CN110269741B - 一种二次膨胀泪点塞的制备方法 - Google Patents

一种二次膨胀泪点塞的制备方法 Download PDF

Info

Publication number
CN110269741B
CN110269741B CN201910453401.5A CN201910453401A CN110269741B CN 110269741 B CN110269741 B CN 110269741B CN 201910453401 A CN201910453401 A CN 201910453401A CN 110269741 B CN110269741 B CN 110269741B
Authority
CN
China
Prior art keywords
mol
concentration
selecting
monomer
initiator
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN201910453401.5A
Other languages
English (en)
Other versions
CN110269741A (zh
Inventor
李金徽
李少军
黄杰辉
杨习锋
曾晨光
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Guangzhou Sun Shing Biotech Co ltd
Original Assignee
Guangzhou Sun Shing Biotech Co ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Guangzhou Sun Shing Biotech Co ltd filed Critical Guangzhou Sun Shing Biotech Co ltd
Priority to CN201910453401.5A priority Critical patent/CN110269741B/zh
Publication of CN110269741A publication Critical patent/CN110269741A/zh
Application granted granted Critical
Publication of CN110269741B publication Critical patent/CN110269741B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F9/00—Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A61F9/007—Methods or devices for eye surgery
    • A61F9/00772—Apparatus for restoration of tear ducts
    • 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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/04—Macromolecular materials
    • A61L31/048—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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/145—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
    • C08F212/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an aromatic carbocyclic ring
    • C08F212/02—Monomers containing only one unsaturated aliphatic radical
    • C08F212/04—Monomers containing only one unsaturated aliphatic radical containing one ring
    • C08F212/14—Monomers containing only one unsaturated aliphatic radical containing one ring substituted by heteroatoms or groups containing heteroatoms
    • 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
    • C08F220/04—Acids; Metal salts or ammonium salts thereof
    • C08F220/06—Acrylic acid; Methacrylic acid; Metal salts or ammonium salts thereof
    • 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
    • C08F220/34—Esters containing nitrogen, e.g. N,N-dimethylaminoethyl (meth)acrylate
    • 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
    • C08F226/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen
    • C08F226/06—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen by a heterocyclic ring containing nitrogen
    • C08F226/10—N-Vinyl-pyrrolidone
    • 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
    • C08J2325/00—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 at least one being terminated by an aromatic carbocyclic ring; Derivatives of such polymers
    • C08J2325/18—Homopolymers or copolymers of aromatic monomers containing elements other than carbon and hydrogen
    • 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
    • C08J2333/02—Homopolymers or copolymers of acids; Metal or ammonium salts thereof
    • 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
    • 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
    • C08J2339/00—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 at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen; Derivatives of such polymers
    • C08J2339/04—Homopolymers or copolymers of monomers containing heterocyclic rings having nitrogen as ring member
    • C08J2339/06—Homopolymers or copolymers of N-vinyl-pyrrolidones

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Surgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Vascular Medicine (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Dispersion Chemistry (AREA)
  • Epidemiology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Biomedical Technology (AREA)
  • Engineering & Computer Science (AREA)
  • Plastic & Reconstructive Surgery (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Materials For Medical Uses (AREA)

Abstract

本发明提供一种二次膨胀泪点塞的制备方法，选用水凝胶类材质，可以直接植入到泪小管中，不接触角膜，减少异物感；植入前和植入过程中，栓塞已经吸水膨胀一次，其性能柔软，手术过程不易损害泪小管；植入到指定位置后，在泪液作用下，再次膨胀，达到固定的作用。制备方法包括：(1)将阴离子单体、阳离子单体、主要单体、交联剂、引发剂与盐溶液充分混合，得到混合溶液；(2)将混合溶液注入到模具中，通过热引发或光引发或催化剂引发成型，得水凝胶；(3)水凝胶经去离子水浸泡、裁切、包装、灭菌。

