Yamakawa I, Ashizawa K, Tsuda T, Watanabe S, Hayashi M, Awazu S
Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
Chem Pharm Bull (Tokyo). 1992 Oct;40(10):2870-2. doi: 10.1248/cpb.40.2870.
The thermal characteristics of poly (DL-lactic acid) (DL-PLA) microspheres containing a hexapeptide (NA: H(CH3)-Arg-Lys-Pro-Trp-tert-Leu-Leu-OEt) with neurotensin activity were investigated. PLA microspheres with a drug content of 1.5-11.0% were prepared by a novel o/w (oil-in-water) solvent evaporation method. Both DL-PLA and NA were amorphous in form, and an increase in heat capacity at glass transition temperature (Tg) of the polymer was observed in DL-PLA microspheres containing NA. The Tg of DL-PLA (PLA2000 bulk) was 307.8 K, while Tg of microspheres containing NA (content 6.0%) shifted to 321.2 K. The Tg of PLA2000 microspheres was found to increase with an increase in the content of NA, and its increasing tendency reached a plateau at an NA content of greater than 6%. The apparent activation energy of glass transition of PLA2000 bulk and the microspheres was calculated to be 86.3 and 99.3 kcal/mol, respectively. As a result of the release test after storage at 4 degrees C and 40 degrees C for 1 month, nearly the same release profiles of NA from PLA2000 microspheres were found. The release rate of NA after the initial release became slow after storage at 45 degrees C for 1 month. This may be attributed mainly to a decrease in surface area caused by the formation of agglomerates of PLA2000 microspheres under conditions near Tg.
对含有具有神经降压素活性的六肽（NA：H(CH3)-Arg-Lys-Pro-Trp-tert-Leu-Leu-OEt）的聚（DL-乳酸）（DL-PLA）微球的热特性进行了研究。通过一种新型的水包油（o/w）溶剂蒸发法制备了药物含量为1.5 - 11.0%的PLA微球。DL-PLA和NA均为无定形形态，在含有NA的DL-PLA微球中观察到聚合物在玻璃化转变温度（Tg）处的热容量增加。DL-PLA（PLA2000本体）的Tg为307.8 K，而含有NA（含量6.0%）的微球的Tg移至321.2 K。发现PLA2000微球的Tg随着NA含量的增加而升高，并且其升高趋势在NA含量大于6%时达到平稳。计算得出PLA2000本体和微球的玻璃化转变的表观活化能分别为86.3和99.3 kcal/mol。在4℃和40℃储存1个月后的释放试验结果表明，从PLA2000微球中释放出的NA具有几乎相同的释放曲线。在45℃储存1个月后，NA的初始释放后的释放速率变慢。这可能主要归因于在接近Tg的条件下PLA2000微球形成团聚体导致表面积减小。
