WO2023212992A1 - Rapid-polymerization medical hydrogel and method for preparing same - Google Patents
Rapid-polymerization medical hydrogel and method for preparing sameDownload PDFInfo
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- WO2023212992A1 WO2023212992A1PCT/CN2022/095931CN2022095931WWO2023212992A1WO 2023212992 A1WO2023212992 A1WO 2023212992A1CN 2022095931 WCN2022095931 WCN 2022095931WWO 2023212992 A1WO2023212992 A1WO 2023212992A1
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- polyethylene glycol
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- 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
- 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
- A61L31/041—Mixtures of macromolecular compounds
- 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
- 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
- C08J3/24—Crosslinking, e.g. vulcanising, of macromolecules
- 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
- C08J3/24—Crosslinking, e.g. vulcanising, of macromolecules
- C08J3/246—Intercrosslinking of at least two polymers
- 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
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/06—Flowable or injectable implant compositions
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- 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
- C08J2371/00—Characterised by the use of polyethers obtained by reactions forming an ether link in the main chain; Derivatives of such polymers
- C08J2371/02—Polyalkylene oxides
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- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
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- C08J2379/00—Characterised by the use of macromolecular compounds obtained by reactions forming in the main chain of the macromolecule a linkage containing nitrogen with or without oxygen, or carbon only, not provided for in groups C08J2361/00 - C08J2377/00
- C08J2379/02—Polyamines
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- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
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- C08J2471/00—Characterised by the use of polyethers obtained by reactions forming an ether link in the main chain; Derivatives of such polymers
- C08J2471/02—Polyalkylene oxides
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- C08J2479/00—Characterised by the use of macromolecular compounds obtained by reactions forming in the main chain of the macromolecule a linkage containing nitrogen with or without oxygen, or carbon only, not provided for in groups C08J2461/00 - C08J2477/00
- C08J2479/02—Polyamines
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- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
- C08K5/00—Use of organic ingredients
- C08K5/16—Nitrogen-containing compounds
- C08K5/17—Amines; Quaternary ammonium compounds
- C08K5/175—Amines; Quaternary ammonium compounds containing COOH-groups; Esters or salts thereof
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- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
- C08K5/00—Use of organic ingredients
- C08K5/16—Nitrogen-containing compounds
- C08K5/20—Carboxylic acid amides
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
- C08K5/00—Use of organic ingredients
- C08K5/36—Sulfur-, selenium-, or tellurium-containing compounds
- C08K5/37—Thiols
Definitions
- the present inventionrelates to biological materials, and more specifically to a rapid polymerization medical hydrogel and a preparation method thereof.
- Hydrogelis a type of polymer with a three-dimensional network structure of hydrophilic groups. Due to the physical and chemical cross-linking between polymers, hydrogel can be swollen but is not soluble in water and can remain a certain shape. At the same time, hydrogels have excellent physical, chemical and biological properties, such as biocompatibility, high elasticity, swelling, etc., and are widely used in the fields of medicine, tissue engineering and medical devices.
- hydrogelsMaterials that can be used to prepare hydrogels include chitosan, alginate, polyethylene glycol, etc.
- Polyethylene glycolis a high molecular polymer, which itself has good biocompatibility and safety. It can be used as a pharmaceutical excipient. Modifying the end groups of polyethylene glycol not only increases its ability to form a hydrogel performance, while retaining the original safety characteristics of polyethylene glycol, making it an ideal hydrogel material.
- the present inventionprovides a rapid polymerization medical hydrogel and a preparation method thereof.
- the rapid polymerization medical hydrogel according to the present inventionis polymerized by a first phase solution and a second phase solution.
- the first phase solutionis composed of vinyl sulfone polyethylene glycol (PEG-VS) dissolved in a first buffer solution.
- the vinyl sulfone polyethylene glycol (PEG-VS)is four-arm vinyl sulfone polyethylene glycol (4-arm-PEG-VS) or eight-arm vinyl sulfone polyethylene glycol (8-arm-PEG-VS)
- the second phase solutionis formed by dissolving an amino compound or mercaptopolyethylene glycol (PEG-SH) in a second buffer solution, and the amino compound is cysteine, dilysine, trilysine or Polyethyleneimine
- the mercapto polyethylene glycol (PEG-SH)is four-arm mercapto polyethylene glycol (4-arm-PEG-SH) or eight-arm mercapto polyethylene glycol (8-arm-PEG-SH).
- the inventor of the present applicationfinally selected four-arm vinyl sulfone polyethylene glycol (4-arm-PEG-VS) or eight-arm vinyl sulfone polyethylene glycol (8-arm-PEG-VS) in the first phase solution.
