Tesamorelin ntsiav tshuajyog ib qho tshuaj formulation uas muaj cov khoom xyaw nquag Tesamorelin, feem ntau yog siv los kho cov kab mob metabolic. Nws yog ib qho kev sib txuas ua ke ntawm kev loj hlob hormone tso tawm cov tshuaj hormones (GHRH) analog uas txhawb kev tso tawm ntawm kev loj hlob hormone (GH) los ntawm hypothalamus, yog li tswj cov txheej txheem physiological xws li rog metabolism, protein synthesis, thiab pob txha loj hlob. Nws tuaj yeem ua ncaj qha rau ntawm GHRH receptor nyob rau hauv lub caj pas anterior pituitary, txhawb kev tso tawm ntawm endogenous loj hlob hormone, es tsis ncaj qha supplementing exogenous loj hlob hormone. Tesamorelin tsuas yog FDA pom zoo tshuaj rau kev kho mob plab plab zom mov (fat metabolism tsis meej) hauv cov neeg mob HIV. Cov neeg mob HIV tej zaum yuav muaj cov rog rov qab (xws li cov rog hauv plab thiab txo qis qis) vim ntev -cov tshuaj tiv thaiv kab mob (ART). Cov tshuaj no tuaj yeem txo cov rog subcutaneous hauv lub plab thiab txhim kho lub cev zoo.
Peb cov khoom
| Khoom npe | Tesamorelin hmoov | Tesamorelin ntsiav tshuaj | Tesamorelin Txhaj |
| Yam khoom | Hmoov | Tablet | ua kua |
| Khoom Purity | Ntau dua lossis sib npaug li 99% | Ntau dua lossis sib npaug li 99% | Ntau dua lossis sib npaug li 99% |
| Khoom Specifications | 100g / 1kg / thiab lwm yam. | 12.5 mg / 20 mg | 2 mg/2 ml |
| Daim ntawv khoom | Organic synthesis | Noj Orally | Organic synthesis |
Tesamorelin COA
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| Certificate of Analysis | ||
| Compound npe | Tesamorelin | |
| Qib | Pharmaceutical qib | |
| CAS Nr. | 218949-48-5 | |
| Ntau | 3 37,3kg | |
| Ntim txheem | 25kg / nruas | |
| Chaw tsim tshuaj paus | Shaanxi BLOOM TECH Co., Ltd | |
| Ntau No. | 202501090033 | |
| MFG | Peb 9, 2025 | |
| EXP | Peb 8, 2028 | |
| Yam khoom | Enterprise txheem | Kev txheeb xyuas qhov tshwm sim |
| Qhov tshwm sim | Dawb los yog yuav luag dawb hmoov | Ua raws |
| Cov ntsiab lus dej | Tsawg dua lossis sib npaug li 5.0% | 0.39% |
| Poob rau ziab | Tsawg dua lossis sib npaug li 1.0% | 0.28% |
| Hnyav Hlau | Pb Tsawg dua lossis sib npaug li 0.5ppm | N.D. |
| Tsawg dua lossis sib npaug li 0.5ppm | N.D. | |
| Hg Tsawg dua lossis sib npaug li 0.5ppm | N.D. | |
| Cd Tsawg dua lossis sib npaug li 0.5ppm | N.D. | |
| Purity (HPLC) | Ntau dua lossis sib npaug li 99.0% | 99.80% |
| Ib leeg impurity | <0.8% | 0.44% |
| Tag nrho microbial suav | Tsawg dua lossis sib npaug li 750cfu / g | 80 |
| E. Coli | Tsawg dua lossis sib npaug li 2MPN / g | N.D. |
| Salmonella | N.D. | N.D. |
| Ethanol (los ntawm GC) | Tsawg dua lossis sib npaug li 5000ppm | 500ppm ua |
| Cia | Khaws rau hauv qhov chaw kaw, tsaus, thiab qhuav hauv qab 2-8 degree | |
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Tesamorelin ntsiav tshuajyog ib qho kev sib txuas ntawm kev loj hlob hormone tso tawm cov tshuaj hormones (GHRH) analog feem ntau siv los kho cov kab mob plab rog metabolism tshwm sim los ntawm kev kho tshuaj tiv thaiv kab mob (ART) hauv cov neeg mob HIV.
