CN114014979A - Preparation method of regenerated cellulose gel microspheres - Google Patents
Preparation method of regenerated cellulose gel microspheres Download PDFInfo
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- CN114014979A CN114014979A CN202111234364.2A CN202111234364A CN114014979A CN 114014979 A CN114014979 A CN 114014979A CN 202111234364 A CN202111234364 A CN 202111234364A CN 114014979 A CN114014979 A CN 114014979A
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- regenerated cellulose
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- cellulose
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- 239000004627 regenerated cellulose Substances 0.000 title claims abstract description 54
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- 238000002360 preparation method Methods 0.000 title claims abstract description 15
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- 230000009471 action Effects 0.000 claims abstract description 8
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- 230000002378 acidificating effect Effects 0.000 claims abstract description 7
- 239000003431 cross linking reagent Substances 0.000 claims abstract description 7
- 239000002904 solvent Substances 0.000 claims abstract description 7
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- 238000005345 coagulation Methods 0.000 claims abstract description 5
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- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- 229920000742 Cotton Polymers 0.000 claims description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 10
- 239000002202 Polyethylene glycol Substances 0.000 claims description 8
- 229920001223 polyethylene glycol Polymers 0.000 claims description 8
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 6
- 239000002585 base Substances 0.000 claims description 6
- 229940057995 liquid paraffin Drugs 0.000 claims description 6
- 238000010907 mechanical stirring Methods 0.000 claims description 6
- 239000005416 organic matter Substances 0.000 claims description 6
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical group ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 claims description 5
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical group CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 claims description 5
- 239000004202 carbamide Substances 0.000 claims description 5
- 230000001112 coagulating effect Effects 0.000 claims description 5
- ZCDADJXRUCOCJE-UHFFFAOYSA-N 2-chlorothioxanthen-9-one Chemical compound C1=CC=C2C(=O)C3=CC(Cl)=CC=C3SC2=C1 ZCDADJXRUCOCJE-UHFFFAOYSA-N 0.000 claims description 4
- 244000025254 Cannabis sativa Species 0.000 claims description 4
- 235000012766 Cannabis sativa ssp. sativa var. sativa Nutrition 0.000 claims description 4
- 235000012765 Cannabis sativa ssp. sativa var. spontanea Nutrition 0.000 claims description 4
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 claims description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 4
- 235000009120 camo Nutrition 0.000 claims description 4
- 235000005607 chanvre indien Nutrition 0.000 claims description 4
- 239000011487 hemp Substances 0.000 claims description 4
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 4
- 229920000053 polysorbate 80 Polymers 0.000 claims description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 claims description 4
- 235000011152 sodium sulphate Nutrition 0.000 claims description 4
- YRHRIQCWCFGUEQ-UHFFFAOYSA-N thioxanthen-9-one Chemical group C1=CC=C2C(=O)C3=CC=CC=C3SC2=C1 YRHRIQCWCFGUEQ-UHFFFAOYSA-N 0.000 claims description 4
- PPZYHOQWRAUWAY-UHFFFAOYSA-N 2-[2-(carboxymethoxy)phenoxy]acetic acid Chemical compound OC(=O)COC1=CC=CC=C1OCC(O)=O PPZYHOQWRAUWAY-UHFFFAOYSA-N 0.000 claims description 3
- KTALPKYXQZGAEG-UHFFFAOYSA-N 2-propan-2-ylthioxanthen-9-one Chemical compound C1=CC=C2C(=O)C3=CC(C(C)C)=CC=C3SC2=C1 KTALPKYXQZGAEG-UHFFFAOYSA-N 0.000 claims description 3
- NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 claims description 3
- 125000004386 diacrylate group Chemical group 0.000 claims description 3
- JVSWJIKNEAIKJW-UHFFFAOYSA-N dimethyl-hexane Natural products CCCCCC(C)C JVSWJIKNEAIKJW-UHFFFAOYSA-N 0.000 claims description 3
- 239000000835 fiber Substances 0.000 claims description 3
- 125000005456 glyceride group Chemical group 0.000 claims description 3
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 3
- 239000003350 kerosene Substances 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 239000003208 petroleum Substances 0.000 claims description 3
- 238000005119 centrifugation Methods 0.000 claims description 2
- 238000004945 emulsification Methods 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 claims 2
- 239000003814 drug Substances 0.000 abstract description 15
- 229940079593 drug Drugs 0.000 abstract description 9
