Ehia mau Cellulose ethers i loko o ka lāʻau lapaʻau?

ʻO nā mea kōkua lāʻau lapaʻau nā mea hoʻohui a me nā adjuvants i hoʻohana ʻia i ka hana ʻana i nā lāʻau lapaʻau a me ka hoʻokumu ʻana i nā palapala kuhikuhi, a he ʻāpana koʻikoʻi o ka hoʻomākaukau lāʻau. E like me ka polymer maoli mea i loaʻa, cellulose ether nā hiʻohiʻona o ka biodegradability, non-toxicity, a me ke kumu kūʻai haʻahaʻa, e like me ka sodium carboxymethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose,Cellulose etherse like me ka hydroxyethyl cellulose a me ka ethyl cellulose he waiwai hoʻohana koʻikoʻi i nā mea hoʻohui lāʻau. I kēia manawa, hoʻohana nui ʻia nā huahana o ka nui o nā ʻoihana cellulose ether home ma waena a me nā haʻahaʻa haʻahaʻa o ka ʻoihana, a ʻaʻole kiʻekiʻe ka waiwai hoʻohui. Pono ka ʻoihana e hoʻololi a hoʻomaikaʻi a hoʻomaikaʻi i nā noi kiʻekiʻe o nā huahana.

He kuleana koʻikoʻi nā excipients lāʻau lapaʻau i ka hoʻomohala ʻana a me ka hana ʻana i nā formulations. No ka laʻana, i loko o ka hoʻomākaukau hoʻokuʻu hoʻomau, hoʻohana ʻia nā mea polymer e like me cellulose ethers ma ke ʻano he lāʻau lapaʻau i loko o nā pellets hoʻokuʻu hoʻomau, nā ʻano hana hoʻokuʻu hoʻokuʻu matrix, nā mea hoʻopuka hoʻokuʻu i uhi ʻia, nā capsules hoʻokuʻu mau, nā kiʻi lāʻau lapaʻau hoʻokuʻu hoʻomau. Ua hoʻohana nui ʻia ka hoʻomākaukau ʻana a me ka hoʻomākaukau ʻana i ka wai. Ma kēia ʻōnaehana, hoʻohana ʻia nā polymers e like me cellulose ethers e like me nā mea lawe lāʻau e kāohi i ka hoʻokuʻu ʻana o nā lāʻau lapaʻau i loko o ke kino o ke kanaka, ʻo ia hoʻi, pono lākou e hoʻokuʻu mālie ʻia i loko o ke kino i kahi manawa i hoʻopaʻa ʻia i loko o kahi manawa e hoʻokō ai i ke kumu o ka mālama pono.

Wahi a ka ʻikepili o ka Consulting and Research Department, aia ma kahi o 500 mau ʻano mea kōkua ma ka mākeke ma koʻu ʻāina, akā ke hoʻohālikelike ʻia me ʻAmelika Hui Pū ʻIa (ʻoi aku ma mua o 1500 mau ʻano) a me ka European Union (ʻoi aku ma mua o 3000 mau ʻano), aia kahi ʻokoʻa nui, a he liʻiliʻi mau nā ʻano. ʻO nā mea hoʻohana lāʻau lapaʻau o koʻu ʻāina He nui ka hiki ke hoʻomohala ʻia o ka mākeke. Ua hoʻomaopopo ʻia ʻo nā mea hoʻohana lāʻau lapaʻau kiʻekiʻe he ʻumi ma ka mākeke o koʻu ʻāina ʻo ia nā capsules gelatin lapaʻau, sucrose, starch, film coating powder, 1,2-propylene glycol, PVP, hydroxypropyl methylcellulose (HPMC), a me nā microcrystalline fibers. Mea kanu, HPC, lactose.

"ʻO ka cellulose ether kūlohelohe ka huaʻōlelo maʻamau no ke ʻano o nā derivatives cellulose i hana ʻia e ka hopena o ka cellulose alkali a me ka etherifying agent ma lalo o kekahi mau kūlana, a he huahana ia e hoʻololi ʻia ai nā pūʻulu hydroxyl ma ka macromolecule cellulose e nā hui ether. ʻO nā huahana lāʻau lapaʻau ma ka waena a me nā wahi kiʻekiʻe o ka ʻoihana a loaʻa ka waiwai hoʻohui kiʻekiʻe ma muli o nā koi koʻikoʻi koʻikoʻi, paʻakikī hoʻi ka hana ʻana o ka cellulose ethers e like me ka mea maʻamau nā papa matrix hoʻokuʻu paʻa, nā mea hoʻoheheʻe ʻia i ka ʻōpū, nā mea hoʻopaʻa microcapsule hoʻokuʻu paʻa, nā mea kiʻi lāʻau hoʻokuʻu mau, etc.

