Recombinant interferons yog ib pawg ntawm cov tshuaj tiv thaiv kab mob siv rau kev kho mob thiab kev tiv thaiv kab mob. Cov proteins uas muaj roj ntsha no yog tsim los ntawm tib neeg lub hlwb hauv kev teb rau kev nkag mus ntawm cov neeg ua haujlwm txawv teb chaws. Hauv cov tshuaj niaj hnub no, cov tshuaj no tau lees paub tias yog qhov zoo tshaj plaws thiab nyab xeeb rau kev kho cov kab mob kis.
Kev faib tawm
Hauv microbiology, muaj ntau dua 20 hom interferons (IFN), uas txawv ntawm cov khoom thiab cov qauv lom neeg. Cov tshuaj raws li lawv tau faib raws li hauv qab no:
- Los ntawm hom khoom xyaw: o alpha-interferon (los yog leukocyte); o beta-interferon (fibroblast); o gamma-interferon (lub cev tsis muaj zog); o lambda-interferon.
- Raws li txoj kev tau txais: o ntuj, tau los ntawm tib neeg cov ntshav leukocytes; o recombinant tib neeg interferon, tsim synthetically (los ntawm genetic engineering).
Alpha- thiab beta-interferons tau ua ke rau hauv tsev neeg Ihom vim qhov zoo sib xws ntawm lawv cov dej num hauv lub cev thiab tib cov amino acid sequences. Gamma thiab lambda interferons raug cais ua nyias hom II thiab III, feem. Thawj tiam ntawm cov proteins ntuj muaj qhov tsis zoo - lawv yuav tsum tau siv cov khoom siv tsis tshua muaj (cov ntshav pub dawb) thiab qib siab ntawm kev ua kom huv ntawm cov proteins txawv teb chaws. Qhov no coj mus rau lawv cov nqi siab thiab tsis tshua muaj txiaj ntsig. Recombinant alpha-interferons tam sim no tuav txoj haujlwm tseem ceeb ntawm cov tshuaj ntawm hom no nyob rau hauv cov nqe lus ntawm kev kawm thiab dav ntawm daim ntawv thov hauv kev kho mob.
Ntse
Ntxiv rau qhov kev faib tawm saum toj no, cov proteins no txawv ntawm cov subtypes. Yog li, pawg ntawm recombinant alpha 2 interferons suav nrog tsawg kawg 24 subtypes uas txawv ntawm ib leeg hauv 24 noob. Lawv tsis zoo ib yam nkaus hauv cov qauv.
Tsis zoo li alpha interferons, beta hloov kho yog encoded los ntawm ib tug paub gene. Ob hom proteins tau qhib los ntawm cov kab mob thiab siv tib receptors hauv lawv cov txheej txheem ntawm kev ua ntawm lwm lub hlwb.
Tus subtype ntawm tib neeg recombinant interferon alpha-2b txawv ntawm alpha-2a los ntawm ob amino acid residues nyob rau hauv cov qauv. Lwm tus ntawm lawv (thiab muaj ntau tshaj li ib puas nyob rau hauv tag nrho) yog tib yam. Yog li, cov kab mob uas lawv tau siv, nrog rau cov kev mob tshwm sim, yog tib yam, tab sis cov tshuaj tiv thaiv ntawm lub cev (kev tsim cov tshuaj tiv thaiv) txawv.
Leukocyte natural interferons kuj raug cais raws li qib kev ua kom huv:
- Native, tus yam ntxwv los ntawm kev tu kom ntiav thiabze li sai tau rau cov khoom qub. Lawv muaj peev xwm loj tshaj plaws rau cov teebmeem immunobiological.
- ntseeg, huv heev. Lawv yog siv feem ntau nyob rau hauv cov ntaub ntawv uas ib tug loj ib koob tshuaj yuav tsum tau muab. Lub homogeneity ntawm muaj pes tsawg leeg ntawm cov kev npaj no nce mus txog 90%.
- sib tov. Lawv tau txais nrog txoj kev ntxuav maj mam. Lub xub ntiag ntawm cytokines ntxiv ua rau nws nyuaj rau standardize cov tshuaj no. Nyob rau tib lub sijhawm, vim qhov no, lawv muaj cov nyhuv immunomodulatory ntau dua, uas ua rau muaj kev nthuav dav ntawm lawv qhov kev nthuav dav.