Kev sib tw thiab kev daws teeb meem rau Tesamorelin Oral Tablets
Gastric acid degradation: Gastric acid (pH 1.5-3.5) tuaj yeem hydrolyze amide thiab ester bonds hauv peptides, ua rau cov tshuaj inactivation.
Txoj hnyuv enzymatic hydrolysis: Trypsin, chymotrypsin, thiab lwm yam enzymes tuaj yeem tshem tawm cov saw hlau polypeptide, cuam tshuam cov qauv tshuaj.
Kev nqus dej noo: Tesamorelin nquag nqus dej ib puag ncig, ua rau clumping lossis degradation.
Cov teeb meem kev ruaj ntseg thiab cov tswv yim tiv thaiv
Enteric coating technology: pH dependent polymers (such as hydroxypropyl methylcellulose phthalate, HPMCP) are used to coat the tablets, making them insoluble in the stomach and releasing the drug after entering the small intestine (pH>5.5).
Enzyme inhibitor co xa: Kev sib txuas cov hnyuv enzyme inhibitors (xws li Camostat, soy trypsin inhibitors) lossis cov tshuaj nkag mus (xws li sodium cholate, sodium lauroyl sulfate) kom txo cov tshuaj degradation thiab txhawb kev nqus.
Stabilizing excipients: Ntxiv cov fillers xws li mannitol thiab lactose, nrog rau cov nplaum xws li hydroxypropyl cellulose (HPC), los txhim kho cov ntsiav tshuaj hardness thiab ya raws.
Qhov hnyav molecular ntau dhau: Lub cev hnyav ntawm Tesamorelin (5111.6 Da) deb tshaj qhov pib rau kev thauj mus los ntawm cov hnyuv (feem ntau<500 Da), resulting in extremely low passive diffusion efficiency.
Polar deg nqi: Cov pab pawg them ntawm peptides (xws li arginine thiab lysine) cuam tshuam nrog phospholipid bilayer ntawm cell membrane, cuam tshuam kev thauj mus los.
Kev Siv Hluav Taws Xob Hluav Taws Xob
Nanocarrier technology: Encapsulating tshuaj nyob rau hauv liposomes, polymer nanoparticles, los yog khoom lipid nanoparticles (SLNs) los txhawb kev nqus los ntawm endocytosis los yog membrane fusion mechanisms. Piv txwv li, kev siv polylactic acid hydroxyacetic acid copolymer (PLGA) los npaj nanoparticles tuaj yeem txhim kho lub sijhawm khaws cov tshuaj hauv txoj hnyuv.
Kev hloov kho tshuaj: Ua kom cov tshuaj lipophilicity los ntawm polyethylene glycol (PEG) lossis fatty acid conjugation hloov kho. Piv txwv li, covalently combining Tesamorelin nrog lauric acid los tsim ib tug prodrug thiab txhim kho daim nyias nyias permeability.
Ionic kua tshuab: siv cov kua ionic (xws li 1-butyl-3-methylimidazolium hexafluorophosphate) kom yaj cov tshuaj thiab tsim cov viscosity tsawg los txhim kho txoj hnyuv mucosal permeability.
Thawj qhov tshwm sim: Tom qab cov tshuaj noj qhov ncauj tau nqus los ntawm txoj hnyuv, qee qhov ntawm nws yog metabolized los ntawm daim siab, ua rau txo qis hauv kev raug mob.
Kev sib txawv ntawm tus kheej: Muaj ib tus neeg sib txawv hauv plab hnyuv pH, kev ua haujlwm enzyme, thiab kev nthuav qhia cov protein, uas cuam tshuam rau qhov sib xws ntawm kev nqus tshuaj.
