环保型改性聚乙烯醇载药膜的制备及其性能研究
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摘要
在生物医药领域,药用生物材料是近几年发展起来的一门新兴学科,是现代药剂学和材料学发展、交叉的产物。聚合物用作药物载体已成为对聚合物材料科学研究的一个非常重要的领域。而膜剂是近年来研制开发的一种新剂型,具有制备工艺简单;使用时涂于患处,形成药膜保护创面,且耐磨性能良好,缓慢释放等优点而备受关注。环保又是任何学科都必须面对的一个重要课题。故而,研究开发具有生物相容性的环保型高分子膜材料具有广阔的前景。
合成高分子成膜材料的成膜性能良好,成膜后的强度与柔韧性能满足膜剂成型与应用要求,在成膜性能如膜抗拉强度,柔软性、吸湿性和水溶性等,都以聚乙烯醇(PVA)为最好。而且,聚乙烯醇,已被广泛用于生物医用材料,安全性试验证明PVA毒性很低,无刺激性,日本和美国等已批准用于医药和食品工业。
此外,PVA形成的凝胶已被广泛地用在制药学中作为药物释放的载体,除了因其具有高亲水性外,还因为其可生物降解、无毒且具有很好的溶胀性能。而且,PVA对药物或其他生物活性的化合物没有选择性,使得该材料作为药物载体的使用范围极为广泛。但目前很少有PVA共价改性的研究报导。
前人研究表明碳纳米管由于其独特的结构和性能使得其具有良好的吸附性能,可作为聚合物膜材料的增强剂,提高膜的力学性能。但是由于碳纳米管较差的溶解熔融性,限制了其应用。
本论文采用成膜性较好的聚乙烯醇为基材,通过分子设计,选择生物相容的乳酸、乙醇酸对其进行改性,制备出水溶性和力学性能好的膜材料,并对其进行了表征。在此基础上,制备了不同载药率的载药膜,并对载药膜的溶解性、力学性能、药物相容性、稳定性等进行充分研究,研究表明,该膜材料上述性能均较好。
此外,通过二元胺对经过球磨短切、酸化,酰氯化的碳纳米管进行化学修饰,制备了结构新颖的碳纳米管衍生物,该衍生物具有一定的溶解性(可溶于DMF、DMSO、DMAc等),可做为聚合物良好的补强剂赋予聚合物优异的性能。
主要研究内容和结论如下:
(1)将精制后的PVA配成一定浓度的水溶液,选用具有生物相容性的乳酸对其进行改性,通过对PVA浓度、乳酸用量、时间等合成工艺条件的研究,确定了最佳合成工艺条件。并通过FTIR、1HNMR和13CNMR对改性产物进行了表征。此外,还研究了增塑剂甘油对膜材料性能的影响。实验结果表明:合成最佳工艺条件为PVA浓度为10%,原料PVA:LA的配比为1:2(g/ml),反应时间为8h。在此条件下制得的膜材料的溶解时间为35s、断裂伸长率为474 %、抗拉强度为50MPa。甘油作为小分子与改性膜进行共混,使膜的断裂伸长率提高到684 %。
(2)通过乙醇酸对PVA进行改性,在此基础上负载不同量的中药,研究了载药膜的溶解性、力学性能、药物相容性、吸湿性、稳定性。实验结果表明:改性膜具有良好的水溶性(溶解时间不到半分钟)及力学性能,且与药物小分子具有良好的相容性,膜具有较小的吸湿性,室温下比较稳定性。
(3)对多壁碳纳米管(MWNTs)进行短切、纯化、酸化、酰氯化后与二元胺反应,制备出碳纳米管碳衍生物,通过TEM、FTIR、13CNMR、1HMNR和TG对共价修饰物进行表征,结果表明二元胺与MWNTs之间的确形成了共价键,实现了MWNTs的芳香胺共价修饰,为制备功能化聚合物/ MWNTs膜奠定了基础。
此类新型功能膜材料具有生物相容性,可溶性及可降解性。该研究在化学、生命科学及材料科学交叉领域中有着重要的理论意义、明确的应用前景,具有良好的社会效益与广阔的市场应用前景。
In the field of biomedicine, pharmaceutical biomaterial is a new developed subject in recent years. It is the development and intersecting product of modern pharmaceutics and material science. Polymeric materials used as the carrier in the controlled release of drugs have become an important research area in the study of polymeric materials science. Further more, as a new medicine dosage, the film dosage has such advantages as the easy preparation technology, the convenient uses, slow release medicine and so on. Therefore the studies of it have been paid much attention. Protecting environment is a very important and indispensable concerning in any field. Thus, it has expansive foregrounds of the research of new environment-friendly biomaterials which are biocompatible.
Synthesize macromolecule film has choiceness formation properties of film. Also the intensity and flexility of the films satisfy the molding and application require of film dosage. PVA has the best formation properties of film such as tsile strength, pliability, moisture absorption and water-solubility. Further it has extensive application as biomedical material. It is proved low-toxicity and no pungency by security experimentation. Japan and USA have already ratified that PVA can used for medicine and food industry.