ʻO ka sodium carboxymethyl cellulose (CMC-Na) ka cellulose ether me ka nui o ka hoʻopuka a me ka hoʻohana ʻana ma ka home a ma waho. ʻO ia ka ionic cellulose ether i hana ʻia mai ka pulupulu a me ka lāʻau ma o ka alkalization a me ka etherification me ka chloroacetic acid. ʻO CMC-Na kahi mea hoʻohana lāʻau lapaʻau maʻamau. Hoʻohana pinepine ʻia ʻo ia ma ke ʻano he mea hoʻopaʻa no ka hoʻomākaukau paʻa ʻana a ma ke ʻano he mānoanoa, mānoanoa a me ka suspending agent no ka hoʻomākaukau ʻana i ka wai. Hiki ke hoʻohana ʻia ma ke ʻano he matrix hoʻoheheʻe wai a me nā mea hana kiʻiʻoniʻoni. Hoʻohana pinepine ʻia ʻo ia ma ke ʻano he kiʻiʻoniʻoni lāʻau hoʻokuʻu hoʻomau a me ka papa matrix hoʻokuʻu hoʻokuʻu ʻia i loko o nā ʻano hoʻokuʻu hoʻokuʻu ʻia.

Ma waho aʻe o ka sodium carboxymethyl cellulose ma ke ʻano he lāʻau lapaʻau, hiki ke hoʻohana ʻia ka sodium croscarmellose ma ke ʻano he lāʻau lapaʻau. ʻO ka sodium carboxymethyl cellulose cross-linked (CCMC-Na) he mea hiki ʻole ke hoʻoheheʻe i ka wai e hana ai ka carboxymethyl cellulose me kahi mea hoʻohui cross-link i kahi mahana (40-80 ° C) ma lalo o ka hana a kahi mea hoʻoheheʻe waika inorganic a hoʻomaʻemaʻe ʻia. ʻO ka mea hoʻohui cross hiki ke propylene glycol, succinic anhydride, maleic anhydride, adipic anhydride, a me nā mea like. Hoʻohana ʻia ka sodium Croscarmellose ma ke ʻano he disintegrant no nā papa, capsules a me nā granules i ka hoʻomākaukau waha. Ke hilinaʻi nei ia i nā hopena capillary a me ka pehu e hoʻokō ai i ka hoʻopau ʻana. Loaʻa iā ia ka compressibility maikaʻi a me ka disintegration ikaika. Ua hōʻike ʻia nā haʻawina e ʻoi aku ka nui o ka pehu o ka sodium croscarmellose i loko o ka wai ma mua o nā mea disintegrants maʻamau e like me ka sodium carboxymethyl cellulose haʻahaʻa a me ka microcrystalline cellulose hydrated.

ʻO ka Methyl cellulose (MC) kahi monoether non-ionic cellulose i hana ʻia mai ka pulupulu a me ka lāʻau ma o ka alkalization a me ka methyl chloride etherification. ʻO ka Methyl cellulose ka wai hoʻoheheʻe maikaʻi loa a paʻa i ka pae pH o 2.0 a 13.0. Hoʻohana nui ʻia ia i nā excipients pharmaceutical, a hoʻohana ʻia i nā papa sublingual, intramuscular injections, ophthalmic preparations, waha capsules, oral suspensions, waha papa a me nā hoʻomākaukau topical. Eia kekahi, i loko o nā hoʻopuka hoʻokuʻu ʻia, hiki ke hoʻohana ʻia ka MC e like me ka hydrophilic gel matrix sustained-release formulation, gastric-soluble coating material, sustained-release microcapsule packaging material, sustained-release drug film material, etc.

