|
1 pahu (10 Vials)
| Ka nui: | |
|---|---|
▎ Abaloparatide Hoʻolālā
Puna: PubChem |
Kaʻina: AVSEHQLLHDKGKSIQDLRRRELLEKLLXKLHTA Hui Molekala: C 174H 300N 56O49 Kaumaha Molekala: 3961 g/mol Helu CAS: 247062-33-5 PubChem CID:76943386 Synonyms: Tymlos; BA058; BIM-44058 |
▎ ʻAbaloparatide ʻImi
He aha ke kumu noiʻi o ka abaloparatide?
ʻO Osteoporosis kahi maʻi maʻamau multifactorial systemic skeletal i hōʻike ʻia e ka iwi iwi haʻahaʻa a me ka hōʻino ʻana o ka microarchitectural o ka iwi iwi. ʻO kēia ka mea e hoʻonui ai i ka palupalu o ka iwi a me ka maʻalahi i ka haʻihaʻi ʻana, me ka ʻāʻī a me ka ʻāʻī o ke kuamoʻo he hopena maʻamau. Hoʻopilikia nui ia i ka maikaʻi o ke ola o ka poʻe maʻi a hoʻonui i ka nui o ke kīnā a me ka make. Me ka wikiwiki o ka poʻe ʻelemakule honua, ke hoʻomau nei ka piʻi ʻana o ka osteoporosis. Ua manaʻo ʻia ʻo 42% -56% o nā wahine a me 27%-29% o nā kāne ma luna o 50 mau makahiki e ʻike i nā haʻihaʻi osteoporotic, e lilo ia i pilikia olakino olakino. ʻO nā lāʻau osteoporosis kuʻuna, e like me nā bisphosphonates a me nā modulators receptor estrogen selective (SERMs), mālama nui i ka iwi iwi ma ke kāohi ʻana i ka hoʻihoʻi ʻana o ka iwi osteoclast. Eia naʻe, ua kaupalena ʻia ko lākou pono no nā poʻe maʻi me ka nui o ka iwi iwi a me ka nui o ka haʻihaʻi. ʻOiai ʻo ka ʻāpana parathyroid hormone (PTH) 1-34 (teriparatide) ka mea anabolic mua i ʻae ʻia e ka US Food and Drug Administration (FDA), me ka hoʻonui ʻana i ka nui o ka iwi a me ka hoʻohaʻahaʻa ʻana i ka haʻihaʻi, ʻo kāna hoʻohana lōʻihi e lawe i nā palena me ka hoʻonui ʻana i ka iwi resorption, hypercalcemia, a me ka piʻi nui o ka osteosarcoma.
E kū'ē i kēia kāʻei kua, ʻo ka hoʻomohala ʻana i nā lāʻau lapaʻau hou e hoʻohui i nā hopena anabolic potent ʻoiai e pale ana i kēia mau drawbacks he mea nui. Ma ke ʻano he peptide pili i ka hormone parathyroid (PTHrP), mālama ka abaloparatide i ka hana anabolic ikaika ʻoiai e hōʻemi ana i ka hopena i ka hoʻihoʻi ʻana o ka iwi a me ka hōʻemi ʻana i ka fluctuations calcium serum, e lilo ia i mea pono no ka osteoporosis.
He aha nā ʻano hana no ka abaloparatide?
Ka launa pū ʻana me Parathyroid Hormone Receptor 1 (PTH1R)
ʻO ka Receptor Selective Activation: ʻO Abaloparatide kahi agonist koho o ka mea hoʻokipa hormone parathyroid 1 (PTH1R). Hōʻike nui ʻia ʻo PTH1R ma ka ʻili o nā cell i loko o nā ʻiʻo e like me ka iwi a me ka puʻupaʻa, e pāʻani ana i kahi kuleana nui i ka hoʻoponopono ʻana i ka metabolism iwi. Hoʻopili pono ʻia ʻo Abaloparatide i ka PTH1R, e hoʻomaka ana i kahi ʻano o nā ala hōʻailona intracellular e hoʻoponopono i ka metabolism iwi. Ma ka hoʻopaʻa ʻana, hoʻāla ia i ka adenylate cyclase, hoʻonui i ka hana intracellular cyclic AMP (cAMP) e hoʻololi i ka hana cellular a me ka metabolism [1,2].