- 238000010526 radical polymerization reaction Methods 0.000 abstract description 9
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- 239000003937 drug carrier Substances 0.000 description 1
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- 238000013467 fragmentation Methods 0.000 description 1
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- 150000004676 glycans Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 238000010550 living polymerization reaction Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
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- 229910052751 metal Inorganic materials 0.000 description 1
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- 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
- C08F251/00—Macromolecular compounds obtained by polymerising monomers on to polysaccharides or derivatives thereof
- C08F251/02—Macromolecular compounds obtained by polymerising monomers on to polysaccharides or derivatives thereof on to cellulose or derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- 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
- C08F2/00—Processes of polymerisation
- C08F2/46—Polymerisation initiated by wave energy or particle radiation
- C08F2/48—Polymerisation initiated by wave energy or particle radiation by ultraviolet or visible light
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J9/00—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2351/00—Characterised by the use of graft polymers in which the grafted component is obtained by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives of such polymers
- C08J2351/02—Characterised by the use of graft polymers in which the grafted component is obtained by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives of such polymers grafted on to polysaccharides
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- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Materials Engineering (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Polymerisation Methods In General (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a preparation method of regenerated cellulose gel microspheres, which comprises the following steps: firstly, dissolving swollen cellulose in a solvent to obtain a cellulose solution, centrifuging to obtain a transparent cellulose solution, adding the transparent cellulose solution into an oil phase and an emulsifier, and stirring to form a suspension system; then adding a cross-linking agent, stirring, carrying out emulsion cross-linking, adding an acidic coagulation bath, and adjusting the pH value of the solution to 5-7 to obtain regenerated cellulose microspheres; and finally, adding the mixture into a bifunctional monomer aqueous solution, uniformly stirring, dropwise adding a water-soluble photoinitiator into the mixed solution, and carrying out polymerization reaction under visible light to obtain the regenerated cellulose gel microspheres. The water-soluble photoinitiator with low biotoxicity and good biocompatibility is utilized to initiate active free radical polymerization with visible light under the action of visible light to prepare the regenerated cellulose-based gel microspheres. The method has simple preparation process and is environment-friendly, and can be used for drugs or enzyme carriers.
Description
Technical Field
The invention belongs to the technical field of preparation of cellulose materials, and particularly relates to a preparation method of regenerated cellulose gel microspheres.
Background
The natural macromolecular compound cellulose is a natural polysaccharide, is derived from plants such as trees, cotton, hemp and the like, can be thoroughly degraded by microorganisms in the nature, is the most abundant natural polymer in the nature, and has wide sources. Besides being used as an adsorbent carrier, the carrier is also a common drug carrier. The cellulose has good biocompatibility and degradability, the skeleton structure is composed of multiple pores, the specific surface area is large, hydroxyl is rich, surface modification is easy to carry out, and a material basis is provided for drug loading. The cellulose microspheres can improve the dispersibility and targeting property of the medicament due to the unique appearance and surface effect, and effectively avoids the inactivation and damage of the medicament in the using process, increases the stability of the medicament and prolongs the lasting period of the medicament by adsorbing or encapsulating the medicament in a porous reticular structure of the cellulose spheres. However, due to the lack of water solubility of cellulose, the network structure formed by the cellulose macromolecular chains may cause drug leakage, and its application is limited. Modification of the outer surface is generally employed to meet the need to reach the target area for drug delivery.
