Nasal Sprays For Treating COVID-19: A Scientifc Note
Dec 04, 2023
Abstract
Kev tswj xyuas kev kho mob ntawm COVID-19 tau ua haujlwm txaus ntshai. Vim tsis muaj kev kho mob tshwj xeeb, cov tshuaj tiv thaiv tau suav tias yog thawj kab ntawm kev tiv thaiv. Innate teb thiab cell-mediated systemic tiv thaiv kab mob, suav nrog cov tshuaj tiv thaiv kab mob, yog lub hom phiaj tseem ceeb ntawm kev xyaum ua txhua yam kev tshawb fawb txog kev tiv thaiv kab mob tiv thaiv kab mob COVID-19. Txawm li cas los xij, vim muaj cov teeb meem uas tau ntsib los ntawm txoj kev pom zoo, lwm txoj hauv kev rau prophylaxis thiab kev kho mob tau dhau los ua qhov xav tau ntawm lub sijhawm. Thawj qhov chaw nkag los ntawm SARS-CoV-2 yog qhov ua pa sab sauv. Cov tshuaj tiv thaiv qhov ntswg twb nyob rau ntau theem ntawm txoj kev loj hlob. Sib nrug los ntawm cov hom phiaj prophylactic, mucosal tiv thaiv kab mob tuaj yeem siv rau kev kho mob ib yam nkaus. Txoj kev qhov ntswg rau kev xa tshuaj muaj ntau yam zoo dua li txoj kev pa. Dhau li ntawm kev muab koob-dawb xa khoom, lawv tuaj yeem tswj hwm tus kheej. Lawv nthuav tawm lub nra hnyav dua vim tias tsis tas yuav muaj tub yees. Cov kab lus tam sim no tsom mus rau ntau yam ntawm cov tshuaj tsuag qhov ntswg txhawm rau tshem tawm COVID-19.
cistanche tubulosa- txhim kho lub cev tiv thaiv kab mob
Ntsiab lus
SARS-CoV-2 · Immunity · Nasal route · Nasal vaccine · Nasal spray · Clinical trials · Devices
Taw qhia
Thaum Lub Kaum Ob Hlis 2019, cov xwm txheej mob ntsws uas tsis paub txog keeb kwm tau tshaj tawm hauv Wuhan, Tuam Tshoj, thiab tau txheeb pom tias yog tus mob ua pa nyuaj ua pa nyuaj rau tus mob coronavirus-2 (SARS CoV-2). Vim muaj kev sib kis ntawm SARS CoV-2 nrog rau ntau txhiab tus neeg tuag, Lub Koom Haum Saib Xyuas Kev Noj Qab Haus Huv Ntiaj Teb (WHO) tau tshaj tawm tias nws yog tus kabmob kis rau lub Peb Hlis 12, 2020. Tus kab mob uas SARS-CoV-2 tus kab mob ua rau yog npe hu ua tus mob coronavirus-2019 (COVID-19) [1, 2]. Txog rau lub Kaum Ob Hlis 2019, tag nrho ntawm 6 tus kab mob coronaviruses (CoV) tau raug txheeb xyuas kom kis tau rau tib neeg, ua rau muaj mob ua pa. The CoVs HCoV229E, HCoVOC43, HCoVNL63, and HKU1 feem ntau ua rau muaj mob me me nrog rau cov kab mob tseem ceeb hauv cov me nyuam mos, cov me nyuam yau, nrog cov neeg laus [3]. Txawm li cas los xij, SARS-CoV thiab Middle East Respiratory Syndrome coronavirus (MERS-CoV), kis tau rau hauv cov pa ua pa uas ua rau mob hnyav thiab ua rau muaj kev phom sij rau tib neeg. SARS-CoV thiab MERS-CoV yog paub tias tau kis los ntawm puav mus rau xibtes civets, dromedary ntxhuav, thiab tom qab ntawd mus rau tib neeg [4].
cistanche tubulosa- txhim kho lub cev tiv thaiv kab mob
Nyem qhov no mus saib Cistanche Enhance Immunity khoom
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Vim muaj kev hloov pauv sai thiab kev sib kis ntawm CoVs, cov tshuaj muaj thiab cov tshuaj tiv thaiv yuav tsum tau hloov kho tas li vim tias cov tshuaj tiv thaiv kab mob tsis zoo txo qis nrog txhua qhov hloov pauv tshiab. Cov kab mob RNA paub tias hloov pauv ntawm tus nqi siab dua piv rau cov kab mob DNA. Muaj cov ntawv ceeb toom tsis tu ncua ntawm ntau qhov kev hloov pauv hauv SARS CoV-2 spike (S) protein gene [5]. Qhov yooj yim uas SARS-CoV-2 tuaj yeem kis tau los ntawm ib tus tswv tsev mus rau lwm tus muab sijhawm ntxiv los hloov pauv. Kev paub txog kev pab cuam sib luag hauv kev nrhiav cov tshiab SARS-CoV-2 kev hloov pauv thiab kev hloov pauv uas tuaj yeem txuas nrog kev hloov kho hauv cov yam ntxwv ntawm tus kab mob. Raws li qhov xwm txheej tam sim no ntawm COVID-19, txoj hauv kev zoo tshaj plaws los tshem tawm tus kab mob yog tiv thaiv kev kis tus kab mob los ntawm kev tiv thaiv kab mob hauv zej zog los ntawm kev tswj hwm ntawm COVID-19 tshuaj tiv thaiv [6]. Txoj kev pib rau kev tsim tshuaj tiv thaiv nyob rau hauv COVID-19 theem kis thoob qhov txhia chaw tau tshwj xeeb ntawm qhov loj, qhov nrawm, thiab kev sib faib network piv rau cov tshuaj tiv thaiv ib txwm muaj [7]. Cov tshuaj tiv thaiv kab mob COVID-19 yog plaub pawg-tag nrho cov kab mob, tshuaj tiv thaiv kab mob protein, kab mob kis kab mob, thiab tshuaj tiv thaiv nucleic acid-based [8]. Txawm li cas los xij, ntau qhov tsis paub tseeb tseem muaj txog tam sim no, sai dua COVID{16}} kev tsim tshuaj tiv thaiv. Kev tsim cov tshuaj tiv thaiv COVID-19 tau nyuaj heev. Lub neej luv luv thiab qhov tshwj xeeb ntawm qhov chaw khaws cia kub kuj yog teeb meem nrog cov tshuaj tiv thaiv. Nws yog ib qho nyuaj rau ua raws li txwv tsis pub txias-chain system muaj peev xwm cia tshuaj tiv thaiv [9]. Yog li ntawd, cov cuab yeej siv tshuaj tiv thaiv ntxiv xws li koob thiab koob txhaj tshuaj tuaj yeem siv los txwv cov tshuaj tiv thaiv. Tus naj npawb ntawm cov koob tshuaj uas ib lub vial tuaj yeem muab tau yog nyob ntawm kev sib xyaw koob txhaj tshuaj-koob, kev txawj ntawm cov tshuaj tiv thaiv, thiab lwm yam. Kev tsis paub meej ntawm cov koob tshuaj tuaj yeem ua rau muaj kev sib tw hauv kev teem caij txhaj tshuaj tiv thaiv. Kev thov rau COVID-19 cov tshuaj tiv thaiv tau dhau los ntawm cov khoom siv, tab sis qhov kev thov hloov pauv tuaj yeem ua rau muaj kev puas tsuaj ntawm cov tshuaj tiv thaiv. Ntau qhov xwm txheej tuaj yeem raug suav hais tias qhov tshuaj tiv thaiv raug muab pov tseg raws li cov neeg sib tw tsawg dua li qhov kev cia siab tau hloov mus txais cov tshuaj tiv thaiv [8].
Kev tsis kam txhaj tshuaj tiv thaiv yog ib qho ntawm qhov cuam tshuam rau kev xav tau hloov pauv. Raws li kev tshawb fawb los ntawm Yigit li al., tshuaj tiv thaiv hesitancy tuaj yeem raug ntaus nqi rau ntau yam kev sib raug zoo, kev nom kev tswv, kev lag luam, kev ntseeg, thiab kab lis kev cai. Txoj kev tshawb no kuj tau qhia txog kev nyiam ntawm cov neeg koom nrog rau cov tshuaj tiv thaiv hauv tsev piv rau txawv teb chaws [10]. Raws li pom tseeb los ntawm cov ntaub ntawv, qee qhov laj thawj ntawm kev tsis kam txhaj tshuaj tiv thaiv yog qhov tsis ntseeg ntawm cov txiaj ntsig ntawm cov tshuaj tiv thaiv, qhov tshwm sim yav tom ntej uas tsis tau xav txog, kev xav rau kev tiv thaiv ntuj, thiab lwm yam. Tsis tas li, kev tsis txaus siab, kev txhaj tshuaj tiv thaiv qaug zog kuj yog ib qho laj thawj vim tias cov tshuaj tiv thaiv tau siv ntau yam tshuaj. Tus nqi txhaj tshuaj tiv thaiv yog lwm qhov teeb meem txwv qhov kev thov rau cov tshuaj tiv thaiv. Raws li kev soj ntsuam los ntawm Tagoe thiab cov kws tshawb fawb, COVID-19 phiaj xwm kev txhaj tshuaj tiv thaiv (vim cov nqi siab dua) raug txwv rau ntau txoj hauv kev rau cov teb chaws tau nyiaj nruab nrab qis [11]. Tsis muaj kev sib koom tes, kev sib txuas lus tsis zoo, thiab kev sib txuas hauv internet hauv kev faib thiab saib xyuas cov tshuaj tiv thaiv tuaj yeem ua rau muaj kev cuam tshuam rau kev saib xyuas tsis zoo ntawm cov kev pab cuam txhaj tshuaj. Raws li cov tshuaj tiv thaiv yuav tsum tau txhaj, cov neeg ua haujlwm tau txais kev cob qhia thiab, yog li ntawd, cov kws kho mob tsis txaus ntseeg tau yog lwm qhov cuam tshuam rau kev xa tshuaj tiv thaiv [12]. Kev txiav txim siab txog cov teeb meem nrog cov tshuaj tiv thaiv thiab qhov siab tshaj SARS-CoV-2 cov kab mob hauv lub qhov ncauj, qhov ntswg lossis qhov ncauj qhov ncauj muab ib qho kev cog lus rau kev txo qis kev kis tus kab mob [13]. Ntawm no, peb tshuaj xyuas kev siv tshuaj tsuag qhov ntswg tam sim no hauv kev ua lag luam uas tej zaum yuav muaj txiaj ntsig zoo hauv kev ua kom tsis muaj zog SARS-CoV-2.