Description

一种二次膨胀泪点塞的制备方法
技术领域
本发明涉及医疗器械领域，具体涉及二次膨胀泪点塞的制备方法。
背景技术
干眼症是指任何原因造成的泪液质量异常或动力学异常，导致泪膜稳定性下降，并伴有眼部不适和眼表组织病变特征的多种疾病的总称，又称角结膜干燥症。
干眼症已成为全球流行性疾病，其患病率有逐渐增加的趋势。其发病机制非常复杂，角膜、结膜、泪腺、睑板腺以及它们之间连接的神经通路共同发挥作用对泪膜形成和泪液分泌的调控作用，维持和保护眼表的正常结构和功能，其中任何一个环节的异常均会破坏眼表正常修复及预防机制，导致干眼。
通过泪点塞封堵泪道，能较好维护泪膜稳定性，缓解干眼症状。其中，栓塞主要分为硅胶塞子和水凝胶类材质栓塞两种。其中硅胶塞制造材料为医用硅胶，一般带有一个帽子，栓塞尾部在泪点外，与角膜接触，有异物感；水凝胶类栓塞分为可降解栓赛和不可降解栓塞，其植入部位为泪小管。可降解栓塞，通常使用胶原制造，一般在2到6个月之间降解。不可降解栓塞中使用较广泛的SmartPlug栓塞，其制备材料为聚丙烯酸脂类，在体温下变形收缩，堵塞泪道。一般的，水凝胶类的泪点塞其干燥状态普遍较硬，植入过程中，容易损坏泪小管壁。
发明内容
本发明提供一种二次膨胀泪点塞的制备方法，选用水凝胶类材质，可以直接植入到泪小管中，不接触角膜等，减少异物感；植入前和植入过程中，栓塞已经吸水膨胀一次，其性能柔软，手术过程不易损害泪小管；植入到指定位置后，在泪液作用下，再次膨胀，达到固定的作用。
本发明一种二次膨胀泪点塞的制备方法的技术方案包括：
(1)将阴离子单体、阳离子单体、主要单体、交联剂、引发剂与盐溶液充分混合，得到混合溶液；
选取甲基丙烯酸、丙烯酸、4-苯乙烯磺酸及其它们的钠盐钾盐中的任一种或几种作为阴离子单体；
选取甲基丙烯酰丙基三甲基氯化铵、甲基丙烯酸二甲氨基乙酯中的任一种或几种作为阳离子单体；
选取甲基丙烯酸羟乙酯、乙烯基吡咯烷酮中的任一种或几种作为主要单体；
选取过硫酸铵、过硫酸钾、水溶性偶氮类引发剂以及水溶性光引发剂中的任意一种或者几种作为引发剂；
选取氯化钠或氯化钾无机盐溶液作为盐溶液；
(2)当引发剂包含过硫酸铵或过硫酸钾时，将混合溶液加入催化剂注入到模具中；当引发剂为水溶性偶氮类引发剂和/或水溶性光引发剂时，将混合溶液直接注入到模具中；
(3)通过热引发、催化剂引发或者光引发聚合，得到水凝胶。
(4)成型好的水凝胶经去离子水浸泡、裁切、包装、灭菌，得泪点塞。
进一步地，选取乙二醇二醋酸酯、聚乙二醇二丙烯酸酯、N，N'-亚甲基双丙烯酰胺中的任一种或者几种作为交联剂。
进一步地，阴离子单体浓度为0.05～6mol/L，阳离子单体浓度为0.05～6mol/L，主要单体浓度为0.05～6mol/L。
进一步地，交联剂浓度为0.01～0.2mol/L。
进一步地，盐溶液浓度为0～3mol/L。
进一步地，引发剂浓度为0.001～0.1mol/L。
进一步地，催化剂为四甲基乙二胺。
经上述方法制得的泪点塞为含水的水凝胶，具有一定生物相容性。植入前已在去离子水中充分溶胀，其直径小于泪小管，植入时栓塞柔软，方便植入且不易损坏泪小管，降低了手术风险。在植入后，泪液中存在的盐类，可使水凝胶泪点塞网络中的正负基团的静电相互作用被破坏，使泪点塞的体积变大，从而适应泪小管尺寸，堵塞泪小管，达到保存泪液的目的，在植入过程能最大限度减少对泪小管的损伤。
具体实施方式
本发明提供一种二次膨胀泪点塞的制备方法，选用水凝胶类材质，可以直接植入到泪小管中，不接触角膜等，减少异物感；植入前已在去离子水中充分溶胀，其性能柔软，手术过程不易损害泪小管；植入到指定位置后，在泪液作用下，再次膨胀，达到固定的作用。
下面对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
实施例一
本发明提供一种二次膨胀泪点塞的制备方法包括：
(1)将4-苯乙烯磺酸钠、甲基丙烯酰丙基三甲基氯化铵、乙烯基吡咯烷酮、乙二醇二醋酸酯、过硫酸铵与氯化钠溶液充分混合，得到混合溶液。
选取4-苯乙烯磺酸钠的浓度为0.5mol/L；
选取甲基丙烯酰丙基三甲基氯化铵的浓度为0.5mol/L；
选取乙烯基吡咯烷酮的浓度为0.5mol/L；
选取乙二醇二醋酸酯的浓度为0.02mol/L；
选取过硫酸铵的浓度为0.02mol/L；
选取氯化钠溶液的浓度为1mol/L；
(2)取1mL混合溶液，加入四甲基乙二胺10μL，用涡轮震荡使其充分混合。