Optimization ntawm bioavailability
Micro needle patch assisted delivery: Ua ke nrog transdermal micro koob thev naus laus zis, microchannels tau tsim nyob rau saum npoo ntawm txoj hnyuv mucosa los txhawb kev nqus tshuaj ncaj qha.
3D tshuab luam ntawv: customized ntsiav tshuaj qauv (xws li ntau- cov ntsiav tshuaj txheej, sustained-tso tawm cores) kom ua tiav lub hom phiaj tso tawm cov tshuaj nyob rau hauv ib feem ntawm txoj hnyuv. Piv txwv li, siv fused deposition modeling (FDM) thev naus laus zis los luam cov ntsiav tshuaj sab hauv uas muaj cov enzyme inhibitors thiab cov ntsiav tshuaj txheej txheej uas muaj cov tshuaj.
Artificial txawj ntse (AI) pab tsim: siv tshuab kev kawm qauv los kwv yees kev sib cuam tshuam ntawm cov tshuaj excipient thiab cov txheej txheem tsis, optimizing ntsiav tshuaj formulations. Piv txwv li, siv cov random hav zoov algorithm los tshuaj xyuas qhov zoo tshaj plaws txheej khoom thickness thiab nanoparticle loading peev.
Kev tsim cov txheej txheem ntawm Tesamorelin qhov ncauj ntsiav tshuaj
Kev npaj cov khoom siv raw
Solid phase synthesis: Using Wang resin as a carrier, amino acids are gradually coupled through Fmoc/tBu strategy to synthesize Tesamorelin linear peptide chains. Cut the resin with trifluoroacetic acid (TFA) to obtain crude peptides, and purify them by high performance liquid chromatography (HPLC) (purity>98%).
Khov kom qhuav: Kho cov kua peptide purified mus rau -80 degree, nqus cov sublime kom tshem tawm cov dej noo, thiab tau txais cov khoom siv hmoov dawb. Khaws ntawm -20℃kom tsis txhob degradation.
kev npaj technology
Enteric coated nanoparticle ntsiav tshuaj
Kev npaj ntawm nanoparticles: Emulsification hnyav evaporation txoj kev tau siv: Tesamorelin (5% w / v) thiab PLGA (10% w / v) tau yaj hauv dichloromethane thiab tov nrog ib theem dej uas muaj polyvinyl cawv (PVA, 2% w / v). Tom qab ultrasonic emulsification, cov organic hnyav tau evaporated, thiab cov nanoparticles tau sau los ntawm centrifugation.
Cov ntsiav tshuaj compression: Sib tov nanoparticles (30% w / w), microcrystalline cellulose (50% w / w), thiab magnesium stearate (2% w / w), qhuav compress kom tau cov ntsiav tshuaj tseem ceeb. Txheej: Muab cov ntsiav tshuaj rau hauv cov tshuaj ethanol uas muaj HPMCP (10% w/v) thiab qhuav los ua ib txheej txheej enteric.
Ionic kua pellet ntsiav tshuaj
Kev npaj ntawm microspheres: Extrusion dov txoj kev: Dissolve Tesamorelin (5% w/v) nyob rau hauv 1-butyl-3-methylimidazolium hexafluorophosphate ionic kua, tov nrog hydroxypropyl methylcellulose (20% w/v), extrude rau hauv ib daim hlab, thiab yob rau hauv microspheres (inch).
Cov ntsiav tshuaj sib dhos: Sib xyaw microspheres (40% w/w), lactose (40% w/w), thiab hla- txuas carboxymethyl cellulose sodium (10% w/w), ntub granulation, ntsiav tshuaj nias, thiab txheej.
Txheej txheem validation thiab optimization
Kev ntsuam xyuas
USP Type II paddle method tau siv los txiav txim siab cov tshuaj tso tawm nkhaus raws li pH 1.2 (pastric kua simulation) thiab pH 6.8 (cov kua hauv plab simulation) cov xwm txheej los xyuas kom meej qhov kev ncaj ncees ntawm cov txheej txheem enteric.
