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CN118662428A - A gel based on stereocomplex action and its preparation method and application - Google Patents

A gel based on stereocomplex action and its preparation method and application Download PDF

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Publication number
CN118662428A
CN118662428A CN202310272153.0A CN202310272153A CN118662428A CN 118662428 A CN118662428 A CN 118662428A CN 202310272153 A CN202310272153 A CN 202310272153A CN 118662428 A CN118662428 A CN 118662428A
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gel
peg
plla
pdla
block
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张田慧
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CHANGCHUN SINOBIOMATERIALS CO LTD
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CHANGCHUN SINOBIOMATERIALS CO LTD
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Abstract

本发明提供了一种基于立体复合作用的凝胶及其制备方法和应用,所述凝胶的制备原料为一种凝胶用组合物,所述组合物包括第一嵌段共聚物、第二嵌段共聚物和多糖;所述第一嵌段共聚物包括聚左旋乳酸嵌段和聚乙二醇嵌段,所述第二嵌段共聚物包括聚右旋乳酸嵌段和聚乙二醇嵌段,第一嵌段共聚物记为PLLA‑PEG,第二嵌段共聚物记为PDLA‑PEG。所述凝胶中,亲水性的PEG的网络结构和亲水性的多糖的网络结构互穿,聚左旋乳酸PLLA和聚右旋乳酸PDLA之间发生立体复合作用,这种立体复合可以看作是一个一个的物理交联点,从而形成具有力学性能的凝胶。所述凝胶的制备方法简单,且获得的凝胶性质可调。

The present invention provides a gel based on stereocomplexation, and a preparation method and application thereof. The raw material for preparing the gel is a gel composition, and the composition includes a first block copolymer, a second block copolymer and a polysaccharide; the first block copolymer includes a poly-L-lactic acid block and a polyethylene glycol block, and the second block copolymer includes a poly-D-lactic acid block and a polyethylene glycol block. The first block copolymer is recorded as PLLA-PEG, and the second block copolymer is recorded as PDLA-PEG. In the gel, the network structure of the hydrophilic PEG and the network structure of the hydrophilic polysaccharide are interpenetrated, and a stereocomplexation occurs between the poly-L-lactic acid PLLA and the poly-D-lactic acid PDLA. This stereocomplexation can be regarded as physical crosslinking points one by one, thereby forming a gel with mechanical properties. The preparation method of the gel is simple, and the properties of the obtained gel are adjustable.

Description

一种基于立体复合作用的凝胶及其制备方法和应用A gel based on stereocomplex action and its preparation method and application

技术领域Technical Field

本发明属于凝胶技术领域,具体涉及一种凝胶用组合物、一种基于立体复合作用的凝胶及其制备方法和应用。The invention belongs to the technical field of gel, and in particular relates to a gel composition, a gel based on stereocomplexation, and a preparation method and application thereof.

背景技术Background Art

聚乙二醇(PEG)是一种惰性的、具有生物相容性的合成聚合物,由环氧乙烷开环聚合而成的聚氧基单元组成。由于PEG具有无毒、无免疫原性、高水溶性等优良特性,已被美国食品和药物管理局批准用于各种生物医学用途。Polyethylene glycol (PEG) is an inert, biocompatible synthetic polymer composed of polyoxy units formed by the ring-opening polymerization of ethylene oxide. Due to its excellent properties such as non-toxicity, non-immunogenicity, and high water solubility, PEG has been approved by the U.S. Food and Drug Administration for various biomedical uses.

聚乳酸(PLA)是最常见的可生物降解聚合物之一,应用于可再生和生物医学等各个领域。聚乳酸形成两种对映体:聚左旋乳酸(PLLA)和聚右旋乳酸(PDLA),它们可以通过氢键形成外消旋体,即所谓的立体复合物。与单个对映体相比,聚乳酸立体复合物表现出更好的物理性能,如更高的熔点,更高的机械强度,以及更好的热稳定性和水解稳定性。这些独特的特性有利于聚乳酸在生物医学领域的应用。在生物医药领域,部分学者已经开始逐渐尝试制备含有聚乳酸立体复合物的胶束、微球和纳米颗粒等药物控制释放体系。但受其严格的制备条件制约,聚乳酸立体复合物在医药领域未能得到大范围应用。Polylactic acid (PLA) is one of the most common biodegradable polymers, used in various fields such as renewable and biomedical. Polylactic acid forms two enantiomers: poly-L-lactic acid (PLLA) and poly-D-lactic acid (PDLA), which can form racemates through hydrogen bonds, the so-called stereocomplexes. Compared with the single enantiomers, the polylactic acid stereocomplexes show better physical properties, such as higher melting point, higher mechanical strength, and better thermal stability and hydrolytic stability. These unique properties are conducive to the application of polylactic acid in the biomedical field. In the field of biomedicine, some scholars have gradually begun to try to prepare drug controlled release systems such as micelles, microspheres and nanoparticles containing polylactic acid stereocomplexes. However, due to its strict preparation conditions, polylactic acid stereocomplexes have not been widely used in the medical field.

发明内容Summary of the invention

为了改善现有技术的不足,本发明的目的是提供一种基于聚乳酸立体复合作用的多糖-聚乳酸凝胶用组合物以及由该组合物形成的凝胶和其制备方法,所述凝胶具有优异的力学性能;所述凝胶的制备方法简单,且获得的凝胶性质可调。最重要的是,这种使用聚乳酸立体复合作用作为凝胶的“交联点”形成的凝胶和用其它交联方法制备的凝胶相比有诸多优点,例如在温和的条件下反应获得,避免使用催化剂、辅助交联剂和其他活性分子等,从而省去了凝胶的纯化步骤,避免有毒催化剂、交联剂等的残留,增加了凝胶的生物安全性。In order to improve the deficiencies of the prior art, the purpose of the present invention is to provide a composition for polysaccharide-polylactic acid gel based on the stereocomplexation of polylactic acid, a gel formed by the composition and a preparation method thereof, wherein the gel has excellent mechanical properties; the preparation method of the gel is simple, and the properties of the obtained gel are adjustable. Most importantly, the gel formed by the stereocomplexation of polylactic acid as the "crosslinking point" of the gel has many advantages over the gel prepared by other crosslinking methods, such as being obtained by reaction under mild conditions, avoiding the use of catalysts, auxiliary crosslinking agents and other active molecules, thereby eliminating the purification step of the gel, avoiding the residue of toxic catalysts, crosslinking agents, etc., and increasing the biosafety of the gel.

