CN108395507A - A kind of preparation method of the lacrimal bolt with drug slow release function - Google Patents
A kind of preparation method of the lacrimal bolt with drug slow release function Download PDFInfo
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- CN108395507A CN108395507A CN201810192574.1A CN201810192574A CN108395507A CN 108395507 A CN108395507 A CN 108395507A CN 201810192574 A CN201810192574 A CN 201810192574A CN 108395507 A CN108395507 A CN 108395507A
- Authority
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- China
- Prior art keywords
- parts
- slow release
- bolt
- lacrimal
- release function
- Prior art date
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- Pending
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- 239000003814 drug Substances 0.000 title claims abstract description 94
- 229940079593 drug Drugs 0.000 title claims abstract description 84
- 238000002360 preparation method Methods 0.000 title claims abstract description 54
- 238000000465 moulding Methods 0.000 claims abstract description 36
- 239000002994 raw material Substances 0.000 claims abstract description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 30
- 239000000017 hydrogel Substances 0.000 claims abstract description 29
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 claims abstract description 21
- 229920002818 (Hydroxyethyl)methacrylate Polymers 0.000 claims abstract description 19
- 238000002791 soaking Methods 0.000 claims abstract description 7
- 238000005406 washing Methods 0.000 claims abstract description 7
- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 claims description 80
- 229910001870 ammonium persulfate Inorganic materials 0.000 claims description 40
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 claims description 31
- 239000003999 initiator Substances 0.000 claims description 30
- KRIOVPPHQSLHCZ-UHFFFAOYSA-N propiophenone Chemical compound CCC(=O)C1=CC=CC=C1 KRIOVPPHQSLHCZ-UHFFFAOYSA-N 0.000 claims description 28
- MPQXHAGKBWFSNV-UHFFFAOYSA-N oxidophosphanium Chemical class [PH3]=O MPQXHAGKBWFSNV-UHFFFAOYSA-N 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 22
- DBCAQXHNJOFNGC-UHFFFAOYSA-N 4-bromo-1,1,1-trifluorobutane Chemical compound FC(F)(F)CCCBr DBCAQXHNJOFNGC-UHFFFAOYSA-N 0.000 claims description 13
- 239000002202 Polyethylene glycol Substances 0.000 claims description 13
- STVZJERGLQHEKB-UHFFFAOYSA-N ethylene glycol dimethacrylate Substances CC(=C)C(=O)OCCOC(=O)C(C)=C STVZJERGLQHEKB-UHFFFAOYSA-N 0.000 claims description 13
- 229920001223 polyethylene glycol Polymers 0.000 claims description 13
- 239000003795 chemical substances by application Substances 0.000 claims description 12
- 125000004386 diacrylate group Chemical group 0.000 claims description 11
- AUONHKJOIZSQGR-UHFFFAOYSA-N oxophosphane Chemical compound P=O AUONHKJOIZSQGR-UHFFFAOYSA-N 0.000 claims description 11
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 239000003431 cross linking reagent Substances 0.000 claims description 4
- KOMNUTZXSVSERR-UHFFFAOYSA-N 1,3,5-tris(prop-2-enyl)-1,3,5-triazinane-2,4,6-trione Chemical compound C=CCN1C(=O)N(CC=C)C(=O)N(CC=C)C1=O KOMNUTZXSVSERR-UHFFFAOYSA-N 0.000 claims description 3
- MDDUHVRJJAFRAU-YZNNVMRBSA-N tert-butyl-[(1r,3s,5z)-3-[tert-butyl(dimethyl)silyl]oxy-5-(2-diphenylphosphorylethylidene)-4-methylidenecyclohexyl]oxy-dimethylsilane Chemical compound C1[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)C(=C)\C1=C/CP(=O)(C=1C=CC=CC=1)C1=CC=CC=C1 MDDUHVRJJAFRAU-YZNNVMRBSA-N 0.000 claims description 3
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 2
- 239000004342 Benzoyl peroxide Substances 0.000 claims description 2
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 claims description 2
- 235000019400 benzoyl peroxide Nutrition 0.000 claims description 2
- GQZONTRHNBGDCL-UHFFFAOYSA-N CC(=O)C.OC1(CC=CC=C1)C Chemical compound CC(=O)C.OC1(CC=CC=C1)C GQZONTRHNBGDCL-UHFFFAOYSA-N 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- -1 acrylic acid glycol ester Chemical class 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims 1
- 230000008961 swelling Effects 0.000 abstract description 13
- 230000000694 effects Effects 0.000 abstract description 11
- 239000000463 material Substances 0.000 abstract description 11
- 206010061218 Inflammation Diseases 0.000 abstract description 5
- 238000002513 implantation Methods 0.000 abstract description 5
- 230000004054 inflammatory process Effects 0.000 abstract description 5
- 238000001356 surgical procedure Methods 0.000 abstract description 4
- 238000012360 testing method Methods 0.000 description 12
- XMLYCEVDHLAQEL-UHFFFAOYSA-N 2-hydroxy-2-methyl-1-phenylpropan-1-one Chemical class CC(C)(O)C(=O)C1=CC=CC=C1 XMLYCEVDHLAQEL-UHFFFAOYSA-N 0.000 description 10
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 9
- 150000002825 nitriles Chemical class 0.000 description 9
- 238000001723 curing Methods 0.000 description 8
- 239000000829 suppository Substances 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 7
- 238000000034 method Methods 0.000 description 6
- 239000002260 anti-inflammatory agent Substances 0.000 description 4
- 229940124599 anti-inflammatory drug Drugs 0.000 description 4
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 208000005189 Embolism Diseases 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 238000003848 UV Light-Curing Methods 0.000 description 3
- 231100000263 cytotoxicity test Toxicity 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- AUHZEENZYGFFBQ-UHFFFAOYSA-N 1,3,5-trimethylbenzene Chemical compound CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 2
- 208000003556 Dry Eye Syndromes Diseases 0.000 description 2
- 206010013774 Dry eye Diseases 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 230000002045 lasting effect Effects 0.000 description 2