cistanche tubulosa- txhim kho lub cev tiv thaiv kab mob
Nasal route rau kev tswj xyuas COVID-19
Lub qhov ntswg epithelium yog qhov chaw tseem ceeb ntawm SARS-CoV-2 tus kab mob, uas txuas ntxiv mus rau txoj kev ua pa uas kuaj pom muaj tus kab mob hnyav [14, 15]. Cov hlwb ntawm lub qhov ntswg ntawm olfactory neuroepithelium tsim muaj ntau ntawm angiotensin-hloov enzyme 2 (ACE2) protein, uas yog 200 mus rau 700 npaug ntau dua li lwm lub qhov ntswg [16]. Kev txhaj tshuaj tiv thaiv qhov ntswg yuav ua rau muaj kev tiv thaiv kab mob hauv cov kab mob mucosal nyob deb. Kev txhaj tshuaj tiv thaiv qhov ntswg tiv thaiv cov kab mob nkag mus rau hauv lub cev los ntawm kev tsim cov tshuaj tiv thaiv kab mob hauv cov ntaub so ntswg mucosal. Mucosal tiv thaiv kab mob ntawm qhov ntswg kab noj hniav yog induced ntawm nasal-associated lymphoid cov ntaub so ntswg [17], uas yog ib tug txheej txheem mucosal tiv thaiv kab mob, muaj xws li B thiab T lymphocytes thiab, antigen-presenting cells [18]. Ib txheej txheej epithelial uas muaj lub cim xeeb (M) hlwb, uas qhia tau hais tias lub luag haujlwm tseem ceeb hauv kev noj tshuaj antigen los ntawm mucosa, tiv thaiv kab mob mucosal. Qhov no pab txhawb kev nqus sai ntawm cov tshuaj tiv thaiv mus rau hauv cov hlab ntsha thiab txhim kho nws cov txiaj ntsig [19–21]. Hauv tib neeg theem I thiab II kev sim tshuaj, cov tshuaj txhaj tshuaj IgG1 isotype-neutralizing monoclonal antibodies tau pom tias tsis muaj kev nkag mus rau hauv cov ntaub so ntswg mucosal [22]. Antibody titers nyob rau hauv lub ntsws yog 200-500 lub sij hawm qis dua piv rau cov nyob rau hauv cov ntshav [23]. Kev txhaj tshuaj txhaj tshuaj ntau ntawm IgG1 isotype-neutralizing monoclonal antibodies kuj tseem tsis tau ua tiav cov tshuaj tiv thaiv kab mob zoo rau ntawm txoj hlab pa. Intravenous tswj ntawm cov tshuaj ua rau cov tshuaj concentration yog diluted nyob rau hauv lub plasma [24]. Rau kev kho cov kab mob mucosal viral, kev tswj hwm mucosal yog ib txoj hauv kev ua kom cov tshuaj infusion. Intranasal-administered antibodies feem ntau tsom rau cov kab mob ua pa, nrog rau kev mus ntev hauv lub qhov ntswg thiab lub ntsws [14, 25]. Thaum muaj cov kab mob sib kis tau zoo heev, cov kws kho mob koom nrog xws li kws muag tshuaj lossis kws saib xyuas neeg mob tuaj yeem txhaj tshuaj tiv thaiv kab mob loj yog tias cov kab mob kis tau zoo li txoj hauv kev nkag mus rau hauv lub cev raug xaiv raws li kev txhaj tshuaj tsis muaj koob. Cov tshuaj tiv thaiv nyob rau hauv daim ntawv ntawm cov kua thiab qhuav hmoov formulations muaj peev xwm muab tau los ntawm txoj kev intranasal. Cov formulations zoo li no tsis muaj teeb meem kev thauj mus los thiab khib nyiab thiab nyob ruaj khov yam tsis tas yuav tsum muaj txoj hlua txias. Ntau microvilli muaj nyob rau hauv lub qhov ntswg mucosal daim nyias nyias, ua rau thaj chaw saum npoo thiab cov ntshav txaus rau kev nqus, ua rau muaj kev tiv thaiv kab mob sai sai [26]. Kev ua raws li tus neeg mob zoo tuaj yeem ua tiav vim qhov yooj yim ntawm kev tswj hwm, tus nqi pheej yig, thiab yooj yim ntawm kev pov tseg. Nrog rau kev tswj hwm intranasal, qhov xav tau tshuaj concentration tuaj yeem ua tiav nyob rau hauv lub hauv nruab nrab paj hlwb ntawm lub ntxeem tau cribriform phaj, uas yog ib qho anatomically ntxeem tau pob txha tam sim no nyob rau hauv lub Upper nasal kab noj hniav. Tsis tas li ntawd, thaum cov tshuaj txhaj rau hauv cov kua cerebrospinal, arachnoid villi ntws mus rau hauv cov hlab ntsha hauv cov hlab ntsha txo qis cov concentration ntawm cov tshuaj. Yog li, kev siv tshuaj intranasal yog qhov muaj txiaj ntsig zoo hauv kev nthuav qhia neurological ntawm COVID-19. Ob peb lwm cov txiaj ntsig tau muab pub dawb los ntawm cov kev mob tshwm sim hauv lub cev, tsom cov tshuaj xa mus rau lub hauv paus paj hlwb, tsis muaj venous kua los yog dilution hauv cov ntshav li no txo cov koob tshuaj, xa hauv daim ntawv vaporized kom ncav cuag lub porous cribriform phaj, tswj kev ncaj ncees ntawm cov ntshav. - lub hlwb barrier [27].
Lub luag haujlwm ntawm secretory IgA thiab IgG rau kom tsis muaj menyuam ua pa
Qhov tshwm sim thawj zaug hauv cov kab mob ntawm cov kab mob ua pa ua pa yog tshwm sim los ntawm kev nce hauv cov kab mob IgA1 protease, uas cuam tshuam rau lub qhov ntswg mucosal tiv thaiv kab mob hauv ib cheeb tsam. [28, 29] ib. Thaum pib, cov tshuaj tiv thaiv polymeric IgA hauv zos tau tso tawm, uas thaiv cov kab mob sib txuas rau lub qhov ntswg epithelial receptors [21]. Ib txhij, cov antigen-loaded dendritic cells (DC) dhau los ua neeg laus thiab tsiv mus rau follicular B cell thiab interfollicular T cell. Ntawm no, lawv nthuav tawm cov hlwb tsis zoo nyob ze rau cov antigens, ua rau qhov pib ntawm kev tiv thaiv kab mob ntawm tes [22]. Activated T cells thiab B lymphoblasts txav mus los ntawm cov hlab ntsha thiab pab txhawb kev tiv thaiv kab mob tom qab tau txais los ntawm antigens. Tsis tas li ntawd, cov tshuaj tiv thaiv kab mob hauv lub cev, uas txuas cov chaw inductive mucosal nrog cov chaw efector, tshaj tawm cov kab mob hauv lub cev [30]. Hauv ib txoj kev tshawb fawb, IgG cov tshuaj tiv thaiv tau zoo dua li cov ntshav plasma IgA ob zaug tiv thaiv SARS-CoV-2 spike protein. Txawm li cas los xij, raws li hom tshuaj tiv thaiv zoo tshaj plaws hauv nasopharynx, IgA dimers tau 15 npaug zoo dua rau tib lub hom phiaj dua li IgA monomers. Yog li ntawd, dimeric IgA tej zaum yuav muaj txiaj ntsig tshwj xeeb rau kev txhaj tshuaj tiv thaiv zoo thiab tiv thaiv SARS-CoV-2 [31].
Cov kab mob kis kab mob ntawm cov hlwb epithelial hauv lub qhov ntswg pharynx pib ua kev cuam tshuam ntawm receptor-binding domain ntawm S protein thiab ACE-2 [32–35]. SARS-CoV-2 kis mus rau lwm lub hlwb epithelial uas qhia ACE-2, tshwj xeeb tshaj yog nyob rau hauv lub plab thiab lub ntsws. Cov ntaub so ntswg, uas yog categorized li nasopharynx, plab, thiab bronchial-associated lymphoid cov ntaub so ntswg, yog densely packed nrog lymphoid hlwb. Cov ntaub so ntswg lymphoid no tshwj xeeb yog tsom los ntawm cov tshuaj tiv thaiv uas nqus tau, uas tau pom tias muaj txiaj ntsig zoo hauv kev tua SARS-CoV-2 [36]. Ob qho tib si sab sauv thiab sab hauv ua pa ua rau pom plasma-derived IgG. IgG ua rau mob los ntawm inducing lub complement system, phagocytes xws li neutrophils thiab macrophages, thiab natural killer (NK) hlwb. Ib qho tseem ceeb ua haujlwm ntawm IgG nyob rau hauv cov hlab ntsws qis yog nws qhov tshwj xeeb ua tawm tsam cov kab mob lossis antigens. IgG2 yog qhov tshwj xeeb tshaj yog qhov chaw cia rau cov tshuaj tiv thaiv kab mob tiv thaiv ntau cov kab mob uas ua rau mob ntsws. Cov kev ua haujlwm tshwj xeeb lossis kev sib raug zoo ntawm IgG cov tshuaj tiv thaiv kab mob rau cov kab mob ua rau opsonization lossis txheej txheej ntawm cov kab mob ua raws li kev sib cuam tshuam nrog nws qhov sib ntxiv cascade. Cov no ua rau lysis, uas tuaj yeem tua cov kab mob ncaj qha lossis ua rau alveolar macrophage rau phagocytize thiab rhuav tshem nws hauv lub cell. Cov protein ntxiv C3b tuaj yeem ua haujlwm ua ib qho opsonin ntxiv uas txhim kho phagocyte adhesion rau ib daim nyias nyias receptor thiab, vim li ntawd, txhawb nqa cov tshuaj tiv thaiv kab mob. Qhov no opsonic antibody, uas yog engulfed los ntawm phagocyte ntawm ib co ntawm tes, muaj peev xwm ntxiv pab tua kab mob intracellularly. Opsonization ntawm cov kab mob tej zaum yuav tshwm sim los ntawm cov tshuaj tiv thaiv hu ua immune opsonin thiab los ntawm surfactant thiab fibronectin fragments hu ua non-immune opsonins [37–39]. Thaum piv rau qhov nqus ntawm cov kab mob uas tsis yog los yog tsis muaj coated, phagocytic uptake ntawm cov kab mob uas muaj peev xwm muaj IgG antibody tsho tiv no ntau dua hauv alveolar macrophages [40].