本发明的目的是通过如下技术方案实现的:The objective of the present invention is achieved through the following technical solutions:

一种凝胶用组合物,所述组合物包括第一嵌段共聚物、第二嵌段共聚物和多糖;所述第一嵌段共聚物包括聚左旋乳酸嵌段和聚乙二醇嵌段,所述第二嵌段共聚物包括聚右旋乳酸嵌段和聚乙二醇嵌段。A composition for gel, comprising a first block copolymer, a second block copolymer and polysaccharide; the first block copolymer comprises a poly-L-lactic acid block and a polyethylene glycol block, and the second block copolymer comprises a poly-D-lactic acid block and a polyethylene glycol block.

本发明中,第一嵌段共聚物记为PLLA-PEG,第二嵌段共聚物记为PDLA-PEG,聚左旋乳酸嵌段记为PLLA嵌段,聚右旋乳酸嵌段记为PDLA嵌段,聚乙二醇嵌段记为PEG嵌段。In the present invention, the first block copolymer is recorded as PLLA-PEG, the second block copolymer is recorded as PDLA-PEG, the poly (L-lactic acid) block is recorded as PLLA block, the poly (D-lactic acid) block is recorded as PDLA block, and the polyethylene glycol block is recorded as PEG block.

本发明首次提出了一种包括PLLA-PEG、PDLA-PEG和多糖的组合物。所述组合物用于形成产品、具体如凝胶时,亲水性的聚乙二醇PEG链段和亲水性的多糖链段会形成互穿网络结构,聚左旋乳酸PLLA链段和聚右旋乳酸PDLA链段之间发生立体复合作用,这种立体复合可以看作是一个一个的物理交联点,具体的形成如图1所示的结构。The present invention proposes for the first time a composition comprising PLLA-PEG, PDLA-PEG and polysaccharide. When the composition is used to form a product, such as a gel, the hydrophilic polyethylene glycol PEG segment and the hydrophilic polysaccharide segment will form an interpenetrating network structure, and a stereocomplexation occurs between the poly-L-lactic acid PLLA segment and the poly-D-lactic acid PDLA segment. This stereocomplexation can be regarded as physical cross-linking points one by one, specifically forming a structure as shown in FIG1 .

根据本发明的实施方式,所述聚乙二醇嵌段来自式A所示的聚合物:According to an embodiment of the present invention, the polyethylene glycol block is derived from a polymer represented by formula A:

式A中,R’为中心分子基团,Y选自-O-、-NH-、-C(=O)O-或-OC(=O)-,x为聚合度,p为≥2的整数。In formula A, R' is a central molecular group, Y is selected from -O-, -NH-, -C(=O)O- or -OC(=O)-, x is the degree of polymerization, and p is an integer ≥2.

根据本发明的实施方式,式A中,R’选自烃基。优选地,式A中,R’选自烷基、烯基、芳基。According to an embodiment of the present invention, in formula A, R' is selected from a hydrocarbon group. Preferably, in formula A, R' is selected from an alkyl group, an alkenyl group, and an aryl group.

根据本发明的实施方式,式A中,R’选自C1-44烃基。优选地,式A中,R’选自C1-44烷基、C2-44烯基、C6-44芳基。优选地,式A中,R’选自C1-24烷基、C2-24烯基、C6-24芳基。优选地,式A中,R’选自C1-12烷基、C2-12烯基、C6-12芳基。优选地,式A中,R’选自C1-6烷基、C2-6烯基、C6-10芳基。According to an embodiment of the present invention, in formula A, R' is selected from C 1-44 hydrocarbon group. Preferably, in formula A, R' is selected from C 1-44 alkyl, C 2-44 alkenyl, C 6-44 aryl. Preferably, in formula A, R' is selected from C 1-24 alkyl, C 2-24 alkenyl, C 6-24 aryl. Preferably, in formula A, R' is selected from C 1-12 alkyl, C 2-12 alkenyl, C 6-12 aryl. Preferably, in formula A, R' is selected from C 1-6 alkyl, C 2-6 alkenyl, C 6-10 aryl.

根据本发明的实施方式,当p为2时,式A所示的聚乙二醇也称为双臂聚乙二醇。当p为≥3的整数时,式A所示的聚乙二醇也称为多臂聚乙二醇。优选地,p为2-16之间的整数。According to an embodiment of the present invention, when p is 2, the polyethylene glycol shown in formula A is also called double-arm polyethylene glycol. When p is an integer ≥ 3, the polyethylene glycol shown in formula A is also called multi-arm polyethylene glycol. Preferably, p is an integer between 2-16.

示例性地,所述多臂聚乙二醇例如为三臂聚乙二醇、四臂聚乙二醇、五臂聚乙二醇、六臂聚乙二醇、七臂聚乙二醇、八臂聚乙二醇、九臂聚乙二醇、十臂聚乙二醇、十一臂聚乙二醇、十二臂聚乙二醇、十三臂聚乙二醇、十四臂聚乙二醇、十五臂聚乙二醇或十六臂聚乙二醇。Exemplarily, the multi-arm polyethylene glycol is, for example, three-arm polyethylene glycol, four-arm polyethylene glycol, five-arm polyethylene glycol, six-arm polyethylene glycol, seven-arm polyethylene glycol, eight-arm polyethylene glycol, nine-arm polyethylene glycol, ten-arm polyethylene glycol, eleven-arm polyethylene glycol, twelve-arm polyethylene glycol, thirteen-arm polyethylene glycol, fourteen-arm polyethylene glycol, fifteen-arm polyethylene glycol or sixteen-arm polyethylene glycol.

根据本发明的实施方式,所述组合物中,PLLA-PEG与PDLA-PEG的质量比为0.001-1000:1,优选的为0.1-10:1,例如为0.001:1、0.005:1、0.01:1、0.05:1、0.1:1、0.5:1、1:1、5:1、10:1、50:1、100:1、200:1、400:1、500:1、800:1或1000:1。According to an embodiment of the present invention, in the composition, the mass ratio of PLLA-PEG to PDLA-PEG is 0.001-1000:1, preferably 0.1-10:1, for example, 0.001:1, 0.005:1, 0.01:1, 0.05:1, 0.1:1, 0.5:1, 1:1, 5:1, 10:1, 50:1, 100:1, 200:1, 400:1, 500:1, 800:1 or 1000:1.