Nā ʻokoʻa mai nā ligand ʻē aʻe: ʻO ka hormone parathyroid (PTH) a me ka parathyroid hormone-related protein (PTHrP) pili pū kekahi i ka PTH1R. ʻOiai ʻo PTH, PTHrP, a me Abaloparatide nā hōʻailona āpau ma o PTH1R, ʻokoʻa ko lākou mau ala hōʻailona lalo. Hōʻike ka PTH a me ka PTHrP i nā pilina like no ka mokuʻāina R^G (GTPγS-sensitive) o PTH1R. ʻO Teriparatid (TPTD, ʻo ia hoʻi, 1-34 PTH) ʻehā mau manawa kiʻekiʻe o ka pilina no ka mokuʻāina R ^ 0 (GTPγS-insensitive) ma mua o PTHrP, e hopena i ka hōʻailona cAMP lōʻihi i hoʻokomo ʻia e TPTD. ʻO ka hoʻohālikelike, ʻo ka abaloparatide, i loaʻa mai PTHrP(1-34), ua hana ʻia no ka hoʻomaikaʻi ʻana i ka paʻa a lanakila i nā pilikia e like me ka nalowale o ka puka aniani anabolic a me ka hypercalcemia e pili ana i ka hoʻohana ʻana i ka TPTD. Ma muli o ka wikiwiki o ka dissociation o ka PTHrP-PTH1R complex ma mua o ka PTH-PTH1R complex, ua hele pū nā hopena osteogenic o PTHrP me ka liʻiliʻi o ka absorption a me ka hypercalcemia ma mua o TPTD. Loaʻa iā Abaloparatide kēia pono pili [1,2,3].
Hooponopono o ka Iwi Metabolism
Hoʻoikaika i ka Osteogenesis: Hoʻoulu ka Abaloparatide i ka hana osteoblast, hoʻonui i ka synthesis a me ka waiho ʻana o ka iwi iwi e hoʻoikaika i ka hana iwi. Hoʻohui a hūnā ʻo Osteoblast i nā ʻāpana ʻāpana iwi e like me ka collagen a me ka osteocalcin, e hoʻoheheʻe mālie ʻia e hana i nā ʻiʻo iwi hou. Hōʻike nā haʻawina i ka mālama ʻana i ka osteoporosis postmenopausal, hoʻonui nui ka abaloparatide i ka nui o ka iwi mineral (BMD) ma nā wahi e pili ana i ka ʻāʻī āpau, ka ʻāʻī femoral, a me ka spine lumbar. Ma ka hoʻoulu ʻana i ka hōʻike ʻana o nā genes pili i ka osteoblast, hoʻoponopono ia i ka synthesis o nā protein koʻikoʻi e like me ka osteocalcin a me ka collagen type I. Hoʻoikaika kēia i ka mānoanoa trabecular a me ka hoʻoikaika ʻana i ka cortical, hoʻonui i ka ikaika skeletal a me ka maikaʻi ʻoiai e hōʻemi ana i ka pilikia fracture [1,2,3].
Hoʻopaʻa ʻana i ka hoʻihoʻi ʻana o ka iwi: ʻOiai ʻo Abaloparatide e hana nui nei ma ke ʻano he mea anabolic agent, hōʻike pū kekahi i kekahi mau hopena pale i ka resorption iwi. Hoʻololi ʻo ia i ka ʻokoʻa a me ka hana o nā osteoclast - nā pūnaewele kuleana no ka resorption iwi e hoʻoheheʻe ai i ka mineral iwi a me ka matrix organik ma ka hoʻokuʻu ʻana i nā mea waikawa a me nā enzyme proteolytic. Hiki i ka Abaloparatide ke hoʻemi i ka nui o ka hoʻihoʻi ʻana o ka iwi ma o ka hoʻohaʻahaʻa ʻana i ka hoʻokaʻawale ʻana o nā cell precursor osteoclast i loko o nā osteoclast oʻo a i ʻole ka pōkole ke ola o nā osteoclast oʻo. I ka manawa like, hoʻololi ia i ka hōʻailona ma waena o nā osteoblasts a me nā osteoclast, e mālama ana i ka equilibrium ikaika ma waena o ka hoʻokumu ʻana o ka iwi a me ka resorption. No ka laʻana, hoʻemi ia i ka hoʻoulu ʻana o ka osteoclast a me ka hana resorptive ma o ka hoʻohaʻahaʻa ʻana i ka osteoblast-secreted receptor activator o ka nuclear factor κB ligand (RANKL). ʻAʻole like me ka teriparatide, ʻaʻole i hoʻonui nui ka abaloparatide i ka hana RANKL, no laila e pale ai i ka nalowale o ka puka aniani anabolic e kū mai ana i ka wā e loaʻa ai ka resorption i ka hoʻokumu ʻana i nā pae hope [1,2,3].
