CN112295031A - Application of silica compound aerogel in blood purification - Google Patents
Application of silica compound aerogel in blood purification Download PDFInfo
- Publication number
- CN112295031A CN112295031A CN201910673714.1A CN201910673714A CN112295031A CN 112295031 A CN112295031 A CN 112295031A CN 201910673714 A CN201910673714 A CN 201910673714A CN 112295031 A CN112295031 A CN 112295031A
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- Prior art keywords
- aerogel
- silica
- blood purification
- blood
- adsorbent
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- 239000004964 aerogel Substances 0.000 title claims abstract description 88
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 title claims abstract description 79
- 210000004369 blood Anatomy 0.000 title claims abstract description 78
- 239000008280 blood Substances 0.000 title claims abstract description 78
- 238000000746 purification Methods 0.000 title claims abstract description 35
- 239000000377 silicon dioxide Substances 0.000 title claims description 34
- -1 silica compound Chemical class 0.000 title claims description 27
- 239000003463 adsorbent Substances 0.000 claims abstract description 19
- 239000000463 material Substances 0.000 claims abstract description 16
- 229910052814 silicon oxide Inorganic materials 0.000 claims abstract description 13
- 239000004965 Silica aerogel Substances 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 13
- OBNDGIHQAIXEAO-UHFFFAOYSA-N [O].[Si] Chemical compound [O].[Si] OBNDGIHQAIXEAO-UHFFFAOYSA-N 0.000 claims description 7
- 239000011159 matrix material Substances 0.000 claims description 6
- 239000000499 gel Substances 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 239000011324 bead Substances 0.000 claims description 4
- 239000011148 porous material Substances 0.000 claims description 4
- 239000002131 composite material Substances 0.000 claims description 3
- 230000001951 hemoperfusion Effects 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 239000011347 resin Substances 0.000 claims description 3
- 229920005989 resin Polymers 0.000 claims description 3
- 239000004925 Acrylic resin Substances 0.000 claims description 2
- 239000004793 Polystyrene Substances 0.000 claims description 2
- 239000011543 agarose gel Substances 0.000 claims description 2
- 230000008081 blood perfusion Effects 0.000 claims description 2
- 239000001913 cellulose Substances 0.000 claims description 2
- 229920002678 cellulose Polymers 0.000 claims description 2
- 239000011521 glass Substances 0.000 claims description 2
- 125000001165 hydrophobic group Chemical group 0.000 claims description 2
- 229920002223 polystyrene Polymers 0.000 claims description 2
- 150000003377 silicon compounds Chemical class 0.000 claims description 2
- 238000001179 sorption measurement Methods 0.000 abstract description 26
- 229920002521 macromolecule Polymers 0.000 abstract description 4
- 239000000126 substance Substances 0.000 abstract description 4
- 238000009826 distribution Methods 0.000 abstract description 2
- 150000002605 large molecules Chemical class 0.000 abstract description 2
- 239000002207 metabolite Substances 0.000 abstract description 2
- 150000003384 small molecules Chemical class 0.000 abstract description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 26
- 102000004889 Interleukin-6 Human genes 0.000 description 20
- 108090001005 Interleukin-6 Proteins 0.000 description 20
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- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 20
- 229940100601 interleukin-6 Drugs 0.000 description 20
- 241000700159 Rattus Species 0.000 description 16
- 241000283973 Oryctolagus cuniculus Species 0.000 description 15
- 241000282472 Canis lupus familiaris Species 0.000 description 13
- 229940109239 creatinine Drugs 0.000 description 13
- 229960001412 pentobarbital Drugs 0.000 description 12
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 12
- 238000002965 ELISA Methods 0.000 description 10
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- 229920001778 nylon Polymers 0.000 description 10
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- 239000007788 liquid Substances 0.000 description 8
- 229930003779 Vitamin B12 Natural products 0.000 description 7
- FDJOLVPMNUYSCM-WZHZPDAFSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+3].N#[C-].N([C@@H]([C@]1(C)[N-]\C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C(\C)/C1=N/C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C\C1=N\C([C@H](C1(C)C)CCC(N)=O)=C/1C)[C@@H]2CC(N)=O)=C\1[C@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]1[C@@H](O)[C@@H](N2C3=CC(C)=C(C)C=C3N=C2)O[C@@H]1CO FDJOLVPMNUYSCM-WZHZPDAFSA-L 0.000 description 7
- 239000011715 vitamin B12 Substances 0.000 description 7
- 235000019163 vitamin B12 Nutrition 0.000 description 7
- 102000015736 beta 2-Microglobulin Human genes 0.000 description 6
- 108010081355 beta 2-Microglobulin Proteins 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 125000005007 perfluorooctyl group Chemical group FC(C(C(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)* 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 235000012239 silicon dioxide Nutrition 0.000 description 5
- 238000001035 drying Methods 0.000 description 4
- 238000002386 leaching Methods 0.000 description 4
- 239000002504 physiological saline solution Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- 230000032683 aging Effects 0.000 description 3
- 230000036772 blood pressure Effects 0.000 description 3
- 238000012258 culturing Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