- PEG-VSand cysteine, dilysine, trilysine, polyethyleneimine, four-arm thiol polyethylene glycol (4-arm-PEG-SH) or eight-arm thiol in the second phase solution
- Polyethylene glycol (8-arm-PEG-SH)is polymerized, which can meet the effect of rapid polymerization to form a hydrogel.
- the molar ratio of the amino group in the amino compound and the vinyl sulfone group in the vinyl sulfone polyethylene glycolis between 1-2:1.
- the molar ratio of the thiol groups in the thiol polyethylene glycol and the vinyl sulfone group in the vinyl sulfone polyethylene glycolis between 1-2:1.
- the mass concentration of the first phase solutionis between 1.0% and 20%.
- the pH of the first buffer solutionis 4.0-7.0.
- the mass concentration of the second phase solutionis between 1.0% and 20%.
- the pH of the second buffer solutionis 7.5-10.0.
- the molecular weight of vinyl sulfone polyethylene glycolis between 5K and 20K.
- the molecular weight of the mercapto polyethylene glycol (PEG-SH)is between 5K and 20K.
- the method for preparing a rapidly polymerizing medical hydrogel according to the present inventionincludes transporting the first phase solution and the second phase solution to the location to be polymerized through a double-lumen microcatheter, and the first phase solution and the second phase solution are once at the location. Mix and polymerize to form a hydrogel.
- the polymerization timeis between 0.5-10s.
- the rapidly polymerizing medical hydrogel according to the present inventioncan be used for isolation protection during radiotherapy for prostate cancer, for example.
- the rayswill pass through the cancer tissue, causing inevitable radiation damage to adjacent normal tissues, such as the rectum.
- a hydrogel spacer formed between the prostate and rectumcan effectively block excess rays and prevent normal tissue from being damaged by radiation.
- the rapidly polymerizing medical hydrogel according to the present inventioncan also be used for isolation protection during radiotherapy for cervical cancer, for example, by setting the location to be polymerized to the location that requires radiation isolation.
- the rapidly polymerizing medical hydrogel according to the present inventionis composed of two different liquids before polymerization, namely the first phase solution and the second phase solution.
- the two liquidscan be mixed quickly (for example, within 0.5s-10s). ) is cross-linked and polymerized to form a hydrogel, and the polymerized hydrogel has high elasticity and can closely adhere to the tissue.
- PEG-VSvinyl sulfone polyethylene glycol
- the vinyl sulfone polyethylene glycol(PEG-VS) is four-arm vinyl sulfone polyethylene glycol (4-arm-PEG-VS), Its molecular formula is as follows:
- the vinyl sulfone polyethylene glycol(PEG-VS) is eight-arm vinyl sulfone polyethylene glycol (8-arm-PEG-VS), and its molecular formula is as follows:
- PEG-SHpolyethylene glycol
- the amino compoundis cysteine.
- the amino compoundis dilysine.
- the amino compoundis trilysine.
- the amino compoundis polyethyleneimine.
- Example 6the mercapto polyethylene glycol (PEG-SH) is four-arm mercapto polyethylene glycol (4-arm-PEG-SH), and its molecular formula is as follows:
- the vinyl sulfone polyethylene glycolis eight-arm mercapto polyethylene glycol (8-arm-PEG-SH), and its molecular formula is as follows:
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- Polymers & Plastics (AREA)
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- Heart & Thoracic Surgery (AREA)
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Abstract
Description
Translated fromChinese本发明涉及生物材料，更具体地涉及一种快速聚合医用水凝胶及其制备方法。The present invention relates to biological materials, and more specifically to a rapid polymerization medical hydrogel and a preparation method thereof.
水凝胶是一类具有亲水基团的三维网络结构的聚合物，由于聚合物间的物理交联和化学交联的作用，水凝胶可以被溶胀，但是并不溶于水，而且可保持一定的形状。同时水凝胶具有优良的理化性能和生物学特性，如生物相容性、高弹性、溶胀性等，广泛应用在医药领域、组织工程和医疗器械领域。Hydrogel is a type of polymer with a three-dimensional network structure of hydrophilic groups. Due to the physical and chemical cross-linking between polymers, hydrogel can be swollen but is not soluble in water and can remain a certain shape. At the same time, hydrogels have excellent physical, chemical and biological properties, such as biocompatibility, high elasticity, swelling, etc., and are widely used in the fields of medicine, tissue engineering and medical devices.