Nasal cycle thiab nasal disease
Lub qhov ntswg kab noj hniav yog thawj kab ntawm kev tiv thaiv kab mob ua pa thiab tseem yog tus neeg nruab nrab rau kev ua pa. Lub qhov ntswg qhov ntswg yog symmetrical thiab yog tsim los ntawm ob leeg pob txha thiab cartilaginous qhov chaw. Lub qhov ntswg valve, qhov tsawg tshaj plaws ntawm lub qhov ntswg raj, tswj qhov ntswg airflow kuj. Sympathetic innervation thiab lub suab nyob rau hauv venous sinusoids nquag tswj qhov dav ntawm qhov ntswg kab noj hniav. Lub voj voog ntawm qhov ntswg (NC) yog qhov tsis txaus ntseeg thiab tsis muaj qhov ntswg qhov ntswg uas tshwm sim thaum nruab hnub, nrog rau qhov ntswg qhov ntswg ntawm txhua sab tom qab los ntawm qhov ntswg qhov ntswg tsis sib haum. NC tuaj yeem pom tsuas yog hauv cov neeg mob uas muaj qhov sib txawv ntawm lub cev thiab lub rhinitis [41]. Lub venous cavernous cov ntaub so ntswg nyob rau hauv lub submucosa ntawm lub turbinate thiab septum dilates los yog constricts thaum lub sij hawm lub qhov ntswg voj voog. Cov cua ntws los ntawm ob qhov ntswg qhov ntswg feem ntau tsis sib xws thaum lub qhov ntswg kis tus kab mob thiab thaum twg lub cev nyob rau hauv lub supine posture thiab asymmetry yog accentuated [42]. Muaj plaub yam txawv ntawm NC qauv, classic (reciprocal congestion / decongestion alterations, tas li ntim tag nrho); parallel (congestion / decongestion tshwm sim hauv qhov ntswg kab noj hniav ib txhij); tsis xwm yeem (kev hloov pauv hauv qhov ntswg ntim yam tsis muaj tus qauv tshwj xeeb thiab qhov ntim qhov ntswg tas li); thiab acyclic (tag nrho qhov ntswg qhov ntswg hauv qhov ntswg tsis txawv) [43].
Mob qhov ntswg
Cov tsos mob ntawm qhov ntswg, nrog rau txham, pruritus, rhinorrhoea, thiab qhov ntswg congestion, raug xa mus rau rhinitis. Ntau hom kev ua xua rhinitis, kab mob rhinitis, thiab tsis ua xua, tsis kis kab mob rhinitis [44].
Kab mob rhinitis
Tus kab mob viral rhinitis yog ib qho kab mob ua pa sab saud thiab feem ntau tshwm sim los ntawm rhinoviruses, coronaviruses, adenoviruses, influenza, parainfluenza, kab mob ua pa syncytial, thiab enteroviruses. Cov kab mob no muaj peev xwm ua kom puas ntsoog junctions ntawm epithelial hlwb, rupture lawv cov khaubncaws sab nraud povtseg, nkag mus rau epithelial hlwb, thiab tswj cov metabolic kev ua si ntawm tus tswv tsev cell, siv nws rau lawv tus kheej txoj kev loj hlob thiab ua rau necrosis ntawm lub host cells [44]. Thaum ib tug neeg tau ntsib tus kab mob ua pa sab saud (URTI), qhov ntswg congested thiab spontaneous thiab reciprocal hloov nyob rau hauv lub qhov ntswg ua pa tsis ua hauj lwm yuav pom tseeb dua. Qhov unilateral qhov ntswg tsis kam nyob rau hauv cov neeg mob URTI yog qhov tseem ceeb tshaj li qhov tsis sib haum xeeb hauv cov neeg noj qab haus huv. Vim qhov nce siab tshaj plaws ntawm qhov ntswg qhov ntswg tsis kam, qhov ntswg qhov ntswg ua rau mob hnyav thiab feem ntau tag nrho unilaterally kaw [41].
Ua xua rhinitis
Allergens yog cov proteins pom nyob rau hauv cov huab cua xws li paj ntoos, mites, tso tawm ntawm kab, tsiaj dander, thiab pwm uas ua rau muaj kev tsis haum rhinitis. Ntau yam ntawm ib puag ncig ua xua tuaj yeem ua rau muaj kev tsis haum rhinitis uas yog tus cwj pwm los ntawm IgE-mediated, hom I hypersensitivity teb. Cov tsos mob ntawm tus kab mob rhinitis muaj xws li rhinorrhoea, qhov ntswg congestion, khawb qhov ntswg, thiab txham uas kav ntev tshaj li ib teev nyob rau ob los yog ntau tshaj hnub sib law liag. Asthma thiab conjunctivitis yog cov kab mob uas muaj feem xyuam nrog kev tsis haum rhinitis. Nws tau pom tias rhinitis cuam tshuam nrog NC qhia. Nasal mucosa o ua rau tsis kam mus rau vascular vasodilatation thiab li no nce siab hauv sinusoids ua rau qhov ntswg congestion. Qhov zaus ntawm kev hloov pauv hloov pauv hauv qhov ntswg qhov ntswg ua rau nce qhov ntswg qhov ntswg; kev tiv thaiv nce thaum tsis haum rhinitis [44].
Tsis-allergic rhinitis
Cov kab mob uas tsis yog-allergic rhinitis yog tshwm sim los ntawm kev poob ntawm cov kab mob endonasal thiab cov tsos mob ntawm cov kab mob ua xua. Ib qho mob ntawm qhov ntswg hauv ob sab hauv ua rau cov tsos mob xws li qhov ntswg txhaws, rhinorrhoea (tom qab los yog sab hauv), txham, los yog qhov ntswg khaus hu ua mob rhinitis. Cov neeg mob uas tsis ua xua rhinitis tuaj yeem raug cais raws li kev siv tshuaj yeeb, tshuaj hormone-induced, senile lossis geriatric, gustatory, occupational, idiopathic, thiab atrophic rhinitis [44].
cistanche tsob nroj-nce kev tiv thaiv kab mob
Tshuaj tsuag qhov ntswg rau txhaj tshuaj tiv thaiv COVID-19
Nyob nruab nrab ntawm COVID-19 kev sib kis, ntau cov tshuaj tiv thaiv kab mob hauv lub cev tau tsim, pom zoo, thiab tau muab tso tawm. Txawm li cas los xij, cov tshuaj tiv thaiv ib txwm raug kev txom nyem los ntawm qhov tsis zoo nrog rau kev cia khoom nyuaj thiab tsis kam txais txoj kev txhaj tshuaj koob. Lub qhov ntswg yog qhov chaw pib ntawm tus kab mob rau kev rov ua dua thiab sib kis, cov tshuaj tiv thaiv qhov ntswg tuaj yeem pom tau tias yog lwm txoj hauv kev zoo rau kev tiv thaiv kab mob. Piv nrog rau cov kev coj noj coj ua, txoj hauv kev ntawm qhov ntswg ntawm kev tswj hwm tuaj yeem ua rau ob qho tib si tshuaj thiab lub cev tiv thaiv kab mob [45]. Tsis tas li ntawd, kev txhawb nqa ncaj qha rau hauv lub qhov ntswg yuav txo tau tus kab mob kis mus rau lwm tus neeg. Cov tshuaj tiv thaiv qhov ntswg tej zaum yuav xav tias yog qhov kev xaiv pheej yig dua hauv cov teb chaws tsim kho [46].
Teeb meem rau kev tsim tshuaj tiv thaiv qhov ntswg
Cov tshuaj tiv thaiv qhov ntswg yuav tsum muaj cov tshuaj tiv thaiv kab mob txhawm rau txhawm rau txhawm rau kho lub cev tiv thaiv kab mob thiab cov tshuaj tiv thaiv kab mob, uas tuaj yeem ua rau lub cev tsis muaj zog. Tsis tas li ntawd, ib qho khoom siv rau kev xa tawm cov ntsiab lus zoo yuav xav tau. Txhawm rau txhawm rau txhaj tshuaj tiv thaiv los ntawm txheej mucosal, cov tshuaj tiv thaiv qhov ntswg yuav tsum tau kov yeej lub qhov ntswg barrier, piv txwv li, nplaum mucosa thiab cilia. Mucociliary clearance ua rau txo qhov nqus ntawm cov tshuaj tiv thaiv. Cov tshuaj tiv thaiv muaj feem ntau yuav ua rau cov tshuaj tiv thaiv Th17 thaum muab intranasally, uas tuaj yeem cuam tshuam kev tshem tawm ntawm SARS-CoV-2 ntawm lub ntsws [45]. Lwm qhov teeb meem yog qhov yuav tsum tau muaj cov cuab yeej xa khoom tshwj xeeb, uas tuaj yeem ua rau lub luag haujlwm nyiaj txiag hauv kev tsim cov tshuaj tiv thaiv [47]. Tsis tas li ntawd, cov ntsiab lus ntawm cov tshuaj tiv thaiv yuav tsum sib haum nrog ntau yam excipients siv nyob rau hauv cov tshuaj tiv thaiv intranasal [48]. Yuav kom txhaj tshuaj tiv thaiv qhov ntswg kom ua tiav, nws yuav tsum muaj peev xwm daws cov teeb meem saum toj no.
