WO2018053696A1 - Nanoporteur pour le traitement de l'endotoxémie - Google Patents
Nanoporteur pour le traitement de l'endotoxémie Download PDFInfo
- Publication number
- WO2018053696A1 WO2018053696A1 PCT/CN2016/099518 CN2016099518W WO2018053696A1 WO 2018053696 A1 WO2018053696 A1 WO 2018053696A1 CN 2016099518 W CN2016099518 W CN 2016099518W WO 2018053696 A1 WO2018053696 A1 WO 2018053696A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- nanocarrier
- powder
- nano
- micro
- treating endotoxemia
- Prior art date
Links
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
- B01J20/282—Porous sorbents
- B01J20/285—Porous sorbents based on polymers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/30—Processes for preparing, regenerating, or reactivating
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F212/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an aromatic carbocyclic ring
- C08F212/02—Monomers containing only one unsaturated aliphatic radical
- C08F212/04—Monomers containing only one unsaturated aliphatic radical containing one ring
- C08F212/06—Hydrocarbons
- C08F212/08—Styrene
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F212/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an aromatic carbocyclic ring
- C08F212/34—Monomers containing two or more unsaturated aliphatic radicals
- C08F212/36—Divinylbenzene
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F218/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an acyloxy radical of a saturated carboxylic acid, of carbonic acid or of a haloformic acid
- C08F218/02—Esters of monocarboxylic acids
- C08F218/04—Vinyl esters
- C08F218/08—Vinyl acetate
Definitions
- ETM Endotoxemia in humans can be divided into two categories: exogenous and endogenous.
- Exogenous endotoxemia is mainly caused by endotoxin released by lysis of bacteria after Gram-negative bacteria infection.
- Endogenous endotoxemia is caused by abnormal metabolism of the intestinal flora or entry into the systemic circulation through an abnormal route.
- LPS lipopolysaccharide
- GNB Gram-negative bacteria
- Lipopolysaccharide has a molecular weight of more than 10,000 and consists of three parts. Similar to phospholipids, it has a hydrophilic head and a hydrophobic tail. Its fatty acyl chain is embedded in the outer membrane of the bacteria, and its sugar chain is exposed to the surface of the bacteria, and its toxic component is mainly lipidoid A.
- Lipid A is a glycolipid that constitutes endotoxin activity and is covalently linked to the heteropolysaccharide chain and released when the bacteria break. A series of reactions caused by release into the blood, eventually leading to systemic damage, irreversible shock and death. LPS interacts with proteins on cell membranes or receptors on specific cell membranes, such as endothelial cells, monocytes, macrophages, etc., causing them to release large amounts of mediators such as oxygen free radicals, arachidonic acid metabolites, platelet activating factor. , 1L-1, 1L-6, 1L-8 and TNF- ⁇ , etc. These mediators are important for the pathology of endotoxin-induced organ damage and septic shock.
- PMB Polymyxin-B immobilized fiber column
- Nanocarriers for clinical use are reported in the literature as liposomes as nanocarriers.
- Liposomes are a membrane material and phospholipids are their main constituents. Its role is to load drugs into the body to play a therapeutic role, liposomes will be ablated in the body. There is no function of adsorbing pathogenic substances to carry the human body.
- the blood perfusion device has been in clinical use for several decades as an auxiliary medical device, and the adsorbent used during the development of activated carbon to macroporous adsorption resin.
- a macroporous adsorption resin Currently widely used is a macroporous adsorption resin. Its role is to carry out the pathogenic substances in the blood out of the body through the blood purification route.
- the inventors have developed a blood perfusion device that is designed to remove blood endotoxin and treat endotoxemia in products to be marketed.
- the object of the present invention is to propose a nano-adsorbing resin carrier technical solution dedicated to endotoxemia, which provides a new therapeutic route for rapid treatment of endotoxemia.
- the nano carrier for treating endotoxemia is a powder of a micro-nano-sized particle size adsorption resin of an amphiphilic glycosylated resin having a polyvinyl acetate as a skeleton; or an amphiphilic structure based on polyvinyl acetate.
- the micro-nano-sized elemental powder of the glycosylated adsorption resin and the glycosylated styrene-divinylbenzene are mixed powders of the micro-nano-sized particle powder of the skeleton lipophilic adsorption resin.
- the elemental or mixed powder has a particle size ranging from 50 to 1000 nm.
- This embodiment can be used to prepare a powder for oral or skin application, or to be compressed into a suppository.
- Embodiment 2 of the present invention the particle size of the elemental or mixed powder ranges from 100 to 200 nm.
- This embodiment can be used for making an injection or an infusion agent for direct use in a patient's site or direct blood for rescue measures.
- the third embodiment of the present invention the powder of the present invention can be used as a single substance, and when mixed, the composition ratio of the mixed powder is 1:1.
- the nanocarrier of the present invention can be directly administered orally, or can be orally administered as a sustained release capsule, or as an injection, an infusion solution, or as a suppository.
- the powder of the present invention can be used in combination with a blood perfusion device filled with a macroporous adsorption resin of the same type of conventional particles.
