Nānā Lapaʻau Intermediates ʻOihana

Nā mea waena lāʻau lapaʻau
ʻO nā mea i kapa ʻia ʻo pharmaceutical intermediates he mau mea waiwai maoli a i ʻole nā ​​​​huahana kemika e pono e hoʻohana ʻia i ka hana synthesis o nā lāʻau lapaʻau.Hiki ke hana ʻia kēia mau huahana kemika i nā mea kanu kemika maʻamau me ka loaʻa ʻole o ka laikini hana lāʻau, a hiki ke hoʻohana ʻia i ka synthesis a me ka hana ʻana i nā lāʻau lapaʻau inā lōʻihi nā mea hōʻailona ʻenehana i nā koi pae.ʻOiai ke hāʻule nei ka synthesis o nā lāʻau lapaʻau ma lalo o ka māhele kemika, ʻoi aku ka paʻakikī o nā koi ma mua o nā huahana kemika maʻamau.Pono nā mea hana o nā lāʻau lapaʻau i hoʻopau ʻia a me nā API e ʻae i ka palapala GMP, ʻoiai ʻaʻole i hana nā mea hana waena, no ka mea, ʻo nā intermediates wale nō ka synthesis a me ka hana ʻana o nā mea kemika, ʻo ia nā huahana kumu a lalo loa i ka kaulahao hana lāʻau. Ua kapa ʻia nā lāʻau lapaʻau, no laila ʻaʻole pono lākou i ka palapala GMP, ka mea e hoʻohaʻahaʻa i ka paepae komo no nā mea hana waena.

ʻoihana waena lāʻau lapaʻau
ʻO nā hui kemika e hana a hoʻoponopono i nā mea kikowaena organik/inorganic a i ʻole API no nā hui lāʻau lapaʻau no ka hana ʻana i nā huahana lāʻau i hoʻopau ʻia e ke kemika a i ʻole ka biological synthesis e like me nā kūlana koʻikoʻi.Maanei ua hoʻokaʻawale ʻia nā kikowaena lāʻau lapaʻau i ʻelua sub-industries CMO a me CRO.

CMO
ʻO ka Contract Manufacturing Organization e pili ana i kahi hui hana ʻaelike, ʻo ia hoʻi, ʻo ka hui lāʻau lapaʻau e hoʻopuka i ke kaʻina hana i kahi hoa.ʻO ke kaulahao ʻoihana o ka ʻoihana CMO lāʻau lapaʻau e hoʻomaka maʻamau me nā lako lāʻau lapaʻau kūikawā.Pono nā ʻoihana i loko o ka ʻoihana e hoʻopuka i nā kumuwaiwai kumu a hana iā lākou i loko o nā mea lāʻau lapaʻau kūikawā, a laila e hana ʻia i mea hoʻomaka API, cGMP intermediates, API a me nā formulations.I kēia manawa, hoʻokumu nā hui lāʻau lapaʻau multinational nui i nā hui hoʻolālā lōʻihi me kahi helu liʻiliʻi o nā mea hoʻolako kumu, a ʻike nui ʻia ke ola o nā ʻoihana i kēia ʻoihana ma o kā lākou mau hoa.

CRO
ʻO ka hui noiʻi ʻaelike (Clinical) e pili ana i kahi hui noiʻi ʻaelike, kahi e hoʻopuka ai nā hui lāʻau lapaʻau i ka mea noiʻi i kahi hoa.I kēia manawa, hoʻokumu nui ʻia ka ʻoihana i ka hana maʻamau, R&D maʻamau a me ka noiʻi ʻaelike lāʻau lapaʻau a me ke kūʻai aku.ʻO ke ʻano o ke ʻano, inā he huahana hou a ʻaʻole paha ka huahana intermediate pharmaceutical, ʻo ka hoʻokūkū koʻikoʻi o ka ʻoihana e hoʻokolokolo ʻia e ka ʻenehana R&D ma ke ʻano he mea mua, i ʻike ʻia i nā mea kūʻai aku a i ʻole nā ​​​​hoa.