Excipients thiab shipping systems
Cov tshuaj tiv thaiv muaj ntau yam tshuaj xws li stabilizers, cryoprotectants, tshuaj tua kab mob, thiab lwm yam, uas ntxiv rau kev tiv thaiv kab mob thiab kev ua tau zoo ntawm cov tshuaj tiv thaiv. Tsis ntev los no, nanocarriers kuj tau muab tso ua ke nyob ntawm seb hom formulation. Raws li kev ruaj ntseg ntawm cov tshuaj tiv thaiv qhov ntswg muaj kev txhawj xeeb, qhov kub thiab txias thiab pH yog qhov tseem ceeb. Stabilizers pab txhim kho cov tshuaj tiv thaiv qhov ntsuas kub. Cov tshuaj tiv thaiv qhov ntswg stabilizers yog arginine, hydrolyzed porcine gelatin, monosodium glutamate, gelatin, sucrose, sorbitol, L-alanine, thiab tricine [49]. Qee qhov feem ntau ua hauj lwm mucosal adjuvants txhawb kev txhaj tshuaj mucosal, tshwj xeeb tshaj yog ntawm txoj kev intranasal, xws li kub-labile enterotoxin, a-galactosyl ceramide (aGalCer) chitosan, thiab cholera toxin. Kev hu xov tooj zoo li receptor agonists tau kawm raws li mucosal adjuvants suav nrog monophosphoryl lipid A, macrophage-activating lipopeptide, thiab cytosine-phosphate-guanine [50].
Cov tshuaj tiv thaiv qhov ntswg
Lactobacillus, ib qho probiotic feem ntau siv hauv yogurt fermentation, tau siv los ua hom tshuaj tiv thaiv kab mob rau cov tshuaj tiv thaiv qhov ntswg. Txoj kev no ua rau lub cev tiv thaiv kab mob hauv zos txo qis kev nkag mus thiab rov ua dua tshiab [51]. Ob peb cov tshuaj tiv thaiv qhov ntswg tau sau tseg hauv Table 1 [52].
Tshuaj tsuag qhov ntswg rau kev kho COVID-19
Txawm hais tias muaj kev txhaj tshuaj tiv thaiv ntau ntxiv thoob plaws ntiaj teb, kev kis tus kab mob tsis zoo li tau qeeb raws li qhov xav tau. Txawm tias tom qab txhaj tshuaj tiv thaiv kab mob parenteral, lub qhov ntswg zoo li txuas ntxiv mus ua qhov chaw kis tus kab mob. Tsis tas li ntawd, kev hloov pauv ntawm tus kab mob siab ua rau kev tiv thaiv kev nyuaj. Nrog rau kev tiv thaiv kab mob, kev kho mob tseem ceeb sib npaug uas txwv tsis pub [53]. Cov tshuaj tua kab mob xws li hydroxychloroquine, remdesivir, lopinavir, thiab cov tshuaj txhawb nqa xws li corticosteroids, thiab ascorbic acid tam sim no tau siv. Cov tshuaj no yog siv los ntawm qhov ncauj lossis hauv txoj hlab ntshav. Raws li qhov tseeb tias lub qhov ntswg yog thawj qhov chaw ntawm kev cuam tshuam los ntawm tus kab mob, kev tshawb nrhiav txoj hauv kev pulmonary rau kev xa tshuaj los tswj tus kab mob COVID-19 yog qhov kev xaiv zoo nkauj. Qhov chaw ntawm tus kab mob tseem ceeb (sab ua pa sab sauv thiab hauv nruab nrab pulmonary airways los ntawm kev sib cuag saum npoo los yog tso tawm ntawm cov dej nqus tau pa), kev txhim kho ntawm COVID-19, thiab cov kab mob ntsws ntawm cov hlab ntsws muaj kev cuam tshuam txog kev kho mob zoo dua rau kev kho mob. COVID-19 [54]. Raws li qhov zoo ntawm tus neeg xa khoom ncaj qha mus rau qhov chaw ntawm tus kab mob thawj zaug, kev tswj hwm qhov ntswg ntawm cov tshuaj tsis ntev los no tau txais kev saib xyuas ntau (Daim duab 1 thiab 2).
Tau ntau xyoo lawm, cov kws tshuaj, tshuaj lom neeg, nrog rau cov ntaub ntawv ntawm kev nyab xeeb rau nitric oxide (NO) siv rau tib neeg tau paub. TSIS yog cuam tshuam rau hauv lub cev tiv thaiv kab mob, kho qhov txhab, vasodilation, neurotransmission, thiab angiogenesis. TSIS tau raug saib tias yog ib tus neeg sib tw muaj peev xwm tiv thaiv SARS-CoV-2 raws li qhia hauv daim duab 3 [55], nrog ntau qhov kev tshawb fawb tau ua los txiav txim siab nws cov txiaj ntsig zoo li kev xaiv tshuaj tsuag qhov ntswg. Cov tshuaj nitric oxide qhov ntswg (NONS) tsim los ntawm SaNOtize tau pom los txo COVID-19 cov kab mob kis mus rau theem tseem ceeb hauv cov neeg mob [56, 57]. Feem ntau intriguingly, nws tau sau tseg tias TSIS txwv tsis pub SARS-CoV replication los ntawm ob hom kev sib txawv. TSIS TAU, los yog nws cov derivatives txo qis palmitoylation ntawm nascent qhia spike (S) protein, uas muaj kev cuam tshuam rau fusion ntawm S protein rau nws cognate receptor, ACE2. Qhov thib ob, nws txo cov kab mob RNA nyob rau hauv thawj theem ntawm tus kab mob replication, uas tuaj yeem yog vim muaj kev cuam tshuam rau ib lossis ob qho tib si ntawm cysteine proteases encoded hauv Orf1a ntawm SARS-CoV [58]. Cov nyhuv ntawm inhaled NO thiab pulmonary vasodilation yog yooj yim nyob rau hauv ib feem los ntawm elevated cellular cyclic guanidine monophosphate GMP (cGMP). Lub cGMP ua rau phosphorylation ntawm cov calcium raws li no, ua rau kom nce Ca{12}}. Qhov no ua rau vasodilation thiab nce oxygen uptake los ntawm lub ntsws [59]. Hauv tebchaws Askiv, SaNOtize, nrog rau Ashford thiab St Peter's Hospitals NHS Foundation Trust thiab Berkshire thiab Surrey Pathology Services, tau qhia tias, hauv tib neeg theem II kev sim tshuaj, SaNOtize cov tshuaj tsuag qhov ntswg yog ib qho tshuaj tiv thaiv kab mob, uas txo qis COVID{{15. }} kis, txo nws lub sijhawm nrog rau qhov mob hnyav. Hauv kev sib piv, ob qhov muag tsis pom kev, cov placebo-tswj theem II sim hauv 79 tus neeg mob tau lees paub COVID-19, SaNOtize txoj kev kho thaum ntxov tau txo qis SARS-Cov-2 titers [60]. Cov neeg mob uas tau txais kev kho mob nrog cov tshuaj tsuag qhov ntswg tau ntsib tus kab mob tag nrho txo qis ntawm 1.362 hauv thawj 24 teev, sib piv rau 95 feem pua. Cov kab mob kis tau poob ntau dua 99 feem pua hauv thawj 72 teev. Tsis muaj qhov tsis zoo tshwm sim hauv cov kev tshawb fawb sib txawv uas suav nrog 7000 tus neeg koom nrog tshawb xyuas cov tshuaj noj tus kheej. Cov tshuaj tsuag tuaj yeem txo qis kev kis kab mob - theem kev sib kis los ntawm tus neeg mob mus rau tus neeg tsis muaj kab mob - ntxiv rau kev xa cov tshuaj tiv thaiv kab mob hauv thawj theem ntawm kev kis kab mob nrog rau lwm tus, tseem yuav tau txhaj tshuaj [61].
cistanche cov txiaj ntsig rau txiv neej-ua kom muaj zog tiv thaiv kab mob
Hydroxypropyl methylcellulose nasal tsuag
Lwm tus neeg sib tw tshawb nrhiav rau kev tswj hwm raws li cov tshuaj tsuag qhov ntswg yog cellulose derivative-hydroxypropyl methylcellulose (HPMC), tseem hu ua hypromellose, uas tsim cov mucoadhesive gel. Raws li HPMC tau raws qhov ntswg mucosa, nws nqus cov kua dej thiab tsim cov gel me me, txheej ntawm lub qhov ntswg, yog li thaiv cov kab mob los ntawm kev cuam tshuam nrog receptors lub luag haujlwm rau kev nkag mus rau hauv cov hlwb. Hauv kev koom tes nrog Israeli Ministry of Health thiab Sheba Medical Center ntawm Tel Hashomer Tsev Kho Mob, Nasus Pharma tau qhia tias lawv cov tshuaj tua kab mob Tafx (muaj HPMC) cuam tshuam tag nrho kev sib kis ntawm ob SARS-CoV-2 alpha thiab beta variants [62]. Tafx kuj tsim ib lub zos acidic (pH 3.5) microenvironment mus rau qhov chaw mucosal uas tseem nyob ruaj khov mus txog 5 h, yog li ua pov thawj tsis zoo rau tus kab mob ciaj sia, nrog me ntsis kev phiv rau tus tswv tsev. Cov kev sim tshuaj ntsuam xyuas yuav muaj txiaj ntsig zoo hauv kev txheeb xyuas cov hom phiaj tseeb dua thiab cov txheej txheem los txhawb kev ua raws. Muab Tafx qhov kev nyab xeeb zoo tshaj plaws thiab muaj txiaj ntsig zoo hauv kev tiv thaiv kev kis kab mob raws li lub npe hu ua qhov muaj feem pheej hmoo kis mob tshwm sim-nws tshwm sim, tias txheej txheej tiv thaiv ntxiv no tuaj yeem ua lub luag haujlwm txo qis kev pheej hmoo kis mob. Raws li cov chaw tsim khoom, 83 cov neeg pe hawm tau siv cov tshuaj tsuag ua ntej thov Vajtswv thiab tom qab 2 lub lis piam tom ntej. Nws tau pom tias tsuas yog ob tus kis tus kab mob no hauv kev ntsuas qhov tseeb ntawm cov tshuaj. Raws li kev tshawb fawb cov kev tshawb fawb, cov neeg uas tau cog lus nws tsis siv tshuaj tsuag raws li qhia los yog tsis siv tshuaj tsuag. Tsis tas li ntawd, nyob rau lub Plaub Hlis 2022, txoj kev tshawb fawb txhawb nqa los ntawm Chulalongkorn University tau sim HPMC-based tshuaj tsuag qhov ntswg uas suav nrog tib neeg IgG1 anti-SARS-CoV-2 antibody cocktail hauv cov neeg ua haujlwm noj qab haus huv. Ib theem 1 ob-dig muag randomized soj ntsuam kev sim tau ua tiav nrog cov ntaub ntawv muaj kev nyab xeeb zoo tau muab [63].