Recombinant human interferon muaj cov protein ntau monospecific. Nws belongs rau ib qho ntawm cov subtypes. Hom b1a hauv kev npaj ntawm recombinant alpha interferon yog tus cwj pwm los ntawm daim ntawv glycosylated (tsis yog-enzymatic ntxiv ntawm qab zib residues rau cov organic protein molecules), thiab b1b yog non-glycolized. Xws li interferons yog 98% homogeneous nyob rau hauv muaj pes tsawg leeg.
Cov yam ntxwv ntawm cov khoom siv ntuj tsim thiab tsim cov khoom siv hluavtaws txiav txim siab qhov txawv ntawm lawv daim ntawv thov. Recombinant interferons muaj cov tshuaj tiv thaiv kab mob thiab tshuaj tiv thaiv kab mob. Nyob rau hauv tej yam ntuj tso nws yog immunomodulatory, thiab kuj muaj ib tug ntau dua kev ua si tiv thaiv kab mob thiab purulent-septic pathologies.
Recombinant interferon npaj
Cov tshuaj siv ntau tshaj plaws ntawm cov tshuaj no yog cov hauv qab no:
- alpha 2a interferon: "Reaferon","Viferon", "Roferon", "Interal";
- alpha 2b interferon: "Intron-A", "Laifferon", "Peginterferon", "Infagel", Inrek;
- alpha 2c interferon: "Berofor";
- beta-interferon: "Interferon-beta-1a", "Fron", "Rebif", "Avonex", "Betaseron", "Betaferon";
- gamma-interferon: "Aktimmun", "Gammaferon", "Ingaron", "Imukin"
Kab mob
Recombinant interferons yog nquag hauv kev kho mob xws li:
- kab mob dermatological: qhov chaw mos herpes, warts, condylomas, papillomatosis, shingles;
- kab mob ophthalmic: o ntawm lub pob txha ntawm lub qhov muag tshwm sim los ntawm tus kab mob herpetic lossis adenovirus (txo lub sijhawm ntawm tus kab mob, kev nce hauv lub sijhawm sib txawv);
- mob kis kab mob ntawm txoj hlab ntsws sab sauv: mob khaub thuas, SARS (kev tiv thaiv xwm txheej kub ntxhov rau cov neeg muaj kev pheej hmoo, nrog rau kev kho mob);
- pathologies ntawm cov kab mob siab hepatobiliary: kab mob siab B, C hauv daim ntawv mob hnyav thiab mob ntev (hais lus kho mob, txo kev tuag txog li 60%);
- AIDS: normalization ntawm kev tiv thaiv kab mob, txo qhov mob hnyav ntawm ntau tshaj li ib nrab ntawm cov neeg mob; txo kev pheej hmoo ntawm AIDS-hais txog Kaposi's sarcoma;
- lwm cov kab mob: CMVI (cytomegalovirus kab mob), uas tshwm sim tawm tsam keeb kwm ntawm kev tiv thaiv kab mob (interferons yog siv rau nws.tiv thaiv), nrog rau tom qab kev hloov pauv; sclerosing panencephalitis (kev mob ntawm lub hlwb).
Cov kev npaj no yog tus cwj pwm los ntawm kev ua haujlwm thoob ntiaj teb ntawm kev tiv thaiv kab mob. Tsis zoo li cov tshuaj chemotherapeutic, lawv tsis ua rau muaj qhov tshwm sim ntawm cov kab mob tiv thaiv kab mob, tab sis cuam tshuam rau cov yam ntxwv ntawm innate, natural tiv thaiv.
Discovery keeb kwm
Interferons tau tshawb pom yuav luag 50 xyoo dhau los. Thawj cov tshuaj tau txais los ntawm cov ntshav ntawm cov neeg pub dawb. Ua li no, cov qe ntshav tau kho nrog cov kab mob, tom qab ntawd lawv pib tsim cov proteins uas muaj kev tiv thaiv. Cov interferon tau txais nyob rau hauv txoj kev no tau zoo heev, tab sis nws cov khoom lag luam loj tau cuam tshuam los ntawm qhov tsis txaus ntawm cov khoom siv raw. Piv txwv li, kom tau txais cov tshuaj xav tau los kho 1 tus neeg mob qog noj ntshav, yuav tsum tau sau cov ntshav los ntawm 200 tus neeg pub dawb.
Nyob rau hauv nruab nrab-80s ntawm lub xyoo pua XX, thawj prerequisites kom tau txais hluavtaws recombinant interferons tshwm sim. Txoj kev loj hlob sai ntawm genetic engineering nyob rau xyoo no coj mus rau kev tsim cov thev naus laus zis tshiab - kev qhia txog cov noob tsim nyog rau hauv cov cheeb tsam ntawm Pseudomonas putida cov kab mob hlwb uas tuaj yeem sib kis tau sai. Qhov no tso cai rau cov synthesis ntawm tib neeg recombinant alpha 2b interferon ntawm kev lag luam. Thawj cov tshuaj tsim nyob rau hauv lub USSR yog hu ua Reaferon.