- the nanocarrier film material with phospholipid as a main component in the prior art has substantial difference: the nanocarrier of the invention is a powder and does not degrade or ablate in vivo; the nanometer powder has high specific surface area and strong Surface adsorption; can penetrate human tissues including blood vessel walls and cell membranes, and has strong affinity adsorption on hydrophobic heads and hydrophilic tails of mucopolysaccharide molecules on bacterial cell walls and blood; adsorption of lipopolysaccharide on bacterial cell walls can promote bacteria The cells are inactivated and have a bactericidal effect; the nanocarrier of the invention can be quickly adsorbed from the blood and carried to carry out the mucopolysaccharide molecules, thereby avoiding binding to the receptors in the body; thereby achieving the purpose of treating endotoxemia.
- amphiphilic or lipophilic glycosylated macroporous medical resin nano-sized particle powder used in the invention has excellent blood compatibility, and has no neurotoxicity and nephrotoxicity, and is in treatment. It also does not cause a loss of a large amount of plasma protein in the blood; it overcomes the disadvantages of the polymyxin B-supported fiber column used in the prior art in Japan.
- the nano-scale carrier powder of the invention is a synthetic chemical product, which has chemical stability in the human environment, and the carrier function is the physical adsorption of Edwardian force in the surface micro-environment of the substance, and does not participate in any biochemical reaction in the body. It provides a safe, effective, fast and inexpensive clinical treatment for endotoxemia.
- the nano-materials of the present invention are capable of removing pathogenic target substances in vivo, which are lipopolysaccharides, and have similar adsorption and scavenging effects on other pathogenic substances having similar lipopolysaccharide molecules and hydrophilic substances on the other side; and other diseases caused by them Have the same therapeutic effect.
Landscapes
- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Analytical Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
L'invention concerne un nanoporteur pour traiter l'endotoxémie, constitué d'une poudre adsorbante polymère micro-nanométrique de qualité médicale d'une résine glycosylée amphiphile à squelette de poly(acétate) de vinyle. En variante, le nanoporteur est une poudre simple adsorbante polymère amphiphile micro-nanométrique d'une résine glycosylée amphiphile avec un squelette de poly(acétate) de vinyle et une poudre complexe adsorbante polymère lipophile micro/nanométrique avec un squelette de styrène-divinylbenzène glycosylé.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/CN2016/099518 WO2018053696A1 (fr) | 2016-09-21 | 2016-09-21 | Nanoporteur pour le traitement de l'endotoxémie |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/CN2016/099518 WO2018053696A1 (fr) | 2016-09-21 | 2016-09-21 | Nanoporteur pour le traitement de l'endotoxémie |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2018053696A1 true WO2018053696A1 (fr) | 2018-03-29 |
Family
ID=61690127
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/CN2016/099518 WO2018053696A1 (fr) | 2016-09-21 | 2016-09-21 | Nanoporteur pour le traitement de l'endotoxémie |
Country Status (1)
Country | Link |
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WO (1) | WO2018053696A1 (fr) |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002263486A (ja) * | 2001-03-14 | 2002-09-17 | Chisso Corp | エンドトキシン吸着体、及びそれを用いたエンドトキシンの除去方法 |
WO2005049653A1 (fr) * | 2003-07-14 | 2005-06-02 | Genway Biotech, Inc. | Composition et procede de separation d'affinite |
CN102361689A (zh) * | 2009-01-22 | 2012-02-22 | 弗雷森纽斯医疗护理德国有限责任公司 | 内毒素吸着剂 |
CN103980403A (zh) * | 2014-05-16 | 2014-08-13 | 李涛 | 一种苯乙烯系离子交换树脂及其制备方法与应用 |
CN104497193A (zh) * | 2014-10-01 | 2015-04-08 | 于杰 | 用于肠道清除包括内毒素的体内毒性物质的一过性载体 |
CN104693332A (zh) * | 2014-10-01 | 2015-06-10 | 于杰 | 糖基化医用大孔吸附树脂 |
-
2016
- 2016-09-21 WO PCT/CN2016/099518 patent/WO2018053696A1/fr active Application Filing
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002263486A (ja) * | 2001-03-14 | 2002-09-17 | Chisso Corp | エンドトキシン吸着体、及びそれを用いたエンドトキシンの除去方法 |
WO2005049653A1 (fr) * | 2003-07-14 | 2005-06-02 | Genway Biotech, Inc. | Composition et procede de separation d'affinite |
CN102361689A (zh) * | 2009-01-22 | 2012-02-22 | 弗雷森纽斯医疗护理德国有限责任公司 | 内毒素吸着剂 |
CN103980403A (zh) * | 2014-05-16 | 2014-08-13 | 李涛 | 一种苯乙烯系离子交换树脂及其制备方法与应用 |
CN104497193A (zh) * | 2014-10-01 | 2015-04-08 | 于杰 | 用于肠道清除包括内毒素的体内毒性物质的一过性载体 |
CN104693332A (zh) * | 2014-10-01 | 2015-06-10 | 于杰 | 糖基化医用大孔吸附树脂 |
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