- 230000031700 light absorption Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 230000000379 polymerizing effect Effects 0.000 description 2
- 238000013269 sustained drug release Methods 0.000 description 2
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Natural products CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- YFPJFKYCVYXDJK-UHFFFAOYSA-N Diphenylphosphine oxide Chemical compound C=1C=CC=CC=1[P+](=O)C1=CC=CC=C1 YFPJFKYCVYXDJK-UHFFFAOYSA-N 0.000 description 1
- 241000920471 Lucilia caesar Species 0.000 description 1
- 108010019160 Pancreatin Proteins 0.000 description 1
- 206010034960 Photophobia Diseases 0.000 description 1
- 206010047513 Vision blurred Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 206010048222 Xerosis Diseases 0.000 description 1
- OACQXSXVIFBVIO-UHFFFAOYSA-N [O].O=C1CCCCC1 Chemical compound [O].O=C1CCCCC1 OACQXSXVIFBVIO-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 210000000795 conjunctiva Anatomy 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000001339 epidermal cell Anatomy 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 239000010687 lubricating oil Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229920002529 medical grade silicone Polymers 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 229940055695 pancreatin Drugs 0.000 description 1
- 238000000016 photochemical curing Methods 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 210000005239 tubule Anatomy 0.000 description 1
- 208000005494 xerophthalmia Diseases 0.000 description 1
Classifications
-
- 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
- C08F283/00—Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G
- C08F283/06—Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G on to polyethers, polyoxymethylenes or polyacetals
- C08F283/065—Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G on to polyethers, polyoxymethylenes or polyacetals on to unsaturated polyethers, polyoxymethylenes or polyacetals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0015—Medicaments; Biocides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0036—Porous materials, e.g. foams or sponges
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/06—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Surgery (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Materials Engineering (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Dispersion Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a kind of preparation methods of the lacrimal bolt with drug slow release function, include the following steps：(1), the raw material for preparing of lacrimal bolt is uniformly mixed, is injected in mold；(2), mold is reacted to 18~26h at 25~88 DEG C, curing molding obtains tentatively molding hydrogel；(3), 5~30min of preliminary molding hydrogel ultraviolet light, further curing molding obtained by step (2) are obtained into molding hydrogel；(4), molding hydrogel obtained by step (3) is removed from the molds, is taken out after 2~4 days with clear water washing by soaking, it is dry to get the lacrimal bolt with drug slow release function.Lacrimal bolt of the present invention adopts hydroxyethyl methacrylate as base material, can with carrying medicament, after implantation of performing the operation can water swelling, reach self-retaining effect, be conducive to surgical procedure；Controllable adjustment drug release rate；It can be chronically implanted, reduce repulsion and inflammation, there is outstanding biocompatibility.
Description
Technical field
The present invention relates to a kind of preparation methods of high molecular material, and in particular to a kind of tear with drug slow release function is small
The preparation method of pipe bolt.
Background technology
Dry eyes, also known as cornea and conjunctiva xerosis refer to since the exception or tear fluid dynamics of tear quality and quantity are abnormal
Caused tear film is unstable and ocular surface injury, so as to cause a kind of disease of eye discomfort symptoms.The clinical symptoms of xerophthalmia are logical
Often show as dry and astringent, foreign matter, pain, burn, eye is itched, blurred vision, eye is rubescent, photophobia, is shed tears.It is carried out using various emboluses
Lacrimal embolism is a kind of newer lacrimal passage sealing technique to be reduced the discharge of tear, is built again by mechanical obstruction lacrimal passage
The balance of vertical ocular tear, improves ocular environment, to the sings and symptoms of substantially reduced patient's dry eyes.But existing lacrimal passage bolt
Filling in product, there are still some shortcomings, are mainly manifested in following aspect：(1) outer fixed function effect is poor, is easy to fall off；(2) it shrinks
Bulking Time is too fast, is unfavorable for surgical procedure；(3) biocompatibility of material is relatively poor, is chronically implanted and easily causes repulsion
And inflammatory reaction.
Lacrimal bolt used at present, it is most commonly seen with silica type.But silica gel is raw material, is in hydrophobicity, need to be with when implantation
Lubricating oil assist, and be implanted into the period be usually no more than one month, therefore it is overdue need replacing, carry out second operation taking-up, often produce
Raw secondary damage leads to the reactions such as bleeding, inflammation, and then phenomena such as generation granulation hyperplasia.Also lacrimal bolt is by poly- to two
The materials such as oxygen cyclohexanone, acrylic acid and medical grade silicon rubber and the embolus obtained, the biocompatibility of such material is relatively poor, long
Phase implantation is easy to induce body rejection and chronic inflammation.
Invention content
It is provided a kind of with drug slow release function it is an object of the invention to overcome the shortcomings of the prior art place
Lacrimal bolt preparation method.
