WO2019085363A1 - 一种水凝胶及其应用 - Google Patents

一种水凝胶及其应用 Download PDF

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WO2019085363A1
WO2019085363A1 PCT/CN2018/078144 CN2018078144W WO2019085363A1 WO 2019085363 A1 WO2019085363 A1 WO 2019085363A1 CN 2018078144 W CN2018078144 W CN 2018078144W WO 2019085363 A1 WO2019085363 A1 WO 2019085363A1
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parts
hydrogel
catalyst
water
thermal initiator
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French (fr)
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李锐聪
曾晨光
杨习锋
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广州新诚生物科技有限公司
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    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/16—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/52—Hydrogels or hydrocolloids
    • 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
    • C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
    • C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
    • C08F220/10—Esters
    • C08F220/20—Esters of polyhydric alcohols or phenols, e.g. 2-hydroxyethyl (meth)acrylate or glycerol mono-(meth)acrylate
    • 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
    • C08J3/00—Processes of treating or compounding macromolecular substances
    • C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
    • C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
    • C08J3/075—Macromolecular gels
    • 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
    • C08J2333/00—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Derivatives of such polymers
    • C08J2333/04—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Derivatives of such polymers esters
    • C08J2333/14—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Derivatives of such polymers esters of esters containing halogen, nitrogen, sulfur, or oxygen atoms in addition to the carboxy oxygen

Definitions

  • the invention relates to a polymer material, in particular to a hydrogel and its application.
  • the nasolacrimal duct is the two channels in which the tears are discharged from the eyes into the nasal cavity.
  • the inner part of the bone is called the inside of the bone, about 12.4 mm. It is called the inner part of the nasal cavity in the outer wall of the nasal cavity and is about 5.32 mm long. It is a common eye disease, which is caused by the stenosis or obstruction of the nasolacrimal duct, which causes the tears to stay in the lacrimal sac. The long-term tearing of the patient has seriously affected the quality of life of the patient.
  • the traditional treatment for such diseases is mainly lacrimal passage and nasal cavity anastomosis, but this type of surgery is not only complicated, but also severely damaged, and it is easy to cause scars after surgery.
  • artificial nasolacrimal duct implantation has been proposed. The stent is implanted into the lacrimal sac and the nasolacrimal duct through retrograde expansion of the nasal cavity, and the original anatomical passage of the lacrimal passage is not changed, the injury is small, and the surgical adaptability is wide.
  • the artificial artificial nasolacrimal duct stent is mainly made of the following materials: (1) Metal material: mostly made of alloy, the support effect is good, but the hardness is high, it is not easy to bend and deform, the lumen clogging rate is high, and the complications are many. (2) Glass: better support, but obvious foreign body sensation; (3) medical silicone rubber: stable physical and chemical properties, non-toxic, non-rejection reaction; but due to the soft texture of silica gel, easy to be congenital The small nasolacrimal duct is squeezed and narrowed, which affects the curative effect; (4) Polyurethane: moderate hardness and good support, but poor biocompatibility, long-term placement is easy to induce body rejection and chronic inflammation.
  • a hydrogel comprising the following raw materials in parts by weight:
  • the crosslinking agent is at least one of polyethylene glycol diacrylate, ethylene glycol dimethacrylate and triallyl isocyanurate;
  • the reaction initiator is a mixture of a thermal initiator and a catalyst Or a photoinitiator.
  • the invention uses hydroxyethyl methacrylate (HEMA) as a substrate to prepare a hydrogel, which has the following advantages: (1) good biocompatibility and stability in human body. (2) good hydrophilicity, good water absorption; (3) strong mechanical properties; (4) hydroxyl groups in the side chain, easy to modify, simple polymerization conditions.
  • HEMA hydroxyethyl methacrylate
  • the obtained hydrogel has better water absorption and properties.
  • the photoinitiator is 2-hydroxy-2-methylpropiophenone and/or 2,4,6-trimethylbenzoyl-diphenylphosphine oxide;
  • the thermal initiator is azodi At least one of isobutyronitrile, benzoyl peroxide, and ammonium persulfate.
  • the photoinitiator is 2-hydroxy-2-methylpropiophenone; the thermal initiator is ammonium persulfate.
