Izinto eziphakathi ziluhlobo olubaluleke kakhulu lweemveliso zeekhemikhali ezintle. Ngokwenyani, luhlobo "lweemveliso ezigqityiweyo", ezisetyenziswa kakhulu ekuhlanganiseni amayeza, izibulali-zinambuzane, iingubo, iidayi kunye neziqholo.

Kwizonyango, kusetyenziswa izixhobo eziphakathi ukuvelisa ii-API.

Ngoko ke yintoni imboni ekhethekileyo yamayeza aphakathi?

01

Ezi zibizwa ngokuba zizinto ezisetyenziswa ngamayeza zizinto ezisetyenziswa ngamakhemikhali okanye iimveliso zamachiza ezisetyenziswa kwinkqubo yokwenziwa kwamayeza.
Le khemikhali, engadingi layisenisi yokuvelisa amayeza, inokuveliswa kwisityalo seekhemikhali esiqhelekileyo kwaye, xa ifikelela kumanqanaba athile, ingasetyenziswa ekuhlanganiseni amayeza.

Umfanekiso

Okwangoku, iintlobo ezithembisayo kakhulu ze-medicament intermediates zezi zilandelayo:

Izixhobo eziphakathi ze-nucleoside.
Olu hlobo lokwenziwa kwamayeza okulwa noGawulayo lusetyenziswa kakhulu yi-zidovudine, evela kwi-United States Glaxo.
IWellcome kunye neBristol-Myers Squibb baphumelele.

Izifo zentliziyo.
Umzekelo, ii-sartans ezenziweyo zisetyenziswa kakhulu kunyango lwe-hypertension ngenxa yesiphumo sazo esipheleleyo sokulwa ne-hypertension, iziphumo ebezingalindelekanga ezimbalwa, ukusebenza ixesha elide (ulawulo oluzinzileyo loxinzelelo lwegazi iiyure ezingama-24) kunye nokukwazi ukusetyenziswa kunye nezinye ii-sartans.
Ngokwezibalo, ngo-2015, imfuno yehlabathi yezinto ezisebenzayo kwi-sartan (i-losartan potassium, i-olmesartan, i-valsartan, i-irbesartan, i-telmisartan, i-candesartan) ifikelele kwiitoni ezingama-3,300.
Intengiso iyonke yayiyi-$21.063 yezigidigidi.

Izixhobo eziphakathi ezifakwe i-fluorine.
Amayeza afakwe i-fluorinated avela kwezi zinto ziphakathi aphuhliswe ngokukhawuleza kwiminyaka yakutshanje ngenxa yokusebenza kwawo kakuhle. Ngo-1970, yi-2% kuphela yamayeza afakwe i-fluorinated awayethengiswa; ngo-2013, yi-25% yamayeza afakwe i-fluorinated ayethengiswa.
Iimveliso ezimeleyo ezifana ne-fluoroquinolone anti-infectious drugs, i-antidepressant fluoxetine kunye ne-antifungal fluconazole zinegalelo elikhulu ekusetyenzisweni kwezonyango, phakathi kwazo apho i-fluoroquinolone anti-infectious drugs ithatha malunga ne-15% yesabelo semarike yehlabathi samayeza alwa nosulelo.
Ukongeza, i-trifluoroethanol iyinxalenye ebalulekileyo yokwenziwa kwe-anesthetics, ngelixa i-trifluoromethylaniline iyinxalenye ebalulekileyo yokwenziwa kwe-antimalarial drugs, i-anti-inflammatory and analgesics, i-anti-prostate drugs kunye ne-anti-depressants, kwaye amathuba emarike abanzi kakhulu.

Ii-Heterocyclic intermediates.
Njengoko i-pyridine kunye ne-piperazine zimela, isetyenziswa kakhulu ekuqulunqweni kwamayeza okulwa nezilonda, amayeza amaninzi esisu, amayeza okulwa nokuvuvukala kunye nokulwa nosulelo, amayeza asebenzayo kakhulu okulwa noxinzelelo lwegazi kunye namayeza amatsha okulwa nomhlaza webele i-letrozole.