根据本发明的实施方式,所述组合物中,PLLA-PEG和PDLA-PEG的质量之和与多糖的质量比为0.001-1000:1,优选的为0.1-100:1,例如为0.001:1、0.005:1、0.01:1、0.05:1、0.1:1、0.5:1、1:1、5:1、10:1、50:1、100:1、200:1、400:1、500:1、800:1或1000:1。According to an embodiment of the present invention, in the composition, the mass ratio of the sum of the masses of PLLA-PEG and PDLA-PEG to the polysaccharide is 0.001-1000:1, preferably 0.1-100:1, for example, 0.001:1, 0.005:1, 0.01:1, 0.05:1, 0.1:1, 0.5:1, 1:1, 5:1, 10:1, 50:1, 100:1, 200:1, 400:1, 500:1, 800:1 or 1000:1.

研究发现,当组合物中同时含有PLLA和PDLA时,有利于立体复合作用的形成。当调整组合物中PLLA-PEG、PDLA-PEG和多糖之间的质量比时,可以调整获得的凝胶中的立体复合作用形成的“物理交联点”,当组合物中PLLA-PEG和PDLA-PEG的含量占比较大时,凝胶中的立体复合作用形成的“物理交联点”越多,凝胶越稳定,力学强度更强,更不容易降解;当组合物中多糖的含量占比较大时,凝胶中的立体复合作用形成的“物理交联点”越少,凝胶越不稳定,力学强度更弱,更易降解。The study found that when the composition contains both PLLA and PDLA, it is conducive to the formation of stereocomplexation. When the mass ratio between PLLA-PEG, PDLA-PEG and polysaccharide in the composition is adjusted, the "physical cross-linking points" formed by the stereocomplexation in the obtained gel can be adjusted. When the content of PLLA-PEG and PDLA-PEG in the composition accounts for a large proportion, the more "physical cross-linking points" formed by the stereocomplexation in the gel, the more stable the gel, the stronger the mechanical strength, and the less prone to degradation; when the content of polysaccharide in the composition accounts for a large proportion, the fewer "physical cross-linking points" formed by the stereocomplexation in the gel, the more unstable the gel, the weaker the mechanical strength, and the easier it is to degrade.

根据本发明的实施方式,所述PLLA-PEG的分子量为200Da~7×105Da,优选的分子量为2500Da~4×104Da。According to an embodiment of the present invention, the molecular weight of the PLLA-PEG is 200Da to 7×10 5 Da, preferably 2500Da to 4×10 4 Da.

根据本发明的实施方式,所述PDLA-PEG的分子量为200Da~7×105Da,优选的分子量为2500Da~4×104Da。According to an embodiment of the present invention, the molecular weight of the PDLA-PEG is 200Da to 7×10 5 Da, preferably 2500Da to 4×10 4 Da.

根据本发明的实施方式,所述PLLA-PEG中,PEG嵌段的分子量为50Da~6×105Da,优选的分子量为1000Da~4×104Da;PLLA嵌段的分子量为100Da~1×105Da,优选的分子量为800Da~6000Da。According to an embodiment of the present invention, in the PLLA-PEG, the molecular weight of the PEG block is 50Da-6×10 5 Da, preferably 1000Da-4×10 4 Da; the molecular weight of the PLLA block is 100Da-1×10 5 Da, preferably 800Da-6000Da.

根据本发明的实施方式,所述PDLA-PEG中,PEG嵌段的分子量为50Da~6×105Da,优选的分子量为1000Da~4×104Da;PDLA嵌段的分子量为100Da~1×105Da,优选的分子量为800Da~6000Da。According to an embodiment of the present invention, in the PDLA-PEG, the molecular weight of the PEG block is 50Da-6×10 5 Da, preferably 1000Da-4×10 4 Da; the molecular weight of the PDLA block is 100Da-1×10 5 Da, preferably 800Da-6000Da.

研究发现,PLLA嵌段或PDLA嵌段的分子量在上述范围时,更有利于“物理交联点”的形成。Studies have found that when the molecular weight of the PLLA block or the PDLA block is within the above range, it is more conducive to the formation of "physical cross-linking points".

根据本发明的实施方式,优选地,所述PLLA-PEG的分子量和所述PDLA-PEG的分子量相同。示例性地,所述PLLA-PEG中的PEG嵌段和所述PDLA-PEG中的PEG嵌段的分子量相同,PLLA嵌段和PDLA嵌段的分子量相同。According to an embodiment of the present invention, preferably, the molecular weight of the PLLA-PEG is the same as the molecular weight of the PDLA-PEG. Exemplarily, the molecular weight of the PEG block in the PLLA-PEG is the same as the molecular weight of the PEG block in the PDLA-PEG, and the molecular weight of the PLLA block is the same as the molecular weight of the PDLA block.

本发明中,若是没有特别的定义,分子量均是指数均分子量。In the present invention, unless otherwise specified, molecular weight refers to number average molecular weight.

根据本发明的实施方式,所述PLLA嵌段来自式B所示的聚合物:According to an embodiment of the present invention, the PLLA block is derived from a polymer represented by formula B:

其中,a为聚合度。Here, a is the degree of polymerization.

根据本发明的实施方式,所述PDLA嵌段来自式C所示的聚合物:According to an embodiment of the present invention, the PDLA block is derived from a polymer represented by formula C:

其中,b为聚合度。Wherein, b is the degree of polymerization.

根据本发明的实施方式,所述PLLA-PEG中,PLLA嵌段与PEG嵌段之间通过连接基团连接,所述连接基团没有特别的限定,例如为-COO-。According to an embodiment of the present invention, in the PLLA-PEG, the PLLA block and the PEG block are connected via a linking group, and the linking group is not particularly limited, for example, -COO-.

根据本发明的实施方式,所述PDLA-PEG中,PDLA嵌段与PEG嵌段之间通过连接基团连接,所述连接基团没有特别的限定,例如为-COO-。According to an embodiment of the present invention, in the PDLA-PEG, the PDLA block and the PEG block are connected via a linking group, and the linking group is not particularly limited, for example, -COO-.

根据本发明的实施方式,所述PLLA-PEG与所述PDLA-PEG可以是商业途径购买的市售产品,也可以是通过本领域已知的方法制备得到的。According to an embodiment of the present invention, the PLLA-PEG and the PDLA-PEG may be commercially available products, or may be prepared by methods known in the art.

根据本发明的实施方式,所述PLLA-PEG例如可以是通过如下方法制备得到的:According to an embodiment of the present invention, the PLLA-PEG can be prepared, for example, by the following method:

将聚乙二醇(PEG)、左旋乳酸(L-LA)和催化剂混合,反应,制备得到所述PLLA-PEG。Polyethylene glycol (PEG), L-lactic acid (L-LA) and a catalyst are mixed and reacted to prepare the PLLA-PEG.