Table 1 Cov tshuaj tiv thaiv qhov ntswg rau COVID-19 kev tswj hwm
Fig. 1 Antibody-induced disease enhancement in macrophage-tropic viruses: non-neutralizing or sub-neutralizing antibodies enhance viral infection of monocytes or macrophages through Fc RIIa driven endocytosis, augmenting the disease (Daim duab tsim nrog biorender.com)
Fig. 2 Antibody-induced kab mob txhim kho nyob rau hauv cov kab mob ua pa-immune complexes yog tsim los ntawm non-neutralizing antibodies thiab viral antigens nyob rau hauv cov ntaub so ntswg ua pa, ua rau cov xwm txheej xws li-secretion ntawm pro-inflammatory cytokines, recruitment ntawm lub cev tiv thaiv kab mob, thiab ua kom lub cev muaj zog. lub complement cascade nyob rau hauv lub ntsws cov ntaub so ntswg. Qhov tshwm sim o tuaj yeem ua rau muaj kev cuam tshuam ntawm txoj hlab pa thiab mob ua pa nyuaj rau cov neeg mob hnyav. (Daim duab tsim nrog biorender.com)
Fig. 3 Lub luag haujlwm Physiological ntawm nitric oxide. Kev sib txawv ntawm nitric oxide tej zaum yuav muaj qhov tseem ceeb hauv kev tswj hwm ntawm SARS CoV-2 (Daim duab tsim siv biorender.com)
Polysaccharides-based nasal spray
Nws tau raug pom tias complex structural sulfated polysaccharides, uas tam sim no nyob rau hauv loj npaum li cas nyob rau hauv ntau hom ntawm marine algae, yuav tiv thaiv tau replication ntawm enveloped kab mob. Cov tshuaj los ntawm cov algae liab zoo li phycocolloid carrageenan nrog rau sulfated polysaccharides tau los ntawm cov xim av thiab ntsuab algae tau pom tias muaj peev xwm tiv thaiv kab mob SARS-COV-2 [64]. Iota-carrageenan-based nasal spray tuaj yeem tiv thaiv SARS-CoV-2 hauv vitro ntawm qib qis li 6 ug / ml, raws li Bansal li al. [65]. Grover et al. tsim cov tshuaj tsuag qhov ntswg uas muaj gellan thiab λ-carrageenan. Thaum kuaj xyuas ob qho tib si prophylaxis thiab kev tiv thaiv kev sib kis, cov tshuab tshuaj tsuag tau pom tias muaj peev xwm tiv thaiv kab mob uas tiv thaiv tus kab mob tag nrho [66]. Marino Med Biotech engineered iota carrageenan cov tshuaj tsuag qhov ntswg los tiv thaiv tus kabmob coronavirus{11}}. Nws tau raug qhia kom inactivate tshiab, sai heev variants. Kev sim hauv vitro tau pom tias qhov sib xyaw ua ke tau ua tiav hauv kev sib ntaus sib tua SARS-CoV-2 hom tsiaj qus thiab peb hom kab txawv uas tau txheeb xyuas raws li British, South African, thiab Brazilian ntau yam. Carragelose, ib tug sulfated polymer muab tau los ntawm liab seaweed, lub tuam txhab nrhiav tsis ntev los no ua los tsim ib txheej ntawm cov mucosa uas coats invading kab mob, ua rau lawv inactive [67]. Qhov ntswg xa cov tshuaj tiv thaiv Mucosal antibodies IgM thiab IgA ua thawj kab ntawm kev tiv thaiv kab mob uas cuam tshuam rau cov mucous membranes. Tsis tas li ntawd, IgM thiab IgA1 tuaj yeem nqus tau thiab nqus tau mus rau hauv cov ntaub so ntswg. Koj et al. engineered rau IgM tshuaj tiv thaiv raws li CR3022 monoclonal antibody thiab tsib IgG1 monoclonal antibodies los tawm tsam qhov kev tawm tsam uas immunoglobulin G (IgG)-raws li kev kho mob. Cov kev tshawb fawb zoo ntawm IgM CoV2-14 (IgM-14) tau sau tseg tias IgM-14 ua tau zoo dua IgG-14 nyob rau hauv cov nqe lus ntawm kev khi, nruab nrab, thiab ACE2 thaiv. Hauv vivo, kev tshawb fawb biodistribution tau pom tias IgM-14 tau tso rau hauv qhov ntswg ntau tshaj 4 hnub tom qab ib koob tshuaj intranasal. Cov txiaj ntsig tseem pom tau tias qhov kev tswj hwm qhov ntswg ntawm IgM-14 muab lub sijhawm nyob ntev thiab feem ntau tsom rau cov kab mob ua pa, yog li txo qis cov kab mob kis tau zoo [14]. IGM Biosciences tsim kho IgM cov tshuaj tiv thaiv kab mob, tau ua theem 1 tib neeg kev sim tshuaj hauv Asmeskas thiab South Africa nrog ib lossis ob koob tshuaj tiv thaiv nrog kev nyab xeeb profles qhia. [68]. Tiziana Life Sciences plc, lub tuam txhab biotech nyob hauv UK, tau ua tiav qhov kev sim tshuaj ntsuam xyuas (Phase 1) ntawm Foralumab (qhov ntswg los tiv thaiv CD3 tib neeg monoclonal antibody), hauv cov tsos mob me me-rau-mob rau COVID-19 cov neeg mob hauv Brazil . Vim nws lub peev xwm los muab kev tiv thaiv kab mob los ntawm kev ua pa los yog plab hnyuv epithelium, Foralumab yog cov pioneer monoclonal antibody uas tuaj yeem siv los ntawm qhov ntswg lossis qhov ncauj. Kev nyab xeeb ntawm qhov ntswg formulation yog tsim nyob rau hauv ib txoj kev tshawb no ua nyob rau hauv ib tug sib koom venture nrog cov kws tshawb fawb los ntawm Harvard Medical School thiab nyob rau hauv kev sim [69].
Neurimmune, tus kws tshaj lij tshuaj tiv thaiv Swiss, thiab Ethris, German RNA biotech, tau tsim cov tshuaj nqus pa RNA (mRNA) cov tshuaj tiv thaiv uas tuaj yeem tiv thaiv kev ua pa hnyav heev ntawm COVID-19 [70]. Neurimmune AG tab tom kawm txog cov txheej txheem immunoglobulin ntawm cov neeg mob COVID-19 zoo, thaum Ethris tsom mus rau kev siv riam phom kho mob ntsws tshiab los muab tib yam. Lub pulmonary SNIM®RNA thev naus laus zis tsim los ntawm Ethris yuav pab tswj hwm mRNA-encoded, neutralizing anti-SARS-CoV-2 cov tshuaj tiv thaiv ncaj qha rau hauv cov neeg mob lub ntsws, yog li muab kev ua tiav sai ntawm kev xav tau pulmonary antibody titers. Kev sib koom tes yuav ua kom muaj kev nce qib ntawm cov tshuaj tshiab no kom ua tiav kev tiv thaiv kev sib kis. Cov tshuaj mRNA yuav raug txhaj ncaj qha mus rau hauv lub ntsws ntawm cov neeg mob cov tsos mob uas siv nanoparticle aerosols tswj los ntawm nebulizers ua rau lub ntsws tso tawm cov tshuaj tiv thaiv hauv zos uas tsis zoo rau SARS-CoV-2 [71].
Qhov ntswg tshuaj muaj glucocorticoid
Glucocorticoid, ciclesonide yog siv rau kev saib xyuas mob hawb pob hauv cov neeg laus nrog rau cov menyuam yaus hnub nyoog qis dua 12 xyoos nyob rau hauv lub npe Alvesco (Covis Pharma, Luxembourg) hauv daim ntawv ntawm kev siv tshuaj tua kab mob siab (80 mus rau 320 g ciclesonide / actuation). Raws li Matsuyama li al., ciclesonide tuaj yeem tiv thaiv SARS-CoV-2 genomic RNA replication los ntawm suppressing tus kab mob endonuclease NSP15 [72]. Raws li Iwabuchi li al., ciclesonide inhalation tau ua tiav hauv kev kho peb kis ntawm COVID-19 mob ntsws. USFDA tsis ntev los no tau lees txais Kev Tshawb Fawb Cov Tshuaj Tshiab rau kev ua haujlwm theem 3 kev sim tshuaj ntsuam xyuas Alvesco (ciclesonide) rau kev kho mob uas tsis yog tsev kho mob, cov tsos mob ntawm tus mob COVID{10}} (12 xyoo thiab laus dua) [73]. Cov kev sim zoo sib xws uas cuam tshuam nrog ciclesonide tau ua rau kev kho mob ntawm COVID-19 hauv ntau lub tebchaws suav nrog Sweden, Kaus Lim Qab Teb, Australia, UK, Asmeskas, thiab Nyij Pooj [74]. Hauv ntau qhov chaw, randomized, ob-dig muag, kev sim tshuaj placebo suav nrog 400 tus neeg mob, nws tau pom tias cov neeg koom nrog uas tau txais ciclesonide pom tsawg dua tom qab lub chaw saib xyuas xwm txheej kub ntxhov los yog mus pw hauv tsev kho mob rau COVID-19- mob ntsig txog [75].