02

Izinto ezisetyenziswa ngamayeza zibalulekile kwikhonkco leshishini lezonyango.

Umfanekiso

Phezulu kukho izinto ezisisiseko zekhemikhali, uninzi lwazo ziimveliso zepetrochemical, ezifana ne-acetylene, i-ethylene, i-propylene, i-butene kunye ne-butadiene, i-toluene kunye ne-xylene.

Ii-Pharmaceutical Intermediates zahlulwe zaba zii-primary intermediates kunye nee-advanced intermediates.
Phakathi kwabo, ababoneleli abaphambili abaphakathi banokubonelela kuphela ngemveliso elula ephakathi kwaye baphambili kuluhlu lwemizi-mveliso abanoxinzelelo olukhulu lokhuphiswano kunye noxinzelelo lwamaxabiso. Ke ngoko, ukuguquguquka kwamaxabiso ezinto ezisisiseko zeekhemikhali kunempembelelo enkulu kubo.

Kwelinye icala, ababoneleli abaphakathi abaphambili abanalo nje kuphela igunya eliqinileyo lokuxoxisana nababoneleli abaphambili, kodwa okubaluleke ngakumbi, kuba benza imveliso yabaphakathi abaphambili abanomxholo ophezulu wobugcisa kwaye bagcina unxibelelwano olusondeleyo neenkampani zamazwe ngamazwe, abachaphazeleki kangako kukutshintsha kwamaxabiso ezinto ezikrwada.

Iindawo eziphakathi ziphantsi kweshishini leekhemikhali ezicociweyo zamayeza.
Abavelisi bee-pharmaceutical intermediates badibanisa ii-intermediates okanye ii-crude APIs, baze bathengise iimveliso ngendlela yeemveliso zeekhemikhali kwiinkampani zamayeza, ezizicocayo zize emva koko zizithengise njengeziyobisi.

Iimveliso ezidityanisiweyo zamayeza ziquka iimveliso eziqhelekileyo kunye neemveliso ezenziwe ngokwezifiso. Ngokwezigaba ezahlukeneyo zenkonzo yokuthumela ngaphandle, iimodeli zoshishino ezenziwe ngokwezifiso zabathengi abaphakathi zinokwahlulwahlulwa ngokubanzi zibe yi-CRO (uphando lwekhontrakthi kunye nophuhliso lwangaphandle) kunye ne-CMO (ukuthunyelwa ngaphandle kwemveliso yekhontrakthi).

Ngaphambili, indlela yokuthumela ngaphandle ishishini le-CMO yayisetyenziswa kakhulu kwiingcali zokwenza amayeza.
Phantsi komzekelo we-CMO, iinkampani zamayeza zithumela imveliso kwamanye amaqabane.
Ke ngoko, uthotho lweshishini luqala ngezixhobo ezikhethekileyo zeyeza.
Iinkampani zoshishino kufuneka zithenge izinto ezisisiseko zekhemikhali kwaye zihlele kwaye zicubungule zibe zizinto ezikhethekileyo ze-pharmaceutical, zize emva koko zicubungule zibe zizinto zokuqala ze-API, ii-cGMP intermediates, ii-API kunye namalungiselelo.

Kodwa, njengoko iinkampani zamayeza zifuna ulawulo lweendleko kunye nokusebenza kakuhle, iinkonzo ezilula zokuthumela imveliso ngaphandle azikwazanga ukuhlangabezana neemfuno zeshishini, imo ye-CDMO (uphando lwemveliso kunye nokuthunyelwa ngaphandle kophuhliso) ivela ngexesha lembali, i-CDMO ifuna amashishini emveliso ngokwezifiso ukuze athathe inxaxheba kumthengi kwinkqubo yophando nophuhliso, ukubonelela ngokuphuculwa kwenkqubo okanye ukulungiswa, ukufezekisa umgangatho wemveliso omkhulu, ukunciphisa iindleko zemveliso,
Inengeniso ephezulu kunemodeli ye-CMO.