Kiʻi 1 Ke kumu hoʻohālike o ka hormone parathyroid (PTH)/teriparatide a me ka peptide pili i ka PTH (PTHrP/abaloparatide activation o parathyroid hormone type 1 receptor (PTH1R)) [4].
Nā hopena ma luna o ka metabolism cartilage (ma nā haʻawina pili i ka osteoarthritis)
Hoʻoikaika i ka Cartilage Matrix Synthesis: Ua hōʻike nā haʻawina i ka osteoarthritis (OA) i ka hana abaloparatide i kahi hopena pale i ka cartilage. Hōʻike nā articular chondrocytes i ka PTH1R, a hoʻāla ʻo Abaloparatide i kēia mea loaʻa, hoʻoulu i nā chondrocytes e synthesize i nā ʻāpana o ka cartilage matrix. No ka laʻana, hōʻike nā haʻawina e hoʻonui ʻo Abaloparatide i ka ʻōlelo lubricin (Prg4), he protein matrix extracellular koʻikoʻi i loko o ka cartilage e koʻikoʻi no ka mālama ʻana i ka lubrication hui a me ka hoʻohaʻahaʻa ʻana i ka friction. Hoʻolaha ia i ka synthesis o ke ʻano II collagen, ka mea nui o ka cartilage matrix, e kōkua i ka mālama ʻana i ka cartilage structural a me ka hana pono. Ma ka hoʻonui ʻana i ka synthesis o kēia mau ʻāpana cartilage matrix, kōkua ʻo Abaloparatide i ka hoʻoponopono ʻana a me ka pale ʻana i ka ʻiʻo cartilage i hōʻino ʻia, e hoʻolōʻihi i ka piʻi ʻana o ka osteoarthritis [5].
Kāohi i ka hypertrophy chondrocyte a me ka degeneration: Hiki i ka Abaloparatide ke kāohi i ke kaʻina hana hoʻokaʻawale hypertrophic o nā chondrocytes. I ka wā o ka maʻi o ka osteoarthritis, loaʻa nā chondrocytes i ka ʻokoʻa hypertrophic, i hōʻike ʻia e ka hoʻonui ʻana i ka nui o ka cell a me ka hōʻike kiʻekiʻe o nā māka hypertrophy kikoʻī e like me ke ʻano X collagen (Col10). ʻO kēia kaʻina hana e alakaʻi i ka hoʻohaʻahaʻa ʻana i ka matrix cartilage a me ka degeneration cartilage. Hōʻike nā haʻawina i ka mālama ʻana iā Abaloparatide e hoʻohaʻahaʻa i ka upregulation o ka hōʻike ʻana o Col10 i loko o ka ʻiʻo cartilage me ka hōʻemi ʻana i ka nui o nā cell hypertrophic-like nui. Hōʻike kēia hiki ke hoʻolōʻihi i ka hoʻokaʻawale ʻana o ka chondrocyte hypertrophic, mālama i ka chondrocyte phenotype maʻamau, no laila e pale ai i ka cartilage a me ka hoʻopaneʻe ʻana i ka piʻi ʻana o ka osteoarthritis [5].
He aha nā mea hoʻohana o Abaloparatide?
Lapaʻau Osteoporosis
Postmenopausal Osteoporosis: ʻO Abaloparatide, kahi agonist koho o ka parathyroid hormone receptor 1 (PTHR1), i hōʻike ʻia no ka mālama ʻana i ka osteoporosis, ʻo ia hoʻi i nā wahine postmenopausal i ka haʻihaʻi a i ʻole ka pane ʻole i nā lāʻau lapaʻau ʻē aʻe. Hoʻonui nui ia i ka nui o ka mineral iwi a hoʻemi i ka hopena a me ka pilikia o nā haʻihaʻi vertebral a me nā non-vertebral hou i nā wahine postmenopausal.
