KR20030059607A - Biodegradable Block Copolymer Based on Polyether and Random Copolymers of Lactide and Caprolactone and There Application - Google Patents
Biodegradable Block Copolymer Based on Polyether and Random Copolymers of Lactide and Caprolactone and There Application Download PDFInfo
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Abstract
Description
본 발명은 의료용으로 사용되는 생체적합성과 생분해성을 지닌 새로운 구조의 고분자 재료의 제조방법과 이의 응용에 관한 것으로 보다 상세하게는 분해속도가 지연되며 분해시 결정성이 저하되어 생체적합성이 우수한 생분해성 블록공중합체의 제조방법 및 이의 응용에 관한 것이다.The present invention relates to a method for producing a polymer material having a new structure with biocompatibility and biodegradability used for medical applications, and more particularly, to a degradation of the decomposition rate and to a decrease in crystallinity during decomposition. It relates to a method for producing a block copolymer and its application.
지방족 폴리에스테르인 폴리카프로락톤, 폴리락티드, 그리고 폴리글리콜라이드와 이들을 이용한 공중합체는 생체적합성과 생분해성을 지니고 있어 의료용으로의 사용이 가능하다. 대표적으로 폴리락티드와 폴리글리콜리드의 공중합체인 폴리(락티드-co-글리코리드)(PLGA)는 약물방출체계의 기질, 세포배양을 위한 지지체(scaffold) 및 봉합사 등으로 응용되고 있다.Aliphatic polyesters such as polycaprolactone, polylactide, and polyglycolide and copolymers using them are biocompatible and biodegradable and can be used for medical purposes. Representatively, poly (lactide-co-glycolide) (PLGA), a copolymer of polylactide and polyglycolide, has been applied as a substrate for drug release systems, scaffolds and sutures for cell culture.
또한 폴리에테르는 친수성 특성을 통하여 단백질 흡착 등을 억제하며 이로 인해 우수한 생체적합성을 나타내는 것으로 알려져 있다. 따라서 소수성 특성을 나타내는 지방족 폴리에스테르와 친수성 특성을 지닌 폴리에테르를 공중합하여 블록공중합체를 형성하게 되면 양친성을 나타내어 혈액에 있는 단백질의 흡착을 억제하여 장시간 사람이나 동물의 몸 속에서 형태를 유지하여 약물방출 등의 다양한 기능을 수행할 수 있다.In addition, polyether is known to exhibit excellent biocompatibility due to the inhibition of protein adsorption through hydrophilic properties. Therefore, when a block copolymer is formed by copolymerizing an aliphatic polyester having hydrophobicity and a polyether having hydrophilicity, it exhibits amphipathicity and suppresses the adsorption of proteins in the blood to maintain its shape in the body of a human or animal for a long time. Various functions such as drug release can be performed.
기존에 널리 사용된 PLGA는 분해 속도가 매우 빨라 1~2개월 이내에 분해가 완료되는 매질로 사용되었다. 그러나 PLGA는 우수한 기계적 강도가 요구되는 필름형태의 제조가 용이하지 않으며 분해가 수개월이 필요한 장시간 응용에는 사용이 어렵고 급격한 분해로 인해 기질 내에 심한 pH의 강하로 단백질 등과 같은 안정성이 저조한 약물의 적용에 어려움이 있다. 반면 단일고분자인 폴리카프로락톤과 폴리락티드를 사용하게 되면 우수한 기계적 물성을 나타내고 분해에 오랜 시간이 걸리는 장점이 있지만 높은 결정성으로 인해 분해시 분해산물이 결정성을 지니고 있어 주변의 세포에 손상을 주는 단점을 지닌다.PLGA, which has been widely used in the past, has been used as a medium in which decomposition is completed within one to two months due to its rapid decomposition rate. However, PLGA is not easy to manufacture in the form of a film requiring good mechanical strength, and it is difficult to use for long-term applications requiring several months of decomposition, and it is difficult to apply poorly stable drugs such as proteins due to severe pH drop in the substrate due to rapid decomposition. There is this. On the other hand, the use of single polymers, polycaprolactone and polylactide, has excellent mechanical properties and takes a long time to decompose.However, due to high crystallinity, decomposition products have crystallinity and damage to surrounding cells. Note has its drawbacks.