可用于制备水凝胶的材料有壳聚糖、海藻酸盐、聚乙二醇等。聚乙二醇是高分子聚合物，其本身具有很好的生物相容性和安全性，可用作药用辅料，对聚乙二醇端基进行改性，既增加了其成水凝胶的性能，又保留了聚乙二醇原有的安全特性，是理想的水凝胶材料。Materials that can be used to prepare hydrogels include chitosan, alginate, polyethylene glycol, etc. Polyethylene glycol is a high molecular polymer, which itself has good biocompatibility and safety. It can be used as a pharmaceutical excipient. Modifying the end groups of polyethylene glycol not only increases its ability to form a hydrogel performance, while retaining the original safety characteristics of polyethylene glycol, making it an ideal hydrogel material.
有报道使用聚乙二醇琥珀酰亚胺酯和聚赖氨酸和聚乙烯亚胺成水凝胶的方法，但是该水凝胶容易水解，而且成水凝胶需要的时间较长。There are reports of using polyethylene glycol succinimide ester, polylysine, and polyethyleneimine to form a hydrogel. However, the hydrogel is easily hydrolyzed, and it takes a long time to form a hydrogel.
发明内容Contents of the invention
为了解决上述现有技术中的水凝胶的成胶时间较长等问题，本发明提供一种快速聚合医用水凝胶及其制备方法。In order to solve the above-mentioned problems of long gelling time of hydrogels in the prior art, the present invention provides a rapid polymerization medical hydrogel and a preparation method thereof.
根据本发明的快速聚合医用水凝胶，其由第一相溶液和第二相溶液聚合而成，所述第一相溶液由乙烯砜聚乙二醇(PEG-VS)溶解于第一缓冲溶液中形成，所述乙烯砜聚乙二醇(PEG-VS)为四臂乙烯砜聚乙二醇(4臂-PEG-VS)或八臂乙烯砜聚乙二醇(8臂-PEG-VS)，所述第二相溶液由氨基化合物或巯基聚乙二醇(PEG-SH)溶解于第二缓冲溶液中形成，所述氨基化合物为半胱氨酸、二赖氨酸、三赖氨酸或聚乙烯亚胺，所述巯基聚乙二醇 (PEG-SH)为四臂巯基聚乙二醇(4臂-PEG-SH)或八臂巯基聚乙二醇(8臂-PEG-SH)。The rapid polymerization medical hydrogel according to the present invention is polymerized by a first phase solution and a second phase solution. The first phase solution is composed of vinyl sulfone polyethylene glycol (PEG-VS) dissolved in a first buffer solution. Formed in, the vinyl sulfone polyethylene glycol (PEG-VS) is four-arm vinyl sulfone polyethylene glycol (4-arm-PEG-VS) or eight-arm vinyl sulfone polyethylene glycol (8-arm-PEG-VS) , the second phase solution is formed by dissolving an amino compound or mercaptopolyethylene glycol (PEG-SH) in a second buffer solution, and the amino compound is cysteine, dilysine, trilysine or Polyethyleneimine, the mercapto polyethylene glycol (PEG-SH) is four-arm mercapto polyethylene glycol (4-arm-PEG-SH) or eight-arm mercapto polyethylene glycol (8-arm-PEG-SH).
本申请的发明人通过大量的创造性劳动，最终选定由第一相溶液中的四臂乙烯砜聚乙二醇(4臂-PEG-VS)或八臂乙烯砜聚乙二醇(8臂-PEG-VS)和第二相溶液中的半胱氨酸、二赖氨酸、三赖氨酸、聚乙烯亚胺、四臂巯基聚乙二醇(4臂-PEG-SH)或八臂巯基聚乙二醇(8臂-PEG-SH)进行聚合，可以满足快速聚合形成水凝胶的效果。Through a lot of creative work, the inventor of the present application finally selected four-arm vinyl sulfone polyethylene glycol (4-arm-PEG-VS) or eight-arm vinyl sulfone polyethylene glycol (8-arm-PEG-VS) in the first phase solution. PEG-VS) and cysteine, dilysine, trilysine, polyethyleneimine, four-arm thiol polyethylene glycol (4-arm-PEG-SH) or eight-arm thiol in the second phase solution Polyethylene glycol (8-arm-PEG-SH) is polymerized, which can meet the effect of rapid polymerization to form a hydrogel.
优选地，所述氨基化合物中的氨基和乙烯砜聚乙二醇中的乙烯砜基团的摩尔量的比介于1-2∶1之间。Preferably, the molar ratio of the amino group in the amino compound and the vinyl sulfone group in the vinyl sulfone polyethylene glycol is between 1-2:1.