At present, the activity of the drug is greatly influenced due to harsh polymerization conditions in the modification process of the polymer, and the application of polymer synthesis in the aspect of drug loading is limited. The appearance of controllable/"living" free radical polymerization provides an effective means for preparing polymer "valves" with controllable molecular weight, narrow molecular weight distribution index and definite structure. In contrast to conventional radical polymerization reactions, the dynamic equilibrium of reversible passive radical polymerization (RDRP) can be achieved by two methods: one is that the propagating radicals themselves can reversibly deactivate to form dormant species that can establish a dynamic equilibrium between an "active state" and a "dormant state" through a catalytic process, such as Atom Transfer Radical Polymerization (ATRP). Another method is degenerative transfer between propagating radicals and dormant species (DTRP), such as reversible addition fragmentation chain transfer radical polymerization (RARF). But the harsh reaction conditions limit their application. In recent years, with the increasing requirements on the safety performance of biological materials, a new controllable/living radical polymerization method is urgently needed. Visible light, as a mild and effective free radical initiation means, can be used to achieve drug loading. At present, visible light initiated living radical polymerization has been gaining attention, such as visible light initiated ATRP polymerization and visible light initiated RAFT polymerization. Although these polymerization methods play a significant role in the biological field, there are still many obstacles to carrying out the polymerization reaction directly in the presence of drugs, mainly because the reaction conditions are high temperature and strong radiation, and the initiator is metal, strong oxidant or other toxic agent, which limits the application in the biological field. The visible light controllable living polymerization of the reaction at room temperature uses visible light as a light source, uses low-toxicity thioxanthone substances as a photoinitiator, has the advantages of mild reaction, low energy, friendliness to bioactive substances and the like, and is suitable for being used as a method for synthesizing other biological materials. Visible light-initiated free radical polymerization provides a more efficient means for the preparation of materials.
Disclosure of Invention
The invention aims to provide a preparation method of regenerated cellulose gel microspheres, which adopts gel with good biocompatibility to block cellulose micropores and can prevent leakage of medicaments to the maximum extent.
The technical scheme adopted by the invention is that the preparation method of the regenerated cellulose gel microspheres is implemented according to the following steps:
step 1, dissolving swollen cellulose in a solvent to obtain a cellulose solution;
step 2, centrifuging the cellulose solution obtained in the step 1 to obtain a transparent cellulose solution, adding the transparent cellulose solution into the oil phase and the emulsifier, and stirring to form a suspension system;
and 4, adding the regenerated cellulose microspheres obtained in the step 3 into the bifunctional monomer aqueous solution, uniformly stirring, dropwise adding a water-soluble photoinitiator into the mixed solution under the action of mechanical stirring, and carrying out polymerization reaction under visible light to obtain the regenerated cellulose gel microspheres.
The present invention is also characterized in that,
in the step 1, the dissolving temperature is 0 to-13 ℃, and the dissolving time is 30-60 min.
In the step 1, the cellulose is cotton fiber, cotton linter or hemp fiber; the concentration of the cellulose solution is 1-4%; the solvent is prepared from the following components in percentage by mass: 12: 41 of strong base, organic matter and water; the strong base is NaOH or LiOH; the organic matter is urea or thiourea.
In step 2, the centrifugation speed is 4000-10000rpm, and the stirring speed is 600-1000 rpm.
In the step 2, the oil phase is any one of liquid paraffin, kerosene, petroleum ether and isooctane; the emulsifier is Span 80, Tween 80 or fatty glyceride; the volume of the cellulose solution and the oil phase was 1: 5-8, wherein the volume ratio of the oil phase to the emulsifier is 25-30: 1.
in the step 3, the cross-linking agent is epichlorohydrin or glutaraldehyde, and the cross-linking time is 1-3 h; the acidic coagulating bath is sulfuric acid, hydrochloric acid or sodium sulfate solution.
In step 4, the bifunctional monomer aqueous solution is formed by mixing a bifunctional monomer and water; the concentration of the bifunctionality monomer aqueous solution is 1 to 5 percent; the bifunctional monomer is polyethylene glycol or polyethylene glycol (glycol) diacrylate; the photoinitiator is thioxanthone catechol-O, O-diacetic acid, 2-chloro-thioxanthone or 2-isopropyl thioxanthone; the mass ratio of the regenerated cellulose microspheres to the bifunctional monomer aqueous solution to the water-soluble photoinitiator is 1: 2: 2.
in the step 4, the polymerization reaction temperature is 25-37 ℃, and the polymerization reaction time is 1-3 h.