根据本发明的实施方式,所述PDLA-PEG例如可以是通过如下方法制备得到的:According to an embodiment of the present invention, the PDLA-PEG can be prepared, for example, by the following method:

将聚乙二醇(PEG)、右旋乳酸(D-LA)和催化剂混合,反应,制备得到所述PDLA-PEG。Polyethylene glycol (PEG), dextrorotatory lactic acid (D-LA) and a catalyst are mixed and reacted to prepare the PDLA-PEG.

根据本发明的实施方式,按照设计链节长度的量将PEG和L-LA混合。或者,按照设计链节长度的量将PEG和D-LA混合。According to an embodiment of the present invention, PEG and L-LA are mixed in an amount according to the designed link length. Alternatively, PEG and D-LA are mixed in an amount according to the designed link length.

根据本发明的实施方式,所述催化剂例如选自Sn(Oct)2。所述催化剂的加入量为混合体系(PEG和L-LA,或PEG和D-LA)总重量的0.01~5wt%。According to an embodiment of the present invention, the catalyst is, for example, selected from Sn(Oct) 2 . The catalyst is added in an amount of 0.01 to 5 wt % of the total weight of the mixed system (PEG and L-LA, or PEG and D-LA).

根据本发明的实施方式,所述反应是在有机溶剂存在的条件下进行的,示例性地,所述有机溶剂例如为甲苯。According to an embodiment of the present invention, the reaction is carried out in the presence of an organic solvent. For example, the organic solvent is toluene.

根据本发明的实施方式,所述反应的温度为110~130℃,所述反应的时间为16~36小时。示例性地,所述反应的温度为120℃,所述反应的时间为24小时。According to an embodiment of the present invention, the reaction temperature is 110-130° C., and the reaction time is 16-36 hours. Exemplarily, the reaction temperature is 120° C., and the reaction time is 24 hours.

根据本发明的实施方式,所述反应结束后还包括:用乙醇沉降后抽滤;再用二氯甲烷溶解和冷乙醚/乙醇混合溶剂沉降三次;真空干燥。According to an embodiment of the present invention, after the reaction is completed, the method further comprises: filtering after settling with ethanol; dissolving with dichloromethane and settling with a cold ether/ethanol mixed solvent three times; and vacuum drying.

根据本发明的实施方式,所述聚乙二醇(PEG)具有式A所示结构式:According to an embodiment of the present invention, the polyethylene glycol (PEG) has a structural formula shown in Formula A:

式A中,R’、Y、x和p的定义如上所述。In formula A, R', Y, x and p are as defined above.

根据本发明的实施方式,所述多糖为水溶性多糖及其衍生物。According to an embodiment of the present invention, the polysaccharide is a water-soluble polysaccharide and its derivatives.

根据本发明的实施方式,所述多糖包括基于天然或通过化学、物理、生物学的方法修饰的如下化合物中的至少一种:透明质酸、琼脂、藻酸盐、胶原、明胶、卡拉胶、纤维素、壳聚糖、甲壳素、环糊精、葡聚糖、结冷胶、糖原、糖胺聚糖、刺梧桐胶、菊粉、果胶、聚葡萄糖、黄原胶和淀粉及其任何药学上可接受的盐;修饰方法包括但不限于糊精化、水解、硫酸化、磷酸化、乙酰化、烷基化、羟烷基化、硒化、羧甲基化、氧化、酶解修饰、接枝共聚等。According to an embodiment of the present invention, the polysaccharide includes at least one of the following compounds based on nature or modified by chemical, physical, or biological methods: hyaluronic acid, agar, alginate, collagen, gelatin, carrageenan, cellulose, chitosan, chitin, cyclodextrin, dextran, gellan gum, glycogen, glycosaminoglycan, karaya gum, inulin, pectin, polydextrose, xanthan gum, and starch, and any pharmaceutically acceptable salts thereof; modification methods include but are not limited to dextrinization, hydrolysis, sulfation, phosphorylation, acetylation, alkylation, hydroxyalkylation, selenization, carboxymethylation, oxidation, enzymatic modification, graft copolymerization, and the like.

根据本发明的实施方式,所述组合物还包括其他组分,所述其他组分包括但不限于抗氧化剂、麻醉剂、抗菌剂、DNA片段、多肽、维生素C、利多卡因、维生素和氨基酸等中的至少一种。According to an embodiment of the present invention, the composition further comprises other components, including but not limited to at least one of antioxidants, anesthetics, antibacterial agents, DNA fragments, polypeptides, vitamin C, lidocaine, vitamins and amino acids.

根据本发明的实施方式,所述组合物还包括溶液,所述溶液为水溶液、生理盐水或磷酸盐缓冲溶液中的至少一种。According to an embodiment of the present invention, the composition further comprises a solution, and the solution is at least one of an aqueous solution, a physiological saline solution or a phosphate buffer solution.

本发明还提供上述组合物的用途,其用于药物、化妆品、医学美容、组织修复、组织填充领域。The present invention also provides uses of the composition, which is used in the fields of medicine, cosmetics, medical cosmetology, tissue repair, and tissue filling.

具体的,用于制备药物、化妆品、医学美容用品、组织修复剂或组织填充剂。Specifically, it is used for preparing medicines, cosmetics, medical beauty products, tissue repair agents or tissue fillers.

根据本发明的实施方式,所述组合物用于制备凝胶;具体的,所述凝胶用于药物、化妆品、医学美容、组织修复、组织填充领域。According to an embodiment of the present invention, the composition is used to prepare a gel; specifically, the gel is used in the fields of medicine, cosmetics, medical cosmetology, tissue repair, and tissue filling.

根据本发明的实施方式,所述组合物可以单独使用,也可以与生物活性化合物组合使用。According to an embodiment of the present invention, the composition can be used alone or in combination with a biologically active compound.

具体的,所述生物活性化合物例如可以选自维生素C、视黄醇、矿物质、抗氧化酶,硫辛酸、活性蛋白等。Specifically, the bioactive compound can be selected from vitamin C, retinol, minerals, antioxidant enzymes, lipoic acid, active proteins, etc.

本发明还提供一种凝胶,所述凝胶的制备原料选自上述的凝胶用组合物。The present invention also provides a gel, wherein the raw materials for preparing the gel are selected from the above-mentioned composition for gel.

根据本发明的实施方式,所述凝胶优选为水凝胶。According to an embodiment of the present invention, the gel is preferably a hydrogel.