ʻO ka Hydroxypropyl methylcellulose (HPMC) he cellulose non-ionic i hui pū ʻia me ka pulupulu a me ka lāʻau ma o ka alkalization a me ka etherification o propylene oxide a me methyl chloride. ʻAʻohe ona, ʻono ʻole, ʻaʻohe mea ʻawaʻawa, hiki ke hoʻoheheʻe ʻia i ka wai anuanu, a me nā gels i ka wai wela. ʻO ka Hydroxypropyl methylcellulose kahi ʻano cellulose i hui ʻia eter e piʻi wikiwiki ana i ka hana, ka ʻai a me ka maikaʻi i nā makahiki he 15 i hala. ʻO ia kekahi o nā mea lapaʻau nui loa i hoʻohana ʻia ma ka home a ma waho. Ua hoʻohana ʻia ma ke ʻano he lāʻau lapaʻau no kahi kokoke i 50 mau makahiki. Nā makahiki o ka mōʻaukala. I kēia manawa, ʻike nui ʻia ka noi ʻana o HPMC ma nā ʻano ʻelima:

ʻO kekahi ma ke ʻano he mea hoʻopaʻa a hoʻopau. Hiki i ka HPMC ke hoʻomaloʻo i ka lāʻau, a hiki iā ia ke hoʻonui i nā haneli mau manawa ma hope o ka lawe ʻana i ka wai, no laila hiki iā ia ke hoʻomaikaʻi nui i ka hoʻoheheʻe ʻana a i ʻole ka hoʻokuʻu ʻana o ka papa. Loaʻa i ka HPMC ka viscosity ikaika, a hiki ke hoʻonui i ka viscosity particle a hoʻomaikaʻi i ka compressibility o nā mea maka me ke ʻano ʻoi a paʻakikī paha. Hiki ke hoʻohana ʻia ka HPMC me ka viscosity haʻahaʻa ma ke ʻano he binder a disintegrant, a ʻo HPMC me ka viscosity kiʻekiʻe hiki ke hoʻohana wale ʻia ma ke ʻano he binder.

ʻO ka lua, hoʻohana ʻia ia ma ke ʻano he mea hoʻokuʻu paʻa a mālama ʻia no ka hoʻomākaukau waha. ʻO ka HPMC kahi mea maʻamau hydrogel matrix i hoʻomākaukau ʻia i hoʻokuʻu ʻia. Hiki ke hoʻohana ʻia ka HPMC o ka papa viscosity haʻahaʻa (5～50mPa·s) ma ke ʻano he mea hoʻopaʻa, mea hoʻonui viscosity a me ka mea hoʻopaneʻe, a hiki ke hoʻohana ʻia ka HPMC o ka papa viscosity kiʻekiʻe (4000～100000mPa·s) no ka hoʻomākaukau ʻana i ka matrix sustained-release papa a me ka sustained-release capsules blocker hydrochloride. nā papa. Hiki ke hoʻoheheʻe ʻia ka HPMC i ka wai o ka ʻōpū, loaʻa nā mea maikaʻi o ka hoʻopili maikaʻi ʻana, ka wai maikaʻi, ka hiki ke hoʻouka lāʻau ikaika a me nā hiʻohiʻona hoʻokuʻu lāʻau ʻaʻole i pili i ka pH. He mea koʻikoʻi nui ka mea lawe hydrophilic i nā ʻōnaehana hoʻomaʻamaʻa hoʻokuʻu ʻia a hoʻohana pinepine ʻia ʻo The hydrophilic gel matrix a me ka uhi mea o ka hoʻomākaukau hoʻokuʻu hoʻomau, a hoʻohana ʻia i ka hoʻomākaukau ʻana i ka ʻōpū a me ka hoʻokuʻu ʻana i ka lāʻau lapaʻau mea kōkua.

ʻO ke kolu he mea hoʻouhi kiʻiʻoniʻoni.HPMCloaʻa nā waiwai hana kiʻiʻoniʻoni maikaʻi. ʻO ke kiʻiʻoniʻoni i hana ʻia e ia he ʻaʻahu, ʻikea, a paʻakikī, ʻaʻole maʻalahi ke hoʻopili i ka wā hana. ʻOi loa no nā lāʻau lapaʻau e maʻalahi ke komo i ka makū a paʻa ʻole, me ka hoʻohana ʻana iā ia ma ke ʻano he papa hoʻokaʻawale hiki ke hoʻomaikaʻi nui i ke kūpaʻa o ka lāʻau lapaʻau a pale ʻO ke kiʻiʻoniʻoni e hoʻololi i ke kala. Loaʻa i ka HPMC nā ʻano kikoʻī viscosity. Inā koho maikaʻi ʻia, ʻoi aku ka maikaʻi a me ke ʻano o nā papa i uhi ʻia ma mua o nā mea ʻē aʻe, a ʻo kona ʻano maʻamau ʻo 2% a 10%.