Nyob rau xyoo tom ntej, kev tshawb fawb tsiaj tau ua tiav ntawm cov tshuaj noCov ntsiab lus ntawm teratogenic thiab toxicity. Kev ntsuam xyuas tau lees paub nws txoj kev nyab xeeb rau tus menyuam hauv plab thiab qhov tsis muaj qhov sib txawv ntawm cov kev mob tshwm sim ntawm cov khoom siv hluavtaws thiab cov tshuaj interferon.
Tom qab ntawd, cov kab mob E. coli tau pib siv kom tau txais cov interferon recombinant, vim lawv tsim cov tshuaj no sai dua. Thawj cov tshuaj tau txais los ntawm lawv lub hauv paus yog hu ua "Reaferon-EC" (los ntawm cov ntawv luv ntawm Latin lub npe ntawm cov kab mob no Escherichia coli). Cov kab mob no kuj tau siv nyob rau hauv feem ntau niaj hnub tsim ntawm recombinant interferons.
Txoj Cai Ua Haujlwm
Interferons yog ib hom tshuaj lom neeg lom neeg uas ua rau tib neeg lub cev tiv thaiv kab mob. Lawv pab txhawb rau kev lees paub thiab kev tawm tsam ntawm alien genetic cov ntaub ntawv. Nrog rau kev nthuav qhia cov kab mob mus rau hauv lub cell, tom qab ob peb feeb, tus naj npawb ntawm cov kab mob nce ntau zaus. Lawv kis mus ntxiv, cuam tshuam rau cov hlwb noj qab haus huv thiab sib npaug dua. Cov txheej txheem no tshwm sim tshwj xeeb tshaj yog nyob rau theem pib ntawm tus kab mob, txij li lub sijhawm no tib neeg lub cev tsis tuaj yeem tsim cov tshuaj interferon uas xav tau.
Ua tsaug rau cov proteins no, kev sib txuas ntawm ntau cov enzymes, tshuaj tiv thaiv kab mob thiab lwm yam khoom ntawm lub cev tiv thaiv kab mob tau tshwm sim. Raws li qhov tshwm sim, cov hlwb ua rau muaj kev tiv thaiv kab mob. Cov txheej txheem hauv qab no kuj txawv, uas cuam tshuam nrog interferons:
- stimulation ntawm macrophages, lawv ua kom nqus tsis tau, cuam tshuam cov hlwb;
- kev loj hlob inhibition thiab kev puas tsuaj ntawm cov hlwb txawv txav(antitumor effect);
- cuam tshuam rau immunocytes (lymphocytes tsim nyob rau hauv cov pob txha pob txha) - cov hlwb tseem ceeb ntawm lub cev tiv thaiv kab mob: NK hlwb, T-lymphocytes, monocytes, macrophages thiab granulocytes; stimulation ntawm lawv cov uas tsis yog tshwj xeeb cytotoxicity;
- ua kom cov synthesis ntawm cov protein uas ua rau muaj kev tiv thaiv ntawm cov hlwb rau cov neeg ua haujlwm txawv teb chaws, hloov cov proteins no mus rau cov neeg nyob sib ze;
- pib ib qho kev tawm tsam uas txhawb kev tsim cov tshuaj tiv thaiv kab mob (tshuaj tiv thaiv kab mob);
- ua kom cov synthesis ntawm tus kheej IFN, uas txo lub sijhawm rov qab los.
Tshwj xeeb yog ci ntsa iab tshuaj tiv thaiv kab mob yog raug rau recombinant interferons alpha 2b, 2a thiab beta. Lawv thaiv kev tsim cov kab mob kis kab mob thiab tiv thaiv kev yug me nyuam ntawm cov kab mob. Ib qho txiaj ntsig tseem ceeb ntawm cov tshuaj raws li lawv yog cov tshuaj toxicity tsawg thiab muaj peev xwm muab tshuaj rau thaum yau.
