Development of New Lipophilic Derivatives of Tetragastrin: Physicochemical Characteristics and Intestinal Absorption of Acyl-tetragastrin Derivatives in Rats

Pharmaceutical Research - Tập 10 Số 10 - Trang 1488-1492 - 1993
Tenma, Takehiro1, Yodoya, Etsuo1, Tashima, Shigeru1, Fujita, Takuya1, Murakami, Masahiro1, Yamamoto, Akira1, Muranishi, Shozo1
1Department of Biopharmaceutics, Kyoto Pharmaceutical University, Kyoto Japan

Tóm tắt

In order to improve the intestinal absorption of tetragastrin (TG), we synthesized lipophilic derivatives of TG by acylation of its N-terminal amino group with acetic acid, caproic acid, and lauric acid. The purified TG derivatives, acetyl-tetragastrin (Ac-TG), caproyl-tetragastrin (Cap-TG), and lauroyl-tetragastrin (Lau-TG), were confirmed to be more lipophilic than the parent TG by high-performance liquid chromatography (HPLC). The pharmacological activities and the intestinal absorption of TG and its derivatives were examined by measuring gastric acid secretion. Stimulation of gastric acid secretion by these derivatives after intravenous administration was stronger than with native TG. When the acetyl- and caproyl-derivatives were administered into the large intestinal loops, a marked increase in gastric acid secretion was observed in comparison with TG, while no significant effect occurred following administration of the TG derivatives into the small intestines. These results indicated that chemical modification of TG with fatty acids improves the absorption of TG from the large intestines.

Từ khóa


Tài liệu tham khảo

citation_title=Advanced delivery systems for peptides and proteins-pharmaceutical considerations; citation_inbook_title=Delivery Systems for Peptide Drugs; citation_publication_date=1986; citation_pages=1-21; citation_id=CR1; citation_author=S. S. Davis; citation_publisher=Plenum Press

citation_journal_title=Crit. Rev. Ther. Drug Carrier Syst.; citation_title=Absorption enhancers; citation_author=S. Muranishi; citation_volume=7; citation_publication_date=1990; citation_pages=1-33; citation_id=CR2

citation_journal_title=Adv. Drug Del. Rev.; citation_title=Penetration and enzymatic barriers to peptide and protein absorption; citation_author=V. H. L. Lee, A. Yamamoto; citation_volume=4; citation_publication_date=1990; citation_pages=171-207; citation_id=CR3

citation_journal_title=Pharm. Res.; citation_title=Prodrug of peptides. 6. Bioreversible derivatives of thyrotropin-releasing hormone (TRH) with increased lipophilicity and resistance to cleavage by the TRH-specific serum enzyme; citation_author=H. Bundgaard, J. Møss; citation_volume=7; citation_publication_date=1990; citation_pages=885-892; citation_id=CR4

citation_journal_title=Int. J. Pharm.; citation_title=Prodrug of peptides. 8. In vitro study of intestinal metabolism and penetration of thyrotropin-releasing hormone (TRH) and its prodrug; citation_author=J. Møss, A. Buur, H. Bundgaard; citation_volume=66; citation_publication_date=1990; citation_pages=183-191; citation_id=CR5

citation_journal_title=Pharm. Res.; citation_title=Synthesis of palmitoyl derivatives of insulin and their biological activities; citation_author=M. Hashimoto, K. Takada, Y. Kiso, S. Muranishi; citation_volume=6; citation_publication_date=1989; citation_pages=171-176; citation_id=CR6

citation_journal_title=Pharm. Res.; citation_title=Lipophilic peptides: Synthesis of lauroyl-thyrotropine-releasing hormone and its biological activities; citation_author=S. Muranishi, A. Sakai, K. Yamada, M. Murakami, K. Takada, Y. Kiso; citation_volume=8; citation_publication_date=1991; citation_pages=649-652; citation_id=CR7

citation_journal_title=J. Control. Release; citation_title=Trials of lipid modification of peptide hormones for intestinal delivery; citation_author=S. Muranishi, M. Murakami, M. Hashidzume, K. Yamada, S. Tajima, Y. Kiso; citation_volume=19; citation_publication_date=1992; citation_pages=179-188; citation_id=CR8

citation_journal_title=J. Pharm. Pharmacol.; citation_title=Improvement of large intestinal absorption of insulin by chemical modification with palmitic acid in rats; citation_author=M. Hashizume, T. Douen, M. Murakami, A. Yamamoto, K. Takada, S. Muranishi; citation_volume=44; citation_publication_date=1992; citation_pages=555-559; citation_id=CR9

citation_journal_title=J. Pharm. Pharmacol.; citation_title=Improvement of intestinal absorption of thyrotropin-releasing hormone by chemical modification with lauric acid; citation_author=K. Yamada, M. Murakami, A. Yamamoto, K. Takada, S. Muranishi; citation_volume=44; citation_publication_date=1992; citation_pages=717-721; citation_id=CR10

citation_journal_title=Nature; citation_title=Structure-function relationships in the active C-terminal tetrapeptide sequence of gastrin; citation_author=J. S. Morley, H. L. Tracy, R. A. Gregory; citation_volume=207; citation_publication_date=1965; citation_pages=1356-1359; citation_id=CR11

citation_journal_title=Arzneim.-Forsch. (Drug Res.); citation_title=The absorption of tetragastrin from different sites in rats and dogs; citation_author=H. M. Jennewein, F. Waldeck, W. Konz; citation_volume=24; citation_publication_date=1974; citation_pages=1225-1228; citation_id=CR12

citation_journal_title=Fed. Proc.; citation_title=Enzymatic degradation of C-terminal tetrapeptide amide of gastrin by mammalian tissue extracts; citation_author=L. Laster, J. H. Walsh; citation_volume=27; citation_publication_date=1968; citation_pages=1328-1330; citation_id=CR13

citation_journal_title=Biochem. Med.; citation_title=Enzymatic deamidation of the C-terminal tetrapeptide amide of gastrin by mammalian tissues; citation_author=J. H. Walsh, L. Laster; citation_volume=8; citation_publication_date=1973; citation_pages=432-449; citation_id=CR14

citation_journal_title=J. Lipid Res.; citation_title=Use of esters of N-hydroxysuccinimide in the synthesis of N-acylamino acids; citation_author=Y. Lapidot, S. Rapport, Y. Wolman; citation_volume=8; citation_publication_date=1967; citation_pages=142-145; citation_id=CR15

citation_journal_title=Br. J. Pharmacol.; citation_title=Continuous recording of gastric secretion in the rat; citation_author=M. N. Ghosh, H. O. Schild; citation_volume=13; citation_publication_date=1958; citation_pages=54-61; citation_id=CR16

Thông tin
Thông tin xuất bản

Pharmaceutical Research

Tập 10 Số 10

1488-1492

Thông tin tác giả