Hoʻohana ʻia ʻehā ma ke ʻano he mea capsule. I nā makahiki i hala iho nei, me ka ulu pinepine ʻana o nā maʻi maʻi holoholona honua, i hoʻohālikelike ʻia me nā capsules gelatin, ua lilo nā capsules mea kanu i mea aloha hou o nā ʻoihana lāʻau a me nā meaʻai. Ua hoʻopuka maikaʻi ʻo Pfizer i ka HPMC mai nā mea kanu kūlohelohe a hoʻomākaukau i nā capsule mea kanu VcapTM. Hoʻohālikelike ʻia me nā capsules hollow gelatin kuʻuna, loaʻa i nā capsules meaʻai nā mea maikaʻi o ka hiki ke hoʻololi ākea, ʻaʻohe pilikia o ka hopena cross-linking, a me ke kūpaʻa kiʻekiʻe. ʻO ka hoʻokuʻu ʻana o ka lāʻau lapaʻau ʻano paʻa, a liʻiliʻi nā ʻokoʻa o kēlā me kēia kanaka. Ma hope o ka hemo ʻana i ke kino o ke kanaka, ʻaʻole ia e komo a hiki ke hoʻokuʻu ʻia. Hoʻokuʻu ʻia mai ke kino. Ma ke ʻano o ka mālama ʻana, ma hope o ka nui o nā hoʻāʻo, ʻaneʻane ʻaʻole palupalu ma lalo o nā kūlana haʻahaʻa haʻahaʻa, a paʻa mau nā waiwai o ka pūpū capsule ma lalo o ka haʻahaʻa kiʻekiʻe, a ʻaʻole pili ʻia nā ʻano kuhikuhi like ʻole o nā capsules mea kanu ma lalo o nā kūlana mālama nui. Me ka hoʻomaopopo ʻana o ka poʻe i nā capsules mea kanu a me ka hoʻololi ʻana o nā manaʻo lāʻau lapaʻau lehulehu ma ka home a ma waho, e ulu wikiwiki ka mākeke no nā capsules mea kanu.

ʻO ka lima ma ke ʻano he mea hoʻomaha. ʻO ka hoʻomākaukau ʻana i ka wai ʻano hoʻokuʻu ʻia he ʻano lāʻau lapaʻau maʻamau i hoʻohana ʻia, ʻo ia kahi ʻōnaehana hoʻopuehu heterogenous kahi e hoʻopuehu ʻia ai nā lāʻau paʻa paʻa ʻole i loko o kahi ʻano hoʻopuehu wai. Hoʻoholo ka paʻa o ka ʻōnaehana i ka maikaʻi o ka hoʻomākaukau ʻana i ka wai hoʻomaha. Hiki i ka HPMC colloidal solution ke ho'ēmi i ka paʻa-wai interfacial tension, e hoʻemi i ka ikehu manuahi o nā ʻāpana paʻa, a hoʻopaʻa i ka ʻōnaehana heterogeneous dispersion. He lāʻau hoʻomaha maikaʻi loa ia. Hoʻohana ʻia ʻo HPMC ma ke ʻano he mānoanoa no nā kulu maka, me kahi maʻiʻo o 0.45% a 1.0%.

ʻO ka Hydroxypropyl cellulose (HPC) kahi monoether non-ionic cellulose i hana ʻia mai ka pulupulu a me ka lāʻau ma o ka alkalization a me ka propylene oxide etherification. Hiki ke hoʻoheheʻe ʻia ka HPC i ka wai ma lalo o 40 ° C a me ka nui o nā solvents polar, a pili kāna hana i ka ʻike o ka hydroxypropyl a me ke degere o ka polymerization. Hiki ke hoʻohālikelike ʻia ka HPC me nā lāʻau lapaʻau like ʻole a maikaʻi ka inertness.

