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Cov khoom lag luam

### Kev Rov Ntsuam Xyuas Cov Txheej Txheem Kev Tshawb Fawb ntawm Ara -290 peptide

Ara -290 yog cov khoom siv tsis-erethropoietic deride raws li eryino acids thiab nrog molecular hnyav ntawm kwv yees li ntawm 1.3 kda. Nws yog tsim los ua kom muaj cov khoom siv ntawm tes tshwj xeeb (xws li Erythropoietin Receptorive, thaum tsis txhob muaj kev cuam tshuam ererthropoetic Hauv qab no yog cov lus piav qhia ntawm cov qauv, cov khoom siv dag zog, cov chaw thov thiab thaj chaw thov kom zoo.

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### 1. Cov qauv kev faib tawm thiab cov yam ntxwv molecular ntawm ara -290

### 1. ** Cov Qauv Txheej Txheem **

- ** Amino acid sequence **: Cov kab ke ntawm ara {1}}} yog **, uas yog ib qho kab luv theptide lossis cyclic qauv.

- ** QAUV MODEYISCATIVS **: UnglyCosylated, txawv ntawm ntuj EPO, ua rau nws muaj kev ruaj khov zoo dua thiab qis dua impunogenicity.

- ** Molecular hnyav **: Txog 1300 teev, yooj yim rau cov ntaub so ntswg nqaij (xws li cov ntshav-lub hlwb barrier).

#### 2. ** Receptor Binding Domain Dovagulation **

- ** Soj ntsuam cov khoom plig **: Kev khi tshwj xeeb rau EPO receptor thiab ib-receptor kos npe rau cov pathwacers (xws li Jak2 \/ stat3), tab sis tsis cuam tshuam rau Erythropoiesis.

- ** Cov qauv-kev sib raug zoo **: Sib cuam tshuam nrog cov recetors los ntawm cov amino acids thiab tyrosine), thiab tswj kev tiv thaiv kev tiv thaiv thiab kho cov haujlwm.

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### 2. Kev tsom xam ntawm lub cev thiab tshuaj lom neeg

#### 1. ** ** Cov teeb meem bysicochemical **

- **Solubility**: easily soluble in water (>10 mg \/ ml) thiab physiological tsis (xws li PBS), tsim nyog rau kev txhaj tshuaj tshuaj.

- ** STABLY **:

- ** Qhov kub thiab txias rhiab ": ruaj khov ntawm 4 degree, khov-qhuav hmoov tuaj yeem khaws cia ntev; Kev npaj ua kua yuav tsum yuav tsum muab tso rau hauv tub yees ntawm lub teeb (2-8 degree).

- ** PHEM PHEEJ PHEM **: Lub Phe Nyob Rau Phe 6-8, yooj yim rau kev thuam hauv cov kua qaub muaj zog acid \/ alkali ib puag ncig.

- ** QAUV THIAB MORPHOLOGIES **: Lub hmoov nplej qhuav yog dawb lossis tawv-dawb, thiab nws yog cov kua tsis muaj xim thiab pob tshab tom qab rov kho dua tshiab.

### 2. ** Cov yam ntxwv me me **

- ** Uv Kev nqus tau **: Qhov ntau tshaj nqus lub ncov yog li 280 nm (pab los ntawm tyrosine seem).

- ** Massures Spectrometry Kev Ntsuam xyuas **: Maldi-Toff Pawg Loj Pom tias yog ib qho ncov, lees paub kev coj dawb huv.

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### 3. Cov ntaub ntawv zoo thiab cov ntawv thov tshuaj kho mob

#### 1. ** Cov ntsiab lus zoo **

- ** Kev nyab xeeb ** Tsis yog Erythropoietic nyhuv, zam kev pheej hmoo ntawm thromomosis.

- ** HOM PHIAJ **: Xaiv cov ntaub so ntswg kho cov teebmeem thiab txo cov teebmeem kev cuam tshuam.

- ** QIB STURITATE **: Kev ntsuas hluavtaws muaj hluav taws xob yog tiv taus enzymatic hydrolysis, thiab ib nrab-lub neej (~ 4 teev) ntev dua li ntawm ntuj nti.

### 2. ** Kawm txog kab mob ntawm kab mob **

- ** Kab mob neurological **:

- ** Cov ntshav qab zib muaj teeb meem **: Txo qhov mob los ntawm kev cuam tshuam NF-κb txoj kev thiab txhawb kev sim ua 30%

- ** Kev raug mob txha caj qaum **: Ua kom muaj Mid3 txoj kev thiab txo kev caws pliav teeb meem.

- ** OB LETABOLIC Cov Kab Mob **:

- ** Diabetchollabe rwj **: nrawm angiogenesis, lub sijhawm kho kom luv los ntawm 40% hauv kev sim tshuaj.

