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Controlled release of insulin from a...

Chen, Quanmin.

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Controlled release of insulin from a novel biodegradable injectable gel system.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Controlled release of insulin from a novel biodegradable injectable gel system./
作者:	Chen, Quanmin.
面頁冊數:	232 p.
附註:	Source: Dissertation Abstracts International, Volume: 67-03, Section: B, page: 1453.
Contained By:	Dissertation Abstracts International67-03B.
標題:	Chemistry, Pharmaceutical. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3209392
ISBN:	9780542578694

Controlled release of insulin from a novel biodegradable injectable gel system.
Chen, Quanmin.

Controlled release of insulin from a novel biodegradable injectable gel system. - 232 p.

Source: Dissertation Abstracts International, Volume: 67-03, Section: B, page: 1453.

Thesis (Ph.D.)--The University of Tennessee Health Science Center, 2006.

The objective of the study was to develop a controlled release dosage form of insulin, which can provide basal level insulin in diabetic rats for 1 to 2 weeks after a single subcutaneous injection.

ISBN: 9780542578694Subjects--Topical Terms:

550957
Chemistry, Pharmaceutical.

Controlled release of insulin from a novel biodegradable injectable gel system.
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245 1 0 $a Controlled release of insulin from a novel biodegradable injectable gel system.
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500 $a Source: Dissertation Abstracts International, Volume: 67-03, Section: B, page: 1453.
500 $a Adviser: Atul J. Shukla.
502 $a Thesis (Ph.D.)--The University of Tennessee Health Science Center, 2006.
520 $a The objective of the study was to develop a controlled release dosage form of insulin, which can provide basal level insulin in diabetic rats for 1 to 2 weeks after a single subcutaneous injection.
520 $a A biodegradable injectable drug delivery gel was prepared by dissolving a biodegradable polymer, poly(lactic-co-glycolic acid) (PLGA), in biocompatible plasticizer(s), triethyl citrate (TEC) and/or acetyl triethyl citrate (ATEC). Insulin was then loaded into the blank gel to form an insulin suspension in the polymer solution. After the insulin-loaded gel was injected subcutaneously, the plasticizer(s) were gradually leached out from the gel and taken away by absorption. The polymer precipitated a solid depot of insulin formed at the injection site. The insulin was released slowly from the depot by a combination of drug diffusion and degradation/erosion of the polymer.
520 $a Bovine insulin was loaded into different gel formulations and the in vitro release of insulin from the gels was tested in phosphate buffered saline (pH 7.4) (PBS). Effect of formulation factors such as polymer concentration, ratio of ATEC:TEC and insulin loading on the release of insulin from the gels was investigated. The release of insulin from gels containing 10% polymer was slower than those prepared with 5% polymer. Gels prepared with one plasticizer, TEC, released the insulin in a zero-order pattern, while gels containing ATEC or ATEC/TEC followed a multi-phase release pattern. Insulin loading did not have a significant impact on the cumulative percent release of insulin. Based on the in vitro release study of the gel formulations, three new formulations were designed and tested in vivo in type 2 diabetic rats (ZDF rats). Blood glucose levels of the ZDF rats were suppressed significantly for up to 5 days after one subcutaneous injection of all the three formulations.
520 $a After the study with bovine insulin, gels of similar compositions were prepared with regular recombinant human insulin (RHI) and tested in vivo. However, the RHI loaded gel formulations only suppressed the blood glucose levels in the ZDF rats for 1 to 2 days after a single subcutaneous injection. Using higher molecular weight polymer and/or increasing insulin loading were not able to prolong the in vivo effect of RHI in the ZDF rats.
520 $a In order to achieve longer control over the release of insulin from the gels, Ultralente insulin crystals (UIC) were harvested from commercially available HumulinRTM. The dried UIC was loaded into the blank gels and tested in vivo. The formulation prepared with 25% PLGA (i.v. 0.09, acid end group), ATEC:TEC=3:1 and 4% UIC was able to suppress the blood glucose levels of the ZDF rats significantly for 10 days after a single subcutaneous injection. The concentration of human insulin in serum was maintained between 200 to 400 mIU/l during this period of time.
520 $a Incorporation of zinc carbonate powder into the UIC-loaded gels further retarded the release of insulin from the gels. The concentration of insulin in the rat serum was maintained at a lower level and the blood glucose levels were suppressed to a lesser extent, but for longer than 10 days, following a single subcutaneous injection of UIC-loaded gels with zinc carbonate powder.
590 $a School code: 0783.
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