Synthesis
Tau txais cov interferons recombinant tshwm sim hauv theem:
- cais ntawm tus xa xov RNA tom qab ua kom muaj kev cuam tshuam ntawm interferon hauv kab lis kev cai;
- synthesis ntawm complementary DNA raws RNA;
- embedding DNA tau nyob rau theem dhau los rau hauv plasmid vectors - extrachromosomal DNA molecules muaj peev xwm ntawm kev ywj pheej luam hauv cov kab mob hlwb thiab lub luag haujlwm rau kev tsim cov protein;
- tau txais cov DNA recombinant;
- synthesis ntawm clones ntawm microorganisms uas tsim interferon;
- rov tsim cov kab mobkab lis kev cai nyob rau nruab nrab nutrient;
- cais cov kab mob hlwb los ntawm centrifugation;
- nag lossis daus ntawm interferon proteins los ntawm kev daws;
- ntxuav ntawm recombinant interferon los ntawm affinity chromatography lossis lwm txoj hauv kev.
Kev nthuav tawm ntawm kab lis kev cai clone tshwm sim hauv kev lag luam hauv cov reactors, thiab cov theem dhau los - hauv chav kuaj. Recombinant IFNs yog tsim tawm sab nraum tib neeg lub cev, tib neeg interferon gene yog embedded nyob rau hauv lawv cov genetic khoom.
Muaj ntau yam kab mob kab mob los ntawm cov protein no tau txais. Hauv qab no yog dab tsi recombinant alpha 2b interferon yog ua los ntawm:
- Escherichia coli (sau ntawm cov khoom tshwm sim intracellularly);
- hay kab mob Bacillussubtilis (tso interferons rau hauv ib puag ncig);
- Pseudomonas aeruginosa Pseudomonas aeruginosa;
- yeast fungi Saccharomycopsis fibuligera.
Cov neeg tsim khoom kawg muaj cov hauv qab no zoo dua lwm tus:
- muaj peev xwm siv cov kab lis kev cai pheej yig;
- sib cais yooj yim thaum sib cais;
- kev ua haujlwm siab (ntau dua 10 npaug piv rau lwm tus);
- txheej txheem ntawm kev ntxiv pawg carbohydrate, zoo ib yam hauv cov txheej txheem rau hauv cov tsiaj hlwb.
Ib daim ntawv
Recombinant interferons 2b, 2a thiab beta muaj nyob rau hauv cov ntawv hauv qab no:
- tshuaj daws tau;
- lyophilizates;
- teev thiab ua movie rauqhov muag;
- qhov ncauj daws;
- tswm ciab thiab microclysters rau kev tswj qhov quav thiab qhov chaw mos;
- tshuaj pleev;
- gels;
- tshuaj;
- aerosols;
- spherical vesicles (liposomes).
Recombinant IFN alpha
Synthetic alpha-interferons tau ua tiav nrog cov proteins ntuj. Lawv ua lub luag haujlwm tseem ceeb hauv kev ua kom lub cev tiv thaiv kab mob hauv tib neeg lub cev, qhib kev tsim cov cytokines tseem ceeb, kho kom haum xeeb ntawm lub cev thiab kev tiv thaiv kab mob, thiab muab kev tiv thaiv kab mob "kev nco"
Cov lus hauv qab no qhia txog cov yam ntxwv tseem ceeb ntawm qee qhov kev npaj rov ua dua interferon ntawm hom no:
| Npe | Type | Ib daim foos | Kev qhia |
| "Reaferon-ES" | Alpha 2a | Lyophilisate rau kev daws rau kev txhaj tshuaj thiab tshuaj pleev ib ce, ampoules thiab vials |
Adults:
Cov menyuam yaus hnub nyoog qis dua 1 xyoos:
|
| "Viferon" | Alpha 2a | xov tshuaj rau qhov quav |
Cov neeg laus thiab menyuam yaus:
Nyob rau hauv cov menyuam yug tshiab:
|
| "Roferon-A" | Alpha 2a | koob txhaj tshuaj |
Viral pathologies:
Cov kab mob ntawm lymphatic system:
Tumours:
|
| "Interal-P" | Alpha 2a | Lyophilisate rau kev txhaj tshuaj |
Adults:
Children:
|
| "Intron-A" | Alpha 2b | Txoj kev kho rau cov hlab ntsha thiab s / c txhaj tshuaj |
kab mob thiab kab mob malignant:
|
| "Laifferon" | Alpha 2b | Kev daws rau kev txhaj tshuaj intramuscular thiab instillation rau hauv lub qhov muag | Similar to "Interal-P" |
| "Infagel" | Alpha 2b | Gel hauv raj rau kev siv sab nraud | Kev kho mob herpes, tiv thaiv kab mob khaub thuas thiab SARS |
| "Rialdiron" | Alpha 2b | Lyophilisate rau IM thiab IV kev tswj hwm | Kab mob piav qhia rau Intron-A, nrog rau zuam-borne encephalitis, mycosis fungoides thiab Cesari syndrome |
| "Berofor" | Alpha 2c | qhov muag poob hauv capillary pipettes | Viral qhov muag kab mob |
Dab neeg tshiabtiam neeg yog pegylated (los yog conjugated) alpha-IFN, uas yog tus cwj pwm los ntawm kev ua haujlwm ntev. Lawv qhia kev ua haujlwm siab hauv kev kho tus kab mob siab viral. Cov no suav nrog Pegasys (IFN-α-2a) thiab Pegintron (tib neeg recombinant interferon 2b).
