Abaloparatide 3mg

ya Abaloparatide Structure Imiterere

Research Abaloparatide Ubushakashatsi

Ni ubuhe bushakashatsi bwakozwe na abaloparatide?

Osteoporose ni indwara isanzwe igizwe na sisitemu yo mu bwoko bwa skeletale irangwa no kugabanuka kwamagufwa make hamwe no kwangirika kwa mikorobe yububiko. Ibi biganisha ku kugabanuka kw'amagufwa no kwandura kuvunika, hamwe no kuvunika ikibuno n'umugongo bikaba ingaruka zisanzwe. Ihindura cyane imibereho yabarwayi kandi ikongera ubumuga nimpfu. Hamwe n’ubwiyongere bw’abatuye isi ku isi, indwara ya osteoporose ikomeje kwiyongera. Bigereranijwe ko 42% -56% byabagore na 27% -29% byabagabo barengeje imyaka 50 bazavunika osteoporotic, bityo bikaba ikibazo cyihutirwa cyubuzima rusange. Ubuvuzi gakondo bwa osteoporose, nka bisphosifone hamwe na modulitori ya estrogene yatoranijwe (SERMs), bigumana cyane cyane ubwinshi bwamagufwa muguhagarika amagufwa ya osteoclast. Nyamara, imikorere yabo igarukira kubarwayi bafite amagufwa yagabanutse cyane kandi bafite ibyago byinshi byo kuvunika. Nubwo imisemburo ya parathiyide (PTH) 1-34 agace (teriparatide) niyo miti ya mbere ya anabolike yemejwe n’ikigo cy’Amerika gishinzwe ibiryo n’ibiyobyabwenge (FDA), kongerera cyane ubwinshi bw’amagufwa no kugabanya ibyago byo kuvunika, gukoresha igihe kirekire bitwara imbogamizi zirimo kongera amagufwa, hypercalcemia, ndetse n’ibyago byiyongera kuri osteosarcoma.

Kuruhande rwibi, guteza imbere imiti yubuvanganzo ihuza ingaruka zikomeye za anabolike mugihe wirinze izo ngaruka ni ngombwa. Nka parathiyide ya parathiyide ifitanye isano na peptide (PTHrP), abaloparatide igumana ibikorwa bikomeye bya anabolike mugihe bigabanya ingaruka ziterwa no gufata amagufwa no kugabanya ihindagurika rya calcium ya calcium, bikagira akamaro kuri osteoporose.

Nubuhe buryo bwo gukora kuri abaloparatide?

Imikoranire na Parathiyide Hormone yakira 1 (PTH1R)

Kwakira Guhitamo Gukora: Abaloparatide ni agoniste yatoranijwe ya parathiyide hormone reseptor 1 (PTH1R). PTH1R igaragara cyane hejuru yingirabuzimafatizo ziri mu ngingo nk'amagufwa n'impyiko, bigira uruhare runini mu kugenga metabolism. Abaloparatide ihuza cyane na PTH1R, itangiza urukurikirane rw'inzira zerekana ibimenyetso byerekana amagufwa. Iyo ihambiriye, ikora adenylate cyclase, ikongera umusaruro w'ingirabuzimafatizo ya AMP (cAMP) kugirango ihindure imikorere ya selile na metabolism ^[1,2].

Itandukaniro nizindi ligande: imisemburo ya Parathiyide (PTH) na poroteyine ya hormone ifitanye isano na poroteyine (PTHrP) nayo ihuza PTH1R. Nubwo PTH, PTHrP, na Abaloparatide ibimenyetso byose binyuze muri PTH1R, inzira zabo zerekana inzira zitandukanye. PTH na PTHrP bagaragaza isano isa na R ^ G (GTPγS-yunvikana) leta ya PTH1R. Teriparatid (TPTD, ni ukuvuga, 1-34 PTH) ifite inshuro enye zifitanye isano na leta ya R ^ 0 (GTPγS-itumva) kurusha PTHrP, bikavamo ibimenyetso bya camp igihe kirekire byatewe na TPTD. Ibinyuranye, abaloparatide, ikomoka kuri PTHrP (1-34), ikozwe muburyo bwo kongera umutekano kandi ikanesha ibibazo nko gutakaza idirishya rya anabolike na hypercalcemia ijyanye no gukoresha TPTD. Kuberako igipimo cyo gutandukana kwa PTHrP-PTH1R cyihuta kuruta icya PTH-PTH1R, ingaruka za osteogeneque za PTHrP ziherekejwe no kwinjirira gake hamwe na hypercalcemia kurusha TPTD. Abaloparatide iragwa iyi nyungu ugereranije ^[1,2,3].