Eyona isezantsi ikakhulu lishishini lemveliso ye-API, kwaye i-API ikubudlelwane phakathi kwe-industrial chain ne-industrial chain kunye nokulungiselela.
Ke ngoko, imfuno yokusetyenziswa kokulungiswa kwamayeza asezantsi iya kuchaphazela ngqo imfuno ye-API, ize emva koko ichaphazele imfuno ye-intermediate.

Ngokwembono yecandelo lonke lezemveliso, abavelisi beyeza bakwinqanaba lokukhula okwangoku, kwaye izinga lenzuzo eliphakathi ngokubanzi liyi-15-20%, ngelixa izinga lenzuzo eliphakathi le-API liyi-20-25%, kwaye izinga lenzuzo eliphakathi lemveliso yeyeza elisezantsi liphezulu njenge-40-50%. Ngokucacileyo, izinga lenzuzo eliphakathi lemveliso elisezantsi liphezulu kakhulu kunelo lemveliso ephezulu.
Ke ngoko, amashishini aphakathi kwamayeza anokwandisa ngakumbi uthotho lwemveliso, anyuse inzuzo yemveliso kwaye aphucule uzinzo lwentengiso ngokuvelisa i-API kwixesha elizayo.

03

Uphuhliso oluphezulu lweshishini lezonyango eTshayina lwaqala ngo-2000.

Ngelo xesha, iinkampani zamayeza kumazwe aphuhlileyo zazinika ingqalelo ngakumbi kuphando lwemveliso nophuhliso kunye nophuhliso lwemarike njengeyona nto iphambili ekukhuphisana ngayo, kwaye zakhawulezisa ukudluliselwa kwezinto eziphakathi kunye nokuhlanganiswa kwamayeza asebenzayo kumazwe asaphuhlayo ngeendleko eziphantsi.
Ke ngoko, ishishini lezonyango eTshayina liphumelele uphuhliso oluhle kakhulu ngokusebenzisa eli thuba.
Emva kweminyaka engaphezu kweshumi yophuhliso oluzinzileyo, ngenkxaso yemithetho nemigaqo-nkqubo yesizwe iyonke, iTshayina ibe sisiseko esibalulekileyo semveliso ephakathi kwicandelo lehlabathi labasebenzi kwishishini lamayeza.

Ukususela ngo-2012 ukuya ku-2018, imveliso yeshishini le-medicine laseTshayina inyuke ukusuka kwi-8.1 yezigidi zeetoni ezinobukhulu bemarike obumalunga ne-168.8 yeebhiliyoni zeerandi ukuya kwi-10.12 yezigidi zeetoni ezinobukhulu bemarike obumalunga ne-2010.7 yeebhiliyoni zeerandi.

Umfanekiso

Ishishini leemveliso eziphakathi zamayeza laseTshayina lifikelele kukhuphiswano olukhulu kwimarike, kwaye kwanamashishini athile emveliso ephakathi akwazile ukuvelisa iimveliso eziphakathi ezinesakhiwo esintsonkothileyo seemolekyuli kunye neemfuno zobugcisa eziphezulu. Inani elikhulu leemveliso ezinempembelelo liqalile ukulawula imarike yamazwe ngamazwe.

Nangona kunjalo, ngokubanzi, ishishini eliphakathi eTshayina lisekwixesha lophuhliso lokuphucula nokuphucula ulwakhiwo lwemveliso, kwaye inqanaba lobuchwepheshe lisephantsi kakhulu.
Iimveliso eziphambili zeyeza zisezezona mveliso ziphambili kushishino lweyeza, kwaye zimbalwa iinkampani ezivelisa inani elikhulu leemveliso eziphambili zeyeza kwaye zixhasa iimveliso eziphakathi zamayeza amatsha anelungelo elilodwa lomenzi.