(3)将溶液注入到内径为1mm的泪点塞模具中，常温下等待2小时，聚合成型，得水凝胶。
(4)水凝胶在去离子水中浸泡三天，将其裁剪为3mm长的样品。最后包装，灭菌得泪点塞。
经上述方法制得的泪点塞，在去离子水中的直径和在泪液中的直径依次递增(1.0mm和1.3mm)，确保了植入时栓塞柔软，方便植入且不易损坏泪小管。在植入后，泪点塞的体积变大，适应泪小管尺寸，堵塞泪小管。
实施例二
本发明提供一种二次膨胀泪点塞的制备方法包括：
(1)将4-苯乙烯磺酸钠、甲基丙烯酸二甲氨基乙酯、乙烯基吡咯烷酮、乙二醇二醋酸酯、偶氮二异丁基脒盐酸盐与氯化钠溶液充分混合，得到混合溶液。
选取4-苯乙烯磺酸钠的浓度为1mol/L；
选取甲基丙烯酸二甲氨基乙酯的浓度为1mol/L；
选取乙烯基吡咯烷酮的浓度为0.5mol/L；
选取乙二醇二醋酸酯的浓度为0.02mol/L；
选取偶氮二异丁基脒盐酸盐的浓度为0.01mol/L；
选取氯化钠溶液的浓度为2mol/L；
(2)将溶液注入到内径为0.8mm的泪点塞模具中，将其放置于60℃温度保温箱中等待5小时，聚合成型，得到泪点塞。
(3)水凝胶经纯化水浸泡三天，在含水态下将其裁剪为3mm长的样品。最后包装，灭菌得泪点塞。
经上述方法制得的含水态直径为0.8mm的泪点塞，在去离子水直径和泪液中的直径依次递增(0.8mm和1.4mm)，确保了植入时栓塞柔软，方便植入且不易损坏泪小管。在植入后，泪点塞的体积变大，适应泪小管尺寸，堵塞泪小管。
实施例三
本发明提供一种二次膨胀泪点塞的制备方法包括：
(1)将甲基丙烯酸钠、甲基丙烯酰丙基三甲基氯化铵、乙烯基吡咯烷酮、乙二醇二醋酸酯、水溶性光引发剂Irgacure 2959与氯化钠溶液充分混合，得到混合溶液。
选取甲基丙烯酸钠的浓度为1mol/L；
选取甲基丙烯酰丙基三甲基氯化铵的浓度为1mol/L；
选取乙烯基吡咯烷酮的浓度为0.5mol/L；
选取乙二醇二醋酸酯的浓度为0.02mol/L；
选取水溶性光引发剂Irgacure 2959的浓度为0.02mol/L；
选取氯化钠溶液的浓度为1mol/L；
(2)将溶液注入到内径为0.6mm的泪点塞模具中，使用365nm紫外光照射10分钟，聚合成型，得到水凝胶。
(3)水凝胶经纯化水流动浸泡冲洗三天，在含水态下将其裁剪为3mm长的样品。最后包装，灭菌得泪点塞。
经上述方法制得的泪点塞，在去离子水直径和泪液中的直径依次递增(0.6mm和1.0mm)，确保了植入时栓塞柔软，方便植入且不易损坏泪小管。在植入后，泪点塞的体积变大，适应泪小管尺寸，堵塞泪小管。
对比例一
(1)将4-苯乙烯磺酸钠、乙烯基吡咯烷酮、乙二醇二醋酸酯、过硫酸铵与氯化钠溶液充分混合，得到混合溶液。
选取4-苯乙烯磺酸钠浓度为1mol/L；
选取乙烯基吡咯烷酮浓度为0.5mol/L；
选取乙二醇二醋酸酯浓度为0.02mol/L；
选取过硫酸铵浓度为0.02mol/L；
选取氯化钠溶液的浓度为1mol/L；
(2)取1mL混合溶液，加入四甲基乙二胺10μL，用涡轮震荡使其充分混合。
(3)将溶液注入到内径为1mm的泪点塞模具中，常温下等待2小时，聚合成型，得到水凝胶。
(4)水凝胶经纯化水浸泡三天，在含水态下将其裁剪为3mm长的样品。最后包装，灭菌得泪点塞。
经上述方法制得的泪点塞。其在去离子水直径和泪液中的直径几乎保持不变(1mm)，无法实现二次溶胀。
对比例二
(1)将乙烯基吡咯烷酮、乙二醇二醋酸酯、过硫酸铵与氯化钠溶液充分混合，得到混合溶液。
选取乙烯基吡咯烷酮浓度为1mol/L；
选取乙二醇二醋酸酯浓度为0.02mol/L；
选取过硫酸铵浓度为0.02mol/L；
选取氯化钠溶液的浓度为1mol/L；
(2)取1mL混合溶液，加入四甲基乙二胺10μL，用涡轮震荡使其充分混合。
(3)将溶液注入到内径为0.8mm的泪点塞模具中，常温下等待2小时，聚合成型，得到水凝胶。
(4)水凝胶经纯化水流动浸泡冲洗三天，在含水态下将其裁剪为3mm长的样品。最后包装，灭菌得泪点塞。
经上述方法制得的泪点塞。其在去离子水直径和泪液中的直径几乎保持不变(0.8mm)，无法实现二次溶胀。
以上实施例仅用以说明本发明的技术方案，而非对其限制；尽管参照前述实施例对本发明进行了详细的说明，本领域的普通技术人员应当理解：其依然可以对前述各实施例所记载的技术方案进行修改，或者对其中部分技术特征进行等同替换；而这些修改或者替换，并不使相应技术方案的本质脱离本发明各实施例技术方案的精神和范围。