  • the catalyst is N,N,N',N'-tetramethylethylenediamine.
  • the hydrogel comprises the following raw materials in parts by weight: 30-60 parts of hydroxyethyl methacrylate, 1-20 parts of polyethylene glycol diacrylate, 30-60 parts of water, and 0.93 of ammonium persulfate. 11.2 parts and 0.93 to 11.2 parts of the catalyst.
  • the water gel obtained by the above formulation has better water absorption properties and mechanical properties.
  • the hydrogel comprises the following raw materials in parts by weight: 40 parts of hydroxyethyl methacrylate, 20 parts of polyethylene glycol diacrylate, 40 parts of water, 5 parts of ammonium persulfate, and 10 parts of a catalyst.
  • the hydrogel prepared by the above formula has the best water absorption performance and mechanical properties.
  • Another object of the present invention is to provide an artificial nasolacrimal tube comprising the above hydrogel.
  • the artificial nasolacrimal duct prepared by using the hydrogel material of the invention has the following advantages: (1) the hydrogel of the invention has good hydrophilicity and high tear guiding efficiency; (2) Better biocompatibility and stability, can achieve longer implantation period, long-term placement is not easy to cause rejection and inflammatory reaction; (3), can be swelled by water, can achieve self-fixation effect; (4) planting The input method is simple and easy to operate.
  • the artificial nasolacrimal duct prepared by the hydrogel material of the invention has a water absorption thickness expansion ratio of 1.5 to 2.
  • the doctor introduces the artificial nasolacrimal duct into the human nasolacrimal duct, and the artificial nasolacrimal duct absorbs water and expands to fill the human nasolacrimal duct to achieve the self-fixing effect.
  • the artificial nasolacrimal duct is in the nasolacrimal duct of the human body.
  • the fixing effect is good, and it is not easy to fall off after the water swells.
  • the invention has the beneficial effects that the invention provides a hydrogel, and the hydrogel of the invention has good hydrophilic property, strong mechanical property and good biocompatibility and stability in the human body. .
  • the invention also provides an artificial nasolacrimal duct comprising the hydrogel of the invention.
  • the artificial nasolacrimal duct containing the hydrogel of the invention can have high tear guiding efficiency, good biocompatibility and stability, can obtain a longer implantation period, and is not easy to cause rejection in long-term implantation. It reacts with inflammation; it can absorb water and swell, and can achieve self-fixation effect; the implantation method is simple and easy to operate.
  • An embodiment of the hydrogel of the present invention comprises the following raw materials in parts by weight: 40 parts of hydroxyethyl methacrylate, 20 parts of a crosslinking agent, 40 parts of water, 5 parts of a thermal initiator and 10 parts of a catalyst;
  • crosslinking agent is polyethylene glycol diacrylate
  • thermal initiator is azobisisobutyronitrile
  • catalyst is N, N, N', N'-tetramethylethylenediamine.
  • An artificial nasolacrimal tube comprising the hydrogel of the present embodiment.
  • the hydrogel of the present embodiment differs from the first embodiment only in the ratio of the thermal initiator to the catalyst.
  • the hydrogel of the present embodiment comprises the following weight. Preparation of raw materials: 40 parts of hydroxyethyl methacrylate, 20 parts of cross-linking agent, 40 parts of water, 5 parts of thermal initiator and 5 parts of catalyst;
  • crosslinking agent is polyethylene glycol diacrylate
  • thermal initiator is azobisisobutyronitrile
  • catalyst is N, N, N', N'-tetramethylethylenediamine.
  • An artificial nasolacrimal tube comprising the hydrogel of the present embodiment.
  • the hydrogel of the present embodiment differs from the first embodiment only in the ratio of the thermal initiator to the catalyst.
  • the hydrogel of the present embodiment comprises the following weight. Preparation of raw materials: 40 parts of hydroxyethyl methacrylate, 20 parts of cross-linking agent, 40 parts of water, 5 parts of thermal initiator and 15 parts of catalyst;
  • crosslinking agent is polyethylene glycol diacrylate
  • thermal initiator is azobisisobutyronitrile
  • catalyst is N, N, N', N'-tetramethylethylenediamine.