优选地，所述巯基聚乙二醇中的巯基和乙烯砜聚乙二醇中的乙烯砜基团的摩尔量的比介于1-2∶1之间。Preferably, the molar ratio of the thiol groups in the thiol polyethylene glycol and the vinyl sulfone group in the vinyl sulfone polyethylene glycol is between 1-2:1.
优选地，所述第一相溶液的质量百分浓度介于1.0％-20％之间。Preferably, the mass concentration of the first phase solution is between 1.0% and 20%.
优选地，所述第一缓冲溶液的PH＝4.0-7.0。Preferably, the pH of the first buffer solution is 4.0-7.0.
优选地，所述第二相溶液的质量百分浓度介于1.0％-20％之间。Preferably, the mass concentration of the second phase solution is between 1.0% and 20%.
优选地，所述第二缓冲溶液的PH＝7.5-10.0。Preferably, the pH of the second buffer solution is 7.5-10.0.
优选地，所述乙烯砜聚乙二醇(PEG-VS)的分子量介于5K-20K之间。Preferably, the molecular weight of vinyl sulfone polyethylene glycol (PEG-VS) is between 5K and 20K.
优选地，所述巯基聚乙二醇(PEG-SH)的分子量介于5K-20K之间。Preferably, the molecular weight of the mercapto polyethylene glycol (PEG-SH) is between 5K and 20K.
根据本发明的快速聚合医用水凝胶的制备方法，其包括通过双腔微导管分别将第一相溶液和第二相溶液输送待聚合位置，第一相溶液和第二相溶液在该位置一旦混合即聚合成水凝胶。The method for preparing a rapidly polymerizing medical hydrogel according to the present invention includes transporting the first phase solution and the second phase solution to the location to be polymerized through a double-lumen microcatheter, and the first phase solution and the second phase solution are once at the location. Mix and polymerize to form a hydrogel.
优选地，聚合时间介于0.5-10s之间。Preferably, the polymerization time is between 0.5-10s.
根据本发明的快速聚合医用水凝胶，可用于例如前列腺癌放射治疗时的隔离保护。放射治疗时，射线会穿过癌组织，对于邻近正常组织会有不可避免的放射损伤，比如直肠。而在前列腺和直肠之间形成一个水凝胶垫片可以有效阻隔多余的射线，避免正常组织受到放射损伤。应该理解，该根据本发明的快速聚合医用水凝胶还可用于例如宫颈癌等放射治疗时的隔离保护，将待聚合位置设定为需放射隔离位置即可。The rapidly polymerizing medical hydrogel according to the present invention can be used for isolation protection during radiotherapy for prostate cancer, for example. During radiation therapy, the rays will pass through the cancer tissue, causing inevitable radiation damage to adjacent normal tissues, such as the rectum. A hydrogel spacer formed between the prostate and rectum can effectively block excess rays and prevent normal tissue from being damaged by radiation. It should be understood that the rapidly polymerizing medical hydrogel according to the present invention can also be used for isolation protection during radiotherapy for cervical cancer, for example, by setting the location to be polymerized to the location that requires radiation isolation.
根据本发明的快速聚合医用水凝胶，在聚合之前为两种不同的液体，即第一相溶液和第二相溶液，在使用时将两种液体混合后可快速(例如0.5s-10s内)交联聚合而成水凝胶，而且聚合后的水凝胶具有较高弹性，能够 和组织密切贴合。The rapidly polymerizing medical hydrogel according to the present invention is composed of two different liquids before polymerization, namely the first phase solution and the second phase solution. When used, the two liquids can be mixed quickly (for example, within 0.5s-10s). ) is cross-linked and polymerized to form a hydrogel, and the polymerized hydrogel has high elasticity and can closely adhere to the tissue.
下面给出本发明的较佳实施例，并予以详细描述。Preferred embodiments of the present invention are given below and described in detail.
实施例1Example 1
配置第一相溶液Prepare first phase solution
首先，用磷酸二氢钠、10％磷酸、纯化水配制PH＝4.0-7.0的第一缓冲溶液。然后，按下表1量称取乙烯砜聚乙二醇(PEG-VS)，用第一缓冲溶液溶解，配制成质量百分浓度介于1.0％-20％之间的第一相溶液。First, prepare a first buffer solution with pH=4.0-7.0 using sodium dihydrogen phosphate, 10% phosphoric acid, and purified water. Then, weigh the vinyl sulfone polyethylene glycol (PEG-VS) according to Table 1, dissolve it in the first buffer solution, and prepare a first phase solution with a mass percentage concentration between 1.0% and 20%.