Claims (3)

1.一种二次膨胀泪点塞的制备方法，其特征在于，包括以下步骤：
(1)将阴离子单体、阳离子单体、主要单体、交联剂、引发剂与盐溶液充分混合，得到混合溶液；
选取甲基丙烯酸、丙烯酸、4-苯乙烯磺酸及其它们的钠盐钾盐中的任一种或几种作为阴离子单体；选取甲基丙烯酰丙基三甲基氯化铵、甲基丙烯酸二甲氨基乙酯中的任一种或几种作为阳离子单体；选取甲基丙烯酸羟乙酯、乙烯基吡咯烷酮中的任一种或几种作为主要单体；选取过硫酸铵、过硫酸钾、水溶性偶氮类引发剂以及水溶性光引发剂中的任意一种或者几种作为引发剂；选取氯化钠或氯化钾无机盐溶液作为盐溶液；
(2)当引发剂包含过硫酸铵或过硫酸钾时，将混合溶液加入催化剂注入到模具中；当引发剂为水溶性偶氮类引发剂和/或水溶性光引发剂时，将混合溶液直接注入到模具中；
(3)通过热引发、催化剂引发或者光引发聚合，得到水凝胶；
(4)成型好的水凝胶经去离子水浸泡、裁切、包装、灭菌，得泪点塞；
所述的阴离子单体浓度为0.05～6mol/L，阳离子单体浓度为0.05～6mol/L，主要单体浓度为0.05～6mol/L；所述的交联剂浓度为0.01～0.2mol/L；所述的盐溶液浓度为1～3mol/L；所述的引发剂浓度为0.001～0.1mol/L。
2.根据权利要求1所述的二次膨胀泪点塞的制备方法，其特征在于，选取乙二醇二醋酸酯、聚乙二醇二丙烯酸酯、N，N'-亚甲基双丙烯酰胺中的任一种或者几种作为交联剂。
3.根据权利要求1所述的二次膨胀泪点塞的制备方法，其特征在于，
催化剂为四甲基乙二胺。
CN201910453401.5A 2019-05-28 2019-05-28 一种二次膨胀泪点塞的制备方法 Active CN110269741B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201910453401.5A CN110269741B (zh) 2019-05-28 2019-05-28 一种二次膨胀泪点塞的制备方法