  • An artificial nasolacrimal tube comprising the hydrogel of the present embodiment.
  • An embodiment of the hydrogel of the present invention comprises the following raw materials by weight: 40 parts of hydroxyethyl methacrylate, 30 parts of a crosslinking agent, 40 parts of water, 5 parts of a thermal initiator and 5 parts of a catalyst;
  • crosslinking agent is polyethylene glycol diacrylate
  • thermal initiator is azobisisobutyronitrile
  • catalyst is N, N, N', N'-tetramethylethylenediamine.
  • An artificial nasolacrimal tube comprising the hydrogel of the present embodiment.
  • An embodiment of the hydrogel of the present invention comprises the following raw materials in parts by weight: 40 parts of hydroxyethyl methacrylate, 20 parts of a crosslinking agent, 30 parts of water, and 11 parts of a photoinitiator;
  • crosslinking agent is polyethylene glycol diacrylate
  • photoinitiator is 2-hydroxy-2-methylpropiophenone
  • An artificial nasolacrimal tube comprising the hydrogel of the present embodiment.
  • An embodiment of the hydrogel of the present invention comprises the following raw materials in parts by weight: 40 parts of hydroxyethyl methacrylate, 20 parts of a crosslinking agent, 30 parts of water, and 11 parts of a photoinitiator;
  • crosslinking agent is triallyl isocyanurate and the photoinitiator is 2,4,6-trimethylbenzoyl-diphenylphosphine oxide.
  • An artificial nasolacrimal tube comprising the hydrogel of the present embodiment.
  • An embodiment of the hydrogel of the present invention comprises the following raw materials by weight: 10 parts of hydroxyethyl methacrylate, 1 part of crosslinking agent, 10 parts of water and 0.042 parts of photoinitiator;
  • crosslinking agent is ethylene glycol dimethacrylate
  • photoinitiator is 2,4,6-trimethylbenzoyl-diphenylphosphine oxide.
  • An artificial nasolacrimal tube comprising the hydrogel of the present embodiment.
  • hydrogel of the present invention comprises the following raw materials by weight: 80 parts of hydroxyethyl methacrylate, 10 parts of a crosslinking agent, 10 parts of water, 10 parts of a thermal initiator and 10 parts of a catalyst;
  • crosslinking agent is polyethylene glycol diacrylate
  • thermal initiator is benzoyl peroxide
  • the catalyst is N, N, N', N'-tetramethylethylenediamine.
  • An artificial nasolacrimal tube comprising the hydrogel of the present embodiment.
  • An embodiment of the hydrogel of the present invention comprises the following raw materials in parts by weight: 10 parts of hydroxyethyl methacrylate, 10 parts of a crosslinking agent, 80 parts of water, 3 parts of a thermal initiator and 3 parts of a catalyst;
  • crosslinking agent is polyethylene glycol diacrylate
  • thermal initiator is azobisisobutyronitrile
  • catalyst is N, N, N', N'-tetramethylethylenediamine.
  • An artificial nasolacrimal tube comprising the hydrogel of the present embodiment.
  • Example 1 100 artificial nasolacrimal ducts in Examples 1, 4, and 5 were randomly selected for cytotoxicity test. Examples 1, 4, and 5 were used as test groups 1 to 3, respectively.
  • the test procedure was as follows: according to the ratio of 125 mg/L. 125 mg of the 1, 4, and 5 hydrogel samples were placed in an EP tube and swelled with distilled water overnight; the next day, the distilled water in the EP tube was blotted, and the hydrogel was autoclaved for 1.5 h, and then dried in an oven; Amount of 0.007g of acrylamide (0.7% acrylamide) was placed in the EP tube; 1 mL of DMEM medium was added to the ultra-clean workbench, the sealing film was wrapped, placed in a small blue bottle, and placed in an incubator.
  • Human immortalized epithelial cells (Hacat) in logarithmic growth phase were digested with trypsin and counted to prepare a cell suspension with a cell density of 7 ⁇ 10 4 cells/mL, and seeded in a 96-well plate at 200 ⁇ L/well.
  • the original culture solution was discarded, the blank control group was exchanged with fresh DMEM medium, the positive control group was exchanged with 0.7% acrylamide, and the experimental group was added with hydrogel extract, which was 200 ⁇ L/ Hole; after incubating for 48 hours in the incubator, the plate was taken out and 20 ⁇ L/well of MTT was added.