이에 본 발명자는 상기 재료들의 단점을 보완하고 수개월에서 1년 정도로 분해를 지연시킬 수 있으며 결정성을 현격히 저하 또는 제거시킬 수 있는 새로운 구조의 생분해성 고분자 재료를 제조하고자 하였다. 최근 들어 카프로락톤과 락티드의 공중합체가 그 조성에 따라 결정성이 저하되며 어느 조성에서는 완전한 비정질(amorphous)의 고분자 재료를 얻을 수 있음이 알려졌다. 또한 공중합체가 단일고분자보다는 분해속도가 빠르다는 사실이 밝혀졌다. 이에 본 발명에서는 락티드와 카프로락톤의 조성을 달리한 랜덤고분자로 이루어진 부분과 친수성과 우수한 생체적합성을 지닌 폴리에테르가 블록 공중합체로 이루어진 고분자 재료의 제조를 통해 상기한 문제점을 극복하고자 노력한 결과 본 발명을 완성하게 되었다.Therefore, the present inventors have attempted to produce a biodegradable polymer material having a new structure that can compensate for the disadvantages of the materials and delay the decomposition from several months to one year and can significantly reduce or eliminate crystallinity. Recently, it has been found that copolymers of caprolactone and lactide have low crystallinity depending on their composition, and that a certain amorphous polymer material can be obtained in some compositions. It has also been found that copolymers degrade faster than single polymers. In the present invention, as a result of trying to overcome the above problems through the production of a polymer material consisting of a block copolymer of a polyether having a hydrophilicity and excellent biocompatibility and a part consisting of random polymers having different compositions of lactide and caprolactone To complete.
따라서 본 발명의 목적은 분해특성이 개선되고, 생체내에서 분해시 결정성을 현저히 저하 또는 제거된 생분해성 블록공중합체의 제조방법을 제공함에 있다.Accordingly, an object of the present invention is to provide a method for preparing a biodegradable block copolymer having improved degradation properties and significantly reduced or eliminated crystallinity upon degradation in vivo.
본 발명의 또 다른 목적으로는 상기 제조된 생분해성 블록공중합체를 다양한 의약분야로의 활용이 가능한 용도를 제공함에 있다.Still another object of the present invention is to provide a biodegradable block copolymer prepared above that can be used in various medical fields.
도 1은 본 발명에 의해 제조된 블록공중합체의1H-NMR 도1 is a 1 H-NMR diagram of the block copolymer prepared according to the present invention
(a) 락티드(L):카프로락톤(C)= 7:3인 경우(L7C3),(a) When lactide (L): caprolactone (C) = 7: 3 (L7C3),
(b) 락티드(L):카프로락톤(C)= 5:5인 경우(L5C5).(b) when lactide (L): caprolactone (C) = 5: 5 (L5C5).
(c) 락티드(L):카프로락톤(C)= 3:7인 경우(L3C7).(c) when lactide (L): caprolactone (C) = 3: 7 (L3C7).
도 2는 본 발명에 의해 제조된 블록공중합체와 비교예로 제조된 고분자의 FT-IR도2 is an FT-IR diagram of a block copolymer prepared according to the present invention and a polymer prepared as a comparative example.
도 3은 본 발명에 의해 제조된 필름의 사진.Figure 3 is a photograph of the film produced by the present invention.
도 4는 본 발명의 시료를 대상으로 한 DSC 관찰결과4 is a DSC observation result for the sample of the present invention
본 발명은 생분해성 블록공중합체의 제조방법으로서,The present invention is a method for producing a biodegradable block copolymer,
카프로락톤과 락티드의 랜덤공중합체와 폴리에테르를 블록공중합하여 생분해성 블록공중합체를 제조하는 방법을 포함한다.And a method for producing a biodegradable block copolymer by block copolymerization of a polyether with a random copolymer of caprolactone and lactide.