PVA gel has been widely used as the carrier of medicine release because of its hydrophilic ability, bio-degradability, no-toxicity and so on. And as the medicine carrier, it has good compatibility with other medicine and bio-compounds, so that it can be widely used as carrier for medicine. Furthermore, it provides good dispersion and coating properties as film material. But there is less study papers about covalence modification of PVA.
Previous results have shown that CNTs has good adsorptive properties so as to be widely used in the field of environment protection and medicine, which may be attributed to the unique structure and properties of the CNTs. However, the application of CNTs has been limited because of its solubility.
In this thesis, we choose PVA as parent metal. Depending on the design of molecule, It is modified by lactic acid and ethanol acid which are biocompatible. The film with well water-solubility and mechanical property is prepared.After charactered with it, The films loaded with different dosage of medicine were prepared. At last, we studied the films' solubility, mechanical properties, medication compatibility, stability, et al. Which indicate that all the above properties are very good.
In addition, after the treatments of the raw MWNTs by ball milting, purification, strong acid treatment, SOCl2, we use duality amine modify it, and the MWNTs ramification with novelty structure are prepared. These ramifications which can solute in DMF, DMSO and DMAc can endow polymer exceptional properties as strengthening agent.
The main content and conclusion:
(1) The refine PVA solution is modified by lactic acid which is biocompatible. After the study of the main factors, such as the concentration of the PVA, the dosage of lactic acid and reaction time of the system, we devised the modification conditions of PVA to make quickly water-soluble film with well solubility and mechanical properties. The structure was token through FTIR, 1HNMR and 13CNMR. In addition, the influence of the film s' properties are studied when we treat it with glycerol as a plasticizer. The results showed: When the concentration of PVA 10%, the rate of PVA: LA is1:2(g/ml) and the reaction time of the system is eight hour, the films' solute time is 35s, negation at break is 474%, tsile strength is 50MPa. The films' negation at break is added to 684% when add glycerol.
(2) After modify PVA with ethanol acid, the films loaded with different dosage of medicine were prepared. And the films' solubility, mechanical properties, medication compatibility, stability, et al. are studied. The results showed: the films' solubility and mechanical properties are favorable, the moisture absorption of the film is low and the film is compatible with medication.
(3) After the treatments of the raw MWNTs by short cutting, purification , strong acid treatment, SOCl2, the MWNT-SOCl is modified by duality amine, and then the MWNTs ramification are prepared. After the characterization of TEM, FTIR, 13CNMR, 1HMNR, TG and so on, we educed that the covalent bond has been formed. The covalence modification of MWNTs with aromatic amine is achieved.
The studies of all these functional film materials are biocompatible and good mechanical properties. It has great academic significance and application foreground on the interaction study of chemistry, life sciences and material sciences. And what’s more, the exploitation of the new film materials has social benefits and expansive progress in the market.
合成高分子成膜材料的成膜性能良好,成膜后的强度与柔韧性能满足膜剂成型与应用要求,在成膜性能如膜抗拉强度,柔软性、吸湿性和水溶性等,都以聚乙烯醇(PVA)为最好。而且,聚乙烯醇,已被广泛用于生物医用材料,安全性试验证明PVA毒性很低,无刺激性,日本和美国等已批准用于医药和食品工业。
此外,PVA形成的凝胶已被广泛地用在制药学中作为药物释放的载体,除了因其具有高亲水性外,还因为其可生物降解、无毒且具有很好的溶胀性能。而且,PVA对药物或其他生物活性的化合物没有选择性,使得该材料作为药物载体的使用范围极为广泛。但目前很少有PVA共价改性的研究报导。
前人研究表明碳纳米管由于其独特的结构和性能使得其具有良好的吸附性能,可作为聚合物膜材料的增强剂,提高膜的力学性能。但是由于碳纳米管较差的溶解熔融性,限制了其应用。
本论文采用成膜性较好的聚乙烯醇为基材,通过分子设计,选择生物相容的乳酸、乙醇酸对其进行改性,制备出水溶性和力学性能好的膜材料,并对其进行了表征。在此基础上,制备了不同载药率的载药膜,并对载药膜的溶解性、力学性能、药物相容性、稳定性等进行充分研究,研究表明,该膜材料上述性能均较好。
此外,通过二元胺对经过球磨短切、酸化,酰氯化的碳纳米管进行化学修饰,制备了结构新颖的碳纳米管衍生物,该衍生物具有一定的溶解性(可溶于DMF、DMSO、DMAc等),可做为聚合物良好的补强剂赋予聚合物优异的性能。
主要研究内容和结论如下:
(1)将精制后的PVA配成一定浓度的水溶液,选用具有生物相容性的乳酸对其进行改性,通过对PVA浓度、乳酸用量、时间等合成工艺条件的研究,确定了最佳合成工艺条件。并通过FTIR、1HNMR和13CNMR对改性产物进行了表征。此外,还研究了增塑剂甘油对膜材料性能的影响。实验结果表明:合成最佳工艺条件为PVA浓度为10%,原料PVA:LA的配比为1:2(g/ml),反应时间为8h。在此条件下制得的膜材料的溶解时间为35s、断裂伸长率为474 %、抗拉强度为50MPa。甘油作为小分子与改性膜进行共混,使膜的断裂伸长率提高到684 %。
(2)通过乙醇酸对PVA进行改性,在此基础上负载不同量的中药,研究了载药膜的溶解性、力学性能、药物相容性、吸湿性、稳定性。实验结果表明:改性膜具有良好的水溶性(溶解时间不到半分钟)及力学性能,且与药物小分子具有良好的相容性,膜具有较小的吸湿性,室温下比较稳定性。
(3)对多壁碳纳米管(MWNTs)进行短切、纯化、酸化、酰氯化后与二元胺反应,制备出碳纳米管碳衍生物,通过TEM、FTIR、13CNMR、1HMNR和TG对共价修饰物进行表征,结果表明二元胺与MWNTs之间的确形成了共价键,实现了MWNTs的芳香胺共价修饰,为制备功能化聚合物/ MWNTs膜奠定了基础。
此类新型功能膜材料具有生物相容性,可溶性及可降解性。该研究在化学、生命科学及材料科学交叉领域中有着重要的理论意义、明确的应用前景,具有良好的社会效益与广阔的市场应用前景。