To achieve the above object, the technical solution that the present invention takes is：A kind of lacrimal bolt with drug slow release function
Preparation method, include the following steps：
(1), the raw material for preparing of lacrimal bolt is uniformly mixed, is injected in mold；
(2), mold is reacted to 18~26h at 25~88 DEG C, curing molding obtains tentatively molding hydrogel；
(3), 5~30min of preliminary molding hydrogel ultraviolet light, further curing molding obtained by step (2) are obtained
Molding hydrogel；
(4), molding hydrogel obtained by step (3) is removed from the molds, is taken out after 2~4 days with clear water washing by soaking,
Drying is to get the lacrimal bolt with drug slow release function；
Wherein, the component for preparing raw material and including following parts by weight of the lacrimal bolt：Hydroxyethyl methacrylate 20~
100 parts, 1~30 part of crosslinking agent, 20~100 parts of water and 0.06~50 part of releaser of reaction；The crosslinking agent is polyethylene glycol two
At least one of acrylate, ethylene glycol dimethacrylate and triallyl isocyanurate；The reaction releaser is
Thermal initiator and photoinitiator.
Lacrimal bolt of the present invention adopts hydroxyethyl methacrylate (HEMA) and is used as base material, can be with carrying medicament, hand
Art implantation after can water swelling, reach self-retaining effect, be conducive to surgical procedure；Controllable adjustment drug release rate, in release
Early period, there is not the phenomenon that burst release, pharmaceutical release time is long；With stronger mechanical property；It can be chronically implanted, the row of reduction
Reprimand and inflammation；Hydroxyl is carried in hydroxyethyl methacrylate side chain, and modification, polymerizing condition can be facilitated simple；With high
Water-wet behavior and outstanding biocompatibility.
The lacrimal bolt of the drying prepared is immersed in the solution containing drug, the porous knot of lacrimal bolt can be utilized
Structure absorbs the drug, and controls the time of immersion, can control the uptake of drug, and user can obtain according to the demand to drug
The lacrimal bolt of relative medicine amount is obtained, drug can be anti-inflammatory drug.
With 2~4 days purposes of clear water washing by soaking it is to remove unreacted preparations original in molding hydrogel in step (3)
Material.
The preparation method simple possible of lacrimal bolt of the present invention, it is low to condition requirement, it is suitable for industrialized production.
The preferred embodiment of preparation method as the lacrimal bolt of the present invention with drug slow release function, it is described
The weight ratio of photoinitiator and thermal initiator is：Photoinitiator：Thermal initiator=1:2.
The lacrimal bolt water-swelling property prepared under the proportioning of above-mentioned photoinitiator and thermal initiator is preferable, it is easier to
Fixed-type, properity is more excellent.
The preferred embodiment of preparation method as the lacrimal bolt of the present invention with drug slow release function, it is described
Photoinitiator is 2- hydroxy-2-methyls propiophenone and/or 2,4,6- trimethylbenzoy-dipheny phosphine oxides；The heat is drawn
Hair agent is at least one of azodiisobutyronitrile, benzoyl peroxide and ammonium persulfate.
The preferred embodiment of preparation method as the lacrimal bolt of the present invention with drug slow release function, it is described
Photoinitiator is the mixture of 2- hydroxy-2-methyls propiophenone and 2,4,6- trimethylbenzoy-dipheny phosphine oxides；It is described
Thermal initiator is the mixture of ammonium persulfate and azodiisobutyronitrile.
The preferred embodiment of preparation method as the lacrimal bolt of the present invention with drug slow release function, it is described
The weight ratio of 2- hydroxy-2-methyls propiophenone and 2,4,6- trimethylbenzoy-dipheny phosphine oxides is：2- hydroxyls -2-
Methyl phenyl ketone：2,4,6- trimethylbenzoy-diphenies phosphine oxide=1:1；The ammonium persulfate and azodiisobutyronitrile
Weight ratio be：Ammonium persulfate：Azodiisobutyronitrile=1:1.
When 2- hydroxy-2-methyls propiophenone and 2, when 4,6- trimethylbenzoy-dipheny phosphine oxides are said ratio,
Photocuring effect is preferable, and when ammonium persulfate and azodiisobutyronitrile are said ratio, solidification effect is best, and efficiency is higher, water suction
Expansion efficiency is higher.
The preferred embodiment of preparation method as the lacrimal bolt of the present invention with drug slow release function, it is described
Lacrimal bolt prepares raw material comprising following parts by weight：35~70 parts of hydroxyethyl methacrylate, polyethyleneglycol diacrylate 1
~10 parts, 1~10 part of ethylene glycol dimethacrylate, 35~70 parts of water, 0.45~5.6 part of 2- hydroxy-2-methyls propiophenone,
Two isobutyl of 0.45~5.6 part of 2,4,6- trimethylbenzoy-diphenies phosphine oxide, 0.45~5.6 part of ammonium persulfate and azo
0.45~5.6 part of nitrile.
Using the lacrimal bolt of said ratio prepare lacrimal bolt that raw material is prepared have good water absorbing properties and
Mechanical property, more preferably, drug effect is more lasting for sustained drug release effect.
The preferred embodiment of preparation method as the lacrimal bolt of the present invention with drug slow release function, it is described
Lacrimal bolt prepares raw material comprising following parts by weight：50 parts of hydroxyethyl methacrylate, 10 parts of polyethyleneglycol diacrylate,
10 parts of ethylene glycol dimethacrylate, 50 parts of water, 2 parts of 2- hydroxy-2-methyls propiophenone, 2,4,6- trimethylbenzoyls-
4 parts of 2 parts of diphenyl phosphine oxide, 4 parts of ammonium persulfate and azodiisobutyronitrile.
