, byemeza ubwiyongere bwimisemburo ya RNA na GH mRNA.

Ku barwayi bakuze bafite imisemburo ikura, CJC1295 Hamwe na DAC ntishobora gusa kunoza imiterere yumubiri, kongera imitsi, no kugabanya ibinure byumubiri ahubwo inazamura imibereho. Gukura imisemburo nayo igira uruhare runini mumubiri ukuze. Ifite uruhare mu kugenzura metabolike ya poroteyine, amavuta, na karubone. Kubura imisemburo ikura bizatera ibibazo nko kongera amavuta yumubiri, kugabanuka kwimitsi, no kugabanuka kwamagufwa. Gukoresha CJC1295 Hamwe na DAC birashobora gukosora ibyo bidasanzwe kurwego runaka no kuzamura imiterere yumubiri wabarwayi.

Kurwanya gusaza: 

Uko imyaka igenda yiyongera, imisemburo ya hormone ikura yumuntu igenda igabanuka buhoro buhoro, bizatera urukurikirane rwimpinduka zijyanye no gusaza. CJC1295 Hamwe na DAC ifite agaciro gakoreshwa muburyo bwo kurwanya gusaza. Irashobora kongera imisemburo ya hormone yo gukura kurwego runaka, ifasha kunoza igabanuka ryimikorere yumubiri ijyanye no gusaza. Kurugero, irashobora kongera ubwinshi bwamagufwa. Gukura imisemburo irashobora guteza imbere ibikorwa bya osteoblasts, kongera amagufwa, no kwirinda osteoporose; kongerera imbaraga imitsi. Gukura imisemburo irashobora gukurura intungamubiri za poroteyine, kongera imitsi n'imbaraga; Kunoza uruhu rworoshye kandi rukayangana. Imisemburo ikura irashobora gutuma uruhu rukomera kandi rukomeye mugutezimbere synthesis ya kolagen ^..

Ubuvuzi bwa siporo no gusubiza mu buzima busanzwe: 

CJC1295 Hamwe na DAC ifite uburyo bushoboka bwo gusubiza mu buzima busanzwe imvune za siporo no kunoza imikorere ya siporo. Irashobora guteza imbere imitsi no kuvugurura no kwihutisha gukira ibikomere. Iyo umukinnyi akomeretse, umubiri ukenera gusana ingirangingo zangiritse vuba bishoboka kugirango ugarure ubushobozi bwimikino. Imisemburo ikura igira uruhare runini muriki gikorwa. Irashobora gutuma ikwirakwizwa ry'uturemangingo no gutandukana, bigatera intungamubiri za poroteyine, kandi byihutisha gusana imitsi n'izindi ngingo ^[4] . Muri icyo gihe, CJC1295 Hamwe na DAC irashobora kongera imbaraga zimitsi no kwihangana no kongera ubushobozi bwimikino. Imisemburo ikura irashobora kongera imitsi no kongera ubushobozi bwimitsi yimitsi, bityo bikongerera imbaraga no kwihangana kwabakinnyi ^[4] .

Indwara ziterwa na metabolike: 

Ku ndwara zimwe na zimwe ziterwa no kubyibuha nk'umubyibuho ukabije no kurwanya insuline, CJC1295 Hamwe na DAC irashobora kugira ingaruka ku mikorere ya metabolisme no gukwirakwiza ibinure kandi ikanongerera imbaraga insuline mu kugenzura imisemburo ikura-insuline imeze nk'ikintu gikura. Umubyibuho ukabije ni indwara isanzwe ihindagurika, kandi kuba bibaho bifitanye isano n'ubusumbane buri hagati yo gufata ingufu no gukoresha. Imisemburo ikura irashobora gutuma ibinure bigabanuka kandi bikongera ingufu, bityo bigafasha kugenzura ibiro byumubiri. Kurwanya insuline bivuga kugabanuka k'umubiri wumva insuline, bigatuma kwiyongera k'isukari mu maraso. Imisemburo ikura irashobora kunoza insuline no kugabanya isukari mu maraso ^[4].

Mu gusoza, CJC1295 Hamwe na DAC yerekanye ingaruka nziza mubice byinshi murwego rwo kugenzura imisemburo ikura. Ifite agaciro gakomeye mu kuvura kubura imisemburo ikura gusa ahubwo no mubuvuzi bwa siporo no gusubiza mu buzima busanzwe ndetse n’ubushakashatsi bwo kurwanya gusaza. Uburyo bumaze igihe bukora bwibikorwa bigabanya inshuro zubuyobozi, kandi umutekano wacyo mwiza no kwihanganira nabyo bitanga inkunga ikomeye mubikorwa byubuvuzi. Nubwo bikiri mubyiciro byubushakashatsi mubice bimwe na bimwe nko kurwanya gusaza, ingaruka zimaze kugaragara zirahagije kugirango zerekane ibyiza byihariye hamwe nuburyo bugari bwo gukoresha mubijyanye nubumenyi bwubuzima hamwe nibindi bijyanye.