Osteoporosis Kane: Ma ke aʻo ʻana a Chandler H no ka osteoporosis kāne me ka hoʻohana ʻana i nā ʻiole orchidectomized (ORX rats, he osteoporosis male model), ʻo ka mālama ʻana i ka Abaloparatide i hoʻonui nui ʻia i ka BMD i ana ʻia e ka dual-energy X-ray absorptiometry (DXA) a me ka peripheral quantitative computed tomography (pQCT) ma nā kahua a me ka spine total body, fe lumbar. Ua hoʻomaikaʻi nui ʻia ka hana trabecular, ka nui o ka iwi, a me ka microarchitecture me ka hoʻonui ʻole ʻana i nā helu osteoclast. Hōʻike kēia i ka loaʻa ʻana o Abaloparatide i nā pono therapeutic kūpono no ka osteoporosis kāne [6].
Hoʻomaʻamaʻa Post-Traumatic Osteoarthritis (PTOA): Ma hope o ka hoʻokomo ʻana o ke kuli PTOA ma o ka medial meniscus destabilization (DMM) o ke kaʻina i loko o 16-week-old male C57BL / 6 mice, i kēlā me kēia lā subcutaneous injections o 40 μg / kg Abaloparatide (a i ʻole saline ma ke ʻano he mana) ua lawelawe ʻia e hoʻomaka ana i 2 mau pule ma hope o ka hana ʻana. Hana ʻia ka nānā ʻana i nā kiko ma 8 mau pule. Hōʻike nā hualoaʻa i ka hoʻohālikelike ʻia me ka hui i mālama ʻia i ka paʻakai, ua hōʻike ka hui i mālama ʻia e Abaloparatide i ka emi ʻana o ka cartilage articular i hoʻoiho ʻia e DMM a mālama ʻia ka ʻiʻo cartilage ʻili o ka tibial. Ua hōʻike ʻia ka loiloi immunohistochemical i ka mālama ʻana o Abaloparatide i hoʻemi i ka upregulation o ke ʻano X collagen (Col10) i loko o ka cartilage, hoʻonui ʻia ka ʻōlelo lubricin (Prg4) i nā wahi cartilage non-calcified, a ua hoʻemi i ka nui o nā cell hypertrophic nui. Ke manaʻo nei ʻo Abaloparatide e hoʻolōʻihi i ka ʻokoʻa hypertrophic a hoʻohana i kahi hopena chondroprotective i ka ʻiole PTOA, e hāʻawi ana i kahi hoʻolālā therapeutic novel no PTOA [5].
ʻO ka hoʻōla hou ʻana o ka iwi alveolar: ʻO ka hoʻihoʻi ʻana o ka iwi alveolar ma hope o ka unuhi ʻana he mea keakea loa ia i ka neʻe ʻana o nā niho orthodontic (OTM) a i ʻole kahi implant. ʻO Tan B synthesized biodegradable, bifunctional bioactive calcium phosphate nanoblossoms (NFs) i hoʻouka ʻia me Abaloparatide (ABL), i kapa ʻia ʻo ABL@NFs. Hōʻike kēia mea i kahi ʻano porous layered, kiʻekiʻe o ka lāʻau encapsulation maikaʻi, a me ka biocompatibility maikaʻi loa. Ua hoʻokuʻu mua ʻia ʻo ABL no ke kiʻi ʻana i nā cell stem, a ukali ʻia e ka hoʻokuʻu mau ʻana o Ca⊃2;⁺ a me PO₄⊃3;⁻ no ka mineralization interfacial in situ. Ua hoʻihoʻi maikaʻi kēia i ka iwi alveolar morphologically a me ka hana me ka ʻole o ka OTM [7].