根据本发明的实施方式,所述凝胶中包括互穿网络结构和基于立体复合作用的结构;所述互穿网络结构是亲水性的PEG链段和亲水性的多糖链段形成的;所述立体复合作用的结构是基于PLLA和PDLA的立体复合作用形成的,具体的,是一个一个的物理交联点。According to an embodiment of the present invention, the gel includes an interpenetrating network structure and a structure based on stereocomplexation; the interpenetrating network structure is formed by hydrophilic PEG segments and hydrophilic polysaccharide segments; the stereocomplexation structure is formed based on the stereocomplexation of PLLA and PDLA, specifically, it is a physical cross-linking point one by one.

根据本发明的实施方式,所述凝胶具有可调的力学性能;具体地,所述凝胶的弹性模量为10~106Pa。According to an embodiment of the present invention, the gel has adjustable mechanical properties; specifically, the elastic modulus of the gel is 10-10 6 Pa.

本发明还提供上述凝胶的制备方法,所述方法包括如下步骤:The present invention also provides a method for preparing the above-mentioned gel, which comprises the following steps:

将PLLA-PEG、PDLA-PEG和多糖在溶液中混合,制备得到所述凝胶。The gel is prepared by mixing PLLA-PEG, PDLA-PEG and polysaccharide in a solution.

根据本发明的实施方式,所述溶液为水溶液、生理盐水或磷酸盐缓冲溶液中的至少一种。According to an embodiment of the present invention, the solution is at least one of an aqueous solution, a physiological saline solution or a phosphate buffer solution.

根据本发明的实施方式,在混合过程中,亲水性的PEG链段和亲水性的多糖链段形成互穿网络结构,聚左旋乳酸PLLA链段和聚右旋乳酸PDLA链段之间发生立体复合作用,这种立体复合可以看作是一个一个的物理交联点,从而形成具有力学性能的凝胶。此外,在混合过程中,多糖链段和亲水性的PEG链段之间还存在氢键作用(如透明质酸中的NH和PEG中的O之间会形成氢键相互作用),这种物理相互作用使凝胶更稳定,力学强度更强,更不容易降解。According to an embodiment of the present invention, during the mixing process, the hydrophilic PEG segments and the hydrophilic polysaccharide segments form an interpenetrating network structure, and a stereocomplex occurs between the poly-L-lactic acid PLLA segments and the poly-D-lactic acid PDLA segments, and this stereocomplex can be regarded as a physical cross-linking point one by one, thereby forming a gel with mechanical properties. In addition, during the mixing process, there is a hydrogen bond between the polysaccharide segments and the hydrophilic PEG segments (such as hydrogen bond interaction between NH in hyaluronic acid and O in PEG), and this physical interaction makes the gel more stable, stronger in mechanical strength, and less prone to degradation.

本发明还提供上述凝胶的用途,其用于药物、化妆品、医学美容、组织修复、组织填充领域。The present invention also provides the use of the gel, which is used in the fields of medicine, cosmetics, medical cosmetology, tissue repair and tissue filling.

根据本发明的实施方式,所述凝胶用于制备药物、化妆品、医学美容用品(如填充剂)、组织修复剂或组织填充剂(如组织支架等)。According to an embodiment of the present invention, the gel is used to prepare medicines, cosmetics, medical cosmetic products (such as fillers), tissue repair agents or tissue fillers (such as tissue scaffolds, etc.).

根据本发明的实施方式,所述凝胶可以单独使用,也可以与生物活性化合物组合使用。According to an embodiment of the present invention, the gel may be used alone or in combination with a bioactive compound.

根据本发明的实施方式,所述凝胶用于面部填充。具体的,所述凝胶用于制备面部填充剂。According to an embodiment of the present invention, the gel is used for facial filling. Specifically, the gel is used for preparing facial fillers.

根据本发明的实施方式,所述凝胶用于制备治疗眼部的药物。According to an embodiment of the present invention, the gel is used to prepare a medicament for treating eyes.

根据本发明的实施方式,所述凝胶用于制备治疗皮肤障碍或皮肤瑕疵的药物,所述皮肤障碍例如为痤疮、红斑和烧伤。According to an embodiment of the present invention, the gel is used to prepare a medicament for treating skin disorders or skin blemishes, such as acne, erythema and burns.

根据本发明的实施方式,所述凝胶用于制备治疗关节炎症的药物。According to an embodiment of the present invention, the gel is used to prepare a medicament for treating joint inflammation.

根据本发明的实施方式,所述凝胶可注射施用,尤其是皮内、中胚层、关节内或眼内注射。According to an embodiment of the present invention, the gel can be administered by injection, in particular by intradermal, mesodermal, intraarticular or intraocular injection.

根据本发明的实施方式,所述凝胶用于抗衰老剂或抗污染剂。According to an embodiment of the present invention, the gel is used as an anti-aging agent or an anti-pollution agent.

根据本发明的实施方式,所述凝胶用于骨、关节、组织的修复。具体的,所述凝胶用于制备骨、关节、组织的修复剂。According to an embodiment of the present invention, the gel is used for repairing bones, joints, and tissues. Specifically, the gel is used for preparing a repair agent for bones, joints, and tissues.

本发明的有益效果:Beneficial effects of the present invention:

本发明提供了一种基于立体复合作用的多糖-聚乳酸凝胶组合物。所述多糖-聚乳酸凝胶组合物包括第一嵌段共聚物、第二嵌段共聚物和多糖;所述第一嵌段共聚物包括聚左旋乳酸嵌段和聚乙二醇嵌段,所述第二嵌段共聚物包括聚右旋乳酸嵌段和聚乙二醇嵌段。所述组合物中,亲水性的PEG的网络结构和亲水性的多糖的网络结构互穿,聚左旋乳酸PLLA和聚右旋乳酸PDLA之间发生立体复合作用,这种立体复合可以看作是一个一个的物理交联点,从而形成具有力学性能的凝胶。所述凝胶的制备方法简单,且获得的凝胶性质可调。这种使用聚乳酸立体复合作用作为凝胶的“交联点”形成的凝胶,和用其它交联方法制备得到的凝胶相比有诸多优点,例如在温和的条件下反应,避免使用催化剂、辅助交联剂和其他活性分子等。The present invention provides a polysaccharide-polylactic acid gel composition based on stereocomplexation. The polysaccharide-polylactic acid gel composition comprises a first block copolymer, a second block copolymer and a polysaccharide; the first block copolymer comprises a poly-L-lactic acid block and a polyethylene glycol block, and the second block copolymer comprises a poly-D-lactic acid block and a polyethylene glycol block. In the composition, the network structure of the hydrophilic PEG and the network structure of the hydrophilic polysaccharide are interpenetrated, and a stereocomplexation occurs between the poly-L-lactic acid PLLA and the poly-D-lactic acid PDLA. This stereocomplexation can be regarded as a physical cross-linking point one by one, thereby forming a gel with mechanical properties. The preparation method of the gel is simple, and the properties of the obtained gel are adjustable. This gel formed by using the stereocomplexation of polylactic acid as the "cross-linking point" of the gel has many advantages compared with the gel prepared by other cross-linking methods, such as reacting under mild conditions, avoiding the use of catalysts, auxiliary cross-linking agents and other active molecules.

