Acta pharmaceutica Nordica最新文献_第3页

Local anaesthetics--comparison of in vitro and in vivo data. 局部麻醉——体外和体内数据的比较。

Acta pharmaceutica Nordica Pub Date : 1992-01-01

A Nyqvist-Mayer

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Fluorescence spectroscopic evaluation of stratum corneum lipids--implications for permeation enhancement. 角质层脂质的荧光光谱评价——渗透增强的意义。

Acta pharmaceutica Nordica Pub Date : 1992-01-01

R O Potts, N A Azimi, T S Spencer, F E Lyttle, D A Chen

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Prodrugs of peptides. 19. Protection of the pyroglutamyl residue against pyroglutamyl aminopeptidase by N-acyloxymethylation and other means. 肽的前药。19. n -酰基甲基化等方法对焦氨酰氨基肽酶对焦氨酰残基的保护作用。

Acta pharmaceutica Nordica Pub Date : 1992-01-01

J Møss, H Bundgaard

{"title":"Prodrugs of peptides. 19. Protection of the pyroglutamyl residue against pyroglutamyl aminopeptidase by N-acyloxymethylation and other means.","authors":"J Møss, H Bundgaard","doi":"","DOIUrl":"","url":null,"abstract":"The N-terminal pyroglutamyl group in several peptides is specifically cleaved by pyroglutamyl aminopeptidase (PAPase I). With the aim of protecting this group against enzymatic cleavage by the prodrug approach, various derivatives of L-pyroglutamyl benzylamide, used as a PAPase I sensitive model pyroglutamyl peptide, were prepared and their stability characteristics determined. The derivatives studied included phenoxycarbonyl, phthalidyl, hydroxymethyl and actoxymethyl derivatives, all formed at the pyroglutamyl NH-moiety. Whereas L-pyroglutamyl benzylamide was rapidly hydrolyzed by PAPase I, all the derivatives were resistant to cleavage by the enzyme. On the other hand, these derivatives, with the exception of the N-phenoxycarbonyl derivative, were readily converted to the parent pyroglutamyl benzylamide by spontaneous or plasma catalyzed hydrolysis, the half-lives of conversion in 80% human plasma being in the range 2.3-8.4 h. The major degradation reaction of the N-phenoxycarbonyl derivative in both buffer and plasma solutions was hydrolytic opening of the pyrrolidone ring. The pH-rate profiles for the degradation of the compounds in aqueous solution were obtained and both specific acid and base catalytic reactions as well as a spontaneous reaction were observed. The results suggest that N-phthalidylation, N-hydroxymethylation and N-acyloxymethylation of pyroglutamyl peptides may be useful prodrug approaches to protect such peptides against cleavage by pyroglutamyl aminopeptidase and hence to improve their delivery characteristics.","PeriodicalId":7082,"journal":{"name":"Acta pharmaceutica Nordica","volume":"4 4","pages":"301-8"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12536227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Cytochrome P-455 nm complex formation in the metabolism of phenylalkylamines. XIII. Enzyme interactions with a series of beta-alkyl-substituted 2-phenylethanamines and corresponding N-hydroxylamines. 细胞色素p - 455nm复合物在苯烷基胺代谢中的形成。十三。酶与一系列-烷基取代的2-苯基乙胺和相应的n -羟胺的相互作用。