ʻO ke kaulahao waiwai makeke huahana lāʻau lapaʻau
Kiʻi
(Kiʻi mai Qilu Securities)

ʻOihana kaulahao o nā ʻoihana waena lāʻau
Kiʻi
(Kiʻi mai Kina ʻOihana ʻIkepili Pūnaewele)

Hoʻokaʻawale i waena o nā lāʻau lapaʻau
Hiki ke hoʻokaʻawale ʻia nā intermediates lāʻau lapaʻau i nā ʻāpana nui e like me nā kahua noi, e like me nā intermediates no nā antibiotics, nā waena no nā lāʻau antipyretic a me nā analgesic, nā mea waena no nā lāʻau lapaʻau cardiovascular a me nā intermediates pharmaceutical no ka anti-cancer.Nui nā ʻano o nā lāʻau lapaʻau kūikawā, e like me ka imidazole, furan, phenolic intermediates, aromatic intermediates, pyrrole, pyridine, biochemical reagents, sulfur-containing, nitrogen-containing, halogen compound, heterocyclic compound, starch, mannitol, microcrystalline cellulose, , dextrin, ethylene glycol, sugar pauka, paʻakai inorganic, ethanol intermediates, stearate, amino acids, ethanolamine, potassium salts, sodium salts a me nā mea waena, etc.
ʻO ka nānā ʻana o ka hoʻomohala ʻana o ka ʻoihana intermediates lāʻau lapaʻau ma Kina
Wahi a IMS Health Incorporated, mai 2010 a 2013, ua hoʻomau ka mākeke lāʻau lapaʻau honua i ka ulu mau ʻana, mai US $ 793.6 biliona ma 2010 a i US $ 899.3 biliona ma 2013, me ka mākeke lāʻau lapaʻau e hōʻike ana i ka ulu wikiwiki mai 2014, ma muli o ka mākeke US. .Me kahi CAGR o 6.14% mai 2010-2015, ke manaʻo nei ka mākeke lāʻau lapaʻau honua e komo i kahi pōʻai ulu lohi mai 2015-2019.Eia nō naʻe, ʻoiai ke koi ikaika nei nā lāʻau lapaʻau, manaʻo ʻia e ikaika loa ka ulu ʻana o ka ʻupena i ka wā e hiki mai ana, me ka mākeke honua no nā lāʻau lapaʻau e kokoke ana iā US $ 1.22 trillion e 2019.
Kiʻi
(Kiʻi mai IMS Health Incorporated)
I kēia manawa, me ka hoʻoponopono hou ʻana o ka ʻoihana o nā hui lāʻau lapaʻau multinational nui, ka hoʻololi ʻana o ka hana multinational a me ka hoʻomaʻamaʻa hou ʻana o ka māhele hana honua, ua lilo ʻo Kina i kumu hana waena koʻikoʻi i ka mahele honua o ka hana ma ka ʻoihana lāʻau.Ua hoʻokumu ka ʻoihana waena o Kina i kahi ʻōnaehana piha piha mai ka noiʻi a me ka hoʻomohala ʻana i ka hana a me ke kūʻai aku.Mai ka hoʻomohala ʻana o nā intermediates pharmaceutical i ka honua, ʻoi aku ka haʻahaʻa o ka pae ʻenehana kaʻina holoʻokoʻa o Kina, ʻo ka nui o nā intermediates pharmaceutical holomua a me nā lāʻau lapaʻau hou e kākoʻo ana i nā ʻoihana hana waena he liʻiliʻi liʻiliʻi, aia i ka pae hoʻomohala o ka hoʻolālā ʻana o ka huahana a me ka hoʻonui. .
Ka waiwai hoʻopuka o ka ʻoihana pharmaceutical intermediates ma Kina mai 2011 a 2015
Kiʻi
(Kiʻi mai ka Hui ʻImi ʻImi ʻOihana Pāʻoihana Kina)
I ka makahiki 2011-2015, ua hoʻonui ʻia ka huahana ʻoihana kemika o Kina i kēlā me kēia makahiki, i ka makahiki 2013, ʻo 568,300 tons ka mea i hoʻopuka ʻia e Kina, 65,700 tons, i ka makahiki 2015, ʻo ka 2015 pharmaceutical pharmaceutical pharmaceutical 6076 output.
ʻO 2011-2015 Kina ka helu ʻana o ka hana ʻoihana lāʻau lapaʻau ma waena o ka ʻoihana.
Kiʻi
(Kiʻi mai ka hale ʻimi noiʻi ʻoihana kalepa ʻo Kina)
ʻOi aku ka maikaʻi o ka hāʻawi ʻana i nā intermediates pharmaceutical ma Kina ma mua o ka noi, a ke piʻi mālie nei ka hilinaʻi ʻana i ka lawe ʻana aku.Eia nō naʻe, ʻoi aku ka nui o ka hoʻokuʻu ʻana o Kina i nā huahana nui e like me ka vitamina C, penicillin, acetaminophen, citric acid a me kāna mau paʻakai a me nā esters, a me nā mea ʻē aʻe. ka waiwai hoʻohui, a ʻo kā lākou hana nui i kumu i ke kūlana o ka hāʻawi ʻana i ka noi ma ka mākeke intermediates pharmaceutical home.Ke hilinaʻi nui nei nā huahana me ka ʻenehana kiʻekiʻe i ka lawe ʻana mai.
No ka pale ʻana i nā kikowaena lāʻau lapaʻau amino acid, ʻo ka hapa nui o nā ʻoihana hana home he ʻano huahana hoʻokahi a me ka maikaʻi ʻole, ʻoi aku ka nui o nā hui biopharmaceutical haole e hana i ka hana o nā huahana.ʻO kekahi mau ʻoihana wale nō me ka noiʻi ikaika a me ka ikaika hoʻomohala, nā ʻoihana hana kiʻekiʻe a me ka ʻike i ka hana nui e hiki ke loaʻa nā waiwai kiʻekiʻe i ka hoʻokūkū.
ʻIkepili o ka ʻoihana waena lāʻau lapaʻau o Kina