附图说明BRIEF DESCRIPTION OF THE DRAWINGS

图1为基于PLLA-PEG、PDLA-PEG和多糖的凝胶之间的相互作用示意图。FIG1 is a schematic diagram of the interaction between gels based on PLLA-PEG, PDLA-PEG and polysaccharides.

具体实施方式DETAILED DESCRIPTION

下文将结合具体实施例对本发明做更进一步的详细说明。应当理解,下列实施例仅为示例性地说明和解释本发明,而不应被解释为对本发明保护范围的限制。凡基于本发明上述内容所实现的技术均涵盖在本发明旨在保护的范围内。The present invention will be described in further detail below in conjunction with specific embodiments. It should be understood that the following embodiments are only exemplary descriptions and explanations of the present invention and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are included in the scope that the present invention is intended to protect.

下述实施例中所使用的实验方法如无特殊说明,均为常规方法;下述实施例中所用的试剂、材料等,如无特殊说明,均可从商业途径得到。Unless otherwise specified, the experimental methods used in the following examples are all conventional methods; the reagents, materials, etc. used in the following examples, unless otherwise specified, can be obtained from commercial channels.

实施例1Example 1

PLLA-PEG和PDLA-PEG的制备Preparation of PLLA-PEG and PDLA-PEG

按照设计链节长度(重复单元的数量)的量将干燥的双臂PEG(即式A中,R’选自-CH2CH2-、Y选自-O-,p=2)、L-LA(或D-LA)和Sn(Oct)2(1wt%)加入到干燥的反应瓶中,加入50mL甲苯,在120℃下搅拌反应24小时。反应完成后,用乙醇沉降后抽滤。真空干燥48小时,得到产物PLLA-PEG或PDLA-PEG。According to the designed chain length (number of repeating units), dry double-arm PEG (i.e., in formula A, R' is selected from -CH 2 CH 2 -, Y is selected from -O-, p=2), L-LA (or D-LA) 2 (1wt%) are added to a dry reaction bottle, 50 mL of toluene is added, and the mixture is stirred at 120°C for 24 hours. After the reaction is completed, the mixture is filtered after precipitation with ethanol. The mixture is vacuum dried for 48 hours to obtain the product PLLA-PEG or PDLA-PEG.

用凝胶渗透色谱(GPC)测定PLLA-PEG和PDLA-PEG的数均分子量(Mn)与重均分子量(Mw)及分子量分布(PDI=Mw/Mn),DMF作为流动相,单分散聚苯乙烯作为标准样品。The number average molecular weight ( Mn ) and weight average molecular weight ( Mw ) and molecular weight distribution (PDI = Mw / Mn ) of PLLA-PEG and PDLA-PEG were determined by gel permeation chromatography (GPC) with DMF as the mobile phase and monodisperse polystyrene as the standard sample.

合成的PLLA-PEG具有如下所式结构:The synthesized PLLA-PEG has the following structure:

其中,n1,m1,p1为聚合度。Wherein, n 1 , m 1 , p 1 are the degree of polymerization.

合成的PDLA-PEG具有如下所式结构:The synthesized PDLA-PEG has the following structure:

其中,n2,m2,p2为聚合度。Where n 2 , m 2 , and p 2 are the degrees of polymerization.

表1实施例1制备得到样品Y1~Y8的组成和性能表征结果Table 1 Composition and performance characterization results of samples Y1 to Y8 prepared in Example 1

其中,a1H NMR信号计算峰积分面积得到的PLLA-PEG或PDLA-PEG的数均分子量;b由GPC测定的PLLA-PEG或PDLA-PEG的数均分子量和分子量分布。Wherein, a is the number average molecular weight of PLLA-PEG or PDLA-PEG obtained by calculating the peak integrated area of 1 H NMR signal; b is the number average molecular weight and molecular weight distribution of PLLA-PEG or PDLA-PEG determined by GPC.

其中,结构简式中,以PLLA5-PEG91-PLLA5为例,其中的PLLA5中的5表述的是乳酸重复单元的数量为5,即上述对应的n1、p1为5;PEG91表述的是乙二醇重复单元的数量为91,即上述对应的m1为91。In the structural formula, taking PLLA 5 -PEG 91 -PLLA 5 as an example, the 5 in PLLA 5 represents the number of lactic acid repeating units is 5, that is, the corresponding n 1 and p 1 are 5; PEG 91 represents the number of ethylene glycol repeating units is 91, that is, the corresponding m 1 is 91.

实施例2Example 2

PLLA-PEG和PDLA-PEG的制备Preparation of PLLA-PEG and PDLA-PEG

其他同实施例1,仅是用四臂PEG(即式A中,R’选自Y选自-O-,p=4)替代实施例1中的双臂PEG,具体的如表2所示。The other aspects are the same as in Example 1, except that a four-arm PEG (i.e., in Formula A, R' is selected from Y is selected from -O-, p=4) to replace the double-arm PEG in Example 1, as shown in Table 2.

表2实施例2制备得到样品Z1~Z6的组成和性能表征结果Table 2 Composition and performance characterization results of samples Z1 to Z6 prepared in Example 2

其中,a1H NMR信号计算峰积分面积得到的PLLA-PEG或PDLA-PEG的数均分子量;b由GPC测定的PLLA-PEG或PDLA-PEG的数均分子量和分子量分布。以(PEG57-PLLA5)4为例,4表示臂数为4,PEG57-PLLA5表示每臂包括PEG链段和PLLA链段,且PEG链段的重复单元数为57,PLLA链段的重复单元数为5。Wherein, a is the number average molecular weight of PLLA-PEG or PDLA-PEG obtained by calculating the peak integral area of 1 H NMR signal; b is the number average molecular weight and molecular weight distribution of PLLA-PEG or PDLA-PEG determined by GPC. Taking (PEG 57 -PLLA 5 ) 4 as an example, 4 means that the number of arms is 4, and PEG 57 -PLLA 5 means that each arm includes a PEG segment and a PLLA segment, and the number of repeating units of the PEG segment is 57, and the number of repeating units of the PLLA segment is 5.