이하 본 발명에 대한 이해의 편의를 도모하기 위해 상기 폴리에테르에 속하는 물질중의 하나로서 폴리에틸렌글리콜 모노메틸에테르가 적용된 하기 일반식 (1)으로 표시되는 바람직한 실시예에 의해 본 발명의 내용을 상세히 설명하기로 한다.Hereinafter, the content of the present invention will be described in detail by a preferred embodiment represented by the following general formula (1) to which polyethylene glycol monomethyl ether is applied as one of the substances belonging to the polyether in order to facilitate the understanding of the present invention. Let's do it.
일반식 (1)General formula (1)
상기 일반식 (1)에서 l,m,n은 양의 유리수로부터 적절히 선택되어지는 임의의 값으로서 카프로락톤과 락티드의 공중합체는 타 공중합체에 비해 결정성이 낮고, 특히 특정 조성비에서는 완전한 비정질의 고분자를 얻는 것도 가능하다.In the general formula (1), l, m, n are arbitrary values suitably selected from positive rational numbers, and the copolymer of caprolactone and lactide has lower crystallinity than other copolymers, especially at a specific composition ratio, and is completely amorphous. It is also possible to obtain a polymer of.
상기 카프로락톤과 락티드의 조성비는 특별한 한정을 요하지는 아니하나 바람직하기로는 무게비(m:l)로 3:97 내지 97:3의 범위로 함이 보다 좋다. 상기와 같이 조성비를 정하는 이유로는 카프로락톤과 락티드의 첨가비 중 어느 하나가 3미만인 경우에는 단일고분자에 대한 장점인 충분한 결정성의 저하효과를 기대하기가 곤란한 경우가 있다. 하지만 상기 범위를 다소 벗어나더라도 본 발명의 실시가 불가능한 것으로 되는 것은 아니므로 본 발명의 권리범위는 이들 범위의 균등영역도 포함한다.The composition ratio of caprolactone and lactide is not particularly limited, but is preferably in the range of 3:97 to 97: 3 in weight ratio (m: l). The reason for determining the composition ratio as described above is that when either of the addition ratio of caprolactone and lactide is less than 3, it may be difficult to expect a sufficient crystallinity deterioration effect, which is an advantage for a single polymer. However, since the scope of the present invention is not impossible even if the scope of the present invention is somewhat out of the range, the scope of the present invention includes equivalent areas of these ranges.
폴리에테르는 친수성이며 생체적합성을 가지는 것에서 선택되어지며, 예를 들면 폴리에틸렌글리콜, 폴리에틸렌글리콜 모노메틸에테르(위 구조식), 폴리프로필렌글리콜, 에틸렌글리콜과 프로필렌글리콜의 블록공중합체 등으로부터 선택된 적어도 1종이 이에 포함될 수 있다.The polyether is selected from hydrophilic and biocompatible, for example, at least one selected from polyethylene glycol, polyethylene glycol monomethyl ether (formula above), polypropylene glycol, block copolymer of ethylene glycol and propylene glycol, and the like. May be included.
상기 폴리에테르는 특별한 한정을 요하지는 않지만 분자량 350 내지 20,000정도에서 선택되어짐이 바람직하다. 이러한 이유는 폴리에테르 단독으로 적용하는 경우 분자량이 350 미만인 경우에는 체내에서 염증을 유발할 우려가 있고, 20,000을 초과하는 경우에는 신장에서 걸러지지 않을 우려가 있다는 실험적 보고에서 기인한다.The polyether is not particularly limited but is preferably selected from about 350 to 20,000 molecular weight. This reason is due to the experimental report that the polyether alone may cause inflammation in the body when the molecular weight is less than 350, and may not be filtered out by the kidney when it exceeds 20,000.
본 발명에 의해 제조된 생분해성 블록공중합체는 분해특성이 개선되고, 결정성이 현저히 저하되는 특성이 있으므로 약물전달을 위한 고분자 매트릭스의 주재로서 적용이 가능하다.The biodegradable block copolymer prepared by the present invention can be applied as a main agent of the polymer matrix for drug delivery since the degradability is improved and the crystallinity is remarkably lowered.