Kev kawm ruaj khov
Hauv kev ntsuas nrawm (40℃/ 75% RH) thiab ntev - kuaj lub sijhawm (25℃/ 60% RH), tsis tu ncua xyuas cov tsos, cov ntsiab lus, thiab lwm yam khoom ntawm cov ntsiav tshuaj kom paub meej txog hnub tas sijhawm (feem ntau ntau dua lossis sib npaug li 24 lub hlis).
Bioequivalence (BE) xeem
Los ntawm kev kawm hla ntawm cov neeg ua haujlwm noj qab haus huv, cov ntshav siab lub sij hawm nkhaus ntawm cov ntsiav tshuaj ntawm qhov ncauj thiab kev txhaj tshuaj yog muab piv los xyuas seb qhov bioavailability ua tau raws li tus qauv (feem ntau yuav tsum muaj cov txheeb ze bioavailability ntau dua lossis sib npaug li 80%).
Qhov tshwj xeeb qhov chaw ntawm Tesamorelin: txawv ntawm lub hom phiaj ntawm kev loj hlob hormone tso tawm peptides (GHRH)
Kev loj hlob hormone tso tawm peptide (GHRH) yog ib qho neuropeptide secreted los ntawm hypothalamus uas tswj cov metabolism, kev loj hlob, thiab kev tiv thaiv kab mob los ntawm kev ua kom lub zais ntawm kev loj hlob hormone (GH) nyob rau hauv lub anterior pituitary caj pas. Ib txwm siv GHRH analogues, xws li Sermorelin, muaj tsawg daim ntawv thov kev kho mob vim lawv ib nrab luv luv -lub neej thiab tsis muaj bioavailability.Tesamorelin ntsiav tshuaj, raws li ib qho kev sib xyaw ua ke GHRH analog, tau pom qhov sib txawv tseem ceeb hauv lawv cov txheej txheem ntawm kev ua, pharmacokinetics, thiab cov ntaub ntawv kho mob los ntawm kev txhim kho cov qauv thiab cov qauv tsim, tshwj xeeb tshaj yog nyob rau hauv kev kho mob ntawm HIV ntsig txog lipid metabolism.
Molecular structural sib txawv: los ntawm ntuj peptides mus rau heev xaiv analogues
Ntuj GHRH yog tsim los ntawm 44 amino acids (GHRH (1-44)), nrog rau nws cov tub ntxhais active cheeb tsam nyob rau ntawm N-terminal amino acids 1-29, ntawm uas 1-21 yog ib tug tseem ceeb sequences thiab 22-29 txhim khu receptor binding affinity. GHRH activates G protein ua ke cov teeb liab txoj kev los ntawm kev khi rau lub extracellular domain ntawm GHRH receptor (GHRH-R) nyob rau hauv lub anterior pituitary caj pas, txhawb GH synthesis thiab tso tawm. Txawm li cas los xij, ntuj GHRH tau yooj yim degraded los ntawm dipeptidyl peptidase IV (DPP-IV) hauv cov ntshav thiab muaj qee yam affinity rau GHRH-R hauv cov ntaub so ntswg uas tsis muaj pituitary xws li rog thiab nqaij, ua rau muaj kev cuam tshuam rau lub hom phiaj.
Tesamorelin ua tiav lub hom phiaj txhim kho los ntawm cov kev hloov kho hauv qab no:
N-terminal acetylation modification: Qhia ib pawg acetyl ntawm N-terminus of histidine (Nws) los thaiv qhov chaw cleavage ntawm DPP-IV thiab ncua ib nrab- lub neej mus rau 2-3 teev (natural GHRH tsuas yog siv sijhawm 5-10 feeb).
D-amino acid hloov pauv: Hloov L-tryptophan ntawm txoj haujlwm 2 nrog D-tryptophan txhawm rau txhim kho stereoselective khi nrog GHRH-R thiab txo qis kev ua haujlwm ntawm lwm yam G protein txuas nrog receptors (xws li VIP receptors).