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- 239000000706 filtrate Substances 0.000 description 3
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- 238000003980 solgel method Methods 0.000 description 3
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- 238000002798 spectrophotometry method Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 238000009413 insulation Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- YVBBRRALBYAZBM-UHFFFAOYSA-N perfluorooctane Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F YVBBRRALBYAZBM-UHFFFAOYSA-N 0.000 description 2
- 229920001296 polysiloxane Polymers 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 206010008479 Chest Pain Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 101000937544 Homo sapiens Beta-2-microglobulin Proteins 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 108090000445 Parathyroid hormone Proteins 0.000 description 1
- 102000003982 Parathyroid hormone Human genes 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 239000004115 Sodium Silicate Substances 0.000 description 1
- BOTDANWDWHJENH-UHFFFAOYSA-N Tetraethyl orthosilicate Chemical compound CCO[Si](OCC)(OCC)OCC BOTDANWDWHJENH-UHFFFAOYSA-N 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 230000010100 anticoagulation Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 238000002615 hemofiltration Methods 0.000 description 1
- 102000047279 human B2M Human genes 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000012567 medical material Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910044991 metal oxide Inorganic materials 0.000 description 1
- 150000004706 metal oxides Chemical class 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 239000002086 nanomaterial Substances 0.000 description 1
- 239000007783 nanoporous material Substances 0.000 description 1
- 239000000199 parathyroid hormone Substances 0.000 description 1
- 229960001319 parathyroid hormone Drugs 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920000734 polysilsesquioxane polymer Polymers 0.000 description 1
- 229920003053 polystyrene-divinylbenzene Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- NTHWMYGWWRZVTN-UHFFFAOYSA-N sodium silicate Chemical compound [Na+].[Na+].[O-][Si]([O-])=O NTHWMYGWWRZVTN-UHFFFAOYSA-N 0.000 description 1
- 229910052911 sodium silicate Inorganic materials 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 229940045136 urea Drugs 0.000 description 1
- 229940116269 uric acid Drugs 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
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
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28014—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their form
- B01J20/28047—Gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3621—Extra-corporeal blood circuits
-
- 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
- B01J20/02—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material
- B01J20/10—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material comprising silica or silicate
- B01J20/103—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material comprising silica or silicate comprising silica
-
- 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
- B01J20/22—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
Abstract
The invention provides an application of silicon oxide aerogel in blood purification, wherein the blood purification material is used as an adsorbent for blood purification; the blood purification material is silicon oxide aerogel. The silicon oxide aerogel material is used as a main body adsorption material for blood purification, and can realize the removal of various exogenous harmful substances and endogenous metabolites with different molecular weight distributions in blood, wherein the removal comprises the effective removal of redundant small molecules with the molecular weight of below 500 and the effective and selective removal of medium and large molecules with the molecular weight of above 500.
Description
Technical Field
The invention belongs to the technical field of medical materials, and particularly relates to a novel blood purification material, namely silica aerogel which is used as a main adsorbent for purifying various toxic substances in blood.
Background
The blood purification is a treatment mode of removing toxins or redundant components accumulated in blood by technologies such as hemodialysis, hemofiltration, hemoperfusion, plasma replacement and the like, and the main working principle of the blood purification is that toxic drugs and metabolic products in the blood of a patient are adsorbed and removed by utilizing the porous adsorption performance of an adsorbent, so that the blood purification effect is achieved. The blood purification adsorbent is generally a porous material with a special size micro-nano structure, and the material not only needs to have larger porosity and specific surface area, but also needs to have good biological and blood compatibility. The mainstream blood purification adsorbing materials in the market at present comprise porous polystyrene-divinylbenzene resin and active carbon. Due to the low adsorption selectivity (especially low adsorption efficiency of the macromolecules) and insufficient biocompatibility, the two types of adsorption materials can cause some complications in the clinical use process, such as fever, chest distress, dyspnea, transient decrease of leukocytes or platelets, and the like, thereby causing potential threats to the safe use of the blood purifier.
