CN104926933A - Endostatin突变体、Endostatin突变体与聚乙二醇的交联物以及它们的应用 - Google Patents
Endostatin突变体、Endostatin突变体与聚乙二醇的交联物以及它们的应用 Download PDFInfo
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- GGXICVAJURFBLW-CEYXHVGTSA-N latanoprost Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1CC[C@@H](O)CCC1=CC=CC=C1 GGXICVAJURFBLW-CEYXHVGTSA-N 0.000 description 1
- 229960001160 latanoprost Drugs 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000006011 modification reaction Methods 0.000 description 1
- 230000002911 mydriatic effect Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 208000001297 phlebitis Diseases 0.000 description 1
- 230000000649 photocoagulation Effects 0.000 description 1
- 238000002428 photodynamic therapy Methods 0.000 description 1
- 210000001747 pupil Anatomy 0.000 description 1
- 238000012113 quantitative test Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 229960003876 ranibizumab Drugs 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 208000004644 retinal vein occlusion Diseases 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 235000015170 shellfish Nutrition 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009182 swimming Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 238000000015 thermotherapy Methods 0.000 description 1
- 229940098465 tincture Drugs 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 238000002525 ultrasonication Methods 0.000 description 1
- 230000004862 vasculogenesis Effects 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
- 210000004127 vitreous body Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/78—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Genetics & Genomics (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Ophthalmology & Optometry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Abstract
Description
锌离子浓度(μM) | 锌离子/蛋白(摩尔比) | |
W-ES待测液 | 0.97±0.07 | 0.97 |
M-ES待测液 | 0.18±0.03 | 0.18 |
7天 | 15天 | |
PEG-W-ES待测液 | 5.07±0.23 | 8.98±0.21 |
PEG-M-ES待测液 | 0.04±0.03 | 0.05±0.03 |
10min | 20min | 30min | 60min | 90min | 120min | 150min | 180min | |
W-ES | 18.79 | 30.47 | 41.60 | 59.52 | 70.26 | 78.35 | 84.17 | 88.65 |
M-ES | 0.07 | 0.05 | 0 | 0 | 0.11 | 0.08 | 0.03 | 0 |
浓度(μg/ml) | 血管数 | 血管抑制率(%) | |
生理盐水 | 79.49±3.51 | 0 | |
PEG-M-ES | 5 | 69.20±2.37* | 12.9 |
PEG-M-ES | 20 | 40.83±6.35*# | 48.6 |
PEG-M-ES | 40 | 24.19±2.38* | 69.6 |
M-ES | 5 | 70.41±3.76* | 11.4 |
M-ES | 20 | 42.00±1.96*# | 47.2 |
M-ES | 40 | 25.57±5.11* | 67.8 |
W-ES | 20 | 58.72±4.92* | 26.1 |
样品 | 浓度(μg/ml) | 荧光值 | 抑制率(%) |
生理盐水 | 0 | 487.3±170.0 | 0 |
PEG-M-ES | 1 | 405.0±161.9* | 16.9 |
PEG-M-ES | 16 | 265.3±100.3*# | 45.6 |
PEG-M-ES | 160 | 94.0±24.4* | 80.7 |
M-ES | 1 | 415.4±127.5* | 14.8 |
M-ES | 16 | 282.9±110.7*# | 41.9 |
M-ES | 160 | 99.2±18.6* | 79.6 |
W-ES | 16 | 350.69±124.71* | 28.0 |
房室参数 | M-ES | PEG-M-ES |
T1/2(d) | 0.94 | 14.67 |
Ke(1/d) | 0.737 | 0.047 |
V1/F(L/kg) | 0.009 | 0.015 |
CL/F(L/d/kg) | 0.007 | 0.001 |
AUC(0-t)(μg/L*d) | 145446.445 | 1362757.32 |
AUC(0-∞)(μg/L*d) | 145446.449 | 1387366.32 |
Ka(1/d) | 0.738 | 0.052 |
t1/2Ka(d) | 0.939 | 13.412 |
Tlag(d) | 0 | 39.019 |
Claims (10)
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PCT/CN2015/000167 WO2015139511A1 (zh) | 2014-03-19 | 2015-03-12 | Endostatin突变体、Endostatin突变体与聚乙二醇的交联物以及它们的应用 |
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CN115721730A (zh) * | 2016-11-10 | 2023-03-03 | 北京普罗吉生物科技发展有限公司 | 聚乙二醇化血管内皮抑制素类似物及其应用 |
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JP6336389B2 (ja) * | 2011-09-09 | 2018-06-06 | チンファ ユニヴァーシティTsinghua University | Atp結合部位に変異を有するエンドスタチン変異体 |
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CN115721730A (zh) * | 2016-11-10 | 2023-03-03 | 北京普罗吉生物科技发展有限公司 | 聚乙二醇化血管内皮抑制素类似物及其应用 |
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