Ivermectin tshuaj tsuag qhov ntswg
Ivermectin (macrolide lactone) tau siv rau cov kab mob tropical xws li helminthiases thiab kab mob kab mob. Kev sim, cov tshuaj kuj tau pom cov tshuaj tiv thaiv kab mob, tiv thaiv kab mob, thiab tshuaj tua kab mob. Caly et al. qhia tau hais tias kev ua haujlwm siab ntawm Ivermectin nyob rau hauv thaj tsam ntawm 2.5–5 M inhibits SARS-CoV-2 multiplication in vitro [76]. Ivermectin inhibits in vitro replication ntawm SARS-CoV-2 thiab qhia tau tias muaj 5000-fold txo qis hauv SARS-CoV-2 viral RNA hauv 2 hnub. Nws kuj tseem docks hauv cheeb tsam ntawm Leucine 91 ntawm qhov dav dav thiab Histidine 378 ntawm SARS-Co2-ACE2 complex, cuam tshuam kev khi rau tib neeg cell membrane [77]. Tsis tas li ntawd, cov ntaub ntawv los ntawm kev sim tshuaj ntsuam randomized ntawm nws cov tshuaj tiv thaiv kab mob hauv SARS-CoV-2-cov tib neeg kis tau tam sim no muaj. Xws li, hauv kev tshawb fawb los ntawm Erreclade li al., nws tau sau tseg tias Ivermectin nyob rau hauv cov ntsiab lus siab tuaj yeem cuam tshuam SARS-CoV-2 replication. Nws tau tshaj tawm tias thaum noj tshuaj hauv qhov ntswg, Ivermectin tuaj yeem ua tiav cov ntsiab lus siab hauv nasopharyngeal cov ntaub so ntswg [78]. Hauv cov qauv npua, cov tshuaj tsuag tau raug pov thawj tias muaj kev nyab xeeb zoo li kev zam zoo, tsis muaj qhov cuam tshuam loj heev [79].
Astodrimer sodium 1% tshuaj tsuag qhov ntswg
Astodrimer sodium, ib tug heev branched dendrimer nthuav tawm cov tshuaj tiv thaiv kab mob ntau ntxiv nrog rau kev ua yeeb yam hauv vitro tiv thaiv ntau hom kab mob SARS-CoV-2. Astodrimer sodium nasal spray tau tshaj tawm los inhibit lossis txo qis SARS-CoV-2 replication thiab nws qhov tshwm sim hauv K18-hACE2 nas los ntawm Paul li al. [56].
Mometasone Furoate tshuaj tsuag qhov ntswg
Ib qho ntawm COVID-19 feem ntau tshwm sim thiab cov tsos mob thaum ntxov yog olfactory impairment [80]. Mometasone Furoate nasal spray tau kawm txog 80 tus neeg mob uas muaj microsomia loj lossis anosmia los ntawm Kasiri li al. los txiav txim seb nws pab tau cov neeg mob tau zoo npaum li cas hauv kev rov zoo los ntawm microsomia loj lossis anosmia spurred los ntawm COVID-19 [81]. Cov txiaj ntsig tau pom tias mob anosmia mob hnyav raws li ntsuas los ntawm COVID-19 tau txhim kho sai dua thaum Mometasone Furoate cov tshuaj tsuag qhov ntswg ua ke nrog kev cob qhia olfactory. Hauv lwm txoj kev tshawb fawb, nws tau pom tias qhov zaus ntawm anosmia raug txo los ntawm 22.9% thaum piv rau pawg tswj hwm [82].
Chlorpheniramine maleate tshuaj tsuag qhov ntswg
Chlorpheniramine yog ib qho tshuaj tiv thaiv kab mob muaj zog uas muaj kev nyab xeeb thiab muaj txiaj ntsig tiv thaiv kab mob khaub thuas sib txawv A / B. Raws li cov ntaub ntawv pov thawj, intranasal kev tswj hwm muaj txiaj ntsig zoo thiab tsis muaj kev phiv. Chlorpheniramine maleate tau tshawb xyuas rau nws cov khoom tiv thaiv kab mob hauv cov tshuaj tua kab mob los ntawm Xu et al. [83]. Cov kev ua ntawm tus kab mob virucidal ntawm tib yam tau raug tshuaj xyuas los ntawm kev siv SARS-CoV-2 cov kab mob kis (USA-WA1/2020 hom) hauv Vero 76 cov kab mob. Txoj kev tshawb fawb tau nthuav tawm tias cov tshuaj tsuag qhov ntswg tau nthuav tawm cov haujlwm muaj zog tiv thaiv kab mob SARS-CoV-2 [122]. Nyob rau hauv ib rooj plaub series muab los ntawm Torres li al. [84], nws tau pom tias cov neeg mob uas muaj tus kab mob qis mus rau nruab nrab-19 morbidity thiab tuag yuav muaj kev txhim kho ntau heev hauv lawv cov tsos mob thiab 50% nqis nqis hauv chav kho mob thaum siv Chlorpheniramine qhov ntswg tshuaj tsuag.
PH94B tshuaj tsuag qhov ntswg
PH94B yog ib qho hluavtaws tshawb nrhiav neurosteroid tsim los ntawm purines. VistaGen Therapeutics, Inc. hauv Teb Chaws Asmeskas tau kho cov tshuaj tua kab mob neuroactive. PH94B ua raws li qhov ntswg chemosensory receptors, yog li ua rau txoj hauv kev synaptic hauv nruab nrab lub paj hlwb uas txwv kev ntxhov siab ntsig txog kev sib raug zoo niaj hnub thiab lwm yam xwm txheej rov ua dua [85]. Hauv theem 2 thiab theem 3 kev sim tshuaj, qhov ua tau zoo ntawm PH94B qhov ntswg tsuag (8 g) hauv kev tswj hwm kev ntxhov siab hauv zej zog tau tsim. Raws li qhov no, VistaGen Therapeutics, Inc. tau pib ib theem 2 kev tshuaj xyuas ntawm PH94B qhov ntswg rau kev kho mob ntawm COVID-19-txoj kev ntxhov siab [86]. Cov tshuaj tsuag tau pom zoo yam tsis muaj kev phiv [87]. Nasal sprays for treatment of SARS-CoV-2 is succed in Table 2.
Table 2 Nasal sprays for treatment of SARS-CoV-2
Nasal platform rau kev tswj xyuas menyuam yaus COVID-19
Cov kab mob sib kis thiab kev kho mob nthuav tawm txog cov txiaj ntsig ntawm SARS-CoV-2 hauv cov neeg mob hauv cov menyuam yaus qhia txog cov teebmeem sib txawv piv rau cov neeg laus. Txawm hais tias COVID-19 zoo li cuam tshuam rau cov menyuam yaus tsis tshua muaj kev cuam tshuam me me tab sis tuaj yeem ua rau muaj teeb meem loj, uas tuaj yeem suav nrog pediatric inflammatory multisystem syndrome (PIMS-TS) [94]. Ib qho laj thawj rau qhov tsawg zaus ntawm cov menyuam yaus tuaj yeem muaj zog tiv thaiv kab mob vim muaj lwm yam kab mob coronavirus lossis lwm yam kab mob ua pa ua pa yav dhau los [95]. Tam sim no tsis muaj kev kho mob tshwj xeeb rau cov menyuam yaus. Txawm li cas los xij, ob qho tshuaj tiv thaiv tau raug tso cai siv thaum muaj xwm txheej ceev los ntawm US Food and Drug Administration. Tsis tas li ntawd, ob peb lwm cov tshuaj tiv thaiv yog nyob rau hauv kev ntsuam xyuas lossis theem-III kev sim tshuaj ntsuam xyuas [96]. Kev nkag mus rau hauv cov hlab ntsha tuaj yeem nyuaj vim muaj kev ntxhov siab los ntawm cov menyuam yaus [97]. Needleless xa tuaj yeem suav tias yog lwm txoj hauv kev zoo rau cov menyuam yaus. Txoj kev qhov ntswg tuaj yeem ua haujlwm rau kev tswj kab mob hauv cov menyuam yaus. Intranasal kev tswj hwm ntawm analgesics, anxiolytics, thiab anticonvulsants tau ua tiav hauv cov menyuam yaus. Tsis muaj ntau yam kev phiv tshuaj ntawm qhov ntswg tau tshaj tawm [98]. Raws li cov lus ceeb toom los ntawm National Institute of Allergy thiab Kab Mob Sib Kis, cov kws tshawb fawb tau tsim cov tshuaj tiv thaiv COVID{11}} rau cov me nyuam mos thiab cov menyuam yaus uas tsuas yog xav tau ib koob tshuaj xwb los ntawm tshuaj tsuag qhov ntswg.