Recombinant beta-IFN
Ntawm cov beta-interferons, 2 subtypes tam sim no txawv - b1a (glycosylated) thiab b1b (non-glycolized). Ntxiv nrog rau cov tshuaj tiv thaiv kab mob thiab tshuaj tiv thaiv kab mob, lawv cuam tshuam rau lub paj hlwb thiab siv los kho ntau yam sclerosis. Cov tshuaj tau muab tshuaj subcutaneously lossis intramuscularly. Nws tau raug pov thawj hauv kev kho mob tias qhov txo qis ntawm qhov tshwm sim ntawm tus kab mob tshwm sim los ntawm yuav luag ib feem peb, tab sis tseem tsis muaj cov txheej txheem meej rau kev ntsuas kev ua tau zoo.
Lub tshuab ua haujlwm ntawm cov tshuaj no yog ua raws li cov xwm txheej hauv qab no:
- Kev khi ntawm interferons nrog cov receptors tshwj xeeb ntawm lub xov tooj ntawm tes, yog li ua kom cov protein ntau nrog cov tshuaj tua kab mob, tshuaj tua kab mob, tshuaj tiv thaiv kab mob.
- Txo cov naj npawb ntawm cov foci tshiab ntawm cov kab mob sclerotic hauv hlwb thiab cov kev hloov pauv atrophic hauv nws cov ntaub so ntswg (kev lees paub los ntawm MRI cov ntaub ntawv).
- Inhibition of leukocyte division thiab lawv tsiv teb tsaws mus rau thaj tsam ntawm qhov mob los ntawm kev txo qis kev tsim cov enzymes proteolytic.
- Ntaus kev tawg ntawm gamma-interferon, uas ua lub luag haujlwm tseem ceeb hauv kev txhim kho ntau yam sclerosis.
Recombinant gamma-IFN
Nyob rau hauv Russia, recombinant gamma interferon yog feem ntau dav tsim ua ib feem ntawm cov tshuaj "Ingaron". Nws yog siv los kho cov kab mob xws li:
- flu (xws li swine flu);
- otitis media (aerosol daim ntawv ntawm cov tshuaj);
- kab mob granulomatous;
- osteopetrosis (congenital familial osteosclerosis);
- kab mob siab B, C;
- AIDS;
- pulmonary tuberculosis;
- kab mob oncological;
- kab mob urogenital;
- chaw mos herpes thiab shingles;
- YHPV;
- mob prostatitis.
Daim ntawv aerosol ntawm tib neeg recombinant gamma interferon kuj yog siv los tiv thaiv tus mob khaub thuas (kua dej ntawm qhov ntswg thiab nasopharynx). Cov tshuaj no thaiv kev tsim cov polypeptides lub luag haujlwm rau kev txhim kho fibrotic hloov hauv daim siab thiab lub ntsws.
Side effects
Thaum kho nrog alpha thiab gamma interferons, mob khaub thuas zoo li feem ntau tau sau tseg tias muaj kev phiv. Nws suav nrog cov yam ntxwv xws li:
- nce lub cev kub;
- mob taub hau thiab mob leeg;
- tsis muaj zog.
Cov tsos mob no feem ntau tshwm sim thaum thawj lossis thib ob ntawm kev kho mob. Lawv tuaj yeem raug tshem tawm los ntawm kev txo qhov koob tshuaj.
Cov kev mob tshwm sim hauv qab no tsis tshua muaj:
- plab hnyuv;
- kev pw tsaug zog;
- thrombocytopenia;
- txo qis hauv qib ntawm leukocytes hauvntshav;
- thyroid hormone intoxication.
Thaum noj beta-interferons, cov xwm txheej tsis zoo hauv qab no kuj yuav tshwm sim:
- mob ntshav siab;
- tachycardia;
- arrhythmia;
- mob siab;
- lub plawv tsis ua hauj lwm;
- txo qis hauv kev txawj ntse;
- kev puas siab puas ntsws - kev nyuaj siab, kev xav tua tus kheej, kev xav tsis zoo, qaug dab peg.