1, pharmaceutical intermediates 'oihana hana ma'amau ka'ina hana
ʻO ka mea mua, e komo i ka noiʻi o ka mea kūʻai aku a me ka hoʻomohala ʻana i ke kahua lāʻau lapaʻau hou, kahi e koi ai i ka ʻoihana R & D kikowaena i kahi mana ikaika.
ʻO ka lua, i ka hoʻonui ʻana o ka huahana pilote o ka mea kūʻai aku, e hoʻokō i ke ala kaʻina o ka hana nui, e koi ana i ka ʻenehana hoʻonui ʻana i ka hiki o ka huahana a me ka hiki ke hoʻomau i ka hoʻomaikaʻi ʻana i ka ʻenehana huahana maʻamau i kekahi manawa ma hope. e hoʻokō i nā pono o ka hana ʻana o ka huahana, hoʻemi mau i ke kumukūʻai hana a hoʻonui i ka hoʻokūkū o ka huahana.
ʻO ke kolu, ʻo ia ka ʻeli ʻana a me ka hoʻomaikaʻi ʻana i ke kaʻina hana o nā huahana i ke kahua o ka hana nui o nā mea kūʻai aku, i mea e hoʻokō ai i nā kūlana maikaʻi o nā hui ʻē aʻe.

2. Nā hiʻohiʻona o ka ʻoihana waena o Kina
Pono ka hana ʻana o nā lāʻau lapaʻau i ka nui o nā kemika kūikawā, ʻo ka hapa nui o ia mau mea i hana mua ʻia e ka ʻoihana lāʻau lapaʻau ponoʻī, akā me ka hoʻonui ʻana i ka mahele o ka hana a me ka holomua o ka ʻenehana hana, ua hoʻoneʻe ka ʻoihana lāʻau i kekahi mau kikowaena lāʻau lapaʻau i nā ʻoihana kemika. no ka hana ana.ʻO nā huahana kemika maikaʻi nā intermediates lāʻau lapaʻau, a ua lilo ka hana ʻana i nā intermediates lāʻau lapaʻau i ʻoihana nui i ka ʻoihana kemika honua.I kēia manawa, pono ka ʻoihana lāʻau lapaʻau o Kina ma kahi o 2,000 mau ʻano mea kemika a me nā mea waena i kēlā me kēia makahiki, me ka koi ʻoi aku ma mua o 2.5 miliona mau tona.ʻOiai ʻo ka hoʻokuʻu ʻia ʻana o nā lāʻau lapaʻau e like me ka lawe ʻana aku i nā lāʻau lapaʻau e kau ʻia i nā palena like ʻole i nā ʻāina e lawe mai ana, a me ka hana ʻana o ka honua o nā intermediates pharmaceutical i nā ʻāina e ulu nei, ʻo nā pono hana lāʻau lapaʻau Kina i kēia manawa o nā mea waiwai a me nā mea waena e hiki ke hoʻohālikelike. , he wahi liʻiliʻi wale nō o ka pono e lawe mai.A ma muli o ka nui o nā kumu waiwai o Kina, ua haʻahaʻa nā kumu kūʻai maka, ua nui nā lāʻau lapaʻau i loaʻa i kahi helu nui o nā mea kūʻai aku.