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201910453401.5A CN110269741B (zh) 2019-05-28 2019-05-28 一种二次膨胀泪点塞的制备方法

Publications (2)

Publication Number Publication Date
CN110269741A CN110269741A (zh) 2019-09-24
CN110269741B true CN110269741B (zh) 2021-10-12

Family

ID=67959168

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201910453401.5A Active CN110269741B (zh) 2019-05-28 2019-05-28 一种二次膨胀泪点塞的制备方法

Country Status (1)

Country Link
CN (1) CN110269741B (zh)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106750021A (zh) * 2016-12-09 2017-05-31 四川师范大学 有机两性共聚高分子互穿网络凝胶的制备方法
CN107793579A (zh) * 2017-10-30 2018-03-13 广州新诚生物科技有限公司 一种水凝胶及其应用
JP2018140969A (ja) * 2017-02-28 2018-09-13 国立大学法人北海道大学 後眼部疾患治療用環状デバイス

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2753106C (en) * 2009-02-20 2016-09-13 Seed Co., Ltd. Hydrogel contact lens for sustained drug release and drug release method using hydrogel contact lens for sustained drug release

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106750021A (zh) * 2016-12-09 2017-05-31 四川师范大学 有机两性共聚高分子互穿网络凝胶的制备方法
JP2018140969A (ja) * 2017-02-28 2018-09-13 国立大学法人北海道大学 後眼部疾患治療用環状デバイス
CN107793579A (zh) * 2017-10-30 2018-03-13 广州新诚生物科技有限公司 一种水凝胶及其应用

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Synthetic pH sensitive polyampholyte hydrogels: A preliminary study;S. Wen;《Colloid & Polymer Science》;19931231;38-49 *

Also Published As

Publication number Publication date
CN110269741A (zh) 2019-09-24

Similar Documents

Publication Publication Date Title
KR101551590B1 (ko) 신체 조직의 물리적 및/또는 화학적 성질에 영향을 주는 광화학적 요법
US20060074370A1 (en) Ocular occluder and method of insertion
CA1338509C (en) Viscoelastic material for ophthalmic surgery
US10010502B2 (en) Device that delivers a sustained low-dose of a myopia-suppressing drug, while preserving pupillary function and accommodation
EA002004B1 (ru) Композиция для офтальмологических хирургических операций (варианты) и способ их осуществления
US8470034B2 (en) Hydrophobic acrylic polymer material for an intraocular lens having enhanced flexibility due to the use of a transfer agent
US4946470A (en) Hard intraocular lens with the shape memory
CN110269741B (zh) 一种二次膨胀泪点塞的制备方法
Ambati et al. Postoperative complications of scleral buckling surgery
US3951528A (en) Method of making polymeric contact lens
Wilson et al. The place of sodium hyaluronate in glaucoma surgery
CN110269742A (zh) 一种空心水凝胶泪点塞的制备方法
US7875661B2 (en) Ordered polymer system and intraocular lens
CN115651217A (zh) 一种二次膨胀的泪点塞的制备方法
CN115651131A (zh) 一种二次膨胀泪点塞的制备方法
CN110200743B (zh) 一种自固定示踪泪点塞及其制备方法
JP4431372B2 (ja) 眼内レンズ
CN100536800C (zh) 用作光消融嵌体的聚合材料
JP2004018472A (ja) 薬剤徐放可能ヒドロゲル材料
RU2201213C1 (ru) Глазные капли "карнозин"
CN115645632A (zh) 一种可降解明胶泪点塞的制备方法
JP5209827B2 (ja) 薬物徐放性医療用デバイス
Beigi et al. Sulphur hexafluoride in the treatment of flat anterior chamber following trabeculectomy
US20240108454A1 (en) Patch to treat corneal perforation
CN115634191A (zh) 药物植入物及其制备方法、角膜接触镜及其制备方法

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant