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首页> 外国专利> PENTABLOCK POLYPEPTIDIC AND HYBRID POLYMERS TO GIVE IN SITU-FORMING INJECTABLE, SELF-HEALING, PH-AND TEMPERATURE-RESPONSIVE HYDROGELS FOR LOCALISED TARGETED DELIVERY OF GEMCITABINE

PENTABLOCK POLYPEPTIDIC AND HYBRID POLYMERS TO GIVE IN SITU-FORMING INJECTABLE, SELF-HEALING, PH-AND TEMPERATURE-RESPONSIVE HYDROGELS FOR LOCALISED TARGETED DELIVERY OF GEMCITABINE

机译：五溴联苯聚合物和杂化聚合物可提供原位形成的可注射，自愈，PH和温度响应的水合物，用于定点靶向吉西他滨的输送

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I ABSTRACT The invention relates: A. The synthesis of new polymeric materials, B. The polymeric materials form hydrogels with unique properties: is self-healable and thus becomes injectable, and additionally is responsive to pH and temperature. C. The polymeric materials form a mixture suitable for targeted delivery of gemcitabine to pancreatic cancer in solid tissue form. The composition consists of the polymeric materials, water and gemcitabine, forming strong hydrogels and transfers gemcitabine selectively to local pancreatic cancer tissue. Two polymeric materials are presented. One is a pentablock tripolymer of poly(L-lysine) and poly(L-histidine-co-y-benzyl L-glutamate), while the other one is a hybrid tetrapolymer containing poly(ethylene oxide), poly(L-lysine) and poly(L-histidine-co-v-benzyl L-glutamate). The polymeric materials are injectable, in-situ forming and rapidly self-healing, they are not cytotoxic up to 400 mg/kg after in vivo studies in mice, according to the National Cancer Institute of USA. The composition responds to temperature and pH through a conversion from liquid to solid and a transformation of the secondary structure of the polymeric material. This multifunctionality allows the mixture to be placed near and in contact with the cancer tissue with the simplest possible application, i.e. via injection with a very thin needle. Furthermore, due to pH- and temperature-responsiveness, the mixtures melt and convert to liquids near the cancer tissue and thus are absorbed selectively by it, while they remain strong hydrogels at the healthy tissue, blocking release of the drug. In this way, the release of the drug is directed only to the cancer tissue. Our invention is unique and operates differently from other pH- and temperature-responsive hydrogel systems where the conversion from viscous liquid to hydrogel is effected in situ due to the lower pH and the higher temperature of the cancer tissues. Our composition is converted in situ from hydrogel to liquid due to conversion of the secondary structure, independently from the pH and temperature, and then melts selectively only towards the cancer tissue due to the lower pH and the higher temperature, delivering and releasing the drug in a targeted and time-controlled manner.
机译：发明内容本发明涉及：A.新型聚合材料的合成，B.聚合材料形成具有独特性质的水凝胶：可自我修复并因此可注射，并且还对pH和温度有响应。 C.聚合物材料形成适合于吉西他滨以实体组织形式靶向递送至胰腺癌的混合物。该组合物由聚合物材料，水和吉西他滨组成，形成牢固的水凝胶并将吉西他滨选择性转移至局部胰腺癌组织。介绍了两种聚合材料。一种是聚（L-赖氨酸）和聚（L-组氨酸-co-y-苄基L-谷氨酸）的五嵌段三元共聚物，而另一种是包含聚（环氧乙烷），聚（L-赖氨酸）的杂化四元共聚物。和聚（L-组氨酸-co-v-苄基L-谷氨酸）。据美国国家癌症研究所称，这种聚合材料是可注射的，原位形成的并且能快速自我修复，在小鼠体内研究后，其高达400 mg / kg的细胞毒性都没有。该组合物通过从液体到固体的转化以及聚合物材料的二级结构的转化来响应温度和pH。这种多功能性使得混合物可以通过最简单的应用即通过用非常细的针头注射而被放置在癌组织附近并与癌组织接触。此外，由于pH和温度响应性，混合物熔化并转化为癌组织附近的液体，因此被癌菌选择性吸收，而它们在健康组织处仍保持强力水凝胶，从而阻止了药物的释放。这样，药物的释放仅针对癌组织。我们的发明是独特的，并且与其他pH值和温度响应型水凝胶系统不同，在该系统中，由于癌症组织的pH值较低和温度较高，因此从粘性液体向水凝胶的转化就地进行。由于二级结构的转换，我们的组合物会从水凝胶原位转化为液体，而不受pH和温度的影响，然后由于较低的pH和较高的温度仅选择性地向癌组织融化，从而在体内释放和释放药物。有针对性和时间控制的方式。

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