Kev saib xyuas kev nyab xeeb thiab kev coj ncaj ncees
Txoj hauv kev ntawm qhov ntswg tuaj yeem muaj ntug sab saud ntawm txoj kev xa khoom ib txwm muaj, tab sis cov ntaub ntawv kho mob txaus yuav tsum tau sau rau kev siv cov tshuaj tsuag qhov ntswg. Tsim kom muaj kev ruaj ntseg profile txaus yuav tsum tau tsim kom paub txog cov txiaj ntsig zoo ntawm cov tshuaj tsuag qhov ntswg hauv cov pej xeem. Cov tswv yim tsim nyog yuav tsum tau muab coj los siv kom tau txais txiaj ntsig zoo dua. Nws yog ib qho tseem ceeb los txiav txim seb yuav ua li cas prophylactic los yog kho cov neeg ua hauj lwm thiab adjuvants cuam tshuam los cuam tshuam lub cev tiv thaiv kab mob [48]. Ib yam li cov tshuaj tiv thaiv ib txwm muaj, kev pheej hmoo ntawm kev txhaj tshuaj tiv thaiv kab mob txhim kho kuj muaj rau cov tshuaj tiv thaiv qhov ntswg. Cov ntaub ntawv soj ntsuam mus sij hawm ntev yog qhov tseem ceeb los xyuas kom meej tias qhov tshwm sim tsis tshua muaj tshwm sim lossis cov kev mob tshwm sim tuaj yeem kov yeej tom qab siv cov tshuaj tsuag qhov ntswg [99]. Rau cov khoom uas tau txais kev tso cai siv thaum muaj xwm txheej ceev, kev soj ntsuam nruj me ntsis yuav tsum tau kuaj xyuas cov xwm txheej tsis tshua muaj, yog tias muaj. Ib qho kev soj ntsuam xyuas kom zoo yuav tsum tau tsim los ntsuas qhov kev nyab xeeb ntawm cov khoom muaj ntawv tso cai thiab. Kev tsis paub thiab tsis ua raws li cov txheej txheem kev nyab xeeb tuaj yeem ua rau muaj kev pheej hmoo kis mob hauv chaw ua haujlwm. Kev tuav tsis raug lossis kev sib cuag ntawm lub qhov ntswg qhov ncauj qhov ntswg thiab tus neeg mob lub qhov ntswg kab noj hniav tuaj yeem ua rau muaj kab mob kis mus rau hauv qhov ntswg qhov ntswg, yog li cuam tshuam kev nyab xeeb [100]. Thaum muab kev kho qhov nqus nqus pa, raug tus neeg ua haujlwm kho mob rau tus neeg mob lub pa tawm aerosols yog ib qho kev txhawj xeeb loj [46]. Ntau yam excipients xws li absorption enhancers thiab preservatives yog siv nyob rau hauv qhov ntswg formulations. Txawm li cas los xij, qee qhov excipients tau paub tias muaj teeb meem rau lub qhov ntswg epithelium. Lawv tuaj yeem cuam tshuam rau kev ua haujlwm ciliary thiab mucociliary clearance. Yog li, cov ntaub ntawv kev nyab xeeb tsim nyog yuav tsum tau sau rau cov khoom siv ntxiv uas yuav tsum tau siv rau hauv kev tsim [101]. Cov kev sim tshuaj tsis tu ncua yuav tsis hais txog ntau yam teeb meem tseem ceeb, suav nrog kev cuam tshuam tsis zoo ntawm cov kev kho mob thiab kev cuam tshuam ntawm kev kis tus kab mob mus rau cov kws kho mob [102]. Cov menyuam yaus thiab cov niam uas muaj menyuam yuav tsum tau txais kev saib xyuas ntxiv thaum tsim kom muaj kev ruaj ntseg profile. Cov kev cai hu rau kev txhim kho cov qauv kev tiv thaiv kom raug siv rau cov menyuam yaus koom nrog kev sim tshuaj [103].
Kev ntsuas kev ua tau zoo ntawm cov tshuaj tiv thaiv qhov ntswg
Qhov kev ua tau zoo ntawm cov tshuaj tiv thaiv yog ntsuas nyob rau theem 3 ntawm kev sim tshuaj. Rau kev ntsuam xyuas kev ua tau zoo ntawm cov tshuaj tiv thaiv, cov ntshav los yog qhov ntswg yog sau los ntawm tus neeg mob tom qab 14-28 hnub ntawm kev tswj hwm. Kev xa tshuaj zoo rau hauv lub qhov ntswg yog nyob ntawm qhov koob tshuaj txaus siv rau lub qhov ntswg mucosa thiab nws lub peev xwm nyob twj ywm hauv zos rau qhov chaw ua haujlwm. Frank et al. tshawb xyuas cov kab mob virus ntawm cov tshuaj tsuag qhov ntswg siv povidone-iodine ua cov tshuaj nquag tawm tsam tus kab mob SARS-CoV-2. Nrog ntau npaum li tsawg li 1.25% concentration ntawm povidone-iodine, nws tau pom cov kab mob ua haujlwm tsis zoo hauv 15 s ntawm kev sib cuag. Cov tshuaj tsuag tsim muaj kev tiv thaiv kev tiv thaiv ntev txog 4 teev thaum tseem txo qis tus kab mob titers thiab nce kis kab mob [104, 105]. Txheeb xyuas qhov ua tau zoo ntawm adenovirus type 5 vectored txhaj tshuaj tiv thaiv kab mob SARS-CoV-2 hauv cov nas thiab tau tshaj tawm tias ib zaug tshuaj tsuag qhov ntswg muaj qhov tseem ceeb hauv lub cev thiab qhov chaw tiv thaiv kab mob. Cov lus teb tseem ceeb tau pom zoo rau tib lub sijhawm tso tawm cov tshuaj tiv thaiv kab mob ntshav qab zib, mucosal antibodies (IgA), nrog rau CD4+ thiab CD8+T hlwb. Sun et al. soj ntsuam kev tiv thaiv kab mob, kev nyab xeeb, thiab kev ua tau zoo ntawm tus kab mob Newcastle tus kab mob, tshuaj tiv thaiv kab mob vector-based tiv thaiv SARS-CoV-2 hauv cov nas thiab hamsters. Nws tau pom tias tom qab kev tswj hwm intranasal, qib siab ntawm anti-SARS-CoV-2 tshwj xeeb IgA thiab IgG2a cov tshuaj tiv thaiv nrog rau T cell-mediated tiv thaiv tau raug ntxias [106].
Hauv kev sim tshuaj me me, Lin thiab cov kws tshawb fawb tau tshawb xyuas qhov ua tau zoo ntawm 35B5- tshuaj tsuag qhov ntswg hauv kev tiv thaiv SARS-CoV-2 variants. Nws tau pom tias cov qauv ntawm qhov ntswg mucosa tau sau nyob rau hauv ib lub sij hawm ntawm 24 teev tom qab siv cov tshuaj tsuag qhov ntswg ua tiav neutralized SARS-CoV-2 variants (xws li Delta thiab Omicron). Thaum 48 thiab 72 teev tom qab tshuaj tsuag qhov ntswg, kev tiv thaiv zoo yog 60% thiab 20%, feem. Lawv txiav txim siab tias cov tshuaj tsuag qhov ntswg ntawm 35B5 formulation muab kev tiv thaiv zoo tshaj 24-teev los ntawm SARS-CoV-2 variations, xws li alpha, beta, delta, lossis omicron forms [107].
Kev sib piv ntawm qhov ntswg thiab vascular txhaj tshuaj
COVID-19 cov tshuaj tiv thaiv kab mob hauv lub cev tau ua pov thawj tias muaj peev xwm tsim tau cov tshuaj tiv thaiv kab mob tseem ceeb uas kho tau raws li kev tiv thaiv kab mob ntawm tes. Tsis tas li ntawd, lawv muaj peev xwm induce mucosal tiv thaiv kab mob. Los ntawm inducing lub secretion ntawm IgA antibody teb tshwj xeeb tshaj yog nyob rau hauv lub qhov ntswg kab noj hniav, lub intranasal SARS-CoV-2 tshuaj tiv thaiv tiv thaiv kab mob kis kab mob, reproduction, shedding raws li zoo raws li kis tau tus kab mob thiab kis tus kab mob. Muaj cov vascularity tseem ceeb hauv cov leeg, cov tshuaj tiv thaiv intramuscular tau nkag mus rau hauv cov hlab ntsha sai. Cov tshuaj tiv thaiv kab mob ua rau lub cev tiv thaiv kab mob. Txawm li cas los xij, cov tshuaj tiv thaiv rov ua dua thiab hloov pauv hauv cov ntaub so ntswg dhau ntawm qhov chaw txhaj tshuaj tuaj yeem ua rau muaj kev cuam tshuam tsis tshua muaj xws li autoimmune cov tshuaj tiv thaiv. Nws tau raug qhia tsis ntev los no tias kev tswj hwm cov tshuaj tiv thaiv los ntawm txoj kev intramuscular thiab kev faib tawm los ntawm cov kab mob hauv lub cev tuaj yeem ua rau platelets-adenoviral vector cuam tshuam, platelets conglomeration, thiab ua kom muaj zog. Cov tshuaj tiv thaiv intranasal tso cai rau cov koob tshuaj qis dua piv rau kev tswj hwm intramuscular. Cov tshuaj tiv thaiv intranasal yuav nyiam dua cov tshuaj tiv thaiv kab mob vascular, tshwj xeeb tshaj yog cov neeg hluas. Kev txhaj tshuaj Intranasal tuaj yeem tswj hwm tus kheej, yog li txo lub nra ntawm kev txhaj tshuaj. Tsis zoo li cov kab mob hauv cov hlab ntsha, lawv yuav tsis xav kom tsis muaj menyuam. Cov tshuaj tiv thaiv kab mob hauv lub cev tuaj yeem tsim los khaws cia hauv chav sov, uas tsis tuaj yeem ua rau cov tshuaj tiv thaiv kab mob vascular [108].