C-terminal truncation thiab functionalization: tuav lub 1-29 core sequence ntawm natural GHRH, tab sis qhia cov uas tsis yog natural amino acids (xws li - methyllysine) los ntawm cov tshuaj synthesis los optimize kev sib cuam tshuam nrog receptor transmembrane domain thiab txhim kho cov teeb liab transduction efficiency.
| Yam ntxwv | Natural GHRH (1-44) | Tesamorelin |
| Amino acid muaj pes tsawg leeg | 44 L-amino acids | 29 amino acids (xws li D-tryptophan) |
| Ib nrab -lub neej | 5-10 feeb | 2-3 teev |
| Receptor xaiv | Tsawg (yooj yim hla qhib VIP receptors) | Siab (tsuas yog qhib GHRH-R) |
| Enzyme stability | Yooj yim degraded los ntawm DPP-IV | Resistant rau enzymatic hydrolysis |
Lub hom phiaj sib txawv hauv receptor binding thiab teeb liab transduction
Kev faib tawm thiab kev ua haujlwm ntawm GHRH receptors
GHRH-R belongs rau G protein coupled receptor (GPCR) tsev neeg thiab feem ntau yog qhia nyob rau hauv anterior pituitary loj hlob hormone hlwb, tab sis kuj nyob rau hauv qis cov ntaub so ntswg adipose, skeletal nqaij, pancreas, thiab lub cev tiv thaiv kab mob. Ib txwm siv GHRH analogs, xws li Sermorelin, tuaj yeem qhib cov ntaub so ntswg uas tsis yog pituitary ib txhij vim lawv qhov kev sib raug zoo tsawg, ua rau muaj kev cuam tshuam rau lub hom phiaj xws li insulin tsis kam lossis lipolysis.
Targeted binding mechanism ntawm Tesamorelin
High affinity khi
Qhov kev sib txuas ntawm Tesamorelin rau GHRH-R (Kd ≈ 0.2 nM) yog qhov siab dua li ntawm GHRH (Kd ≈ 1.5 nM), vim muaj kev sib cuam tshuam ntawm hydrophobic ntawm nws cov D-tryptophan thiab lub voj extracellular ntawm receptor.
Molecular docking simulations tau pom tias C-terminal - methyllysine ntawm Tesamorelin tuaj yeem muab tso rau hauv lub hnab ntim hydrophobic ntawm receptor transmembrane domain, stabilizing lub receptor conformation thiab txhawb G s protein activation.
Lub koom haum tshwj xeeb ua kom
Pituitary qhov tseem ceeb lub hom phiaj: Qhov concentration ntawm Tesamorelin nyob rau hauv lub caj pas pituitary yog 10-20 zaug siab dua hauv cov ntshav, vim yog lub siab permeability ntawm pituitary capillary txaj rau cov loj molecular peptides thiab lub zos loj dua GHRH-R qhia ntom ntom piv rau peripheral cov ntaub so ntswg.
Peripheral cov ntaub so ntswg desensitization: Kev siv lub sij hawm ntev ntawm Tesamorelin tsis upregulate GHRH-R qhia nyob rau hauv rog los yog nqaij, thaum ntuj GHRH tej zaum yuav ua rau receptor downregulation vim muaj kev txhawb zog, ua rau cov tshuaj tiv thaiv.
Teeb liab txoj kev xaiv
Tesamorelin ntsiav tshuajFeem ntau ua rau G s-cAMP PKA txoj hauv kev, txhawb nqa GH noob hloov pauv, thiab muaj kev ua kom tsis muaj zog ntawm G i lossis G q txoj hauv kev (uas tuaj yeem kho cov rog rog lossis cov lus teb inflammatory).
Cov kev sim tsiaj tau pom tias kev kho mob Tesamorelin tsis ua rau muaj kev tso tawm cov roj fatty acids dawb los ntawm cov nas adipose cov ntaub so ntswg, thaum sib npaug ntawm cov tshuaj GHRH tuaj yeem ua rau cov ntshav plasma dawb fatty acid ntau ntxiv.
Cim npe nrov: Tesamorelin ntsiav tshuaj, lwm tus neeg, manufacturers, hoobkas, lag luam wholesale, yuav, nqe, tej, kev muag khoom