  • the relative nucleation rate of the cells was converted into a gradation reaction to evaluate the cytotoxicity of the samples.
  • the evaluation criteria are shown in Table 1:
  • Level 0 or Class 1 reaction indicates that the material sample is not toxic; in the second-order reaction, it is necessary to observe the cell morphology by microscope, and combine with the change of cell morphology to judge whether the material sample is toxic to the cells; the reaction of level 3 or above, Indicate that the material sample is toxic to the cells.
  • the artificial nasolacrimal duct of the present invention can absorb water and swell, and the water absorbing thickness expansion ratio is 1.5 to 2, and it is not easy to fall off after expansion, and the self-fixing effect is achieved, wherein the water absorbing thickness expansion rate of the embodiment 1 is the highest; It can be seen from the water absorbing thickness expansion ratios of Examples 1 to 3 that the water absorbing thickness expansion ratio is higher when the weight ratio of the thermal initiator to the catalyst is 1:2; the water absorbing thickness expansion ratios of Examples 5 and 6 can be It can be seen that when the photocatalyst is 2-hydroxy-2-methylpropiophenone, the water swelling effect is better.

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Abstract

提供了一种水凝胶，包含以下重量份的制备原料：甲基丙烯酸羟乙酯10～80份、交联剂1～20份、水10～80份和反应引发物0.042～36份；所述交联剂为聚乙二醇二丙烯酸酯、二甲基丙烯酸乙二醇酯和异氰脲酸三烯丙酯中的至少一种；所述反应引发物为热引发剂和催化剂的混合物或光引发剂。所述水凝胶亲水性能好，具有较强的力学性能，在人体内有较好的生物相容性和稳定性。还提供了一种含有所述水凝胶的人工鼻泪管，该人工鼻泪管具有较高的泪液引导效率，较好的生物相容性和稳定性，能获得更长的植入周期，长期置入也不容易引起排斥和炎症反应；可吸水膨胀，能达到自固定效果；植入方式简单，易操作。

Description

一种水凝胶及其应用 技术领域
本发明涉及一种高分子材料，具体涉及一种水凝胶及其应用。
背景技术