cistanche tubulosa- txhim kho lub cev tiv thaiv kab mob
Kev xa khoom tshuaj thiab kev tsim khoom siv
Txawm hais tias muaj txiaj ntsig zoo ntawm kev xa cov tshuaj intranasal, lub qhov ntswg tuaj yeem poob rau cov kev txwv xws li qis permeability rau qee yam tshuaj xws li hydrophilic molecules, peptides, proteins, thiab nucleotides, ceev mucociliary clearance, thiab biodegradation [109]. Kev xa tshuaj thiab kev txhim kho cov cuab yeej yog qhov tseem ceeb rau kev tsim cov tshuaj muaj txiaj ntsig thiab txhim khu kev qha intranasal. Peb tus yuam sij koom tes tswj kev xa cov tshuaj los ntawm txoj kev ntawm qhov ntswg uas yog: cov tshuaj, lub tsheb xa khoom, thiab cov cuab yeej tswj xyuas, piv txwv li, cov cuab yeej. Cov tshuaj uas tsis muaj molecular-hnyav (qis dua 300 Da) tuaj yeem yooj yim dhau los ntawm cov kab dej ntawm lub qhov ntswg thaum siv cov tshuaj hnyav molecular, tus nqi permeation yog qhov tseem ceeb, uas yog ntaus nqi rau cov tshuaj physiochemical. Nasal mucosa yog lipophilic, tso cai rau kom zoo dua permeation ntawm lipophilic tshuaj. Cov tshuaj hydrophilic tuaj yeem siv rau hauv daim ntawv ntawm prodrug [110]. Passive diffusion absorbs qhov ntswg qhov ntswg ua dej, cov tshuaj hydrophilic, thaum cov tshuaj lipophilic zoo li tau nqus los ntawm kev nqus dej. Chirality tuaj yeem cuam tshuam rau kev nqus cov tshuaj los ntawm qhov ntswg mucosa; Yog li ntawd, kev txiav txim siab yuav tsum tau muab thaum xaiv cov isomer [111]. Peptides thiab cov proteins tuaj yeem ua rau lub cev tsis zoo thaum hla cov txheej txheem epithelial, yog li nthuav tawm cov bioavailability tsawg. Enzymatic degradation tuaj yeem zam tau siv cov plhaub tiv thaiv zoo li micelles, thiab liposomes lossis siv cov enzyme inhibitors [112]. Viscous tus me nyuam lub tsheb prolongs lub sij hawm sib cuag ntawm cov tshuaj nrog qhov ntswg mucosa uas ua rau kom lub sij hawm permeation. pH ntawm formulation yuav tsum tau hloov ntawm 4.5 thiab 6.5, kom tsis txhob muaj qhov ntswg qhov ntswg. Tsis tas li ntawm acidic pH, lysozymes tau qhib, uas rhuav tshem cov kab mob [88]. Lub qhov ntswg absorption enhancer yuav tsum tau rau lub qhov ntswg tis ntawm hydrophilic los yog siab molecular hnyav tshuaj rau cov tshuaj kom dhau lub qhov ntswg daim nyias nyias nyob rau hauv ib tug npaum li cas txaus rau kev siv kho mob. CPE-215®, Intravail®, ChiSysTM, PecSysTM, thiab CriticalSorbTM yog cov piv txwv ntawm kev nqus tshuaj ntxiv thiab kev hloov pauv uas tam sim no tau tsim los ua lag luam rau ntau yam tshuaj los ntawm CPEX Pharma, Aegis Therapeutics, Archimedes Pharma Ltd., thiab Critical Pharmaceuticals Ltd, raws li [113]. Cov tswv yim tshiab los tsim kom muaj txiaj ntsig zoo ntawm qhov ntswg rau cov khoom xyaw tshwj xeeb yog tam sim no nyob rau hauv ntau theem ntawm kev tshawb fawb thiab kev loj hlob. Kev kho qhov ntswg tshiab kho cov thev naus laus zis, tsheb tsim los tiv thaiv cov tshuaj catabolism los ntawm mucosal enzymes, thiab kev hloov kho yog qee qhov ntawm cov no.
Khoom siv rau kev xa tshuaj
Ntau yam khoom siv muaj rau kev xa tshuaj qhov ntswg. Cov cuab yeej yuav tsum muaj peev xwm xa cov ntawv ntau npaum li cas vim tias cov qauv yuav xa tuaj tuaj yeem yog hmoov, kua, lossis hauv daim ntawv aerosol [114]. Kev xa cov tshuaj rau qhov ntswg ua haujlwm zoo tshaj plaws thaum cov khoom siv tshuaj tsuag, mucociliary clearance, deposition, dissolution, thiab nqus mus rau hauv tus account. Cov khoom siv rau kev xa tshuaj tuaj yeem cuam tshuam cov kev txwv no. Cov cuab yeej siv yuav tsum tsis muaj teeb meem los txwv cov kev ua tsis tau zoo, tab sis rau cov txiaj ntsig zoo li kev nqus dej ntau ntxiv, kev tso tawm kom zoo, thiab lwm yam, kev siv tshuab siab dhau los ua qhov tseem ceeb [112]. Cov cuab yeej siv lub qhov ntswg thiab lawv cov txheej txheem yuav tsum tau npaj ua ib txoj hauv kev uas tiv thaiv lub ntsws thiab qhov ntswg los ntawm ntau yam kev phom sij [115]. Qee cov khoom siv thiab lawv cov yam ntxwv tau piav qhia hauv Table 3.
Table 3 Cov khoom siv rau kev xa tshuaj
Lub neej yav tom ntej ntawm qhov ntswg xa cov ntsiab lus
Txog niaj hnub no, hmoov, tshuaj tsuag, tee, gels, thiab lwm yam kev tswj hwm rau hauv lub qhov ntswg tau tsim. Novel formulations muaj xws li mucoadhesive dlaws, microparticles, liposomes, qhov ntswg inserts, thermosensitive thiab pH-sensitive nasal gels, micelles, thiab lwm yam. Lub hom phiaj tseem ceeb ntawm lub qhov ntswg xa tshuaj yog los txhim kho qhov ntswg epithelial permeability thiab tiv tauj lub sij hawm ntawm qhov chaw nqus. Ntau cov tswv yim yog siv los txhim kho intranasal absorption, nrog rau kev hloov pauv rau cov mucus txheej, nruj junctions, thim rov qab micelle ntau lawm, extraction los ntawm co-micellization, thiab kev siv surfactants thiab enzyme inhibitors. Tsis ntev los no, bio adhesives tau dav siv los ua kom lub sijhawm sib cuag ntawm qhov chaw nqus. Kev ua tau zoo ntawm multilamellar micelles thiab liposomal micelle formulations kuj tau kawm. Nasal inserts yog tsim los ntawm lyophilization los yog gasification. Lawv tuaj yeem tso tawm cov khoom muaj txiaj ntsig hauv kev tswj hwm. Ntau yam khoom xa tuaj muaj nyob rau hauv kev tswj hwm intranasal. Metered dose inhalers, nebulizers, thiab lwm yam, muaj. Rau cov tshuaj thiab tshuaj tiv thaiv kab mob, lub tswv yim xa khoom tshwj xeeb tau muab los ntawm lub tuam txhab Norwegian. Txhawm rau tiv thaiv qhov tso tawm ntawm cov khoom me me hauv lub ntsws, lawv tau tsim ib qho khoom xa tuaj rau ob sab [121].
Lus xaus
COVID-19 tus kab mob kis thoob ntiaj teb tau cuam tshuam rau tib neeg hauv yuav luag txhua cheeb tsam hauv ntiaj teb. Cov koom haum tshawb fawb sib txawv thiab cov koom haum saib xyuas kev noj qab haus huv tau ua haujlwm ntawm kev tsim cov tshuaj tiv thaiv thiab kev kho mob tshwj xeeb tiv thaiv SARS-CoV-2. Txawm hais tias tam sim no muaj ntau yam tshuaj tiv thaiv tau pom zoo siv los tiv thaiv COVID-19, lawv raug kev txom nyem los ntawm kev tsis txaus siab xws li kev tsis kam txhaj tshuaj ntawm cov tib neeg, kev siv tshuaj ntau vim lawv lub sijhawm luv luv thiab tsis muaj kev faib khoom kom raug. Qhov yuav tsum tau ua kom qhuav qhuav ntawm cov tshuaj tiv thaiv ua rau muaj kev sib tw logistical. Ib zaug ntxiv, txoj hauv kev intramuscular, ua cov txheej txheem invasive, hesitancy tau sau tseg ntawm cov tib neeg. Tsis tas li ntawd, tsis muaj cov ntaub ntawv txaus txaus los tsim kev nyab xeeb ntawm cov poj niam cev xeeb tub thiab menyuam yaus. Raws li kev kho mob, tseem muaj qhov tsis muaj kev kho tshwj xeeb. Kev txhaj tshuaj tiv thaiv kab mob thiab kev kho mob los ntawm txoj kev parenteral thiab txoj kev ntawm qhov ncauj tuaj yeem ua rau muaj kev cuam tshuam hauv lub cev. Raws li qhov no, yog tias cov tshuaj tsuag qhov ntswg raug txiav txim siab, lawv tuaj yeem tiv thaiv tus kab mob ntawm qhov chaw nkag nws tus kheej, txo qis kev sib kis mus rau qhov tob. Kev tswj tsis tau koob yuav ua rau muaj kev tsis txaus siab ntawm cov menyuam yaus. Ntau cov tshuaj tiv thaiv qhov ntswg nrog rau cov tshuaj tsuag qhov ntswg rau kev kho mob yog nyob rau hauv kev sim tshuaj. Cov tshuaj tsuag qhov ntswg tuaj yeem pom tias yog ib qho kev cog lus rau kev tiv thaiv COVID-19. Kev cia siab rau yav tom ntej suav nrog kev koom ua ke hauv vivo cov ntaub ntawv nrog cov txiaj ntsig kho mob. Cov kauj ruam hauv qhov kev taw qhia no twb tau pib ua pov thawj los ntawm qhov tseeb tias muaj pes tsawg tus tshuaj tsuag qhov ntswg yog nyob rau hauv kev sim tshuaj thiab ob peb ntawm lawv tau txais kev tso cai siv thaum muaj xwm ceev. Ntau qhov kev pib ua tsis tu ncua yuav qhib qhov rooj rau lwm txoj hauv kev rau kev tiv thaiv thiab kev kho mob ntawm COVID-19. Kev txhaj tshuaj tiv thaiv parenteral nrog rau kev kho qhov ntswg tuaj yeem pab ua kom tiav lub hom phiaj ntawm kev tshem tawm tus kab mob.
Cov ntaub ntawv
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