97699-68-8Relevant academic research and scientific papers
ABSORBABLE BRANCHED POLYESTERS AND POLYURETHANES
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Paragraph 0212-0214, (2014/05/25)
The present invention relates to the discovery of a new class of hydrolysable isocyanates, hydrolysable branched polyols and branched absorbable polyesters and polyurethanes prepared therefrom. The resultant absorbable polymers are useful for drug delivery, stents, highly porous foam, reticulated foam, tissue engineering, tissue adhesives, adhesion prevention, bone wax formulations, medical device coatings, surface modifying agents and other implantable medical devices. In addition, these absorbable polymers can have a controlled hydrolytic degradation profile.
Controlled Release of Nitric Oxide And Drugs From Functionalized Macromers And Oligomers
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Page/Page column 22, (2012/02/15)
The present invention provides NO and, optionally, drug releasing macromers and oligomers wherein the drug molecule and NO releasing moiety are linked an absorbable macromer or oligomeric chain susceptible to hydrolytic degradation and wherein the macrome
Controlled Release of Nitric Oxide And Drugs From Functionalized Macromers And Oligomers
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, (2010/08/22)
The present invention provides NO and, optionally, drug releasing macromers and oligomers wherein the drug molecule and NO releasing moiety are linked an absorbable macromer or oligomeric chain susceptible to hydrolytic degradation and wherein the macrome
Synthesis and anti-inflammatory activity of a series of N-substituted naproxen glycolamides: Nitric oxide-donor naproxen prodrugs
Ranatunge, Ramani R.,Augustyniak, Michael E.,Dhawan, Vijay,Ellis, James L.,Garvey, David S.,Janero, David R.,Letts, L. Gordon,Richardson, Stewart K.,Shumway, Mathew J.,Trocha, A. Mark,Young, Delano V.,Zemtseva, Irina S.
, p. 2589 - 2599 (2007/10/03)
A series of glycolamide naproxen prodrugs containing a nitrate group as a nitric oxide (NO) donor moiety has been synthesized. These compounds were evaluated for their anti-inflammatory activity, naproxen release, and gastric tolerance. Compounds 4a, 4b,
CHEMICAL COMPOUNDS CONTAINING TOCOPHEROL AND AT LEAST ONE ADDITIONAL PHARMACEUTICAL ACTIVE SUBSTANCE
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Page/Page column 27-29, (2010/02/10)
The invention relates to chemical compounds in the form of racemates, enantiomers and/or diastereomers of general formula (I), wherein R represents the non-modified part of a variable pharmaceutical active substance molecule, B represents a spacer and Toc and corresponds to formula (II), R′, R′′ and R′′′ are H or methyl for tocopherol and A is C=X, SOm, X and/or CH2. X is O, S or NR1 (n = 1) and/or S or NR1 (n = 0) and B is a group X-R 2 y, wherein Y is C=X, SOm or C (XR 3 ) R4, and n is 0 - 6, preferably 0,1, 2 or 3 and m represents 1 or 2. R1 represents H, C1 - C10 -alkyl, preferably C1 - C6-alkyl and/or aryl, Het or an aryl radical and/or a Het radical connected via a C1 - C6 spacer, preferably C1 - C3 and R2 is selected from the group containing alkene, arylene and/or Het spacer and combinations thereof and can be combined directly with each other or via the A radical and/or via the group XO-A-Xp, wherein o and p can be equal or different and are 0, 1 or 2, and R3 and R4 represent H, C1 - C10 alkyl, preferably C1-C6-alkyl and/or aryl, Het or an aryl radical and/or a Het radical bound by means of a C1 - C6, preferably C1 - C3 spacer.
Nitrosated nonsteroidal antiinflammatory compounds, compositions and methods of use related applications
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Page/Page column 36, (2010/11/30)
The invention describes novel nitrosated nonsteroidal antiinflammatory drugs (NSAIDs) and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated NSAID, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one nitrosated NSAID, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated NSAID, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides methods for treating inflammation, pain and fever; for treating gastrointestinal disorders; for facilitating wound healing; for treating and/or preventing gastrointestinal, renal and/or respiratory toxicities resulting from the use of nonsteroidal antiinflammatory compounds; for treating inflammatory disease states and/or disorders; and for treating and/or preventing ophthalmic diseases and/or disorders.
Low molecular weight proteins as carriers for renal drug targeting. Preparation of drug-protein conjugates and drug-spacer derivatives and their catabolism in renal cortex homogenates and lysosomal lysates
Franssen,Koiter,Kuipers,Bruins,Moolenaar,De Zeeuw,Kruizinga,Kellogg,Meijer
, p. 1246 - 1259 (2007/10/02)
Low molecular weight proteins (LMWPs) are known to be reabsorbed and catabolized primarily by the proximal tubular cells of the kidneys. As such, LMWPs might serve as drug carriers that release drugs site-specifically in the kidney. We tested this concept in vitro by coupling different drugs to the LMWP lysozyme both directly (amide bond) and via different spacers: oligopeptides (amide bond), (poly-)α-hydroxy acids (ester bond), and a pH sensitive cis-aconityl spacer (amide bond). The capability of the kidney to release the parent drug from such drug-spacer derivatives and drug-LMWP conjugates by enzymatic or chemical hydrolysis of the bond was tested by incubation experiments in renal cortex homogenates and lysosomal lysates. Directly coupled conjugates of terminal carboxyl group containing drugs and lysozyme were catabolized to single amino acids, but did not result in release of the parent drug. The amide bond between the drug and the final amino acid (lysine) appeared to be stable in the incubation milieu. Different oligopeptide spacers coupled to the drugs showed similar results: the oligopeptide itself was cleaved but the amide bond between the drug and different single amino acids remained untouched. Only amide bonds of derivatives of carboxylic drugs with peptide structures themselves were cleaved. Some of the directly coupled conjugates of terminal amino drugs and oligopeptides showed clear release of the parent drug whereas others were stable. Terminal amino drugs were rapidly released from an acid-sensitive cis-aconityl spacer. Terminal carboxyl group containing drugs were enzymatically released from their glycolic and lactic ester spacers at different rates. These kinds of drugs were also released as parent drug from LMWP conjugates with ester spacers like L-lactic acid. Increasing spacer length by intercalating a tetra(L-lactic acid) molecule between the drug and the protein further increased the extent and rate of drug release, indicating increased accessability of the bond to the enzymes. Terminal amino group containing drugs were rapidly generated as parent drug from LMWP conjugates using an acid-sensitive spacer. In addition the conjugates were found to be adequately stable in plasma, considering their rapid clearance from the bloodstream. It is concluded that LMWPs may indeed be of use as carriers for specific renal delivery of drugs, since renal cortex homogenates and lysosomal lysates are able to catabolize the protein and generate the parent drug from drug-LMWP conjugates bearing suitable spacers. The option of enzymatic release is limited by the narrow specificity of the lysosomal enzymes. This has profound implications for the synthesis of suitable conjugates, since the nature of the drug itself, the type of bond and also spacer length largely determine whether release of the parent drug will occur. Tailor-made spacers containing the correct mode of attachment and the right spacer length are required for this option. Chemical hydrolysis using acid-sensitive linkers, is suggested as a viable alternative approach.