Amabwiriza yo Guhindura Amagufwa

Gutezimbere kwa Osteogenezi: Abaloparatide itera ibikorwa bya osteoblast, kongera synthesis hamwe no gushira matrike yamagufa kugirango itere amagufwa. Osteoblasts ikomatanya kandi ikarekura ibice by'amagufwa ya matrix nka kolagen na osteocalcine, bigenda bigabanuka buhoro buhoro kugirango bibe ingingo nshya y'amagufwa. Ubushakashatsi bwerekana ko mu kuvura osteoporose nyuma yo gucura, abaloparatide yongerera cyane ubwinshi bwamagufwa yamagufwa (BMD) ahantu harimo ikibuno cyose, ijosi ryumugore, hamwe numugongo. Mugukangura imvugo ya genes zifitanye isano na osteoblast, igenga synthesis ya proteine ​​zingenzi nka osteocalcine nubwoko bwa I kolagen. Ibi bitera umubyimba wa trabecular no gukomera kwa cortical, kongera imbaraga za skeletale hamwe nubwiza mugihe bigabanya ibyago byo kuvunika ^[1,2,3].

Kubuza amagufwa Resorption: Mugihe Abaloparatide ikora cyane nka anabolike, irerekana kandi ingaruka zimwe na zimwe zibuza amagufwa. Ihindura itandukaniro nigikorwa cya osteoclasts-selile zishinzwe gufata amagufwa ashonga imyunyu ngugu na matrise kama irekura ibintu bya acide na enzymes za proteolyique. Abaloparatide irashobora kugabanya igipimo cyamagufwa yo kugabanya gutandukanya ingirabuzimafatizo ya osteoclast preursor muri osteoclasts ikuze cyangwa kugabanya igihe cyo kubaho kwa osteoclasts ikuze. Mugihe kimwe, ihindura ibimenyetso hagati ya osteoblasts na osteoclasts, ikomeza kuringaniza imbaraga hagati yamagufwa na resorption. Kurugero, igabanya ibikorwa bya osteoclast hamwe nibikorwa bya resorptive igabanya osteoblast-isohoka-reseptor reseptor ikora ibintu bya kirimbuzi κB ligand (RANKL). Bitandukanye na teriparatide, abaloparatide ntabwo yongera cyane umusaruro wa RANKL, bityo ikarinda gutakaza idirishya rya anabolike riba mugihe resorption irenze gushingwa mubyiciro byanyuma ^[1,2,3].

Igishushanyo 1 Icyitegererezo cya hormone ya parathiyide (PTH) / teriparatide na peptide ifitanye isano na PTH (PTHrP / abaloparatide gukora ya hormone ya parathiyide yo mu bwoko bwa 1 reseptor (PTH1R)) ^[4].

Ingaruka kuri Cartilage Metabolism (mubushakashatsi bujyanye na Osteoarthritis)

Itezimbere Synthesis ya Cartilage: Ubushakashatsi bwakozwe muri osteoarthritis (OA) bwerekanye ko abaloparatide igira ingaruka zo gukingira karitsiye. Chondrocytes ya articular yerekana PTH1R, kandi Abaloparatide ikora iyi reseptor, itera chondrocytes guhuza ibice bigize matrise ya karitsiye. Kurugero, ubushakashatsi bwerekana Abaloparatide yongera imvugo ya lubricine (Prg4), proteine ​​yingenzi ya matrike idasanzwe muri karitsiye ningirakamaro mugukomeza amavuta hamwe no kugabanya ubushyamirane. Itezimbere kandi synthesis yubwoko bwa II kolagen, igice cyibanze cya matrise ya karitsiye, ifasha kugumana imiterere yimikorere nubusugire bwimikorere. Mu kongera synthesis yibi bice bya matrise, Abaloparatide ifasha mugusana no kurinda ingirangingo zangiritse, bidindiza iterambere rya osteoarthritis ^[5].

Kubuza hypertrophy ya chondrocyte no kwangirika: Abaloparatide irashobora guhagarika hypertrophique itandukanya chondrocytes. Mugihe cya osteoarthritis igenda itera imbere, chondrocytes ikora hypertrophique itandukanye, irangwa no kwiyongera kwingirabuzimafatizo no kwerekana ibimenyetso byerekana ibimenyetso bya hypertrophyme nkubwoko X collagen (Col10). Iyi nzira iganisha ku kwangirika kwa matrix na karitsiye. Ubushakashatsi bwerekana ko kuvura Abaloparatide bigabanya kugenzura imvugo ya Col10 mu ngingo za karitsiye mu gihe bigabanya umubare w’ingirabuzimafatizo nini zimeze nka hypertrophique. Ibi birerekana ko bishobora kugabanya umuvuduko wa chondrocyte hypertrophique, bikagumana fenotipike isanzwe ya chondrocyte, bityo bikarinda karitsiye kandi bikadindiza iterambere rya osteoarthritis ^[5].

Ni ubuhe buryo bukoreshwa na Abaloparatide?