Ibyerekeye Umwanditsi

Ibikoresho byavuzwe haruguru byose byakorewe ubushakashatsi, byahinduwe kandi byakozwe na Cocer Peptides.

Umwanditsi w'ikinyamakuru

Teichman SL ni impuguke ifite uburambe kandi bukomeye mubijyanye n'ubuvuzi no guteza imbere ibiyobyabwenge. Afitanye isano rya bugufi n’ibigo byinshi bizwi n’amasosiyete, nk’amashyirahamwe Concentr Analges Inc, Teichman Drug Dev Consulting, Kaminuza y’ubuvuzi ya Wroclaw, BEAT Biotherapeut Corp, Corthera Inc hamwe n’amasosiyete akorana nayo Corthera, Chiasma, ARYx Therapeut Inc, n'ibindi. Ibice bye byumwuga bikubiyemo ibintu byinshi birimo sisitemu yumutima nimiyoboro yumutima & Cardiology, General & Internal Medicine, Engineering, Endocrinology & Metabolism, na Pharmacology & Farumasi, hamwe nibikorwa byiza yagezeho nintererano cyane cyane mugutezimbere ibiyobyabwenge na biotherapi. Teichman SL yanditse murutonde rwibisobanuro [3].

Imirongo ijyanye

1 Gukoresha Ibiyobyabwenge & Gukoresha nabi, 2016,51 (1): 73-84.DOI: 10.3109 / 10826084.2015.1082595.

[2] Timms M, Ganio K, Steel R. Uburyo bwo kwemeza ihohoterwa rya CJC-1295 mu ngero zingana na plasma ya LC-MS / MS [J]. Kwipimisha no gusesengura ibiyobyabwenge, 2019,11 (8): 1248-1257.DOI: 10.1002 / dta.2599.

[3] Teichman SL, Neale A, Lawrence B, n'abandi. Kumara igihe kirekire imisemburo ikura (GH) hamwe na insuline imeze nkikura rya I isohoka na CJC-1295, igereranya rimaze igihe kinini ryerekana imisemburo ya GH irekura, kubantu bakuze bafite ubuzima bwiza [J]. Ikinyamakuru cya Clinical Endocrinology & Metabolism, 2006,91 (3): 799-805.DOI: 10.1210 / jc.2005-1536.

[4] Alba M, Fintini D, Sagazio A, n'abandi. Imiyoborere ya buri munsi ya CJC-1295, igereranya imisemburo ikura-imisemburo ikura (GHRH) igereranya imikurire yimbeba ya GHRH knockout [J]. Ikinyamakuru cyo muri Amerika cya Physiology-Endocrinology na Metabolism, 2006,291 (6): E1290-E1294.DOI: 10.1152 / ajpendo.00201.2006.

[5] Timms M, Ganio K, Forbes G, n'abandi. Ikirangantego cya immuno polymerase cyerekana uburyo bwo kumenya CJC-1295 hamwe nindi mikorere ikura-imisemburo ikura imisemburo igereranya plasma imwe [J]. Kwipimisha no gusesengura ibiyobyabwenge, 2019,11 (6): 804-812.DOI: 10.1002 / dta.2554.

[6] Jetté L, Léger R, Thibaudeau K, n'abandi. Gukura kwa hormone gusohora kwabantu (hGRF) _1-29 -ibinyabuzima bya albumin bioconjugates ikora reseptor ya GRF kuri pitoito yimbere yimbeba :: Kumenyekanisha CJC-1295 nkikigereranyo kirekire cya GRF [J]. Endocrinology, 2005,146 (7): 3052-3058.DOI: 10.1210 / en.2004-1286.

INGINGO ZOSE N'AMAKURU Y’IBICURUZWA BITANZWE KURI URU RUBUGA BISANZWE KUBONA AMAKURU N'INTEGO Z'UBUREZI.  

Ibicuruzwa byatanzwe kururu rubuga bigenewe gusa mubushakashatsi bwa vitro. Mu bushakashatsi bwa vitro (Ikilatini: * mu kirahure *, bisobanura mu bikoresho by'ibirahure) bikorwa hanze y'umubiri w'umuntu. Ibicuruzwa ntabwo ari imiti, ntabwo byemejwe n’ikigo cy’Amerika gishinzwe ibiryo n’ibiyobyabwenge (FDA), kandi ntigomba gukoreshwa mu gukumira, kuvura, cyangwa gukiza indwara iyo ari yo yose y’ubuvuzi, indwara, cyangwa indwara. Birabujijwe rwose n'amategeko kwinjiza ibyo bicuruzwa mumubiri wabantu cyangwa inyamaswa muburyo ubwo aribwo bwose.