Using the lacrimal bolt of said ratio prepare lacrimal bolt that raw material is prepared have good water absorbing properties and
Mechanical property, sustained drug release effect is best, and drug effect is the most lasting.
Another object of the present invention, which also resides in, provides a kind of system using the lacrimal bolt with drug slow release function
The lacrimal bolt with drug slow release function that Preparation Method is prepared.
The beneficial effects of the present invention are：The present invention provides a kind of preparations of the lacrimal bolt with drug slow release function
Method.Lacrimal bolt of the present invention with drug slow release function adopts hydroxyethyl methacrylate as base material, can bear
Carry drug, operation implantation after can water swelling, reach self-retaining effect, be conducive to surgical procedure；Controllable adjustment drug release rate,
In the early period of release, there is not the phenomenon that burst release, pharmaceutical release time is long；With stronger mechanical property；It can plant for a long time
Enter, reduces repulsion and inflammation；Hydroxyl is carried in hydroxyethyl methacrylate side chain, and modification, polymerizing condition can be facilitated simple；
With high water-wet behavior and outstanding biocompatibility.
Description of the drawings
Fig. 1 is the test result of the medicine-releasing performance of the lacrimal bolt with drug slow release function described in embodiment 1；
Fig. 2 is the test knot of the medicine-releasing performance of the lacrimal bolt with drug slow release function described in Examples 1 to 9
Fruit；
Fig. 3 is the swelling behavior test result of the lacrimal bolt with drug slow release function described in Examples 1 to 9.
Specific implementation mode
To better illustrate the object, technical solutions and advantages of the present invention, below in conjunction with specific embodiment to the present invention
It is described further.
Embodiment 1
A kind of embodiment of the preparation method of lacrimal bolt of the present invention with drug slow release function, including following step
Suddenly：
(1), the raw material for preparing of lacrimal bolt is uniformly mixed, is injected in mold；
(2), mold is reacted for 24 hours, curing molding at 50 DEG C, obtains tentatively molding hydrogel；
(3), preliminary molding hydrogel obtained by step (2) is placed in UV curing, ultraviolet light 10min, into one
Curing molding is walked, molding hydrogel is obtained；
(4), molding hydrogel obtained by step (3) is removed from the molds, is taken out after 3 days, is done with clear water washing by soaking
It is dry to get the lacrimal bolt with drug slow release function；
Wherein, the component for preparing raw material and including following parts by weight of the lacrimal bolt：50 parts of hydroxyethyl methacrylate,
10 parts of polyethyleneglycol diacrylate, 10 parts of ethylene glycol dimethacrylate, 50 parts of water, 4 parts of photoinitiator and thermal initiator 8
Part；
The photoinitiator is 2- hydroxy-2-methyls propiophenone and 2,4,6- trimethylbenzoy-dipheny phosphine oxides
Mixture；The weight ratio of the 2- hydroxy-2-methyls propiophenone and 2,4,6- trimethylbenzoy-dipheny phosphine oxides
For 2- hydroxy-2-methyl propiophenones：2,4,6- trimethylbenzoy-diphenies phosphine oxide=1:1；
The thermal initiator is the mixture of ammonium persulfate and azodiisobutyronitrile；Two isobutyl of the ammonium persulfate and azo
The weight ratio of nitrile is：Ammonium persulfate：Azodiisobutyronitrile=1:1.
The tool that a kind of preparation method using the lacrimal bolt with drug slow release function described in the present embodiment is prepared
There is the lacrimal bolt of drug slow release function.
Embodiment 2
A kind of embodiment of the preparation method of lacrimal bolt of the present invention with drug slow release function, the present embodiment institute
That states lacrimal suppository preparation method and embodiment 1 the difference is that only that prepare thermal initiator and the light in raw material of lacrimal bolt draw
The ratio for sending out agent is different, and lacrimal bolt described in the present embodiment prepares raw material comprising following parts by weight：Hydroxyethyl methacrylate 50
Part, 10 parts of polyethyleneglycol diacrylate, 10 parts of ethylene glycol dimethacrylate, 50 parts of water, 6 parts of photoinitiator and thermal initiation
6 parts of agent；
The photoinitiator is 2- hydroxy-2-methyls propiophenone and 2,4,6- trimethylbenzoy-dipheny phosphine oxides
Mixture；The weight ratio of the 2- hydroxy-2-methyls propiophenone and 2,4,6- trimethylbenzoy-dipheny phosphine oxides
For 2- hydroxy-2-methyl propiophenones：2,4,6- trimethylbenzoy-diphenies phosphine oxide=1:1；
The thermal initiator is the mixture of ammonium persulfate and azodiisobutyronitrile；Two isobutyl of the ammonium persulfate and azo
The weight ratio of nitrile is：Ammonium persulfate：Azodiisobutyronitrile=1:1.
Embodiment 3
A kind of embodiment of the preparation method of lacrimal bolt of the present invention with drug slow release function, the present embodiment institute
That states lacrimal suppository preparation method and embodiment 1 the difference is that only that prepare thermal initiator and the light in raw material of lacrimal bolt draw
The ratio for sending out agent is different, and lacrimal bolt described in the present embodiment prepares raw material comprising following parts by weight：Hydroxyethyl methacrylate 50
Part, 10 parts of polyethyleneglycol diacrylate, 10 parts of ethylene glycol dimethacrylate, 50 parts of water, 8 parts of photoinitiator and thermal initiation
4 parts of agent；
The photoinitiator is 2- hydroxy-2-methyls propiophenone and 2,4,6- trimethylbenzoy-dipheny phosphine oxides
Mixture；The weight ratio of the 2- hydroxy-2-methyls propiophenone and 2,4,6- trimethylbenzoy-dipheny phosphine oxides
For 2- hydroxy-2-methyl propiophenones：2,4,6- trimethylbenzoy-diphenies phosphine oxide=1:1；
The thermal initiator is the mixture of ammonium persulfate and azodiisobutyronitrile；Two isobutyl of the ammonium persulfate and azo
The weight ratio of nitrile is：Ammonium persulfate：Azodiisobutyronitrile=1:1.