在例1-例2，例8-例9和例14-例15中，该乙烯砜聚乙二醇(PEG-VS)为四臂乙烯砜聚乙二醇(4臂-PEG-VS)，其分子式如下：In Examples 1-2, 8-9 and 14-15, the vinyl sulfone polyethylene glycol (PEG-VS) is four-arm vinyl sulfone polyethylene glycol (4-arm-PEG-VS), Its molecular formula is as follows:
其中，R1为季戊四醇，n＝1-250。Among them, R1 is pentaerythritol, n=1-250.
在例3-例7和例10-例13中，该乙烯砜聚乙二醇(PEG-VS)为八臂乙烯砜聚乙二醇(8臂-PEG-VS)，其分子式如下：In Examples 3 to 7 and 10 to 13, the vinyl sulfone polyethylene glycol (PEG-VS) is eight-arm vinyl sulfone polyethylene glycol (8-arm-PEG-VS), and its molecular formula is as follows:
其中，R2为三季戊四醇，n＝1-250。Among them, R2 is tripentaerythritol, n=1-250.
配置第二相溶液Prepare second phase solution
首先，用四硼酸钠与10％磷酸或20％氢氧化钠配制PH＝7.5-10.0的第二缓冲溶液。然后，按下表1量称取氨基化合物或巯基聚乙二醇(PEG-SH)，用第二缓冲溶液溶解，配制成质量百分浓度介于1.0％-20％之间的第二相溶液。First, prepare a second buffer solution with pH=7.5-10.0 using sodium tetraborate and 10% phosphoric acid or 20% sodium hydroxide. Then, weigh the amino compound or mercapto polyethylene glycol (PEG-SH) according to Table 1, dissolve it in the second buffer solution, and prepare a second phase solution with a mass percentage concentration between 1.0% and 20%. .
在例1、例7和例14中，氨基化合物为半胱氨酸。In Examples 1, 7 and 14, the amino compound is cysteine.
在例2、例8和例15中，氨基化合物为二赖氨酸。In Examples 2, 8 and 15, the amino compound is dilysine.
在例3、例9和例11中，氨基化合物为三赖氨酸。In Examples 3, 9 and 11, the amino compound is trilysine.
在例4、例10和例12中，氨基化合物为聚乙烯亚胺。In Examples 4, 10 and 12, the amino compound is polyethyleneimine.
在例6中，该巯基聚乙二醇(PEG-SH)为四臂巯基聚乙二醇(4臂-PEG-SH)，其分子式如下：In Example 6, the mercapto polyethylene glycol (PEG-SH) is four-arm mercapto polyethylene glycol (4-arm-PEG-SH), and its molecular formula is as follows:
其中，R3为季戊四醇，n＝1-250。Among them, R3 is pentaerythritol, n=1-250.
在例5和例13中，该乙烯砜聚乙二醇(PEG-SH)为八臂巯基聚乙二醇(8臂-PEG-SH)，其分子式如下：In Examples 5 and 13, the vinyl sulfone polyethylene glycol (PEG-SH) is eight-arm mercapto polyethylene glycol (8-arm-PEG-SH), and its molecular formula is as follows:
其中，R4为三季戊四醇，n＝1-250。Among them, R4 is tripentaerythritol, n=1-250.
制备水凝胶Preparing hydrogels
将2.0ml第一相溶液抽取至3ml的第一注射器中，将2.0ml第二相溶液抽取至3ml的第二注射器中，将第一和第二注射器分别和双腔微导管连接，同时推动注射器，待双腔微导管远端流出溶液时计时开始，观察到流出溶液成凝胶后计时结束，得到的聚合时间如下表1所示：Extract 2.0 ml of the first phase solution into the 3 ml first syringe, and 2.0 ml of the second phase solution into the 3 ml second syringe. Connect the first and second syringes to the double-lumen microcatheter respectively, and push the syringes at the same time. , the timing starts when the solution flows out of the distal end of the double-lumen microcatheter, and ends when the outflowing solution is observed to gel. The obtained polymerization time is shown in Table 1 below:
表1Table 1
以上所述的，仅为本发明的较佳实施例，并非用以限定本发明的范围，本发明的上述实施例还可以做出各种变化。即凡是依据本发明申请的权利要求书及说明书内容所作的简单、等效变化与修饰，皆落入本发明专利的权利要求保护范围。本发明未详尽描述的均为常规技术内容。The above are only preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various changes can be made to the above-mentioned embodiments of the present invention. That is to say, all simple and equivalent changes and modifications made based on the claims and description of the present invention fall within the scope of protection of the claims of the patent of the present invention. What is not described in detail in the present invention is conventional technical content.
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