Umuti wa Osteoporose

Osteoporose ya Postmenopaose: Abaloparatide, agoniste watoranijwe wa parathiyide hormone reseptor 1 (PTHR1), yerekanwa kuvura osteoporose, cyane cyane ku bagore nyuma yo gucura bafite ibyago byo kuvunika cyangwa kutitabira ubundi buvuzi. Yongera cyane ubwinshi bwamagufwa yamagufwa kandi igabanya kwandura ningaruka zo kuvunika kwurugingo rushya no kutagira vertebral kubagore nyuma yo gucura.

Osteoporose yumugabo: Mu bushakashatsi bwa Chandler H kuri osteoporose yumugabo ukoresheje imbeba za orchidectomize (imbeba ya ORX, urugero rwa osteoporose yumugabo), kuvura Abaloparatide byatumye ubwiyongere bukabije bwa BMD bupimwa nimbaraga ebyiri X-ray absorptiometry (DXA) hamwe na tomografiya yuzuye ya pompe (pQCT) ku mbuga zirimo umubiri wose. Yateje imbere cyane trabecular, ubwinshi bwamagufwa, hamwe na microarchitecture itongeye umubare wa osteoclast. Ibi byerekana ko Abaloparatide ifite inyungu zo kuvura osteoporose yumugabo ^[6].

Nyuma yo guhahamuka Osteoarthritis (PTOA) Umuti: Nyuma yo kwinjizwa mu ivi PTOA binyuze mu kubaga medial meniscus destabilisation (DMM) mu mbeba z’ibyumweru 16 by’imbeba C57BL / 6, inshinge zo munsi ya buri munsi ya 40 μg / kg Abaloparatide (cyangwa saline nkigenzura) yatanzwe guhera ibyumweru 2 nyuma yo kubagwa ibyumweru 6 nyuma yo kubagwa ibyumweru 6. Isesengura ry'inyama ryakozwe mu byumweru 8. Ibisubizo byerekanye ko ugereranije nitsinda rivuwe na saline, itsinda ryavuwe na Abaloparatide ryagaragaje igabanuka rya DMM iterwa na articular artilage kandi ikabika uduce twinshi twa tibial surface. Isesengura rya Immunohistochemical ryerekanye ko kuvura Abaloparatide byagabanije kugenzura ubwoko bwa X kolagen (Col10) muri karitsiye, kongera imvugo ya lubricine (Prg4) mu bice bya karitsiye itabaruwe, kandi bigabanya umubare w’uturemangingo twinshi twa hypertrophique. byerekana ko Abaloparatide itinda gutandukanya hypertrophique kandi ikagira ingaruka za chondroprotective mumbeba PTOA, itanga ingamba nshya zo kuvura PTOA ^[5].

Kuvugurura amagufwa ya Alveolar: Nyuma yo gukuramo amagufwa ya alveolar resorption ibuza cyane gukurikira amenyo ya ortodontique (OTM) cyangwa gushyirwaho. Tan B yashushanyije biodegradable, ikora bioactive calcium fosifate nanoblossoms (NFs) yuzuye Abaloparatide (ABL), yitwa ABL @ NFs. Ibi bikoresho byerekana imiterere itandukanye, gukoresha ibiyobyabwenge byinshi, hamwe na biocompatibilité nziza. ABL yabanje kurekurwa kugirango ishake ingirabuzimafatizo, hanyuma ikurikirwa irekurwa rya Ca⊃2; ⁺ na PO₄⊃3; ⁻ kugirango habeho imyunyu ngugu. Ibi byagarutsweho neza mumagufwa ya alveolar kandi akora cyane atabangamiye OTM ^[7].

Hypoparathyroidism (HPT): Chamseddin R yatangaje ko umukobwa w’imyaka 39 ufite iatrogène HPT yananiwe kugera ku kigero gisanzwe cya calcium ya calcium nubwo vitamine D ikabije cyane, inyongera ya calcium, hamwe n’inshinge za PTH (rPTH). Nyuma yubuyobozi bwubutaka bwa abaloparatide binyuze mumashanyarazi ya Simplicity hamwe no gukurikiranira hafi no gufata imiti yihariye, calcium ya calcium yagumye ihagaze kuri 9 mg / dL nyuma y amezi 2. Mugihe cy'amezi 4, yagumanye calcium ya calcium isanzwe idafite hypocalcemia mugihe yagabanije buhoro buhoro calcium yo mu kanwa hamwe na vitamine D yiyongera ^[3].