ʻO ka hydroxypropyl cellulose i pani haʻahaʻa(L-HPC)Hoʻohana nui ʻia e like me ka disintegrant papa a me ka binder. ʻO kona mau hiʻohiʻona: maʻalahi ke kaomi a me ka hana, ka hoʻohana ikaika, ʻoi aku ka paʻakikī o ka hana ʻana, nā palaka a me nā papa palaka, hoʻohui i ka L －HPC hiki ke hoʻomaikaʻi i ka paʻakikī o ka papa a me ka ʻōlinolino o ka helehelena, a hiki iā ia ke hoʻopau koke i ka papa, hoʻomaikaʻi i ka maikaʻi o loko o ka papa, a hoʻomaikaʻi i ka hopena curative.

Hiki ke hoʻohana ʻia ka hydroxypropyl cellulose kiʻekiʻe (H-HPC) ma ke ʻano he mea hoʻopaʻa paʻa no nā papa, granules a me nā granules maikaʻi i ka māla lāʻau. Loaʻa i ka H-HPC nā waiwai hana kiʻiʻoniʻoni maikaʻi loa, a ʻo ka hopena kiʻiʻoniʻoni he paʻakikī a elastic, hiki ke hoʻohālikelike ʻia me nā plasticizers. Ma ka hui pū ʻana me nā mea hoʻopili anti-wet coating, hiki ke hoʻomaikaʻi hou ʻia ka hana o ke kiʻiʻoniʻoni, a hoʻohana pinepine ʻia e like me ka mea hoʻonaninani kiʻiʻoniʻoni no nā papa. Hiki ke hoʻohana ʻia ʻo H-HPC ma ke ʻano he mea matrix no ka hoʻomākaukau ʻana i nā papa hoʻokuʻu hoʻokuʻu ʻia matrix, nā pellets hoʻokuʻu ʻia a me nā papa hoʻokuʻu hoʻokuʻu pālua.

ʻO ka Hydroxyethyl cellulose (HEC) he monoether non-ionic cellulose i hana ʻia mai ka pulupulu a me ka lāʻau ma o ka alkalization a me ka etherification ethylene oxide. Hoʻohana nui ʻia ʻo HEC ma ke ʻano he mānoanoa, colloidal protection agent, adhesive, dispersant, stabilizer, suspending agent, film-forming agent a me nā mea hoʻokuʻu lohi i ka lāʻau lapaʻau. Hiki ke hoʻohana ʻia i nā emulsion, ʻaila, a me nā kulu maka no ka lāʻau lapaʻau. ʻO ka wai waha, nā papa paʻa, nā capsules a me nā ʻano hana ʻē aʻe. Ua hoʻokomo ʻia ʻo Hydroxyethyl cellulose i ka US Pharmacopoeia/US National Formulary a me European Pharmacopoeia.

ʻO Ethyl cellulose (EC) kekahi o nā mea i hoʻohana nui ʻia i ka wai-insoluble cellulose derivatives. ʻAʻole ʻawaʻawa ʻo EC, paʻa, ʻaʻole hiki ke hoʻoheheʻe ʻia i ka wai, ka waikawa a i ʻole nā ​​hopena alkaline, a hiki ke hoʻoheheʻe ʻia i nā mea hoʻoheheʻe kūlohelohe e like me ka ethanol a me ka methanol. ʻO ka mea hoʻoheheʻe maʻamau i hoʻohana ʻia he mea hoʻoheheʻe hui ʻia o toluene/ethanol 4/1 (kaumaha). He nui nā hoʻohana ʻana o EC i ka hoʻomākaukau ʻana i ka lāʻau lapaʻau, a hoʻohana nui ʻia e like me ka mea lawe a me nā microcapsules, ka uhi ʻana i nā mea hana kiʻiʻoniʻoni, etc. nā pellets hoʻokuʻu mau, ma ke ʻano he mea kōkua encapsulation e hoʻomākaukau ai i nā microcapsules hoʻokuʻu mau; hiki ke hoʻohana nui ʻia ma ke ʻano he mea lawe mea hoʻohana ʻia e hoʻomākaukau i nā dispersion paʻa; hiki ke hoʻohana nuiʻia i kaʻenehana lāʻau lapaʻau ma keʻano he mea hana kiʻiʻoniʻoni a me ka uhi pale, a hiki ke hoʻohanaʻia e like me ka mea hoʻopili a me ka hoʻopihapiha. Ma ke ʻano he pale pale no nā papa, hiki iā ia ke hōʻemi i ka naʻau o nā papa i ka haʻahaʻa a pale i nā lāʻau mai ka lilo ʻana a me ka pōʻino e ka wai; hiki iā ia ke hana i kahi papa hoʻokuʻu lohi a me ka microencapsulate i ka polymer e hoʻokuʻu mau i ka hopena lāʻau.