实施例3Example 3

PLLA-PEG、PDLA-PEG与透明质酸混合制备水凝胶Preparation of hydrogels by mixing PLLA-PEG, PDLA-PEG and hyaluronic acid

分别将实施例1中的Y5、Y6和透明质酸钠(HA)溶解在去离子水中,使之完全溶解。将溶解好的Y5、Y6和透明质酸钠溶液按预定的比例混合,置于37℃的水浴中达到平衡,倒置小管,如果30秒内不流动,则可认为样品溶液转变为凝胶状态。Dissolve Y5, Y6 and sodium hyaluronate (HA) in deionized water respectively to completely dissolve them. Mix the dissolved Y5, Y6 and sodium hyaluronate solutions in a predetermined ratio, place them in a 37°C water bath to reach equilibrium, invert the tube, and if there is no flow within 30 seconds, it can be considered that the sample solution has turned into a gel state.

将所得凝胶进行流变测试。流变测试是在Anton Paar MCR 302流变仪上,室温条件下进行的。为了防止水蒸发,将盖子盖在样品的顶部。转子与平板之间的间隙设置为0.3mm,转子直径为25mm,温度:25℃,应力:1%,频率范围:0.1~10Hz。G’指弹性模量,G”指黏性模量。弹性模量G’用于评估凝胶通过弹性储存能量的能力,黏性模量G”用于评估凝胶通过热耗散能量的能力。损耗因子Tanδ(G”/G’)用于评估凝胶粘性和弹性行为的相对重要性。The obtained gel was subjected to rheological tests. The rheological tests were carried out on an Anton Paar MCR 302 rheometer at room temperature. To prevent water evaporation, a lid was placed on the top of the sample. The gap between the rotor and the plate was set to 0.3 mm, the rotor diameter was 25 mm, the temperature was 25 °C, the stress was 1%, and the frequency range was 0.1-10 Hz. G’ refers to the elastic modulus, and G” refers to the viscous modulus. The elastic modulus G’ is used to evaluate the ability of the gel to store energy through elasticity, and the viscous modulus G” is used to evaluate the ability of the gel to dissipate energy through heat. The loss factor Tanδ(G”/G’) is used to evaluate the relative importance of the viscous and elastic behavior of the gel.

凝胶样品及性质如下表所示:The gel samples and properties are shown in the following table:

从上表可知,PLLA-PEG和PDLA-PEG单独存在时,不能形成凝胶,这是因为单独的PLLA或PDLA不能形成交联点。当PLLA-PEG和PDLA-PEG同时存在时,可以形成凝胶,说明PLLA和PDLA之间形成了立体复合作用。在一定范围内,在Y5、Y6、HA的质量比不变时,随着Y5、Y6、HA的总浓度增加,凝胶的强度增加;在Y5、Y6、HA的总浓度不变时,随着Y5+Y6/HA的质量比增加时,凝胶的强度增加。As can be seen from the above table, when PLLA-PEG and PDLA-PEG exist alone, gel cannot be formed, because PLLA or PDLA alone cannot form cross-linking points. When PLLA-PEG and PDLA-PEG exist at the same time, gel can be formed, indicating that a stereocomplex effect is formed between PLLA and PDLA. Within a certain range, when the mass ratio of Y5, Y6, and HA remains unchanged, the strength of the gel increases with the increase of the total concentration of Y5, Y6, and HA; when the total concentration of Y5, Y6, and HA remains unchanged, the strength of the gel increases with the increase of the mass ratio of Y5+Y6/HA.

实施例4Example 4

PLLA-PEG、PDLA-PEG与透明质酸混合制备水凝胶Preparation of hydrogels by mixing PLLA-PEG, PDLA-PEG and hyaluronic acid

分别将实施例2中的Z3、Z4和透明质酸钠(HA)溶解在去离子水中,使之完全溶解。具体实施步骤同实施例3。Dissolve Z3, Z4 and sodium hyaluronate (HA) in deionized water respectively to completely dissolve them. The specific implementation steps are the same as those in Example 3.

凝胶样品及性质如下表所示:The gel samples and properties are shown in the following table:

从上表可知,PLLA-PEG和PDLA-PEG单独存在时,不能形成凝胶,这是因为单独的PLLA或PDLA不能形成交联点。当PLLA-PEG和PDLA-PEG同时存在时,可以形成凝胶,说明PLLA和PDLA之间形成了立体复合作用。在一定范围内,在Z3、Z4、HA的质量比不变时,随着Z3、Z4、HA的总浓度增加,凝胶的强度增加。As can be seen from the above table, when PLLA-PEG and PDLA-PEG exist alone, gel cannot be formed, because PLLA or PDLA alone cannot form cross-linking points. When PLLA-PEG and PDLA-PEG exist at the same time, gel can be formed, indicating that a stereocomplex effect is formed between PLLA and PDLA. Within a certain range, when the mass ratio of Z3, Z4, and HA remains unchanged, the strength of the gel increases with the increase of the total concentration of Z3, Z4, and HA.

以上,对本发明的实施方式进行了说明。但是,本发明不限定于上述实施方式。凡在本发明的精神和原则之内,所做的任何修改、等同替换、改进等,均应包含在本发明的保护范围之内。The above is an explanation of the embodiments of the present invention. However, the present invention is not limited to the above embodiments. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims (10)