I kēia manawa, pono ʻo Kina e kākoʻo i nā mea waiwai a me nā mea waena o nā ʻano ʻoi aku ma mua o 2500 mau ʻano, ua hiki ke koi makahiki i 11.35 miliona tons.Ma hope o 30 mau makahiki o ka hoʻomohala ʻana, ua hiki ke hoʻohālikelike ʻia nā pono hana lāʻau lapaʻau o Kina i nā mea kemika a me nā mea waena.ʻO ka hana ʻana o nā mea waena ma Kina ka mea nui i nā lāʻau antibacterial a me antipyretic.

I loko o ka ʻoihana, ʻeono mau hiʻohiʻona o ka ʻoihana waena o Kina: ʻO ka mea mua, ʻo ka hapa nui o nā ʻoihana he ʻoihana pilikino, hana maʻalahi, ʻaʻole nui ka nui o ka hoʻopukapuka kālā, ma waena o nā miliona a i ʻelua tausani miliona yuan;ʻO ka lua, ʻo ka māhele ʻāina o nā ʻoihana e pili pono ana, ʻo ka nui ma Taizhou, Zhejiang Province a me Jintan, Jiangsu Province ke kikowaena;ʻO ke kolu, me ka hoʻonui nui ʻana o ka ʻāina i ka mālama ʻana i ke kaiapuni, ke piʻi nei ke kaomi ʻana i nā ʻoihana e kūkulu i nā keʻena mālama mālama kaiapuni. e hoʻomohala i nā huahana hou a i ʻole e hoʻomaikaʻi mau i ke kaʻina hana i mea e loaʻa ai ka waiwai kiʻekiʻe;ʻO ka lima, ʻoiai ʻoi aku ka kiʻekiʻe o ka loaʻa ʻana o ka waiwai o nā lāʻau lapaʻau ma mua o nā huahana kemika maʻamau, a ʻo ke kaʻina hana ka mea like, ʻoi aku ka nui o nā ʻoihana liʻiliʻi liʻiliʻi e hui pū i nā pae o ka hana ʻana i nā intermediates lāʻau lapaʻau, e hopena i ka hoʻokūkū ikaika loa i ka ʻoihana. , i ka hoʻohālikelike ʻia me ka API, he haʻahaʻa ka palena waiwai o ka hana ʻana i nā intermediates, a ua like ke kaʻina hana o ka API a me nā intermediates lāʻau lapaʻau, no laila ʻaʻole hana wale kekahi mau ʻoihana i nā mea waena, akā hoʻohana pū i kā lākou pono ponoʻī e hoʻomaka i ka hana ʻana i ka API.Ua hōʻike ka poʻe loea i ka hana ʻana o nā lāʻau lapaʻau i ke alakaʻi o ka hoʻomohala ʻana i ka API he ʻano hiki ʻole.Eia nō naʻe, ma muli o ka hoʻohana hoʻokahi o ka API, e nā ʻoihana lāʻau lapaʻau he hopena nui, hoʻomohala pinepine nā ʻoihana kūloko i nā huahana akā ʻaʻohe mea hoʻohana i ka hanana.No laila, pono nā mea hana e hoʻokumu i kahi pilina paʻa paʻa me nā hui lāʻau lapaʻau, i mea e hōʻoia ai i ke kūʻai aku ʻana i nā huahana.