또한 본 발명에 의해 제조되는 생분해성 블록공중합체는 기계적 강도가 우수하므로 인공장기제조용 지지체의 주재료로도 활용함이 가능하며, 필름제조특성이 우수하여 세포유도재생을 위한 장벽 멤브레인의 주재료로도 활용할 수 있다.In addition, the biodegradable block copolymer prepared by the present invention is excellent in mechanical strength, so it can be used as a main material of the support for the manufacture of artificial organs. Can be.
이하, 본 발명의 내용을 실시예에 의해 자세히 설명하지만, 이들 실시예는 단지 본 발명을 예시하기 위한 것으로, 본 발명을 제한하지는 않는다.Hereinafter, the content of the present invention will be described in detail by way of examples, but these examples are only for illustrating the present invention, and do not limit the present invention.
<비교예 1> 에틸렌글리콜과 락티드의 블록공중합체(L10C0)의 제조Comparative Example 1 Preparation of Block Copolymer (L10C0) of Ethylene Glycol and Lactide
에틸렌글리콜과 락티드로 이루어진 블록 공중합체의 제조과정은 다음과 같다. 분자량이 5000인 한쪽 말단에 -OH기를 지닌 폴리에틸렌글리콜 3g과 15g의 락티드를 톨루엔에 용해시킨 후 온도를 130℃로 고정하고 환류를 시키면서 5시간동안 용액 상에서 개환 중합을 수행하였다. 사용된 촉매는 스태노스 옥토에이트이다. 상기 과정을 통해 제조된 시료는 새로이 제조된 고분자 재료의 비교 물질로 사용되었다.The manufacturing process of the block copolymer consisting of ethylene glycol and lactide is as follows. 3 g of polyethylene glycol having -OH groups and 15 g of lactide at one end having a molecular weight of 5000 were dissolved in toluene, and then ring-opening polymerization was performed on the solution for 5 hours while fixing the temperature at 130 ° C and refluxing. The catalyst used is stanose octoate. The sample prepared by the above process was used as a comparative material of the newly prepared polymer material.
<비교예 2> 에틸렌글리콜과 카프로락톤의 블록공중합체(L0C10)의 제조Comparative Example 2 Preparation of Block Copolymer (L0C10) of Ethylene Glycol and Caprolactone
에틸렌글리콜과 카프로락톤으로 이루어진 블록 공중합체의 제조는 다음과 같다. 분자량이 5000인 한쪽 말단에 -OH기를 지닌 폴리에틸렌글리콜 3g과 15g의 카프로락톤 단량체를 톨루엔에 용해시킨 후 온도를 130℃로 고정하고 환류를 시키면서 5시간동안 용액 상에서 개환 중합을 수행하였다. 사용된 촉매는 스태노스 옥토에이트이다. 상기 과정을 통해 제조된 시료는 새로이 제조된 고분자 재료의 비교 물질로 사용되었다.The preparation of the block copolymer consisting of ethylene glycol and caprolactone is as follows. 3 g of polyethylene glycol having -OH groups and 15 g of caprolactone monomer at one end having a molecular weight of 5000 were dissolved in toluene, and then ring-opening polymerization was performed on the solution for 5 hours while fixing the temperature at 130 ° C and refluxing. The catalyst used is stanose octoate. The sample prepared by the above process was used as a comparative material of the newly prepared polymer material.
<비교예 3,4> 폴리락티드(PLA)와 폴리카프로락톤(PCL) 단일고분자의 제조Comparative Example 3,4 Preparation of Polylactide (PLA) and Polycaprolactone (PCL) Single Polymer
락티드 5g과 스태노스 옥토에이트를 촉매로 사용하여 락티드의 개환 반응을 통해 150??에서 괴상 중합을 수행하였다. 같은 방법으로 카프로락톤의 괴상 중합을 수행하였다. 이를 통하여 비교물질인 폴리락티드와 폴리카프로락톤 단일고분자(도2의 PLA, PCL 참조)를 얻었다. 상기 과정을 통해 제조된 시료는 새로이 제조된 고분자 재료의 비교 물질로 사용되었다.The bulk polymerization was carried out at 150 ° C. through the ring-opening reaction of lactide using 5 g of lactide and stanose octoate as a catalyst. In the same manner, the bulk polymerization of caprolactone was carried out. Through this, a polylactide and a polycaprolactone single polymer (see PLA and PCL of FIG. 2) were obtained. The sample prepared by the above process was used as a comparative material of the newly prepared polymer material.