The tool that a kind of preparation method using the lacrimal bolt with drug slow release function described in the present embodiment is prepared
There is the lacrimal bolt of drug slow release function.
Embodiment 4
A kind of embodiment of the preparation method of lacrimal bolt of the present invention with drug slow release function, the present embodiment institute
That states lacrimal suppository preparation method and embodiment 1 the difference is that only that prepare thermal initiator and the light in raw material of lacrimal bolt draw
The difference of agent is sent out, lacrimal bolt prepares raw material comprising following parts by weight described in the present embodiment：50 parts of hydroxyethyl methacrylate,
10 parts of polyethyleneglycol diacrylate, 10 parts of ethylene glycol dimethacrylate, 50 parts of water, 4 parts of photoinitiator and thermal initiator 8
Part；
The photoinitiator is 2- hydroxy-2-methyl propiophenones；The thermal initiator is two isobutyl of ammonium persulfate and azo
The mixture of nitrile；The weight ratio of the ammonium persulfate and azodiisobutyronitrile is：Ammonium persulfate：Azodiisobutyronitrile=1:1.
The tool that a kind of preparation method using the lacrimal bolt with drug slow release function described in the present embodiment is prepared
There is the lacrimal bolt of drug slow release function.
Embodiment 5
A kind of embodiment of the preparation method of lacrimal bolt of the present invention with drug slow release function, the present embodiment institute
That states lacrimal suppository preparation method and embodiment 1 the difference is that only that prepare thermal initiator and the light in raw material of lacrimal bolt draw
The difference of agent is sent out, lacrimal bolt prepares raw material comprising following parts by weight described in the present embodiment：50 parts of hydroxyethyl methacrylate,
10 parts of polyethyleneglycol diacrylate, 10 parts of ethylene glycol dimethacrylate, 50 parts of water, 4 parts of photoinitiator and thermal initiator 8
Part；
The photoinitiator is 2- hydroxy-2-methyls propiophenone and 2,4,6- trimethylbenzoy-dipheny phosphine oxides
Mixture；The weight ratio of the 2- hydroxy-2-methyls propiophenone and 2,4,6- trimethylbenzoy-dipheny phosphine oxides
For 2- hydroxy-2-methyl propiophenones：2,4,6- trimethylbenzoy-diphenies phosphine oxide=1:1；The thermal initiator was
Ammonium sulfate.
The tool that a kind of preparation method using the lacrimal bolt with drug slow release function described in the present embodiment is prepared
There is the lacrimal bolt of drug slow release function.
Embodiment 6
A kind of embodiment of the preparation method of lacrimal bolt of the present invention with drug slow release function, the present embodiment institute
State the difference for preparing raw material that the difference is that only lacrimal bolt of lacrimal suppository preparation method and embodiment 1, the present embodiment
The lacrimal bolt prepares raw material comprising following parts by weight：35 parts of hydroxyethyl methacrylate, polyethyleneglycol diacrylate 1
Part, 1 part of ethylene glycol dimethacrylate, 35 parts of water, 0.9 part of photoinitiator and 1.8 parts of thermal initiator；
The photoinitiator is 2- hydroxy-2-methyls propiophenone and 2,4,6- trimethylbenzoy-dipheny phosphine oxides
Mixture；The weight ratio of the 2- hydroxy-2-methyls propiophenone and 2,4,6- trimethylbenzoy-dipheny phosphine oxides
For 2- hydroxy-2-methyl propiophenones：2,4,6- trimethylbenzoy-diphenies phosphine oxide=1:1；
The thermal initiator is the mixture of ammonium persulfate and azodiisobutyronitrile；Two isobutyl of the ammonium persulfate and azo
The weight ratio of nitrile is：Ammonium persulfate：Azodiisobutyronitrile=1:1.
The tool that a kind of preparation method using the lacrimal bolt with drug slow release function described in the present embodiment is prepared
There is the lacrimal bolt of drug slow release function.
Embodiment 7
A kind of embodiment of the preparation method of lacrimal bolt of the present invention with drug slow release function, the present embodiment institute
State the difference for preparing raw material that the difference is that only lacrimal bolt of lacrimal suppository preparation method and embodiment 1, the present embodiment
The lacrimal bolt prepares raw material comprising following parts by weight：70 parts of hydroxyethyl methacrylate, polyethyleneglycol diacrylate
7.2 parts of 10 parts, 10 parts of ethylene glycol dimethacrylate, 70 parts of water, 3.6 parts of photoinitiator and thermal initiator；
The photoinitiator is 2- hydroxy-2-methyls propiophenone and 2,4,6- trimethylbenzoy-dipheny phosphine oxides
Mixture；The weight ratio of the 2- hydroxy-2-methyls propiophenone and 2,4,6- trimethylbenzoy-dipheny phosphine oxides
For 2- hydroxy-2-methyl propiophenones：2,4,6- trimethylbenzoy-diphenies phosphine oxide=1:1；
The thermal initiator is the mixture of ammonium persulfate and azodiisobutyronitrile；Two isobutyl of the ammonium persulfate and azo
The weight ratio of nitrile is：Ammonium persulfate：Azodiisobutyronitrile=1:1.