Disclosure of Invention
The aerogel is a novel micro-nano porous material (the specific surface area can be as high as 1000 m)3More than g), has the characteristics of low density, low thermal conductivity, high specific surface area, high porosity and the like, and is mainly applied to the technical fields of heat preservation, heat insulation, sound insulation and the like. At present, there is no report of the application of aerogel materials in the field of blood purification. The inventor of the application develops the aerogel taking the silicon oxide compound as the main body for the first time and takes the aerogel as the main body adsorbent for purifying the blood, so that various endogenous and exogenous harmful molecules in the blood can be efficiently adsorbed, and the better biological and blood compatibility of the silicon oxide compound can also provide guarantee for the biological safety of the material in the using process.
In order to solve the problems of low adsorption efficiency, low biocompatibility and the like existing in the clinical use process of the current blood purification technology, the silica compound aerogel is used as an adsorption main body material for blood purification, and cell and blood compatibility experiments prove that the silica compound aerogel has good biological and blood compatibility, and on the basis, the silica compound aerogel can realize safe and efficient adsorption of various endogenous and exogenous harmful substances in blood.
In order to achieve the above purpose, the invention provides the following technical scheme:
application of silica aerogel in blood purification is provided.
According to the invention, the silica aerogel is used as an adsorbent for blood purification.
According to the invention, the building units of the silica aerogel are a multi-silicon-based oxide composite system, and the silica aerogel is exemplified by: silica, organic-inorganic composite silica, (poly) silsesquioxane, substituted (poly) silsesquioxane, organic-inorganic hybrid and the like (poly) silsesquioxane and the like.
According to the invention, the specific adsorption performance of the silica compound aerogel can be realized by modifying the silica compound aerogel, for example, heparin modification can adjust the anticoagulation performance of the aerogel; the modification of the hydrophilic and hydrophobic groups in different proportions can adjust the hydrophilic and hydrophobic properties of the aerogel.
According to the present invention, silica compound aerogel for blood purification can be prepared by a sol-gel method. Specifically, a silica compound aerogel and/or a doping system containing the silica compound aerogel is obtained by modifying, aging and drying through a sol-gel method.
According to the invention, the silica aerogel can be used as an adsorbent alone, or can be doped or loaded in a carrier matrix in a physical or chemical mode to form a doped system of the silica-containing aerogel and then used as the adsorbent.
Wherein, the doping system of the silicon-oxygen compound-containing aerogel can be silicon-oxygen compound aerogel doped or loaded on a carrier matrix; the carrier matrix can be, for example, organic-inorganic porous resins and gel materials, such as cellulose, agarose gel, glass beads, magnetic beads, polystyrene, polyacrylic resin, and the like.
According to the present invention, the source of the silica compound aerogel is not particularly limited, and for example, the silica compound aerogel can be prepared by a method known in the art, such as polysilsesquioxane aerogel and a method for preparing the same described in chinese patent 201710186516.3, or silica aerogel obtained by hydrolyzing, gelling, modifying, aging, drying, etc. orthosilicate.
Illustratively, the silica aerogel is obtained by taking organic siloxane (silicon ester) or sodium silicate as a main precursor component and removing liquid in the gel through a sol-gel method and drying, and in order to improve the mechanical property, the hydrophilic and hydrophobic property, the gap adjustment, the adsorption exclusion and other properties of the aerogel in the preparation process, one or more additives such as acid, alkali, organic matters, inorganic matters, metal oxides, high molecular monomers, polymers and the like can be correspondingly added in the processes of sol-gel, aging, liquid replacement and the like, and the proportion of the additives can be adjusted.
According to the invention, the pore diameter of the silica aerogel is 3-200nm, preferably 20-70nm, and the specific surface area is 400-1500m2Per g, preferably 500-1000m2(ii)/g; the porosity is greater than 80%. The silicone compound may be a mixture of a plurality of silicone compounds of different pore sizes.
According to the invention, the appearance of the silica aerogel is not particularly limited, and can be, for example, square, spherical and other amorphous powders or blocks, and preferably, the silica aerogel has a spherical appearance with a diameter of >100 micrometers.