Acta pharmaceutica Nordica Pub Date : 1992-01-01

K H Jönsson, M Stefek, B Lindeke

{"title":"Cytochrome P-455 nm complex formation in the metabolism of phenylalkylamines. XIII. Enzyme interactions with a series of beta-alkyl-substituted 2-phenylethanamines and corresponding N-hydroxylamines.","authors":"K H Jönsson, M Stefek, B Lindeke","doi":"","DOIUrl":"","url":null,"abstract":"The formation of Metabolic Intermediate (MI) complexes from a series of beta-alkylsubstituted 2-phenylethanamines and corresponding N-hydroxylamines is investigated during NADPH-dependent metabolism in liver microsomes from phenobarbital pretreated rats. The beta-alkyl substituents are methyl, dimethyl, ethyl, di-ethyl, n-propyl, di-n-propyl and i-propyl groups. The amines are synthesized by LiAlH4-reduction of the corresponding nitriles, which are prepared through alkylation of the enolate anion of phenylacetonitrile. The hydroxylamines are prepared either by oxidation of the corresponding benzylimines with m-chloroperbenzoic acid and subsequent hydrolysis of the initially formed 3-phenyloxaziridines, or by H2O2-mediated oxidation of the corresponding amines in the presence of catalytic amounts of sodium tungstate, followed by reduction with cyanoborohydride. The amines are found to be completely devoid of complexing activity, while the hydroxylamines form the MI complex at high rates. Complex formation from these substrates thus parallels the known behaviour of 2-phenylethanamine and its corresponding N-hydroxylamine. Since N-oxygenation is known to be a prerequisite for MI complex formation from amines our results suggest that the beta-alkylated 2-phenylethanamines are metabolized exclusively through other pathways. In accordance with this hypothesis, capillary GC-analysis of the incubation mixture of 2-phenylpropanamine shows no formation of N-hydroxylated metabolites; only 2-phenylpropanol, a metabolite formed through the deamination pathway, is found.","PeriodicalId":7082,"journal":{"name":"Acta pharmaceutica Nordica","volume":"4 2","pages":"105-9"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12560658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Formulation aspects on dermatological preparations and transdermal drug delivery systems. 皮肤制剂和透皮给药系统的配方方面。

Acta pharmaceutica Nordica Pub Date : 1992-01-01

H E Junginger

引用次数: 0

Reconstructed skin as a tool in the development of topical drugs for dermatology. 重建皮肤作为皮肤病局部药物开发的工具。

Acta pharmaceutica Nordica Pub Date : 1992-01-01

P J Wauben-Penris

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Topical drugs and cosmetics. 外用药物和化妆品。

Acta pharmaceutica Nordica Pub Date : 1992-01-01

I R White

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Skin irritancy evaluated by laser Doppler flowmetry. 用激光多普勒血流法评价皮肤刺激性。

Acta pharmaceutica Nordica Pub Date : 1992-01-01

J E Wahlberg

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Visions of the future for transdermal drug delivery. 透皮给药的未来展望。

Acta pharmaceutica Nordica Pub Date : 1992-01-01

F Theeuwes

引用次数: 0

Chemical stability of insulin. 3. Influence of excipients, formulation, and pH. 胰岛素的化学稳定性。3.赋形剂、配方和pH的影响。

Acta pharmaceutica Nordica Pub Date : 1992-01-01

J Brange, L Langkjaer

{"title":"Chemical stability of insulin. 3. Influence of excipients, formulation, and pH.","authors":"J Brange, L Langkjaer","doi":"","DOIUrl":"","url":null,"abstract":"The influence of auxiliary substances and pH on the chemical transformations of insulin in pharmaceutical formulation, including various hydrolytic and intermolecular cross-linking reactions, was studied. Bacteriostatic agents had a profound stabilizing effect--phenol > m-cresol > methylparaben--on deamidation as well as on insulin intermolecular cross-linking reactions. Of the isotonicity substances, NaCl generally had a stabilizing effect whereas glycerol and glucose led to increased chemical deterioration. Phenol and sodium chloride exerted their stabilizing effect through independent mechanisms. Zinc ions, in concentrations that promote association of insulin into hexamers, increase the stability, whereas higher zinc content had no further influence. Protamine gave rise to additional formation of covalent protamine-insulin products which increased with increasing protamine concentration. The impact of excipients on the chemical processes seems to be dictated mainly via an influence on the three-dimensional insulin structure. The effect of the physical state of the insulin on the chemical stability was also complex, suggesting an intricate dependence of intermolecular proximity of involved functional groups. At pH values below five and above eight, insulin degrades relatively fast. At acid pH, deamidation at residue A21 and covalent insulin dimerization dominates, whereas disulfide reactions leading to covalent polymerization and formation of A- and B-chains prevailed in alkaline medium. Structure-reactivity relationship is proposed to be a main determinant for the chemical transformation of insulin.","PeriodicalId":7082,"journal":{"name":"Acta pharmaceutica Nordica","volume":"4 3","pages":"149-58"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12590842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0