The tool that a kind of preparation method using the lacrimal bolt with drug slow release function described in the present embodiment is prepared
There is the lacrimal bolt of drug slow release function.
Embodiment 8
A kind of embodiment of the preparation method of lacrimal bolt of the present invention with drug slow release function, the present embodiment institute
Lacrimal suppository preparation method is stated to include the following steps：
(1), the raw material for preparing of lacrimal bolt is uniformly mixed, is injected in mold；
(2), mold is reacted into 26h at 88 DEG C, curing molding obtains tentatively molding hydrogel；
(3), preliminary molding hydrogel obtained by step (2) is placed in UV curing, ultraviolet light 30min, into one
Curing molding is walked, molding hydrogel is obtained；
(4), molding hydrogel obtained by step (3) is removed from the molds, is taken out after 4 days, is done with clear water washing by soaking
It is dry to get the lacrimal bolt with drug slow release function；
Wherein, lacrimal bolt described in the present embodiment prepares raw material comprising following parts by weight：Hydroxyethyl methacrylate 20
Part, 1 part of ethylene glycol dimethacrylate, 20 parts of water, 0.02 part of photoinitiator and 0.04 part of thermal initiator；
The photoinitiator is 2- hydroxy-2-methyls propiophenone and 2,4,6- trimethylbenzoy-dipheny phosphine oxides
Mixture；The weight ratio of the 2- hydroxy-2-methyls propiophenone and 2,4,6- trimethylbenzoy-dipheny phosphine oxides
For 2- hydroxy-2-methyl propiophenones：2,4,6- trimethylbenzoy-diphenies phosphine oxide=1:1；
The thermal initiator is the mixture of ammonium persulfate and azodiisobutyronitrile；Two isobutyl of the ammonium persulfate and azo
The weight ratio of nitrile is：Ammonium persulfate：Azodiisobutyronitrile=1:1.
The tool that a kind of preparation method using the lacrimal bolt with drug slow release function described in the present embodiment is prepared
There is the lacrimal bolt of drug slow release function.
Embodiment 9
A kind of embodiment of the preparation method of lacrimal bolt of the present invention with drug slow release function, the present embodiment institute
Lacrimal suppository preparation method is stated to include the following steps：
(1), the raw material for preparing of lacrimal bolt is uniformly mixed, is injected in mold；
(2), mold is reacted into 18h at 25 DEG C, curing molding obtains tentatively molding hydrogel；
(3), preliminary molding hydrogel obtained by step (2) is placed in UV curing, ultraviolet light 5min, further
Curing molding obtains molding hydrogel；
(4), molding hydrogel obtained by step (3) is removed from the molds, is taken out after 2 days, is done with clear water washing by soaking
It is dry to get the lacrimal bolt with drug slow release function；
Wherein, the component for preparing raw material and including following parts by weight of lacrimal bolt described in the present embodiment：Hydroxyethyl methacrylate
30 parts of 100 parts of ethyl ester, 30 parts of triallyl isocyanurate, 100 parts of water, 20 parts of photoinitiator and thermal initiator；
The photoinitiator is 2- hydroxy-2-methyls propiophenone and 2,4,6- trimethylbenzoy-dipheny phosphine oxides
Mixture；The weight ratio of the 2- hydroxy-2-methyls propiophenone and 2,4,6- trimethylbenzoy-dipheny phosphine oxides
For 2- hydroxy-2-methyl propiophenones：2,4,6- trimethylbenzoy-diphenies phosphine oxide=1:1；
The thermal initiator is the mixture of ammonium persulfate and azodiisobutyronitrile；Two isobutyl of the ammonium persulfate and azo
The weight ratio of nitrile is：Ammonium persulfate：Azodiisobutyronitrile=1:1.
The tool that a kind of preparation method using the lacrimal bolt with drug slow release function described in the present embodiment is prepared
There is the lacrimal bolt of drug slow release function.
Embodiment 10
It is prepared by the preparation method for randomly selecting the lacrimal bolt with drug slow release function in 100 embodiments 1,6,8
Made of lacrimal bolt carry out cytotoxicity test.Respectively as test group 1~3, test process is embodiment 1,6,8：According to
The ratio standard of 125mg/L weighs 1,6,8 hydrogel sample 125mg and is positioned in EP pipes, water-swellable overnight with distilling；Second
It blots the distilled water in EP pipes, after hydrogel is carried out high pressure sterilization 1.5h, is dried in baking oven；Weigh the third of 0.007g simultaneously
Acrylamide (0.7% acrylamide) is positioned in EP pipes；The DMEM culture solutions that 1mL is all added in superclean bench impregnate,
Sealed membrane is wrapped, and is stood in small green bottle, is put into incubator and is incubated 48h；The people of logarithmic growth phase immortalizes epidermal cell
(Hacat), it is digested with pancreatin, cell count, the cell suspension that cell density is 7 × 104cell/mL is made, is inoculated in 96 holes
Plate is 200 holes μ L/；After being cultivated for 24 hours in incubator, original fluid is discarded, blank control group is handed over fresh DMEM culture solutions
It changes, positive controls are exchanged with 0.7% acrylamide, and the leaching liquor of hydrogel is added in experimental group, are 200 holes μ L/；In culture
After case culture 48h, the MTT in 20 holes μ L/ is added in withdrawing plate, continues to cultivate 4-6h；Then liquid in hole is discarded, 150 μ L/ are added
The DMSO in hole vibrates 10min, detects absorbance value (OD) under 490nm wavelength with microplate reader detection, takes four hole average values, carefully
Born of the same parents are with respect to appreciation rate (relative growth rate, RGR)=(test group light absorption value/control group light absorption value) × 100%.It will
Cell is converted to six order reactions to evaluate the cytotoxicity degree of sample with respect to appreciation rate, and evaluation criterion is shown in Table 1：
Table 1 reacts grade scale
Note：0 grade or 1 order reaction, show that material sample does not have toxicity；2 order reactions need to use micro- sem observation cell
Form, the variation of combination cell form, carry out judgement material sample has nontoxicity to cell；The reaction of 3 grades or more ranks, explanation
Material sample is toxic to cell.