According to the invention, after the leaching liquor of the silica compound aerogel is used for culturing cells for 24 hours, the cell survival rate is more than 95%.
According to the invention, the silicon oxide aerogel is directly contacted with cells, and the cell survival rate is more than 95% after the cells are cultured for 24 hours.
According to the invention, the silicon-oxygen compound gasGel, after being pre-washed by heparin, the adsorption quantity of the gel to fibrinogen is lower than 0.4 mu g/cm2The adsorption amount to thrombin is more than 0.4 mu g/cm2。
According to the invention, blood contacted with the silica compound aerogel is filtered by a nylon filter screen and then injected back into model animals (female non-pregnant period), such as rats (3mL/250g), rabbits (30mL/3kg) and dogs (100mL/10kg), no obvious anaphylactic reaction occurs in the tested animals within 72 hours, and tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) inflammatory factors in serum of the model animals are respectively lower than 100pg/mL and 50pg/mL by enzyme-linked immunosorbent assay, which indicates that the silica compound aerogel has excellent blood and biocompatibility.
According to the invention, the silica compound aerogel has better adsorption capacity on micromolecules with the molecular weight less than or equal to 500, such as sodium pentobarbital, uric acid, creatinine and urea in blood.
Illustratively, the adsorption rate of 1.0g of silicon oxide aerogel on 25mL of sodium pentobarbital with the concentration of more than or equal to 50mg/L is more than 70 percent; the adsorption rate of 1.0g of silicon oxide aerogel to 25mL of creatinine with the creatinine concentration of more than or equal to 25mg/L is more than 50%.
According to the invention, the silica compound aerogel has better adsorption capacity on medium molecules with the molecular weight of 500-5000, such as bilirubin and vitamin B12 in blood.
Illustratively, the adsorption rate of 1.0g of silicon oxide aerogel on 25mL of vitamin B12 with the concentration of more than or equal to 15mg/L is more than 80%.
According to the invention, the silica compound aerogel has good adsorption capacity on macromolecules with the molecular weight more than or equal to 5000, such as parathyroid hormone, beta 2 microglobulin and the like in blood.
Illustratively, the adsorption rate of 1.0g of silicon oxide aerogel on 25mL of beta 2 microglobulin with the concentration of more than or equal to 3.0 mu g/L is not less than 30%.
The invention also provides a method for purifying blood, wherein the method comprises the step of contacting the blood to be purified with the silicon compound aerogel.
The invention also provides application of the silicon oxide aerogel in preparing blood purification equipment.
According to the invention, the blood purification device is, for example, a hemoperfusion cartridge.
According to the invention, the silica aerogel is used as an adsorbent in a blood perfusion device.
The invention also provides blood purification equipment, wherein the blood purification equipment comprises an adsorbent, and the adsorbent is the silica compound aerogel disclosed by the invention.
According to the present invention, the adsorbent used in the blood purification apparatus may be a mixture of one or more silica compound aerogels, and a doped system of silica compound containing aerogels.
The invention has the beneficial effects that:
the invention provides an application of a silicon-oxygen compound aerogel in blood purification, wherein the silicon-oxygen compound aerogel is used as an adsorbent for blood purification. The silicon oxide aerogel material is used as a main body adsorption material for blood purification, and can realize the removal of various exogenous harmful substances and endogenous metabolites with different molecular weight distributions in blood, wherein the removal comprises the effective removal of redundant small molecules with the molecular weight of below 500 and the effective and selective removal of medium and large molecules with the molecular weight of above 500.
Detailed Description
The preparation method of the present invention will be described in further detail with reference to specific examples. It is to be understood that the following examples are only illustrative and explanatory of the present invention and should not be construed as limiting the scope of the present invention. All the technologies realized based on the above-mentioned contents of the present invention are covered in the protection scope of the present invention.
The experimental methods used in the following examples are all conventional methods unless otherwise specified; reagents, materials and the like used in the following examples are commercially available unless otherwise specified.
Reference is made to the preparation of (poly) silsesquioxane aerogels used in the following examples: RSCANDance, 2017,7(52): 32861-32865).
Reference is made to the preparation of perfluorooctyl (poly) silsesquioxane aerogels used in the following examples: RSC Adance,2017,7(52): 32861-32865.
The silica aerogel used in the following examples was prepared by hydrolyzing tetraethoxysilane, gelling, and drying at room temperature.