The invention has the beneficial effects that: the method comprises the steps of preparing regenerated cellulose microspheres from natural cellulose which is widely distributed in the natural world and has good biocompatibility as a carrier to load drugs, and then preparing the regenerated cellulose-based gel microspheres by initiating active free radical polymerization with visible light under the action of the visible light by using a water-soluble photoinitiator with low biotoxicity and good biocompatibility. The method has simple preparation process and is environment-friendly, and can be used for drugs or enzyme carriers.
Drawings
FIG. 1 is a surface topography of regenerated cellulose microspheres prepared by the method of the present invention;
FIG. 2 is a surface topography of a regenerated cellulose gel microsphere prepared by the method of the present invention;
FIG. 3 is a diagram showing the distribution of pore size of regenerated cellulose microspheres prepared by the method of the present invention;
FIG. 4 is a diagram showing the distribution of pore size of regenerated cellulose gel microspheres prepared by the method of the present invention.
Detailed Description
The present invention will be described in detail below with reference to the accompanying drawings and specific embodiments.
The invention relates to a preparation method of regenerated cellulose gel microspheres, which is implemented according to the following steps:
step 1, dissolving swollen cellulose in a solvent to obtain a cellulose solution;
the dissolving temperature is 0 to-13 ℃, and the dissolving time is 30-60 min;
the cellulose is cotton fiber, cotton linter or hemp fiber; the concentration of the cellulose solution is 1-4%;
the solvent is prepared from the following components in percentage by mass: 12: 41 of strong base, organic matter and water; the strong base is NaOH or LiOH; the organic matter is urea or thiourea;
step 2, centrifuging the cellulose solution obtained in the step 1 to obtain a transparent cellulose solution, adding the transparent cellulose solution into the oil phase and the emulsifier, and stirring at a high speed to form a suspension system;
the centrifugal speed is 4000-10000rpm, and the stirring speed is 600-1000 rpm;
the oil phase is any one of liquid paraffin, kerosene, petroleum ether and isooctane;
the emulsifier is Span 80, Tween 80 or fatty glyceride;
the volume of the cellulose solution and the oil phase was 1: 5-8, wherein the volume ratio of the oil phase to the emulsifier is 25-30: 1;
the cross-linking agent is epichlorohydrin or glutaraldehyde, and the cross-linking time is 1-3 h;
the acidic coagulating bath is sulfuric acid, hydrochloric acid or sodium sulfate solution;
step 4, adding the regenerated cellulose microspheres obtained in the step 3 into a bifunctional monomer aqueous solution, uniformly stirring, dropwise adding a water-soluble photoinitiator into the mixed solution under the action of mechanical stirring, and carrying out polymerization reaction under visible light to obtain regenerated cellulose gel microspheres;
the bifunctionality monomer aqueous solution is formed by mixing bifunctionality monomers and water; the concentration of the bifunctionality monomer aqueous solution is 1 to 5 percent; the bifunctional monomer is polyethylene glycol (PEG) or polyethylene glycol (glycol) diacrylate (PEGDA);
the photoinitiator is thioxanthone catechol-O, O-diacetic acid (TX-Ct), 2-chloro-thioxanthone (CTX) or 2-Isopropyl Thioxanthone (ITX);
the mass ratio of the regenerated cellulose microspheres to the bifunctional monomer aqueous solution to the water-soluble photoinitiator is 1: 2: 2;
the polymerization temperature is 25-37 ℃, and the polymerization time is 1-3 h.