鼻泪管是眼泪从眼睛排入鼻腔的两个管道，位于骨性官腔内的称为骨内部，约12.4mm，位于鼻腔外侧壁粘膜内的称为鼻内部，长约5.32mm。溢泪是常见的一种较常见的眼病，因鼻泪管狭窄或阻塞，致使泪液滞留于泪囊之内引起的多发病，该疾病患者长期流泪，严重影响患者的生活质量。目前治疗此类疾病的传统的治疗手段主要是泪道探通术跟泪囊鼻腔吻合术，但该类手术不仅操作复杂，损伤严重，还容易导致术后遗留疤痕。针对现有手术方法的不足，有人提出了人工鼻泪管植入术。经由鼻腔逆行扩张将支架植入泪囊及鼻泪管，不改变泪道原有解剖通道，损伤小，手术适应性广。
目前常见的人工鼻泪管支架主要是由以下材料制作而成：(1)金属材料：多由合金制成，支撑作用较好，但硬度高不易弯曲变形，管腔堵塞率高，并发症多，目前已经很少用；(2)玻璃：支撑作用较好，但异物感明显；(3)医用硅橡胶：理化性质稳定、无毒、无排斥反应；但由于硅胶质地较软，易被先天细小的鼻泪管挤压而变窄，影响疗效；(4)聚氨基甲酸乙酯：硬度适中支撑作用较好，但生物相容性较差，长期置入容易诱发机体排斥反应和慢性炎症。
发明内容
本发明的目的在于克服现有技术存在的不足之处而提供一种水凝胶及其应用。
为实现上述目的，本发明采取的技术方案为：一种水凝胶，包含以下重量份的制备原料：
甲基丙烯酸羟乙酯10～80份、交联剂1～20份、水10～80份和反应引发物 0.042～36份；
所述交联剂为聚乙二醇二丙烯酸酯、二甲基丙烯酸乙二醇酯和异氰脲酸三烯丙酯中的至少一种；所述反应引发物为热引发剂和催化剂的混合物或光引发剂。
本发明用甲基丙烯酸羟基乙酯(HEMA)作为基材，制得一种水凝胶，所述水凝胶具有以下优点：(1)在人体内有较好的生物相容性和稳定性；(2)亲水性佳，拥有良好的吸水性能；(3)具有较强的力学性能；(4)侧链中带有羟基，能够方便改性，聚合条件简单。
优选地，所述热引发剂和催化剂的重量之比为：热引发剂：催化剂＝1:2。
当热引发剂和催化剂采用上述配比时，制得的水凝胶的吸水性和性能较佳。
优选地，所述光引发剂为2-羟基-2-甲基苯丙酮和/或2,4,6-三甲基苯甲酰基-二苯基氧化膦；所述热引发剂为偶氮二异丁腈、过氧化苯甲酰和过硫酸铵中的至少一种。
优选地，所述光引发剂为2-羟基-2-甲基苯丙酮；所述热引发剂为过硫酸铵。优选地，所述催化剂为N,N,N',N'-四甲基乙二胺。
优选地，所述水凝胶包含以下重量份的制备原料：甲基丙烯酸羟乙酯30～60份、聚乙二醇二丙烯酸酯1～20份、水30～60份、过硫酸铵0.93～11.2份和催化剂0.93～11.2份。
采用上述配方制得的水凝胶的吸水性能和力学性能较佳。
更优选地，所述水凝胶包含以下重量份的制备原料：甲基丙烯酸羟乙酯40份、聚乙二醇二丙烯酸酯20份、水40份、过硫酸铵5份和催化剂10份。
采用上述配方制得的水凝胶吸水性能和力学性能最佳。
本发明的另一目的在于提供一种包含上述水凝胶的人工鼻泪管。
选用本发明所述水凝胶材料制备而成的人工鼻泪管，具有以下优点：(1) 本发明所述水凝胶亲水性好，具有较高的泪液引导效率；(2)、具有较好的生物相容性和稳定性，能获得更长的植入周期，长期置入也不容易引起排斥和炎症反应；(3)、可吸水膨胀，能达到自固定效果；(4)植入方式简单，易操作。本发明所述水凝胶材料制备而成的人工鼻泪管的吸水厚度膨胀率为1.5～2。在治疗过程中，医生将人工鼻泪管导入人体鼻泪管内，人工鼻泪管吸水膨胀，填充人体的鼻泪管，达到自固定的效果，所述人工鼻泪管在人体的鼻泪管内的固定效果好，吸水膨胀后不容易脱落。
本发明的有益效果在于：本发明提供了一种水凝胶，本发明所述水凝胶亲水性能好，具有较强的力学性能，在人体内有较好的生物相容性和稳定性。本发明还提供了一种含有本发明所述水凝胶的人工鼻泪管。含有本发明所述水凝胶的人工鼻泪管能具有较高的泪液引导效率，较好的生物相容性和稳定性，能获得更长的植入周期，长期置入也不容易引起排斥和炎症反应；可吸水膨胀，能达到自固定效果；植入方式简单，易操作。
附图说明
图1为实施例1～9所述人工鼻泪管的溶胀性能测试结果。
具体实施方式
为更好的说明本发明的目的、技术方案和优点，下面将结合具体实施例对本发明作进一步说明。
实施例1
本发明所述水凝胶一种实施例，包含以下重量份的制备原料：甲基丙烯酸羟乙酯40份、交联剂20份、水40份、热引发剂5份和催化剂10份；
其中，所述交联剂为聚乙二醇二丙烯酸酯，所述热引发剂为偶氮二异丁腈，所述催化剂为N,N,N',N'-四甲基乙二胺。
一种包含本实施例所述水凝胶的人工鼻泪管。