3, nā pale komo ʻoihana
①Paʻa nā mea kūʻai aku
Hoʻopili ʻia ka ʻoihana lāʻau lapaʻau e kekahi mau hui lāʻau lapaʻau multinational.E akahele loa ka oligarchs pharmaceutical i kā lākou koho ʻana i nā mea lawelawe outsourcing a he manawa lōʻihi ka nānā ʻana no nā mea hoʻolako hou.Pono nā hui CMO lāʻau lapaʻau e hoʻokō i nā ʻano kamaʻilio o nā mea kūʻai aku ʻokoʻa, a pono e hana i kahi manawa lōʻihi o ka loiloi mau ma mua o ka loaʻa ʻana o ka hilinaʻi o nā mea kūʻai mai lalo, a laila lilo lākou i mea hoʻolako kumu.
②Paʻa ʻenehana
ʻO ka hiki ke hāʻawi i nā lawelawe hoʻohui waiwai ʻenehana kiʻekiʻe ka pōhaku kihi o kahi hui lawelawe outsourcing lāʻau.Pono nā hui CMO lāʻau lapaʻau e uhaʻi i nā bottlenecks ʻenehana a i ʻole blockages i ko lākou ala kumu a hāʻawi i nā ala hoʻoponopono lāʻau lapaʻau e hōʻemi pono i nā kumukūʻai hana lāʻau.Me ka loaʻa ʻole o ka wā lōʻihi, ke kumu kūʻai nui i ka noiʻi a me ka hoʻomohala ʻana a me nā ʻenehana ʻenehana, paʻakikī i nā ʻoihana ma waho o ka ʻoihana ke komo maoli i ka ʻoihana.
③Paʻa kālena
He mea paʻakikī i nā hui CMO ke kūkulu i kahi R&D hoʻokūkū a me ka hui hana i loko o kahi manawa pōkole e hoʻokumu i kahi kumu hoʻohālike cGMP-compliant.
④Ka pale hoʻoponopono maikaʻi
ʻO ka FDA a me nā keʻena hoʻoponopono lāʻau ʻē aʻe ua lilo i mea koʻikoʻi i kā lākou koi ʻana i ka maikaʻi, a ʻo nā huahana i hala ʻole i ka loiloi ʻaʻole hiki ke komo i nā mākeke o nā ʻāina lawe mai.
⑤ Nā pale hoʻoponopono kaiapuni
ʻO nā hui lāʻau lapaʻau me nā kaʻina hana kahiko e halihali i nā kumukūʻai hoʻomalu pollution kiʻekiʻe a me ke kaomi hoʻoponopono, a ʻo nā hui lāʻau lapaʻau kuʻuna e hana nui i ka pollution kiʻekiʻe, ka hoʻohana ʻana i ka ikehu kiʻekiʻe a me nā huahana haʻahaʻa haʻahaʻa (e laʻa me ka penicillin, nā huaora, a me nā mea ʻē aʻe).ʻO ka mālama ʻana i ka hana hou a me ka hoʻomohala ʻana i ka ʻenehana lāʻau lapaʻau ʻōmaʻomaʻo ua lilo i alakaʻi hoʻomohala e hiki mai ana o ka ʻoihana CMO lāʻau.