<실시예 1~3> 생분해성 블록공중합체의 제조<Examples 1 to 3> Preparation of biodegradable block copolymer
하기 표 1에 나타낸 단량체의 무게 비율로 중합반응을 수행하였다. 반응은 폴리에틸렌글리콜 모노메틸에테르에 포함된 -OH 작용기와 스태노스 옥토에이트를 촉매로 사용하여 락티드와 카프로락톤의 개환 반응을 통해 톨루엔 상에서 용액 중합으로 수행되었다. 단량체의 무게 비율은 3g으로 고정된 폴리에틸렌글리콜에 대해 락티드와 카프로락톤의 양을 15g으로 고정한 후 각 단분자의 무게 비율이 7:3(L7C3), 5:5(L5C5), 3:7(L3C7)이 되도록 설계하였다.The polymerization was carried out at the weight ratio of the monomer shown in Table 1. The reaction was carried out by solution polymerization on toluene via ring-opening reaction of lactide and caprolactone using -OH functional groups and stanose octoate contained in polyethylene glycol monomethyl ether as catalysts. The weight ratio of the monomers was fixed to 3 g of polyethylene glycol and the amount of lactide and caprolactone was fixed to 15 g, and then the weight ratio of each single molecule was 7: 3 (L7C3), 5: 5 (L5C5), 3: 7 ( L3C7).
<표 1> 조성TABLE 1 Composition
이때 얻어진 블록공중합체의 구조는 도 1과 2의1H NMR, FT-IR을 이용하여 확인할 수 있다.The structure of the block copolymer obtained at this time can be confirmed using 1 H NMR, FT-IR of FIGS.
<시험예 1> 수평균 분자량<Test Example 1> Number average molecular weight
상기 비교예 1 및 2와 실시예 1 내지 3에 의해 제조된 각각의 시료를 CDCl3를 사용하여 3중량%로 녹여 균일한 용액을 제조한 뒤 수소 핵자기 공명 분광법을사용하여 수평균 분자량을 산출하였다(표 2).Each sample prepared by Comparative Examples 1 and 2 and Examples 1 to 3 was dissolved at 3% by weight using CDCl 3 to prepare a uniform solution, and then a number average molecular weight was calculated using hydrogen nuclear magnetic resonance spectroscopy. (Table 2).
<표 2> 분자량TABLE 2 Molecular Weight
<시험예 2> 기계적 물성 및 함수율Test Example 2 Mechanical Properties and Water Content
상기 실시예 1 내지 3과 비교예 1~4까지 수행하여 만들어진 각각의 시료를 테트라하이드로퓨란(Tetrahydrofuran)을 사용하여 6중량%씩 녹여 균일한 용액을 제조한 뒤 실시예 1~3의 경우는 테프론 플레이트를 사용하여 용매를 증발시킨 후 필름을 제조하였다. 비교예 1~4의 경우는 열 압착기를 사용하여 각 시료의 녹는점 이상에서 필름을 제조하였다. 제조된 필름은 진공으로 수 일 간 건조한 후 증류수가 든 용기 내에 넣어 시간에 따른 함수율을 측정하였다. 도 3은 상기 과정으로 제조된 필름의 사진이다.Each sample prepared by performing Examples 1 to 3 and Comparative Examples 1 to 4 was dissolved by 6% by weight using tetrahydrofuran to prepare a uniform solution, and in the case of Examples 1 to 3, Teflon Films were prepared after the solvent was evaporated using the plate. In the case of Comparative Examples 1-4, the film was manufactured more than the melting point of each sample using the thermocompressor. The prepared film was dried in a vacuum for several days and placed in a container containing distilled water to measure the moisture content over time. 3 is a photograph of the film produced by the above process.