实施例2
本发明所述水凝胶一种实施例，本实施例所述水凝胶与实施例1的不同之处仅在于热引发剂和催化剂的比不同，本实施例所述水凝胶包含以下重量份的制备原料：甲基丙烯酸羟乙酯40份、交联剂20份、水40份、热引发剂5份和催化剂5份；
其中，所述交联剂为聚乙二醇二丙烯酸酯，所述热引发剂为偶氮二异丁腈，所述催化剂为N,N,N',N'-四甲基乙二胺。
一种包含本实施例所述水凝胶的人工鼻泪管。
实施例3
本发明所述水凝胶一种实施例，本实施例所述水凝胶与实施例1的不同之处仅在于热引发剂和催化剂的比不同，本实施例所述水凝胶包含以下重量份的制备原料：甲基丙烯酸羟乙酯40份、交联剂20份、水40份、热引发剂5份和催化剂15份；
其中，所述交联剂为聚乙二醇二丙烯酸酯，所述热引发剂为偶氮二异丁腈，所述催化剂为N,N,N',N'-四甲基乙二胺。
一种包含本实施例所述水凝胶的人工鼻泪管。
实施例4
本发明所述水凝胶一种实施例，包含以下重量份的制备原料：甲基丙烯酸羟乙酯40份、交联剂30份、水40份、热引发剂5份和催化剂5份；
其中，所述交联剂为聚乙二醇二丙烯酸酯，所述热引发剂为偶氮二异丁腈，所述催化剂为N,N,N',N'-四甲基乙二胺。
一种包含本实施例所述水凝胶的人工鼻泪管。
实施例5
本发明所述水凝胶一种实施例，包含以下重量份的制备原料：甲基丙烯酸羟乙酯40份、交联剂20份、水30份、光引发剂11份；
其中，所述交联剂为聚乙二醇二丙烯酸酯，所述光引发剂为2-羟基-2-甲基 苯丙酮。
一种包含本实施例所述水凝胶的人工鼻泪管。
实施例6
本发明所述水凝胶一种实施例，包含以下重量份的制备原料：甲基丙烯酸羟乙酯40份、交联剂20份、水30份、光引发剂11份；
其中，所述交联剂为异氰脲酸三烯丙酯，所述光引发剂为2,4,6-三甲基苯甲酰基-二苯基氧化膦。
一种包含本实施例所述水凝胶的人工鼻泪管。
实施例7
本发明所述水凝胶一种实施例，包含以下重量份的制备原料：甲基丙烯酸羟乙酯10份、交联剂1份、水10份和光引发剂0.042份；
其中，所述交联剂为二甲基丙烯酸乙二醇酯，所述光引发剂为2,4,6-三甲基苯甲酰基-二苯基氧化膦。
一种包含本实施例所述水凝胶的人工鼻泪管。
实施例8
本发明所述水凝胶一种实施例，包含以下重量份的制备原料：甲基丙烯酸羟乙酯80份、交联剂10份、水10份、热引发剂10份和催化剂10份；
其中，所述交联剂为聚乙二醇二丙烯酸酯，所述热引发剂为过氧化苯甲酰，所述催化剂为N,N,N',N'-四甲基乙二胺。
一种包含本实施例所述水凝胶的人工鼻泪管。
实施例9
本发明所述水凝胶一种实施例，包含以下重量份的制备原料：甲基丙烯酸羟乙酯10份、交联剂10份、水80份、热引发剂3份和催化剂3份；
其中，所述交联剂为聚乙二醇二丙烯酸酯，所述热引发剂为偶氮二异丁腈， 所述催化剂为N,N,N',N'-四甲基乙二胺。
一种包含本实施例所述水凝胶的人工鼻泪管。
实施例10
随机抽取100支实施例1、4、5中的人工鼻泪管进行细胞毒性测试，实施例1、4、5分别作为试验组1～3，测试过程为：按照125mg/L的比例标准，称量1、4、5水凝胶样品125mg放置于EP管内，用蒸馏水溶胀过夜；第二天吸干EP管内的蒸馏水，将水凝胶进行高压灭菌1.5h后，在烘箱烘干；同时称量0.007g的丙烯酰胺(0.7％的丙烯酰胺)放置于EP管内；在超净工作台中都加入1mL的DMEM培养液浸泡，封口膜包好，立于小青瓶中，放入培养箱中孵育48h；取对数生长期的人永生化表皮细胞(Hacat)，用胰酶消化，细胞计数，制成细胞密度为7×104cell/mL的细胞悬液，接种于96孔板，为200μL/孔；于培养箱中培养24h后，弃去原培养液，空白对照组用新鲜DMEM培养液交换，阳性对照组用0.7％的丙烯酰胺交换，实验组加入水凝胶的浸提液，为200μL/孔；于培养箱培养48h后，取出板，加入20μL/孔的MTT，继续培养4-6h；然后弃去孔内液体，加入150μL/孔的DMSO，振荡10min，用酶标仪检测在490nm波长下检测光吸收值(OD)，取四孔平均值，细胞相对增值率(relative growth rate，RGR)＝(试验组吸光值/对照组吸光值)×100％。
将细胞相对增值率转换为六级反应来评价样品的细胞毒性程度，评价标准见表1：