I ka hōʻuluʻulu ʻana, ʻo ka sodium carboxymethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxyethyl cellulose a me ka ʻaila-soluble ethyl cellulose e hoʻokumu ʻia i ko lākou mau mea. nā mea hana kiʻiʻoniʻoni, nā mea capsule a me nā mea hoʻomaha. Ke nānā nei i ka honua, ua ʻike kekahi mau hui multinational haole (Shin-Etsu Japan, Dow Wolff a me Ashland) i ka mākeke nui no ka cellulose pharmaceutical ma Kina i ka wā e hiki mai ana, a ma ka hoʻonui ʻana a i ʻole ka hui ʻana, ua hoʻonui lākou i ko lākou alo i kēia kahua. Hoʻokomo kālā i loko o ka noi. Ua hoʻolaha ʻo Dow Wolff e hoʻonui ʻo ia i ka nānā ʻana i ka hoʻokumu ʻana, nā mea hoʻohui a me nā pono o ka mākeke hoʻomākaukau lāʻau lapaʻau Kina, a e hoʻoikaika pū kāna noiʻi noiʻi e hoʻokokoke i ka mākeke. Ua hoʻokumu ka Wolff Cellulose Division o Dow Chemical a me Colorcon Corporation o ʻAmelika Hui Pū ʻIa i kahi hui hoʻomākaukau hoʻokuʻu hoʻomau i hoʻopaʻa ʻia ma ka honua. Loaʻa iā ia ma mua o 1,200 mau limahana ma 9 mau kūlanakauhale, 15 mau waihona waiwai a me 6 mau hui GMP. Hāʻawi nā loea noiʻi noiʻi i nā lawelawe i nā mea kūʻai aku ma kahi o 160 mau ʻāina. Loaʻa iā Ashland nā kumu hana ma Beijing, Tianjin, Shanghai, Nanjing, Changzhou, Kunshan a me Jiangmen, a ua hoʻokomo i nā kikowaena noiʻi ʻenehana ʻekolu ma Shanghai a me Nanjing.

Wahi a nā helu helu mai ka pūnaewele o ka China Cellulose Association, i ka makahiki 2017, ʻo ka hana home o cellulose ether he 373,000 tons a ʻo ka nui o ke kūʻai aku he 360 ​​tausani tons. I ka makahiki 2017, ʻo ka nui kūʻai maoli o ka ionicCMChe 234,000 tons, he mahuahua o 18.61% makahiki-ma-makahiki, a me ka nui kuai o non-ionic CMC he 126,000 tons, he mahuahua o 8.2% makahiki-ma-makahiki. Ma waho aʻe o ka HPMC (building material grade) huahana non-ionic,HPMC(Pharmaceutical grade), HPMC (food grade), HEC, HPC, MC, HEMC, etc. ua piʻi aʻe i ke ʻano, a ua hoʻomau ka hoʻonui ʻana a me ke kūʻai aku. Ke ulu wikiwiki nei nā cellulose ethers home no nā makahiki he ʻumi, a ua lilo ka huahana i mea mua ma ka honua. Eia nō naʻe, hoʻohana nui ʻia ka hapa nui o nā huahana cellulose ether ma ka waena a me ka haʻahaʻa o ka ʻoihana, a ʻaʻole kiʻekiʻe ka waiwai hoʻohui.

I kēia manawa, ʻo ka hapa nui o nā ʻoihana cellulose ether home i kahi manawa koʻikoʻi o ka hoʻololi a me ka hoʻomaikaʻi ʻana. Pono lākou e hoʻonui i ka noiʻi a me ka hoʻomohala ʻana i nā huahana, hoʻonui mau i nā ʻano huahana, hoʻohana piha iā Kina, ka mākeke nui loa o ka honua, a hoʻonui i nā hana e hoʻomohala i nā mākeke ʻē aʻe i hiki ai i nā ʻoihana ke hoʻonui koke i ka hiki. E hoʻopau i ka hoʻololi a me ka hoʻomaikaʻi ʻana, e komo i ka waena waena a kiʻekiʻe o ka ʻoihana, a hoʻokō i ka hoʻomohala maikaʻi a me ka ʻōmaʻomaʻo.