Example 1
The invention relates to a preparation method of regenerated cellulose gel microspheres, which is implemented according to the following steps:
precooling a NaOH/urea/water solution with the mass ratio of 7/12/41 to-12 ℃, then adding 40mL of water solution containing 3g of cotton linters, and dissolving for 50min to obtain a cellulose solution; the obtained cellulose solution was then centrifuged at 8000rpm to obtain a transparent cellulose solution, which was then added to 2mL of Span 80 and 50mL of liquid paraffin, and stirred at 800rpm for 30min to form a suspension system. Then, 1mL of epichlorohydrin was added dropwise to the resulting suspension, and the resulting suspension was stirred at 1000rpm for 3 hours to emulsify and crosslink. Then adding acid coagulation bath sulfuric acid and adjusting the pH value of the solution to 7 to obtain the regenerated cellulose microspheres. The resulting 5mg regenerated cellulose microspheres were added to 50mL of a 0.2mg/mL photoinitiator TX-Ct solution and stirred for 15 minutes. Then, 50mL of 10 wt% aqueous solution of bifunctional monomer PEGDA was rapidly added to the mixture, and under the action of mechanical stirring, the mixture was irradiated with an LED lamp for 1.5 hours to perform polymerization reaction, thereby obtaining regenerated cellulose gel microspheres.
Example 2
The invention relates to a preparation method of regenerated cellulose gel microspheres, which is implemented according to the following steps:
precooling the NaOH/urea/water solution with the mass ratio of 7/12/41 to-13 ℃, then adding 40mL of water solution containing 2g of cotton fibers, and dissolving for 30min to obtain the cellulose solution. The obtained cellulose solution was then centrifuged at 8000rpm to obtain a clear cellulose solution, which was then added to 2mL of Tween 80 and 50mL of liquid paraffin, and stirred at 800rpm for 30min to form a suspension system. Then, 1mL of glutaraldehyde was added dropwise to the resulting suspension, followed by stirring at 1000rpm for 3 hours to emulsify and crosslink. Then adding acid coagulation bath sulfuric acid and adjusting the pH value of the solution to 7 to obtain the regenerated cellulose microspheres. The 10mg regenerated cellulose microspheres obtained were added to 100mL of a 0.2mg/mL photoinitiator TX-Ct solution and stirred for 15 minutes. Then, 100mL of 10 wt% aqueous solution of bifunctional monomer PEGDA was rapidly added to the mixture, and under the action of mechanical stirring, the mixture was irradiated with an LED lamp for 3 hours to perform polymerization reaction, thereby obtaining regenerated cellulose gel microspheres.
Example 3
The invention relates to a preparation method of regenerated cellulose gel microspheres, which is implemented according to the following steps:
precooling NaOH/thiourea/aqueous solution with the mass ratio of 7/12/41 to-12 ℃, then adding 40mL of aqueous solution containing 4g of cotton linters which are swelled in advance, and dissolving for 1h to obtain cellulose solution. The resulting cellulose solution was then centrifuged at 8000rpm to give a clear cellulose solution, which was then added to 4mL of Span 80 and 100mL of liquid paraffin and stirred at 800rpm for 30min to form a suspension system. Then, 1mL of epichlorohydrin was added dropwise to the resulting suspension, followed by stirring at 1000rpm for 3 hours to emulsify and crosslink. Then adding acid coagulating bath sodium sulfate and adjusting the pH value of the solution to 7 to obtain the regenerated cellulose microspheres. The resulting 5mg regenerated cellulose microspheres were added to 50mL of a 0.2mg/mL photoinitiator TX-Ct solution and stirred for 15 minutes. Then, 50mL of 10 wt% aqueous solution of bifunctional monomer PEGDA is rapidly added into the mixture, and under the action of mechanical stirring, the mixture is irradiated by an LED lamp for 2 hours for polymerization reaction, so that the regenerated cellulose gel microspheres are obtained.