表1 反应分级标准
Figure PCTCN2018078144-appb-000001
注：0级或者1级反应，表明材料样品没有毒性；2级反应，需要采用显微镜观察细胞形态，结合细胞形态的变化，来判断材料样品对细胞有无毒性；3级或以上级别的反应，说明材料样品对细胞有毒性。
细胞毒性测试结果见表2。
表2 细胞毒性测试结果
组别 1 2 3 和 平均值 校正值 RGR RGR％ 分级
试验组1 2.148 2.367 2.407 6.922 2.307 1.544 1.0510 105.10％ 1
试验组2 2.066 1.875 1.858 5.799 1.933 1.170 0.8806 88.06％ 1
试验组3 2.212 1.698 1.958 5.85 1.95 1.187 0.8883 88.88％ 1
对照组 2.275 2.163 2.148 6.586 2.195 1.432 / / /
空白组 0.732 0.787 0.769 2.288 0.763 0 / / /
从表2的结果可以看出，RGR均在80％以上，说明本发明所述水凝胶制备而成的人工鼻泪管无毒性。
实施例11
将厚度相同的实施例1～9所述人工鼻泪管进行溶胀性能测试，测试结果见图1。
从图1可以看出，本发明所述人工鼻泪管可以吸水膨胀，吸水厚度膨胀率为1.5～2，膨胀后不易脱落，达到自固定的效果，其中实施例1的吸水厚度膨胀率最高；从实施例1～3的吸水厚度膨胀率可以看出，热引发剂和催化剂的重量比为1:2时，吸水厚度膨胀率更高；从实施例5和实施例6的吸水厚度膨胀率可以看出，光催化剂为2-羟基-2-甲基苯丙酮时，吸水膨胀效果更好。
最后所应当说明的是，以上实施例仅用以说明本发明的技术方案而非对本发明保护范围的限制，尽管参照较佳实施例对本发明作了详细说明，本领域的 普通技术人员应当理解，可以对本发明的技术方案进行修改或者等同替换，而不脱离本发明技术方案的实质和范围。

Claims (8)

  1. 一种水凝胶，其特征在于，包含以下重量份的制备原料：
    甲基丙烯酸羟乙酯10～80份、交联剂1～20份、水10～80份和反应引发物0.042～36份；
    所述交联剂为聚乙二醇二丙烯酸酯、二甲基丙烯酸乙二醇酯和异氰脲酸三烯丙酯中的至少一种；所述反应引发物为热引发剂和催化剂的混合物或光引发剂。
  2. 如权利要求1所述水凝胶，其特征在于，所述热引发剂和催化剂的重量之比为：热引发剂：催化剂＝1:2。
  3. 如权利要求1所述水凝胶，其特征在于，所述光引发剂为2-羟基-2-甲基苯丙酮和/或2,4,6-三甲基苯甲酰基-二苯基氧化膦；所述热引发剂为偶氮二异丁腈、过氧化苯甲酰和过硫酸铵中的至少一种。
  4. 如权利要求1所述水凝胶，其特征在于，所述光引发剂为2-羟基-2-甲基苯丙酮；所述热引发剂为过硫酸铵。
  5. 如权利要求1所述水凝胶，其特征在于，所述催化剂为N,N,N',N'-四甲基乙二胺。
  6. 如权利要求3所述水凝胶，其特征在于，所述水凝胶包含以下重量份的制备原料：甲基丙烯酸羟乙酯30～60份、聚乙二醇二丙烯酸酯1～20份、水30～60份、过硫酸铵0.93～11.2份和催化剂0.93～11.2份。
  7. 如权利要求3所述水凝胶，其特征在于，所述水凝胶包含以下重量份的制备原料：甲基丙烯酸羟乙酯40份、聚乙二醇二丙烯酸酯20份、水40份、过硫酸铵5份和催化剂10份。
  8. 一种包含权利要求1～7中任一项所述水凝胶的人工鼻泪管。
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Publication number Priority date Publication date Assignee Title
CN110269741B (zh) * 2019-05-28 2021-10-12 广州新诚生物科技有限公司 一种二次膨胀泪点塞的制备方法
CN110269742A (zh) * 2019-05-28 2019-09-24 广州新诚生物科技有限公司 一种空心水凝胶泪点塞的制备方法
CN110643055A (zh) * 2019-10-08 2020-01-03 宁波瑞瑧生物科技有限公司 水凝胶及其制备方法、生物膜固定装置和应用