1.一种凝胶用组合物,其中,所述组合物包括第一嵌段共聚物、第二嵌段共聚物和多糖;所述第一嵌段共聚物包括聚左旋乳酸嵌段和聚乙二醇嵌段,所述第二嵌段共聚物包括聚右旋乳酸嵌段和聚乙二醇嵌段,第一嵌段共聚物记为PLLA-PEG,第二嵌段共聚物记为PDLA-PEG。1. A composition for gel, wherein the composition comprises a first block copolymer, a second block copolymer and a polysaccharide; the first block copolymer comprises a poly-L-lactic acid block and a polyethylene glycol block, the second block copolymer comprises a poly-D-lactic acid block and a polyethylene glycol block, the first block copolymer is denoted as PLLA-PEG, and the second block copolymer is denoted as PDLA-PEG. 2.根据权利要求1所述的凝胶用组合物,其中,所述组合物中,PLLA-PEG与PDLA-PEG的质量比为0.001-1000:1。2. The gel composition according to claim 1, wherein the mass ratio of PLLA-PEG to PDLA-PEG in the composition is 0.001-1000:1. 优选地,所述组合物中,PLLA-PEG和PDLA-PEG的质量之和与多糖的质量比为0.001-1000:1。Preferably, in the composition, the mass ratio of the sum of the masses of PLLA-PEG and PDLA-PEG to the mass of the polysaccharide is 0.001-1000:1. 3.根据权利要求1或2所述的凝胶用组合物,其中,所述聚乙二醇嵌段来自式A所示的聚合物:3. The composition for gel according to claim 1 or 2, wherein the polyethylene glycol block is derived from a polymer represented by formula A: 式A中,R’为中心分子基团,Y选自-O-、-NH-、-C(=O)O-或-OC(=O)-,x为聚合度,p为≥2的整数。In formula A, R' is a central molecular group, Y is selected from -O-, -NH-, -C(=O)O- or -OC(=O)-, x is the degree of polymerization, and p is an integer ≥2. 优选地,式A中,R’选自烃基。Preferably, in formula A, R' is selected from a hydrocarbon group. 优选地,式A中,R’选自烷基、烯基、芳基。Preferably, in formula A, R' is selected from alkyl, alkenyl, and aryl. 优选地,p为3-16之间的整数。Preferably, p is an integer between 3-16. 优选地,所述PLLA-PEG的分子量为200Da~7×105Da,所述PDLA-PEG的分子量为200Da~7×105Da。Preferably, the molecular weight of the PLLA-PEG is 200Da to 7×10 5 Da, and the molecular weight of the PDLA-PEG is 200Da to 7×10 5 Da. 优选地,所述PLLA-PEG中,PEG嵌段的分子量为50Da~6×105Da,优选的分子量为1000Da~4×104Da;PLLA嵌段的分子量为100Da~1×105Da,优选的分子量为800Da~6000Da。Preferably, in the PLLA-PEG, the molecular weight of the PEG block is 50Da to 6×10 5 Da, preferably 1000Da to 4×10 4 Da; the molecular weight of the PLLA block is 100Da to 1×10 5 Da, preferably 800Da to 6000Da. 优选地,所述PDLA-PEG中,PEG嵌段的分子量为50Da~6×105Da,优选的分子量为1000Da~4×104Da;PDLA嵌段的分子量为100Da~1×105Da,优选的分子量为800Da~6000Da。Preferably, in the PDLA-PEG, the molecular weight of the PEG block is 50Da to 6×10 5 Da, preferably 1000Da to 4×10 4 Da; the molecular weight of the PDLA block is 100Da to 1×10 5 Da, preferably 800Da to 6000Da. 4.根据权利要求1-3任一项所述的凝胶用组合物,其中,所述组合物还包括其他组分,所述其他组分包括但不限于抗氧化剂、麻醉剂、抗菌剂、DNA片段、多肽、维生素C、利多卡因、维生素和氨基酸等中的至少一种。4. The gel composition according to any one of claims 1 to 3, wherein the composition further comprises other components, including but not limited to at least one of antioxidants, anesthetics, antibacterial agents, DNA fragments, polypeptides, vitamin C, lidocaine, vitamins and amino acids. 优选地,所述组合物还包括溶液,所述溶液为水溶液、生理盐水或磷酸盐缓冲溶液中的至少一种。Preferably, the composition further comprises a solution, and the solution is at least one of an aqueous solution, a physiological saline solution or a phosphate buffer solution. 5.权利要求1-4任一项所述的凝胶用组合物的用途,其用于制备药物、化妆品、医学美容用品、组织修复剂或组织填充剂。5. Use of the gel composition according to any one of claims 1 to 4 for preparing medicines, cosmetics, medical cosmetic products, tissue repair agents or tissue fillers. 6.一种凝胶,所述凝胶的制备原料选自权利要求1-4任一项所述的凝胶用组合物。6. A gel, wherein the raw material for preparing the gel is selected from the composition for gel according to any one of claims 1 to 4. 7.根据权利要求6所述的凝胶,其中,所述凝胶中包括互穿网络结构和基于立体复合作用的结构;所述互穿网络结构是亲水性的PEG链段和亲水性的多糖链段形成的;所述立体复合作用的结构是基于PLLA和PDLA的立体复合作用形成的一个一个的物理交联点。7. The gel according to claim 6, wherein the gel comprises an interpenetrating network structure and a structure based on stereocomplexation; the interpenetrating network structure is formed by hydrophilic PEG segments and hydrophilic polysaccharide segments; the stereocomplexation structure is a physical cross-linking point formed one by one based on the stereocomplexation of PLLA and PDLA. 8.权利要求6或7所述的凝胶的制备方法,所述方法包括如下步骤:8. A method for preparing the gel according to claim 6 or 7, comprising the following steps: 将PLLA-PEG、PDLA-PEG和多糖在溶液中混合,制备得到所述凝胶。The gel is prepared by mixing PLLA-PEG, PDLA-PEG and polysaccharide in a solution. 9.权利要求6或7所述的凝胶的用途,其用于制备药物、化妆品、医学美容用品、组织修复剂或组织填充剂。9. Use of the gel according to claim 6 or 7 for preparing medicines, cosmetics, medical cosmetic products, tissue repair agents or tissue fillers. 10.根据权利要求9所述的用途,所述凝胶用于制备药物、化妆品、填充剂或组织支架。10. The use according to claim 9, wherein the gel is used for preparing medicines, cosmetics, fillers or tissue scaffolds. 优选地,所述凝胶用于制备面部填充剂;或者,所述凝胶用于制备治疗眼部的药物;或者,所述凝胶用于制备治疗皮肤障碍或皮肤瑕疵的药物,所述皮肤障碍例如为痤疮、红斑和烧伤;或者,所述凝胶用于制备治疗关节炎症的药物;或者,所述凝胶用于抗衰老剂或抗污染剂;或者,所述凝胶用于制备骨、关节、组织的修复剂。Preferably, the gel is used to prepare a facial filler; or, the gel is used to prepare a drug for treating the eyes; or, the gel is used to prepare a drug for treating skin disorders or skin blemishes, such as acne, erythema and burns; or, the gel is used to prepare a drug for treating joint inflammation; or, the gel is used for an anti-aging agent or an anti-pollution agent; or, the gel is used to prepare a bone, joint or tissue repair agent.
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