Example 1
Dispersing 8.0mg of sodium pentobarbital and 4.0mg of creatinine in 100mL of water to prepare an aqueous solution with the concentration of 80mg/L of sodium pentobarbital and the concentration of 40mg/L of creatinine, then dispersing 4.0g of silica aerogel in the aqueous solution, dividing the aqueous solution into 4 parts, placing the 4 parts in a constant-temperature shaking table at 37 ℃ for 30min, 1h, 1.5h and 2h, filtering and filtering out solids, and testing the concentrations of the sodium pentobarbital and the creatinine in the liquid by using a spectrophotometry method, wherein the results show that the concentrations of the sodium pentobarbital and the creatinine in 4 groups of filtrate are respectively less than 8.0mg/L and 6.0mg/L, namely the adsorption rate of the sodium pentobarbital is not less than 90 percent, and the adsorption efficiency of the creatinine is not less than 85 percent.
Example 2
Dispersing 8.0mg of sodium pentobarbital and 4.0mg of creatinine in 100mL of water to prepare an aqueous solution with the concentration of 80mg/L of sodium pentobarbital and the concentration of 40mg/L of creatinine, dispersing 4.0g of (poly) silsesquioxane aerogel in the aqueous solution, dividing the aqueous solution into 4 parts, placing the 4 parts in a constant-temperature shaking table at 37 ℃ for 30min, 1h, 1.5h and 2h, filtering to remove solids, and testing the concentrations of the sodium pentobarbital and the creatinine in the liquid by using a spectrophotometry method, wherein the results show that the concentrations of the sodium pentobarbital and the creatinine in 4 groups of filtrate are respectively less than 8.0mg/L and 6.0mg/L, namely the adsorption rate of the sodium pentobarbital is not less than 90%, and the adsorption efficiency of the creatinine is not less than 85%.
Example 3
Dispersing 2.5mg of vitamin B12 in 100mL of water to prepare a 25mg/L aqueous solution of vitamin B12, dispersing 4.0g of perfluorooctane (poly) silsesquioxane aerogel in the aqueous solution, dividing the solution into 4 parts, placing the 4 parts in a constant-temperature shaking table at 37 ℃ for 30min, 1h, 1.5h and 2h, filtering to remove solids, and testing the concentration of vitamin B12 in the liquid by using a spectrophotometry method, wherein the results show that the concentration of the vitamin B12 in 4 groups of filtrate is less than 1mg/L, namely the adsorption efficiency of the vitamin B12 is not less than 95%.
Example 4
1.0mg of recombinant human β 2 microglobulin expressed by escherichia coli was weighed and dispersed in 25ml of Tris-HCl buffer system (pH 7.0), and then 1.0g of perfluorooctane (poly) silsesquioxane aerogel was dispersed therein and placed in a 37 ℃ constant temperature shaker for 2 hours. The Roche beta 2 microglobulin kit is used for testing the concentration of the beta 2 microglobulin in the liquid, and the result shows that the concentration of the beta 2 microglobulin in the liquid is less than 15mg/L, namely the adsorption efficiency of the beta 2 microglobulin is not lower than 62.5%.
Example 5
Respectively soaking 0.2g of silicon dioxide aerogel, 0.2g of (poly) silsesquioxane aerogel and 0.2g of perfluorooctyl (poly) silsesquioxane aerogel in 10mL of Tris-HCl buffer solution for 24 hours, filtering and taking liquid to obtain aerogel leaching solutions S1, S2 and S3, culturing mouse fibroblasts for 24 hours by using the three leaching solutions, and measuring that the cells are cultured for 24 hours by using the aerogel leaching solutions by using an MTT method, wherein the survival rate of the cells is more than 95%.
Example 6
Respectively paving 2-3 particles of silicon dioxide aerogel, (poly) silsesquioxane aerogel and perfluorooctyl (poly) silsesquioxane aerogel at the bottom of a 96-well plate, directly contacting with mouse fibroblasts, and culturing the cells in a DMEM culture medium for 24 hours, wherein the survival rate of the cells under the condition of direct contact with the aerogel is over 95 percent by an MTT method.