CN110859999B (zh) * 2019-10-11 2021-02-02 南方医科大学 一种三维血管网络水凝胶的构建方法
CN112480309B (zh) * 2020-11-25 2021-12-28 复旦大学 一种可变形智能水凝胶机器人及其制备方法
CN112480308B (zh) * 2020-11-25 2022-03-18 复旦大学 一种智能水凝胶及其制备方法
CN112592493B (zh) * 2020-11-25 2022-01-28 复旦大学 一种可巡游可收集水面塑料污染物的智能水凝胶机器人及其制备方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1730515A (zh) * 2005-08-26 2006-02-08 徐州恩华药业集团有限责任公司 一种制备水凝胶的方法
CN105367712A (zh) * 2015-10-29 2016-03-02 温州医科大学 一种复合水凝胶及其制备方法
CN106633121A (zh) * 2016-11-15 2017-05-10 深圳先进技术研究院 用于三维打印的粘土基水凝胶基质及其制备方法和应用
CN107206119A (zh) * 2014-12-09 2017-09-26 实体科学有限责任公司 具有生物相容性层的医疗设备涂层
CN107698720A (zh) * 2017-10-30 2018-02-16 广州新诚生物科技有限公司 一种人工鼻泪管及其制备方法

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1424115A (zh) * 2002-12-06 2003-06-18 暨南大学 组织工程支架材料及其制备方法
CN103815986B (zh) * 2014-02-27 2016-08-17 广州新诚生物科技有限公司 人工鼻泪管
CN104042295B (zh) * 2014-06-23 2017-01-11 复旦大学附属眼耳鼻喉科医院 一种亲水润滑抗菌泪道管及其制备方法
CN104274865B (zh) * 2014-10-09 2016-02-10 王晓然 一种可降解临时人工泪道
CN106750377A (zh) * 2015-11-20 2017-05-31 温州医科大学 水凝胶、用于制备水凝胶的组合物及水凝胶制备方法
CN105418858B (zh) * 2015-12-23 2018-08-17 江苏海伦隐形眼镜有限公司 具有高透氧性的硅水凝胶材料、角膜接触镜及其制备方法
CN105536053B (zh) * 2015-12-29 2018-10-02 哈尔滨工业大学 一种作为人工晶状体材料的亲水性形状记忆水凝胶
CN106543356B (zh) * 2016-10-11 2018-11-30 华中科技大学 一种水凝胶避孕套及其制备方法
CN106901873B (zh) * 2017-03-09 2019-01-04 首都医科大学附属北京同仁医院 人工晶状体的制作方法

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1730515A (zh) * 2005-08-26 2006-02-08 徐州恩华药业集团有限责任公司 一种制备水凝胶的方法
CN107206119A (zh) * 2014-12-09 2017-09-26 实体科学有限责任公司 具有生物相容性层的医疗设备涂层
CN105367712A (zh) * 2015-10-29 2016-03-02 温州医科大学 一种复合水凝胶及其制备方法
CN106633121A (zh) * 2016-11-15 2017-05-10 深圳先进技术研究院 用于三维打印的粘土基水凝胶基质及其制备方法和应用
CN107698720A (zh) * 2017-10-30 2018-02-16 广州新诚生物科技有限公司 一种人工鼻泪管及其制备方法

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