- ** O ** o thiab cov kab mob autounmune **:

- ** Downumatoid mob caj dab ** Downregulate tnf- thiab il -6 kev qhia thiab ua rau mob pob txha.

- ** Lwm daim teb **:

- ** MYOCARDial ischemia-Reperfusion raug mob **: Txo cov oxidative kev nyuaj siab thiab tiv thaiv myocardial myocardial.

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### 4. DOSAGE daim ntawv thiab xa khoom

### 1. ** Cov ntaub ntawv uas twb muaj lawm os **

- ** Kev txhaj tshuaj **: feem ntau yog subcutaneous lossis kev txhaj tshuaj tiv thaiv, nrog cov xyoob ntoo, nrog cov xyoob ntoo muaj txiaj ntsig ntawm {1}}%.

- ** ** Cov ntsiab lus npaj tau **: Cov kua txiv lossis cov tshuaj pleev cov yeeb yaj kiab siv rau cov tawv nqaij mob rau cov tawv nqaij, nrog cov kev nqus cov nqi nqus ntawm li 15%.

#### 2. ** Kev xa tawm tshiab dua tshiab **

- ** Nanocarrier ** ** Liposome Encapsulation Txuas ntxiv lub neej ib nrab-lub neej rau {2}} teev.

- ** Kev tso tawm cov lus rub tawm **: Ploga tsom iav ua tiav kev tso nyiaj rau 7 hnub tom qab ib koob tshuaj.

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### 5. Kws muag tshuaj thiab tshuaj lom

### 1. ** Dynamics hauv vivo **

- ** Rho tawm **: TMAX yog li 1 teev tom qab txhaj tshuaj, thiab CMAX yog linearly ntsig txog koob.

- ** Kev faib tawm ** Dav faib tawm hauv cov nqaij thiab puas, nrog cerebrospinal kua dej ncav cuag 20% ntawm ntshav.

- ** Metabolism thiab ua kom zoo nkauj thiab lub raum yog lub ntsiab excretion txoj kev, tsis muaj kev sib txuam.

### 2. ** Cov ntaub ntawv nyab xeeb **

- **Acute toxicity**: LD50 >100 mg \/ kg (rat), tsis muaj kev puas tsuaj hauv nruab nrog cev tau pom.

- ** THAWJ HOM PHIAJ **: Tsis muaj tus kabmob tiv thaiv kab mob lossis hematogical kev txawv txav tom qab kev tswj hwm rov qab ua ntej rau 90 hnub.

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### 6. Kev ua lag luam cov zeem muag thiab R & D kev nce qib

#### 1. ** Qha duab patent **

- Cov Qej Patent npog cov kab sib chaws (US 8,618,081) thiab siv (EP 2,5056), thiab lub sijhawm tiv thaiv yog txog 2030.

### 2. ** Ntu kawm ntawv

- ** TEASE II ua tiav **: Cov Neuropathy ntshav qab zib (NCT022238), sarcoidosis (NCT01618344).

- ** PARVE III phiaj xwm **: Multicenter sib tsoo ntawm tus mob ntshav qab zib mob mob ntshav qab zib.

#### 3. ** Kev sib tw sib tw "

- ** VS. Opioids **: Tsis muaj kev tiv thaiv, zoo dua kev nyab xeeb kom ntev.

- ** VS. Kev faib tshuaj lom neeg kab mob (xws li anti-tnf-) **: Tus nqi qis (kwv yees kev kho mob ib xyoos ib zaug<$5k), suitable for a wide range of populations.

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### 7. Cov lus qhia sib tw thiab yav tom ntej

### 1. ** Teeb meem uas twb muaj lawm **

- ** QIB QHOV MUAG Bioavailaby **:<1%, enteric-coated or carrier technology needs to be developed.

- ** Kev tshawb fawb txog kev ntsuas mechanist yog xav tau los txhawb cov ntawv thov cov qog thiab cov kab mob ophthhalmic.

### 2. ** Kev tawg (

- ** ** Kev ua kom zoo rau cov qauv ": qhia cov amino acids los txhim kho enzyme tsis kam.

- ** Kev kho kev kho mob **: Synergistically txhawb cov ntaub so ntswg uas tsim nrog kav xovtooj.

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### xaus

Ara -290}} Tau ua lub hnub qub tshiab hauv ntau qhov kev kho raws li nws cov kev nyab xeeb ntawm kev ua thiab kev nyab xeeb zoo heev. Nyob rau yav tom ntej, nrog kev nrhav ntawm cov kev xa tawm thev naus laus zis thiab kev nthuav dav ntawm kev taw qhia, nws yuav tsum tau xaiv txoj haujlwm tseem ceeb hauv kev tswj hwm cov kab mob no. Ib txoj kev nkag siab tob txog nws cov yam ntxwv molecular thiab kev kho mob yuav ua kom nrawm dua thaum chaw kuaj mob.