필름의 성형성으로 미루어 볼 때 본 발명의 실시예에 의한 블록공중합체가 기계적 물성 측면에서 우수함을 확인할 수 있었으며, 또한 락티드와 카프로락톤이 랜덤화되어 결정성이 감소된 실시예 1~3의 경우 수분 흡입량이 30 중량% 내외로 산출되어 공중합만을 이룬 비교예 1, 2와 단일 중합체인 비교예 3, 4에 비해 함수 능력이 우수하게 나타났으며, 기존에 보고된 에틸렌글리콜과 락티드-글리콜리드 공중합체에 비해 필름의 투명성이 증진되었다.Considering the moldability of the film, it was confirmed that the block copolymer according to the embodiment of the present invention is excellent in terms of mechanical properties, and also in Examples 1 to 3 in which the crystallization was reduced due to the randomization of lactide and caprolactone. In this case, the water intake amount was calculated to be about 30% by weight, and the water-containing ability was superior to Comparative Examples 1 and 2, which were copolymerized only, and Comparative Examples 3 and 4, which were homopolymers, and previously reported ethylene glycol and lactide-glycol. The transparency of the film is enhanced compared to the lead copolymer.
<시험예 3> 결정성Test Example 3 Crystallinity
상기 실시예 1 내지 3과 비교예 1~2까지 수행하여 만들어진 각각의 시료를 대상으로 공지의 시차 주사 열량계(DSC)를 이용해 각각의 결정성을 관찰하였다(도 4). 관찰 결과 L0C10(비교예 2)에서 L5C5(실시예 2)로 갈수록 또한 L10C0(비교예 1)에서 L5C5(실시예 2)로 갈수록 녹는점이 왼쪽으로 이동하고, 녹는점의 면적도 줄어드는 것으로 보아 블록을 이루는 한쪽부분이 랜덤화할수록 결정성이 감소하는 성향이 관찰되었다. 반면에 대조구인 비교예 4의 PCL은 녹는점이 60℃, 유리전이온도는 -60℃로 관찰되었으며, 비교예 3의 PLA는 녹는점이 175℃, 유리전이온도는 60℃로 관찰되었다.For each of the samples prepared by performing Examples 1 to 3 and Comparative Examples 1 to 2, the crystallinity was observed using a known differential scanning calorimeter (DSC) (FIG. 4). Observation results show that the melting point shifts to the left and the area of the melting point decreases as it goes from L0C10 (Comparative Example 2) to L5C5 (Example 2) and from L10C0 (Comparative Example 1) to L5C5 (Example 2). The tendency of the crystallinity to decrease was observed as one part was randomized. On the other hand, PCL of Comparative Example 4, the control, the melting point was observed at 60 ℃, glass transition temperature of -60 ℃, PLA of Comparative Example 3 was observed at the melting point of 175 ℃, glass transition temperature of 60 ℃.
실제로 시차 주사 열량계를 통해 계산되어진 결정화도(crystallinity %)의 수치를 보면 실시예 1~3의 시료는 약 6~38% 정도(특히 실시예 2의 경우에는 녹는점이 거의 관찰되지 않아 결정성이 거의 사라져 비정질의 성향을 보임이 관찰되었다. 결정화도 6.7%)로서 비교예 3~4의 단일 고분자인 PLA와 PCL의 결정화도(50-60%)에 비해 낮게 측정되었다.In fact, the value of crystallinity (%) calculated by differential scanning calorimeter shows that about 6 to 38% of the samples of Examples 1 to 3 (particularly, in Example 2, almost no melting point is observed and crystallinity is almost disappeared. The crystallinity was observed, which was lower than the crystallinity (50-60%) of PLA and PCL, which are the single polymers of Comparative Examples 3-4.