Cytotoxicity test the results are shown in Table 2.
2 cytotoxicity test result of table
From the results shown in Table 2, RGR illustrates the tear that hydrogel of the present invention is prepared 80% or more
Tubule bolt is non-toxic.
Embodiment 11
The lacrimal bolt that the preparation method of the lacrimal bolt with drug slow release function is prepared described in detection embodiment 1
Drug release process, test method is as follows：The lacrimal bolt with drug slow release function will be prepared to weigh, be denoted as W0, then
It is immersed in anti-inflammatory drug solution, setting different time is drawn liquid medicine and taken out, and blots surface moisture with filter paper, weighs and inhale
Weight after medicine swelling, is denoted as Wt, carrying drug ratio=(Wt-W0)/W0× 100%, detect and record the lacrimal bolt of different carrying drug ratios
Drug release process.
Specifically test process is：To be impregnated in anti-inflammatory drug solution 12h, for 24 hours, 36h, carrying drug ratio is respectively pHEMA-1：
53.26%, pHEMA-2：65.33%, pHEMA-3：68.21%, carry out medicament slow release experiment：Respectively by pHEMA-1, pHEMA-
2, the lacrimal bolt of the different drugloading rates of tri- kinds of pHEMA-3 immerses in phosphate buffer, takes out 1mL at regular intervals and supplements
Same volume phosphate buffer carries out ultravioletvisible absorption analysis under certain wavelength, drug release rate-is obtained by calculation
The curve graph of time, test result are shown in Fig. 1.
The lacrimal bolt with drug slow release function described in embodiment 1 is can be seen that drug from the test result of Fig. 1
Slow release effect is good, and the phase before releasing, the generation of burst release phenomenon does not also occur, and pharmaceutical release time is long.
Lacrimal bolt with drug slow release function described in Examples 1 to 9 impregnates 36h in anti-inflammatory drug, then carries out medicine
Object sustained release experiment, is obtained by calculation the curve graph of drug release rate-time, test result is shown in Fig. 2.
The lacrimal bolt with drug slow release function described in Examples 1 to 9 is can be seen that medicine from the test result of Fig. 2
Object slow release all has good effect, illustrates that lacrimal bolt of the present invention has the function of drug slow release.
Embodiment 12
By the preparation method preparation of the lacrimal bolt with drug slow release function described in the identical Examples 1 to 9 of thickness
At lacrimal bolt carry out swelling behavior test, test result is shown in Fig. 3.
From figure 3, it can be seen that lacrimal bolt of the present invention can be 1.5~2 with water swelling, thickness swelling rate,
It is not easily to fall off after expansion, achieve the effect that self-retaining, wherein the thickness swelling rate highest of embodiment 1；From Examples 1 to 3
Thickness swelling rate to can be seen that the weight ratio of photoinitiator and thermal initiator be 1:When 2, thickness swelling rate is more
It is high；From the thickness swelling rate of embodiment 1,4,5 can be seen that photoinitiator be 2- hydroxy-2-methyls propiophenone and 2,4,
The mixture of 6- trimethylbenzoy-dipheny phosphine oxides；And 2- hydroxy-2-methyls propiophenone and 2,4,6- trimethylbenzene first
The weight ratio of acyl group-diphenyl phosphine oxide is 2- hydroxy-2-methyl propiophenones：2,4,6- trimethylbenzoy-diphenies
Phosphine oxide=1:1；Thermal initiator is the mixture of ammonium persulfate and azodiisobutyronitrile；And ammonium persulfate and azodiisobutyronitrile
Weight ratio be：Ammonium persulfate：Azodiisobutyronitrile=1:When 1, thickness swelling rate higher.
Finally, it should be noted that the above embodiments are merely illustrative of the technical solutions of the present invention rather than is protected to the present invention
The limitation of range is protected, although being explained in detail to the present invention with reference to preferred embodiment, those skilled in the art should
Understand, technical scheme of the present invention can be modified or replaced equivalently, without departing from the essence of technical solution of the present invention
And range.
Claims (8)
1. a kind of preparation method of the lacrimal bolt with drug slow release function, which is characterized in that include the following steps：
(1), the raw material for preparing of lacrimal bolt is uniformly mixed, is injected in mold；
(2), mold is reacted to 18~26h at 25~88 DEG C, curing molding obtains tentatively molding hydrogel；
(3), 5~30min of preliminary molding hydrogel ultraviolet light, further curing molding obtained by step (2) must be molded
Hydrogel；
(4), molding hydrogel obtained by step (3) is removed from the molds, is taken out after 2~4 days, is done with clear water washing by soaking
It is dry to get the lacrimal bolt with drug slow release function；
Wherein, the component for preparing raw material and including following parts by weight of the lacrimal bolt：Hydroxyethyl methacrylate 20~100
Part, 1~30 part of crosslinking agent, 20~100 parts of water and 0.06~50 part of releaser of reaction；The crosslinking agent is two propylene of polyethylene glycol
At least one of acid esters, ethylene glycol dimethacrylate and triallyl isocyanurate；The reaction releaser draws for heat
Send out agent and photoinitiator.