Okwangoku, iinkampani ezikuluhlu lwe-A-share ezikhuphisanayo ngakumbi kushishino oluphakathi yiYaben Chemical, Lianhua Technology, Boten, kunye neWanrun, eziceba ukutyala imali eyi-630 yezigidi zeeyuan ekwakheni iiprojekthi ze-pharmaceutical intermediates kunye ne-API ezinomthamo we-A iyonke weetoni eziyi-3,155 ngonyaka.
Baqhubeka nokuphuhlisa uluhlu lweemveliso ngophando nophuhliso, ukuze bafumane iindlela ezintsha.

I-Yaben Chemical Co., Ltd. (300261): Iimveliso zethu eziphambili ziquka amayeza aphakathi okulwa nomhlaza, amayeza aphakathi okulwa nesifo sokuwa kunye namayeza aphakathi okulwa neentsholongwane.
Phakathi kwazo, i-ABAH, iyeza elichasene nesifo sokuwa, laqaliswa ngokusemthethweni ukuveliswa ngo-Okthobha ka-2014, elinomthamo weetoni ezili-1,000.
Itekhnoloji yokubiliswa kwee-enzyme yaziswa ngempumelelo kwi-cardiovascular intermediates ukuphucula ukukhuphisana kweemveliso.
Ngowama-2017, le nkampani yathenga i-ACL, inkampani yamayeza esebenzayo eMalta, ikhawulezisa ulwakhiwo lwayo kwimarike yezonyango yamazwe ngamazwe kwaye iqhuba utshintsho kunye nokuphuculwa kwesiseko sasekhaya.

I-BTG (300363): igxile kwishishini le-CMO elisebenzisa amayeza amatsha/i-API eyenzelwe wena, iimveliso eziphambili zi-pharmaceutical intermediates ze-anti-hepatitis C, i-anti-AIDS, i-hypolipidemia kunye ne-analgesia, kwaye ngumthengisi oyintloko we-Sofebuvir intermediates ye-Gilead's anti-hepatitis C.
Ngowama-2016, ingeniso iyonke yeziyobisi ezilwa nesifo seswekile kunye ne-anti-hepatitis C ifikelele kwi-660 yezigidi, nto leyo eyenza i-50% yengeniso iyonke.
Nangona kunjalo, ukusukela ngo-2017, ngenxa yokunyangwa kancinci kancinci kwezigulane ze-hepatitis C kunye nokuncipha kwenani lezigulana, ukuthengiswa kweGilead ngamayeza e-hepatitis C kwaqala ukwehla. Ngaphezu koko, ngokuphelelwa kwamalungelo omenzi, kwaqaliswa amayeza amaninzi okulwa ne-hepatitis C, kwaye ukhuphiswano lwaqhubeka nokuqina, nto leyo eyabangela ukwehla kwee-odolo eziphakathi kunye nengeniso.
Okwangoku, inkampani itshintshe ukusuka kwishishini le-CMO ukuya kwishishini le-CDMO ukuze yakhe iqonga leenkonzo zehlabathi eliphambili kwiinkampani zamayeza.

Itekhnoloji yoManyano (002250):
Iimveliso ze-Pharmaceutical Intermediates zibandakanyeka kakhulu kwiziyobisi zokulwa nomhlaza, i-autoimmune, iziyobisi zokubola, iziyobisi zentliziyo, iziyobisi zeswekile, amayeza okudakumba, iziyobisi zokudakumba, iziyobisi zokudakumba, iziyobisi zokudakumba, iziyobisi zokudakumba, iziyobisi zokudakumba, zonke ezinje nge-basic zikwimimandla yonyango yemarike edumileyo nebanzi kwihlabathi liphela, ukukhula ngokukhawuleza kwiminyaka yakutshanje, izinga lokukhula kwengeniso elidibeneyo limalunga ne-50%.
Phakathi kwazo, “imveliso yonyaka yeetoni ezingama-300 zeChunidine, iitoni ezingama-300 zeFluzolic Acid kunye neetoni ezingama-200 zeCyclopyrimidine Acid Project” iye yafakwa kwimveliso ngokulandelelana ukususela ngo-2014.