Fig. 1 and fig. 2 are surface topography diagrams of the regenerated cellulose microspheres and the regenerated cellulose gel microspheres prepared by the method of the present invention, respectively, the regenerated cellulose microspheres show good spherical topography, the particle size of the microspheres is about 35 μm, and the surfaces of the microspheres have a grid porous structure. This is due to the direct regeneration of microspheres from cellulose solution in the quasi-gel state and their formation by physical cross-linking and hydrogen bonding interactions, the phase inversion of their sol-gel leads to a porous structure on the cellulose surface. After the PEGDA polymer cross-linked shell is grafted, the particle size of the microsphere is increased, the diameter is about 41 mu m, the surface is smooth, and the pore size of the regenerated cellulose microsphere is effectively improved, which shows that the PEGDA polymer shell is successfully grafted on the surface of the cellulose microsphere. FIGS. 3 and 4 are the pore size distribution diagrams of the prepared regenerated cellulose microspheres and regenerated cellulose gel microspheres, respectively, and the pore size ranges from 20-100nm to 20 nm. This indicates that the use of PEG gel with good biocompatibility to block the cellulose micropores can improve the pore size to the maximum extent.
Claims (8)
1. A preparation method of regenerated cellulose gel microspheres is characterized by comprising the following steps:
step 1, dissolving swollen cellulose in a solvent to obtain a cellulose solution;
step 2, centrifuging the cellulose solution obtained in the step 1 to obtain a transparent cellulose solution, adding the transparent cellulose solution into the oil phase and the emulsifier, and stirring to form a suspension system;
step 3, adding a cross-linking agent into the suspension system obtained in the step 2, stirring, carrying out emulsification cross-linking, then adding an acidic coagulation bath, and adjusting the pH value of the solution to 5-7 to obtain regenerated cellulose microspheres;
and 4, adding the regenerated cellulose microspheres obtained in the step 3 into the bifunctional monomer aqueous solution, uniformly stirring, dropwise adding a water-soluble photoinitiator into the mixed solution under the action of mechanical stirring, and carrying out polymerization reaction under visible light to obtain the regenerated cellulose gel microspheres.
2. The method for preparing regenerated cellulose gel microspheres according to claim 1, wherein in the step 1, the dissolution temperature is 0 to-13 ℃ and the dissolution time is 30 to 60 min.
3. The method for preparing regenerated cellulose gel microspheres according to claim 1, wherein in the step 1, the cellulose is cotton fiber, cotton linter or hemp fiber; the concentration of the cellulose solution is 1-4%; the solvent is prepared from the following components in percentage by mass: 12: 41 of strong base, organic matter and water; the strong base is NaOH or LiOH; the organic matter is urea or thiourea.
4. The method for preparing regenerated cellulose gel microspheres according to claim 1, wherein in the step 2, the centrifugation rate is 4000-10000rpm and the stirring rate is 600-1000 rpm.
5. The method for preparing regenerated cellulose gel microspheres according to claim 1, wherein in the step 2, the oil phase is any one of liquid paraffin, kerosene, petroleum ether and isooctane; the emulsifier is Span 80, Tween 80 or fatty glyceride; the volume of the cellulose solution and the oil phase was 1: 5-8, wherein the volume ratio of the oil phase to the emulsifier is 25-30: 1.
6. the method for preparing regenerated cellulose gel microspheres according to claim 1, wherein in the step 3, the crosslinking agent is epichlorohydrin or glutaraldehyde, and the crosslinking time is 1-3 h; the acidic coagulating bath is sulfuric acid, hydrochloric acid or sodium sulfate solution.
7. The method for preparing regenerated cellulose gel microspheres according to claim 1, wherein in step 4, the aqueous solution of bifunctional monomer is formed by mixing bifunctional monomer and water; the concentration of the bifunctionality monomer aqueous solution is 1 to 5 percent; the bifunctional monomer is polyethylene glycol or polyethylene glycol (glycol) diacrylate; the photoinitiator is thioxanthone catechol-O, O-diacetic acid, 2-chloro-thioxanthone or 2-isopropyl thioxanthone; the mass ratio of the regenerated cellulose microspheres to the bifunctional monomer aqueous solution to the water-soluble photoinitiator is 1: 2: 2.
8. the method for preparing regenerated cellulose gel microspheres according to claim 1, wherein in the step 4, the polymerization temperature is 25-37 ℃ and the polymerization time is 1-3 h.
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