Example 7
3mL of blood of an experimental rat (250g, female non-pregnant period) is extracted intravenously, the experimental rat dynamically contacts with a mixed system of 0.12g of silicon dioxide aerogel and 1.5mL of physiological saline for 15s, the mixed system is filtered by a 300-mesh nylon filter screen to separate the aerogel, the separated aerogel is injected back into the body of the rat, and the blood pressure, the heart rate and various external physiological indexes of the experimental rat are continuously monitored for 72 hours, so that no obvious allergic indication is shown. In addition, the tumor necrosis factor alpha (TNF-alpha) and the interleukin-6 (IL-6) inflammatory factor in the serum of rats are respectively lower than 100pg/mL and 50pg/mL after 1h, 24h, 48h and 72h of blood returning measured by an enzyme-linked immunosorbent assay.
Example 8
3mL of blood of an experimental rat (250g, female non-pregnant period) is extracted intravenously, the experimental rat dynamically contacts with a mixed system of 0.12g of (poly) silsesquioxane aerogel and 1.5mL of normal saline for 10s, the mixed system is filtered by a 300-mesh nylon filter screen to separate the aerogel, the aerogel is injected back into the rat body, and the blood pressure, the heart rate and various external physiological indexes of the experimental rat are continuously monitored for 72 hours, so that no obvious allergic indication is shown. In addition, the tumor necrosis factor alpha (TNF-alpha) and the interleukin-6 (IL-6) inflammatory factor in the serum of rats are respectively lower than 100pg/mL and 50pg/mL after 1h, 24h, 48h and 72h of blood returning measured by an enzyme-linked immunosorbent assay.
Example 9
3mL of blood of an experimental rat (250g, female non-pregnant period) is extracted intravenously, the experimental rat dynamically contacts with a mixed system of 0.12g of perfluorooctyl (poly) silsesquioxane aerogel and 1.5mL of physiological saline for 10s, the mixed system is filtered by a 300-mesh nylon filter screen to separate the aerogel and then is injected back into the rat body, and the blood pressure, the heart rate and various external physiological indexes of the experimental rat are continuously monitored for 72 hours, so that no obvious allergic indication is shown. In addition, the tumor necrosis factor alpha (TNF-alpha) and the interleukin-6 (IL-6) inflammatory factor in the serum of rats are respectively lower than 100pg/mL and 50pg/mL after 1h, 24h, 48h and 72h of blood returning measured by an enzyme-linked immunosorbent assay.
Example 10
30mL of blood of an experimental rabbit (3kg, female non-pregnant period) is extracted intravenously, the experimental rabbit is in dynamic contact with a mixed system of 1.2g of silicon dioxide aerogel and 15mL of normal saline for 60s, the mixed system is filtered by a 300-mesh nylon filter screen to separate the aerogel, the aerogel is injected into the female rabbit again, various physiological indexes of the experimental rabbit are continuously monitored within 72 hours, and no obvious allergic indication appears. In addition, when the blood returns for 1h, 24h, 48h and 72h by enzyme-linked immunosorbent assay, the inflammatory factors of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) in the serum of the rabbit are respectively lower than 100pg/mL and 50 pg/mL.
Example 11
30mL of blood of the experimental rabbit (3kg, female non-pregnant period) is extracted intravenously, the experimental rabbit is in dynamic contact with a mixed system of 1.2g of (poly) silsesquioxane aerogel and 15mL of normal saline for 60s, the mixed system is filtered by a 300-mesh nylon filter screen to separate the aerogel, and then the aerogel is injected into the female rabbit again, all physiological indexes of the experimental rabbit are continuously monitored within 72 hours, and no obvious allergic indication appears. In addition, when the blood returns for 1h, 24h, 48h and 72h by enzyme-linked immunosorbent assay, the inflammatory factors of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) in the serum of the rabbit are respectively lower than 100pg/mL and 50 pg/mL.
Example 12
The method comprises the steps of drawing 30mL of blood of an experimental rabbit (3kg, female non-pregnant period) through veins, enabling the blood to dynamically contact with a mixed system of 1.2g of perfluorooctyl (poly) silsesquioxane aerogel and 15mL of normal saline for 60s, filtering and separating the aerogel through a 300-mesh nylon filter screen, injecting the aerogel back into the female rabbit, and continuously monitoring various physiological indexes of the experimental rabbit within 72 hours to ensure that no obvious allergic indication appears. In addition, when the blood returns for 1h, 24h, 48h and 72h by enzyme-linked immunosorbent assay, the inflammatory factors of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) in the serum of the rabbit are respectively lower than 100pg/mL and 50 pg/mL.