ʻO Refractory Hypoparathyroidism (HPT): Ua hōʻike ʻo Chamseddin R i kahi wahine 39 makahiki me ka HPT iatrogenic i hiki ʻole ke hoʻokō i nā pae calcium serum maʻamau ʻoiai ʻo ka nui o ka huaʻa D, nā mea hoʻohui calcium, a me nā inikini PTH (rPTH) recombinant. Ma hope o ka lawelawe subcutaneous o ka abaloparatide ma o ka Simplicity patch me ka nānā pono ʻana a me ka hoʻopili pilikino ʻana, ua paʻa kona serum calcium ma 9 mg/dL ma hope o 2 mau mahina. Ma nā mahina 4, mālama ʻo ia i ka calcium serum maʻamau me ka ʻole o nā manawa hypocalcemia ʻoiai e hōʻemi mālie ana i ka calcium waha a me ka hoʻohui ʻana i ka vitamin D [3].
Ka Hoʻoulu ʻana i ka Spinal Fusion: I ka hoʻoponopono hou ʻana o ka cervical-thoracic, ua hoʻohana ʻia ka abaloparatide e hoʻoikaika i ka hui ʻana o ka spinal i nā maʻi me ka mōʻaukala o ka ʻōpū o ka ʻōpū a me ka nui o nā ʻoki ʻokiʻoki i hāʻule ʻole. ʻO Parikh S et al. ua hōʻike i kahi maʻi wahine 66 makahiki i hoʻomaka i kēlā me kēia lā 80 mcg Abaloparatide lapaʻau ʻelua pule ma hope o ka hana no kahi papa 12-wiki i hoʻolālā ʻia. Hōʻike ka Cervical CT scans ma 3 a me 6 mau mahina i hoʻōla maikaʻi ʻia ka cervical-thoracic fusion me ka ʻole o nā hōʻailona o ka nonunion [8].
Ka hopena
ʻO nā kikowaena noiʻi lapaʻau o Abaloparatide i ka mālama ʻana i ka osteoporosis. Hōʻike ʻia ia no nā wahine postmenopausal me ka osteoporosis i ka haʻihaʻi kiʻekiʻe a i ʻole ka pane ʻole ʻana i nā lāʻau lapaʻau ʻē aʻe, e hoʻonui nui ana i ka iwi mineral density (BMD) a me ka hōʻemi ʻana i ka pōʻino vertebral a me ka non-vertebral fracture. No ka osteoporosis kāne, hōʻike nā haʻawina holoholona i ka piʻi ʻana o ka BMD ma nā wahi he nui a me ka hoʻomaikaʻi ʻana i ka microarchitecture iwi, e hōʻike ana i ka waiwai therapeutic kūpono. I loko o ka osteoarthritis post-traumatic, hoʻemi ia i ka nalo ʻana o ka cartilage a kāohi i ka hypertrophy chondrocyte e pale i ka cartilage. Ma ka hana hou ʻana o ka iwi alveolar, ʻo nā mea ABL@NFs i hoʻopiha ʻia me kēia lāʻau lapaʻau e hoʻoikaika i ka hana hou ʻana o ka iwi, e hāʻawi ana i kahi hopena no ka hoʻoponopono ʻana i ka iwi post-orthodontic. Kākoʻo ka noiʻi i kona hoʻohana ʻana i ka hypoparathyroidism refractory a me ka hoʻoulu ʻana i ka spinal fusion.
No ka mea kakau
ʻO nā mea i ʻōlelo ʻia ma luna nei ua noiʻi ʻia, hoʻoponopono ʻia a hōʻuluʻulu ʻia e Cocer Peptides.
Mea kākau moʻolelo ʻepekema
He mea noiʻi ʻo Bin T ma ke Keʻena ʻOihana Kimia, Ke Kulanui ʻo Peking, ʻoihana loea i nā nanomaterials a me kā lākou noi i ka ʻenekinia biomedical. Kākoʻo kāna hana i ka hoʻolālā a me ka synthesis o nā nanostructures hana no ka hāʻawi ʻana i ka lāʻau lapaʻau a me ka hoʻoulu hou ʻana o nā kiko. Ua kākau pū ʻo Tan i nā puke he nui i ke alakaʻi ʻana i nā nūpepa ʻepekema, e hāʻawi ana i nā holomua i nā nanomedicine a me nā lāʻau lapaʻau hou. Ua helu ʻia ʻo Bin T ma ka ʻōlelo kuhikuhi [7].