In the field of biomedicine, pharmaceutical biomaterial is a new developed subject in recent years. It is the development and intersecting product of modern pharmaceutics and material science. Polymeric materials used as the carrier in the controlled release of drugs have become an important research area in the study of polymeric materials science. Further more, as a new medicine dosage, the film dosage has such advantages as the easy preparation technology, the convenient uses, slow release medicine and so on. Therefore the studies of it have been paid much attention. Protecting environment is a very important and indispensable concerning in any field. Thus, it has expansive foregrounds of the research of new environment-friendly biomaterials which are biocompatible.
Synthesize macromolecule film has choiceness formation properties of film. Also the intensity and flexility of the films satisfy the molding and application require of film dosage. PVA has the best formation properties of film such as tsile strength, pliability, moisture absorption and water-solubility. Further it has extensive application as biomedical material. It is proved low-toxicity and no pungency by security experimentation. Japan and USA have already ratified that PVA can used for medicine and food industry.
PVA gel has been widely used as the carrier of medicine release because of its hydrophilic ability, bio-degradability, no-toxicity and so on. And as the medicine carrier, it has good compatibility with other medicine and bio-compounds, so that it can be widely used as carrier for medicine. Furthermore, it provides good dispersion and coating properties as film material. But there is less study papers about covalence modification of PVA.
Previous results have shown that CNTs has good adsorptive properties so as to be widely used in the field of environment protection and medicine, which may be attributed to the unique structure and properties of the CNTs. However, the application of CNTs has been limited because of its solubility.
In this thesis, we choose PVA as parent metal. Depending on the design of molecule, It is modified by lactic acid and ethanol acid which are biocompatible. The film with well water-solubility and mechanical property is prepared.After charactered with it, The films loaded with different dosage of medicine were prepared. At last, we studied the films' solubility, mechanical properties, medication compatibility, stability, et al. Which indicate that all the above properties are very good.
In addition, after the treatments of the raw MWNTs by ball milting, purification, strong acid treatment, SOCl2, we use duality amine modify it, and the MWNTs ramification with novelty structure are prepared. These ramifications which can solute in DMF, DMSO and DMAc can endow polymer exceptional properties as strengthening agent.
The main content and conclusion:
(1) The refine PVA solution is modified by lactic acid which is biocompatible. After the study of the main factors, such as the concentration of the PVA, the dosage of lactic acid and reaction time of the system, we devised the modification conditions of PVA to make quickly water-soluble film with well solubility and mechanical properties. The structure was token through FTIR, 1HNMR and 13CNMR. In addition, the influence of the film s' properties are studied when we treat it with glycerol as a plasticizer. The results showed: When the concentration of PVA 10%, the rate of PVA: LA is1:2(g/ml) and the reaction time of the system is eight hour, the films' solute time is 35s, negation at break is 474%, tsile strength is 50MPa. The films' negation at break is added to 684% when add glycerol.
(2) After modify PVA with ethanol acid, the films loaded with different dosage of medicine were prepared. And the films' solubility, mechanical properties, medication compatibility, stability, et al. are studied. The results showed: the films' solubility and mechanical properties are favorable, the moisture absorption of the film is low and the film is compatible with medication.
(3) After the treatments of the raw MWNTs by short cutting, purification , strong acid treatment, SOCl2, the MWNT-SOCl is modified by duality amine, and then the MWNTs ramification are prepared. After the characterization of TEM, FTIR, 13CNMR, 1HMNR, TG and so on, we educed that the covalent bond has been formed. The covalence modification of MWNTs with aromatic amine is achieved.
The studies of all these functional film materials are biocompatible and good mechanical properties. It has great academic significance and application foreground on the interaction study of chemistry, life sciences and material sciences. And what’s more, the exploitation of the new film materials has social benefits and expansive progress in the market.
引文
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