Guteza imbere uruti rwumugongo: Mugikorwa cyo kubaga cervical-thoracic verisiyo yo kubaga, abaloparatide yakoreshejwe mugutezimbere uruti rwumugongo kubarwayi bafite amateka y’ihungabana ry’inkondo y'umura ndetse no kubagwa inkondo y'umura. Parikh S n'abandi. yatangaje ko umurwayi w’umugore w’imyaka 66 watangije buri munsi 80 mcg Abaloparatide ivura Abaloparatide ibyumweru bibiri nyuma yo kubagwa kugirango amasomo ateganijwe mu byumweru 12. Isuzuma rya Cervical CT mu mezi 3 na 6 ryerekanye neza gukira neza kwa nyababyeyi-thoracic nta kimenyetso cyo kudahuza ^[8].

Umwanzuro

Ubuvuzi bwa Abaloparatide bushingiye ku kuvura osteoporose. Yerekanwa ku bagore nyuma yo gucura bafite ostéoporose bafite ibyago byinshi byo kuvunika cyangwa kutitabira ubundi buvuzi, byongera cyane ubucucike bwamagufwa yamagufwa (BMD) no kugabanya ibyago byo kuvunika kwa vertebral na vertebral. Kubagabo osteoporose yumugabo, ubushakashatsi bwinyamanswa bwerekana BMD yiyongereye ahantu henshi no kunoza mikorobe yububiko, byerekana agaciro ko kuvura. Muri osteoarthritis nyuma yo guhahamuka, igabanya igihombo cya karitsiye kandi ikabuza hypertrophy ya chondrocyte kugirango irinde karitsiye. Mu kuvugurura amagufwa ya alveolar, ibikoresho bya ABL @ NFs byuzuye uyu muti biteza imbere amagufwa, bitanga igisubizo cyo gusana amagufwa nyuma ya ortodontique. Ubushakashatsi nabwo bushigikira imikoreshereze yabwo ya hypoparathyroidism no kuzamura umugongo.

Ibyerekeye Umwanditsi

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

Umwanditsi w'ikinyamakuru

Bin T ni umushakashatsi mu ishami rya chimie, kaminuza ya Peking, inzobere mu bijyanye na nanomaterial ndetse nibisabwa mu buhanga bw’ibinyabuzima. Igikorwa cye cyibanze ku gishushanyo mbonera no guhuza imikorere ya nanostructures yo gutanga ibiyobyabwenge bigamije no kuvugurura ingirangingo. Tan yafatanije kwandika ibitabo byinshi mu binyamakuru bya siyansi bayobora, agira uruhare mu iterambere muri nanomedicine no kuvura ibintu bishya. Bin T yashyizwe ku rutonde rwerekana [7].

Imirongo ijyanye

[1] Shirley M. Abaloparatide: Icyemezo cya mbere cyisi yose. Ibiyobyabwenge 2017; 77 (12): 1363-1368.DOI: 10.1007 / s40265-017-0780-7.

[2] Sleeman A, Clements JN. Abaloparatide: Uburyo bushya bwa farumasi kuri osteoporose. Ikinyamakuru cyo muri Amerika cyubuzima-Sisitemu Farumasi 2019; 76: 130-135.https: //api.semanticscholar.org/CorpusID: 59338650.

. Imyitozo ya Endocrine 2023; 29: S57-S58.DOI: 10.1016 / j.eprac.2023.03.131.

[4] Thompson JC, Wanderman N, Anderson PA, Freedman BA. Abaloparatide n'Umugongo: Isubiramo Ryerekana. Ibikorwa byo kwa muganga mu myaka ya 2020; 15: 1023-1033. DOI: 10.2147 / CIA.S227611.

[5] Landgrave S, Ishii T, Maynard R, n'abandi. 302 Abaloparatide nkubuvuzi bushya bwa osteoarthritis nyuma yo kubyara. Ikinyamakuru cya siyansi yubuvuzi nubuhinduzi 2022; 6: 53. DOI: 10.1017 / cts.2022.166.

[6] Chandler H, Lanske B, Varela A, n'abandi. Abaloparatide, igitabo gishya cya osteoanabolic PTHrP igereranya, yongera ubwinshi bwamagufwa ya cortical na trabecular hamwe nubwubatsi mu mbeba za orchiectomized mukongera amagufwa atarinze kongera amagufwa. Amagufa ya 2019; 120: 148-155.DOI: 10.1016 / j.amagufa.2018.10.012.

[7] Tan B, Wu Y, Wang R, n'abandi. Biodegradable Nanoflowers hamwe na Abaloparatide Spatiotemporal Imicungire yimikorere ya Alveolar Amagufwa. Amabaruwa ya Nano 2024. Https://api.semanticscholar.org/CorpusID:267655299.

[8] Parikh S, Lubitz SE, Sharma A. MON-365 Gukoresha igitabo gishya cya Abaloparatide kugeza Augment Fusion Fusion mu barwayi barimo kubagwa Cervicothoracic. Ikinyamakuru cya Sosiyete Endocrine 2020; 4 (Umugereka_1): 365.DOI: 10.1210 / jendso / bvaa046.108.

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.