Example 13
100mL of experimental beagle dog (10kg, female non-pregnant period) blood is extracted intravenously, dynamically contacts with a mixed system of 4.0g of silicon dioxide aerogel and 50mL of physiological saline for 180s, is filtered by a 300-mesh nylon filter screen to separate the aerogel, and is injected back into the body of the experimental beagle dog, and no obvious allergic indication is shown after various physiological indexes of the beagle dog within 72 hours after blood return are detected. In addition, after the blood returning is measured for 1h, 24h, 48h and 72h by the enzyme-linked immunosorbent assay, the inflammatory factors of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) in the beagle serum are respectively lower than 100pg/mL and 50 pg/mL.
Example 14
The experimental beagle dog (10kg, female non-pregnant period) blood is extracted intravenously and 100mL, the beagle dog is in dynamic contact with a mixed system of 4.0g of (poly) silsesquioxane aerogel and 50mL of normal saline for 180s, the beagle dog is re-injected into the body of the experimental beagle dog after being filtered and separated by a 300-mesh nylon filter screen, and all physiological indexes of the beagle dog within 72 hours after blood return are detected, so that no obvious allergic indication is shown. In addition, after the blood returning is measured for 1h, 24h, 48h and 72h by the enzyme-linked immunosorbent assay, the inflammatory factors of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) in the beagle serum are respectively lower than 100pg/mL and 50 pg/mL.
Example 15
The experimental beagle dog (10kg, female non-pregnant period) blood is extracted intravenously and 100mL, the beagle dog is in dynamic contact with a mixed system of 4.0g perfluorooctyl (poly) silsesquioxane aerogel and 50mL physiological saline for 180s, the mixed system is filtered by a 300-mesh nylon filter screen to separate the aerogel, and then the aerogel is injected back into the beagle dog for the experiment, and all physiological indexes of the beagle dog within 72 hours after blood return are detected, so that no obvious allergic indication is shown. In addition, after the blood returning is measured for 1h, 24h, 48h and 72h by the enzyme-linked immunosorbent assay, the inflammatory factors of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) in the beagle serum are respectively lower than 100pg/mL and 50 pg/mL.
The embodiments of the present invention have been described above. However, the present invention is not limited to the above embodiment. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. Application of silica aerogel in blood purification is provided.
2. Use according to claim 1, wherein the silica aerogel is used as an adsorbent for blood purification.
3. Use according to claim 1 or 2, wherein the building units of the silica aerogel are complex systems of silica-based oxides, such as, for example: silica, organic-inorganic composite silica, (poly) silsesquioxane, substituted (poly) silsesquioxane, organic-inorganic hybrid and the like (poly) silsesquioxane and the like.
4. Use according to any one of claims 1 to 3, wherein the silica aerogel is modified, for example heparin-modified, and other hydrophilic groups, or hydrophobic groups.
5. The use according to any one of claims 1 to 4, wherein the silica aerogel can be used as an adsorbent alone or after being physically or chemically doped or supported in a carrier matrix to form a doped system of silica aerogel.
Preferably, the doping system of the silicon-oxygen compound-containing aerogel can be a silicon-oxygen compound aerogel doped or supported on a carrier matrix; the carrier matrix can be, for example, organic-inorganic porous resins and gel materials, such as cellulose, agarose gel, glass beads, magnetic beads, polystyrene, polyacrylic resin, and the like.
6. Use according to any one of claims 1 to 3, wherein the silica aerogel has a pore diameter of from 3 to 200nm, preferably from 20 to 70nm, and a specific surface area of from 400 to 1500m2Per g, preferably 500-1000m2(ii)/g; the porosity is greater than 80%.
7. A method of blood purification, wherein the method comprises contacting blood to be purified with an aerogel of a silicon compound.
8. Use of silica aerogel for the preparation of a blood purification device.
9. Use according to claim 8, wherein the blood purification apparatus is, for example, a hemoperfusion apparatus.
Preferably, the use of said silica aerogel as an adsorbent in a blood perfusion device.
10. A blood purification apparatus, wherein the blood purification apparatus comprises an adsorbent, and the adsorbent is the silicon oxide aerogel according to any one of claims 1 to 6.
Preferably, the adsorbent used in the blood purification apparatus may be a mixture of one or more silica compound aerogels, or a doped system of silica compound-containing aerogels.
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| WO2008055208A1 (en) * | 2006-11-01 | 2008-05-08 | New Jersey Institute Of Technology | Aerogel-based filtration of gas phase systems |
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