4. Nā ʻoihana i helu ʻia ma waena o nā lāʻau lapaʻau kūloko
Mai ke kūlana o ke kaulahao ʻoihana, ʻo nā hui 6 i helu ʻia o nā kemika maikaʻi e hana ana i nā intermediates lāʻau lapaʻau aia ma ka haʻahaʻa haʻahaʻa o ke kaulahao ʻoihana.Inā paha i ka mea hoʻolako lawelawe outsourcing ʻoihana a i ʻole API a me ka hoʻonui ʻia ʻana, ʻo ka ikaika ʻenehana ka ikaika hoʻoikaika mau.
Ma ke ʻano o ka ikaika ʻenehana, makemake ʻia nā ʻoihana me ka ʻenehana i ke alakaʻi honua, ka ikaika mālama mālama a me ka hoʻokomo kālā kiʻekiʻe ma R&D.
Pūʻulu I: Lianhua Technology a me Arbonne Chemical.ʻEwalu mau ʻenehana koʻikoʻi ʻo Lianhua Technology e like me ka ammonia oxidation a me ka fluorination e like me kāna ʻenehana ʻenehana, nona ka hydrogen oxidation ma ka pae alakaʻi honua.He alakaʻi alakaʻi honua ʻo Abenomics i nā lāʻau lapaʻau chiral, ʻoi aku hoʻi i kāna ʻenehana hoʻokaʻawale kemika a me ka racemization, a loaʻa iā ia ka waiwai R&D kiʻekiʻe loa, ʻo ia ka 6.4% o ka loaʻa kālā.
Pūʻulu II: ʻenehana Wanchang a me ʻenehana Yongtai.ʻO Wanchang Technology ke ʻano wai ʻawaʻawa hydrocyanic ʻo ia ke kumu kūʻai haʻahaʻa a me ke kaʻina hana kiʻekiʻe loa no ka hana ʻana i nā esters acid prototrizoic.ʻO Yongtai Technology, ma ka ʻaoʻao ʻē aʻe, ʻike ʻia no kāna mau kemika maikaʻi fluorine.
Pūʻulu III: Tianma Fine Chemical a me Bikang (i kapa ʻia ʻo Jiuzhang ma mua).
Hoʻohālikelike i ka ikaika ʻenehana o nā hui i helu ʻia
Kiʻi
Hoʻohālikelike o nā mea kūʻai aku a me nā hiʻohiʻona kūʻai aku o nā ʻoihana waena lāʻau i helu ʻia
Kiʻi
Ka hoʻohālikelike ʻana i ka noi o lalo a me ka pōʻai ola patent o nā huahana o nā hui i helu ʻia
Nā kiʻi
Ka nānā ʻana i ka hoʻokūkū huahana o nā ʻoihana i helu ʻia
Nā kiʻi
ʻO ke ala e hoʻomaikaʻi ai i nā mea waena kemika maikaʻi
Nā kiʻi
(Nā kiʻi a me nā mea waiwai mai Qilu Securities)
Nā manaʻolana hoʻomohala o ka ʻoihana waena o Kina
Ma ke ʻano he ʻoihana koʻikoʻi i ke kahua o ka ʻoihana kemika maikaʻi, ua lilo ka lāʻau lapaʻau i mea nui o ka hoʻomohala ʻana a me ka hoʻokūkū i nā makahiki he 10 i hala iho nei, me ka holomua o ka ʻepekema a me ka ʻenehana, ua hoʻomohala mau ʻia nā lāʻau lapaʻau no ka pono o ke kanaka, ka synthesis. ʻO kēia mau lāʻau lapaʻau e hilinaʻi nei i ka hana ʻana o nā intermediates pharmaceutical kiʻekiʻe, no laila ua pale ʻia nā lāʻau hou e nā patent, ʻoiai ʻaʻohe pilikia o nā mea waena me lākou, no laila ke komo nei ka lāʻau lapaʻau hou ma ka home a ma waho ʻO ka wahi hoʻomohala mākeke a me ka manaʻo noi. he olelo hoopomaikai loa.
Nā kiʻi

I kēia manawa, ʻike nui ʻia ka ʻimi noiʻi o nā intermediates lāʻau i ka synthesis o nā pūhui heterocyclic, fluorine-containing compounds, chiral compounds, biological compounds, etc. Aia nō kekahi ʻokoʻa ma waena o ka hoʻomohala ʻana i nā intermediates pharmaceutical a me nā koi o ka ʻoihana lāʻau. ma Kina.ʻAʻole hiki ke hoʻonohonoho ʻia kekahi mau huahana me nā koi ʻenehana kiʻekiʻe no ka hana ʻana ma Kina a hilinaʻi nui i ka lawe ʻana mai, e like me ka piperazine anhydrous, propionic acid, a me nā mea ʻē aʻe. ʻAʻole kūpono ke kumukūʻai a me ka maikaʻi, e pili ana i ka hoʻokūkū o nā huahana lāʻau lapaʻau a pono e hoʻomaikaʻi i ke kaʻina hana, e like me TMB, p-aminophenol, D-PHPG, etc.
Manaʻo ʻia i nā makahiki e hiki mai ana, e nānā ka noiʻi lāʻau hou o ka honua i nā ʻano lāʻau lapaʻau he 10 e hiki mai ana: nā lāʻau hoʻomaikaʻi o ka lolo, nā lāʻau anti-rheumatoid arthritis, nā lāʻau anti-AIDS, anti-hepatitis a me nā lāʻau viral ʻē aʻe, lipid. - nā lāʻau hoʻohaʻahaʻa, nā lāʻau anti-thrombotic, nā lāʻau anti-tumor, platelet-activating factor antagonists, glycoside cardiac stimulants, antidepressants, anti-psychotic and anti-anxiety drugs, etc. ka hoʻomohala ʻana i nā kikowaena lāʻau lapaʻau a me kahi ala nui e hoʻonui ai i kahi mākeke hou.