2. the preparation method of the lacrimal bolt with drug slow release function as described in claim 1, which is characterized in that the light draws
Hair agent and the weight ratio of thermal initiator are：Photoinitiator：Thermal initiator=1:2.
3. the preparation method of the lacrimal bolt with drug slow release function as described in claim 1, which is characterized in that the light draws
It is 2- hydroxy-2-methyls propiophenone and/or 2,4,6- trimethylbenzoy-dipheny phosphine oxides to send out agent；The thermal initiator
For at least one of azodiisobutyronitrile, benzoyl peroxide and ammonium persulfate.
4. the preparation method of the lacrimal bolt with drug slow release function as described in claim 1, which is characterized in that the light draws
Send out the mixture that agent is 2- hydroxy-2-methyls propiophenone and 2,4,6- trimethylbenzoy-dipheny phosphine oxides；The heat is drawn
Send out the mixture that agent is ammonium persulfate and azodiisobutyronitrile.
5. the preparation method of the lacrimal bolt with drug slow release function as claimed in claim 4, which is characterized in that the 2- hydroxyls
The weight ratio of base -2- methyl phenyl ketones and 2,4,6- trimethylbenzoy-dipheny phosphine oxides is 2- hydroxy-2-methyl benzene
Acetone：2,4,6- trimethylbenzoy-diphenies phosphine oxide=1:1；The weight of the ammonium persulfate and azodiisobutyronitrile
The ratio between be：Ammonium persulfate：Azodiisobutyronitrile=1:1.
6. the preparation method of the lacrimal bolt with drug slow release function as claimed in claim 3, which is characterized in that the tear is small
Pipe bolt prepares raw material comprising following parts by weight：35~70 parts of hydroxyethyl methacrylate, polyethyleneglycol diacrylate 1~10
Part, 1~10 part of ethylene glycol dimethacrylate, 35~70 parts of water, 0.45~5.6 part of 2- hydroxy-2-methyls propiophenone, 2,4,
0.45~5.6 part of 6- trimethylbenzoy-diphenies phosphine oxide, 0.45~5.6 part of ammonium persulfate and azodiisobutyronitrile
0.45~5.6 part.
7. the preparation method of the lacrimal bolt with drug slow release function as claimed in claim 3, which is characterized in that the tear is small
Pipe bolt prepares raw material comprising following parts by weight：50 parts of hydroxyethyl methacrylate, 10 parts of polyethyleneglycol diacrylate, diformazan
10 parts of base acrylic acid glycol ester, 50 parts of water, 2 parts of 2- hydroxy-2-methyls propiophenone, 2,4,6- trimethylbenzoyls-hexichol
4 parts of 2 parts of base phosphine oxide, 4 parts of ammonium persulfate and azodiisobutyronitrile.
8. a kind of preparation method system using the lacrimal bolt with drug slow release function described in any one of claim 1~7
Lacrimal bolt with drug slow release function made of standby.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810192574.1A CN108395507A (en) | 2018-03-08 | 2018-03-08 | A kind of preparation method of the lacrimal bolt with drug slow release function |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810192574.1A CN108395507A (en) | 2018-03-08 | 2018-03-08 | A kind of preparation method of the lacrimal bolt with drug slow release function |
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| CN108395507A true CN108395507A (en) | 2018-08-14 |
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|---|---|---|---|
| CN201810192574.1A Pending CN108395507A (en) | 2018-03-08 | 2018-03-08 | A kind of preparation method of the lacrimal bolt with drug slow release function |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109350355A (en) * | 2018-11-30 | 2019-02-19 | 西安市第四医院 | A kind of SMILE operation source corneal stroma lens lacrimal passage bolt and preparation method thereof |
| CN111821098A (en) * | 2020-08-20 | 2020-10-27 | 蒋正轩 | Lacrimal passage cannula |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103289099A (en) * | 2013-06-07 | 2013-09-11 | 中科院广州化学有限公司 | Amphiphilic acid-sensitive ternary molecular brush polymer constructed acid-sensitive nanocapsule |
| CN107698720A (en) * | 2017-10-30 | 2018-02-16 | 广州新诚生物科技有限公司 | A kind of artificial nasolacrimal canal and preparation method thereof |
-
2018
- 2018-03-08 CN CN201810192574.1A patent/CN108395507A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103289099A (en) * | 2013-06-07 | 2013-09-11 | 中科院广州化学有限公司 | Amphiphilic acid-sensitive ternary molecular brush polymer constructed acid-sensitive nanocapsule |
| CN107698720A (en) * | 2017-10-30 | 2018-02-16 | 广州新诚生物科技有限公司 | A kind of artificial nasolacrimal canal and preparation method thereof |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109350355A (en) * | 2018-11-30 | 2019-02-19 | 西安市第四医院 | A kind of SMILE operation source corneal stroma lens lacrimal passage bolt and preparation method thereof |
| CN109350355B (en) * | 2018-11-30 | 2023-09-12 | 西安市第四医院 | Corneal stroma lens lacrimal passage plug from SMILE operation and preparation method thereof |
| CN111821098A (en) * | 2020-08-20 | 2020-10-27 | 蒋正轩 | Lacrimal passage cannula |
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