<시험예 3> 표면 친수성Test Example 3 Surface Hydrophilicity
상기 실시예 1∼3과 비교예 1∼4에 의해 제조된 각각의 시료와 중합에 사용된 폴리에틸렌글리콜을 테트라하이드로퓨란을 사용하여 3중량%로 녹여 균일한 용액을 제조한 뒤 용액을 실리콘 웨이퍼에 스핀 코팅하여 용매를 증발시킨 후 접촉각을측정하였다. 이를 통하여 폴리에틸렌글리콜이 함유된 고분자가 더욱 친수성을 나타내며 그 중에서도 새로이 제조된 블록공중합체가 기존의 폴리에틸렌글리콜 블록과 락티드 블록으로 이루어지거나 에틸레글리콜 블록과 카프로락톤 블록으로 이루어진 블록 공중합체보다 우수한 표면 친수성을 나타내었다.Each sample prepared in Examples 1 to 3 and Comparative Examples 1 to 4 and polyethylene glycol used for polymerization were dissolved at 3% by weight using tetrahydrofuran to prepare a uniform solution. The contact angle was measured after evaporating the solvent by spin coating. As a result, the polymer containing polyethylene glycol is more hydrophilic, and the newly prepared block copolymer is composed of the existing polyethylene glycol block and the lactide block or the surface copolymer of the ethyl glycol block and the caprolactone block. Hydrophilicity was shown.
<표 3> 실시예 1∼3과 비교예 1∼4의 접촉각 측정 결과<Table 3> Contact angle measurement result of Examples 1-3 and Comparative Examples 1-4
<시험예 4> 가수 분해 특성Test Example 4 Hydrolysis Characteristics
시험예 2에서 제조한 고분자 필름(실시예 1)을 산도가 7.4인 완충 용액에 담그고 온도가 50℃인 항온조에서 일주일마다 증류수를 교체하면서 일정 기간 동안 가수 분해 특성을 확인하고 그 결과를 하기 표 3에 나타내었다.The polymer film prepared in Test Example 2 (Example 1) was immersed in a buffer solution having an acidity of 7.4, and the distilled water was replaced every week in a thermostat at 50 ° C. to check the hydrolysis characteristics for a certain period. Shown in
<표 4> 실시예 1의 가수 분해 추이TABLE 4 Hydrolysis Trend of Example 1
본 발명에 의하면 생분해성 블록공중합체의 분해특성이 개선되어 수개월 내지는 1년 이내에 분해가 완료되도록 하며, 생체내에서 분해시 결정성을 현저히 저하시키거나 제거할 수 있어 약물 등의 방출매체로서 그 활용가치가 클 뿐만 아니라 종래 생분해성 블록공중합체에 비해 기계적 특성이 매우 우수하여 각종 의료용 재료로도 그 가치가 지대하다.According to the present invention, the decomposition property of the biodegradable block copolymer is improved to allow the decomposition to be completed within several months or one year, and it can significantly reduce or remove the crystallinity when decomposed in vivo, and use it as a release medium for drugs. In addition to the great value, the mechanical properties are very excellent compared to the conventional biodegradable block copolymers, so the value is also great for various medical materials.
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| US8309623B2 (en) | 2008-03-28 | 2012-11-13 | Industrial Technology Research Institute | Biodegradable copolymer and thermosensitive material |
| KR20210010178A (en) * | 2019-07-19 | 2021-01-27 | 한국과학기술연구원 | Biodegradable polymeric film comprising an extracellular matrix and uses thereof |
| WO2023083265A1 (en) * | 2021-11-10 | 2023-05-19 | 北京渼颜空间生物医药有限公司 | Polyethylene glycol monomethyl ether-polylactic acid copolymer, and preparation method therefor and use thereof |
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| JP3220331B2 (en) * | 1993-07-20 | 2001-10-22 | エチコン・インコーポレーテツド | Absorbable liquid copolymers for parenteral administration |
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| US8309623B2 (en) | 2008-03-28 | 2012-11-13 | Industrial Technology Research Institute | Biodegradable copolymer and thermosensitive material |
| KR101145175B1 (en) * | 2010-02-12 | 2012-05-14 | 아주대학교산학협력단 | Biocompatible and temperature-sensitive polyethyleneglycol/polyester block copolymer with high biodegradable property |
| KR20210010178A (en) * | 2019-07-19 | 2021-01-27 | 한국과학기술연구원 | Biodegradable polymeric film comprising an extracellular matrix and uses thereof |
| WO2023083265A1 (en) * | 2021-11-10 | 2023-05-19 | 北京渼颜空间生物医药有限公司 | Polyethylene glycol monomethyl ether-polylactic acid copolymer, and preparation method therefor and use thereof |
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