Amino oral application

After oral application, bacitracin is hardly absorbed by the gastrointestinal tract and, therefore, its distribution in tissues is considered negligible (6). Approximately 95% of an orally administered dose is excreted via feces, and only 3% or less via urine. Bacitracin is primarily metabolized to desamidobacitracin and further to smaller peptides and amino acids. Main metabolites identified in feces are bacitracin A, Bi, B2, F, desamidobacitracin, and catabolic peptides. In urine and bile, only hydrolytic cleavage products such as small peptides are present. 

Panthenol is absorbed via passive diffusion after topical or oral application and then enzymatically oxidized to pantothenic acid. This is a component of coenzyme A and acyl carrier protein, and as such of great importance in fatty acid, carbohydrate, and amino acid metabolism. Deficiency leads to uncharacteristic symptoms such as headaches, apathy, gastrointestinal disturbances, palpitations, and paraesthesia typically in the feet, also known as burning feet syndrome. Wound healing is impaired. The recommended daily allowance is 5 to 7 mg.112... 

In contrast, there are substances like some nitrofurane derivatives for which the presence of particular molecular structures is the decisive condition. Thus, a nitrofurane derivative prepared by Casini and his co-workers (87) has shown bacteriostatic properties similar to classical low molecular preparations of nitrofurane, e.g. l-[5-(nitrofurfuryliden)amino]hydantoine. The polymeric substance shows an activity considerably longer than that of the reference substance if parenterally applied, whereas oral application gives no effect. This is easy to understand because, as already mentioned, polymers cannot be resorbed in the digestive tract. Here, the active polymeric substance [22] has been prepared by condensation of 5-nitrofuraldehyde with poly(acryloylhydrazide). 

The indication for administering BCAA in patients with hepatic encephalopathy to compensate amino-acid imbalance was proposed by J.E. Fischer et al. in 1974, and implemented parenterally. However, oral application of BCAA for an adequate treatment period also has beneficial effects on cirrhosis and HE (7.) improvement in protein tolerance and the nutritional condition, (2.) improvement in cerebral functions (II8, 122), probably due to an amelioration of liver function, (2.) stimulation of ammonia detoxification with a positive nitrogen balance (118), (4.) reduction in or normalization of AAA levels, and (5.) promotion of glutamine synthesis with a favourable effect on the cells of the immune system and on renal function. By means of BCAA, it was possible to prolong the survival time and delay the occurrence of liver failure in rats with CC -induced cirrhosis. (123, 126) However, there are diverging results, which need further clarification. In principle, the use of BCAA is considered to be a necessary form of supplementary treatment for catabolic metabolism in cirrhosis (124,125, 127, 128, 130-132), in (also latent) HE and after curative resection of hepatocellular carcinoma. (I2l) (s. p. 280)... 

Loading tests are not necessary for the diagnosis of amino acid transport disorders. However, pathophysiologically they may help in differentiating between different types of cystinuria by oral application of cystine and dibasic amino acids followed by analysis of plasma amino acids. The polyamines putrescine and cadaverine are produced intestinally, absorbed and excreted into the urine. Loading with dibasic amino acids will result in increased production of these polyamines [9, 10]. 

An example of a simple CZE method for peptide analysis and characterization is the one developed for protegrin IB-367.37 IB-367 is a peptide containing 17 amino acid residues that possess antimicrobial properties, and it is being developed for treatment of oral mucositis associated with aggressive cancer chemotherapy as well as other topical applications. This polycationic product was chemically synthesized using solid-phase and purified by preparative reversed-phase HPLC. IB-367 is rich in cysteine and arginine residues. 

The drawback of this highly potent class of inhibitors is their toxicity (Stryer 1988). Only few representatives are known to be non-toxic. Therefore, enzyme inhibitors that are not based on amino acids are only of theoretical interest for oral drug delivery and other applications in human. Nevertheless, they might be interesting as lead compounds to develop novel potent and nontoxic inhibitors. 

The use of 2,7-dimethyl-3,8-dinitrodipyrazolo[l,5-a,l, 5 -d]pyrazine-4,9-dione - a new labeling reagent for liquid chromatographic analysis of amino acids - is offered [671], Application of the method to quality control of commercially available oral polyaminoacid formulations is described. 1,2-1 ii acetyl -4,4-di n i (ropyrazol idi ne and products of its further nitration have been obtained [672],... 

Figure 2.10 Amphetamine 30, methamphetamine 31, and methylenedioxymethamphetamine 32 (MDMA, ecstasy, XTC) are lipophilic compounds with good oral bioavailability they easily cross the blood-brain barrier to exert central nervous system effects. Dopamine 33, norepinephrine (noradrenalin) 34, and epinephrine (adrenaline) 35 are polar phenethylamines they have poor oral efficacy and do not pass the blood-brain barrier, producing only peripheral effects after intravenous application. Ephedrine 36 has intermediate lipophilicity besides its peripheral effects it also acts as a central stimulant. Although L-dopa 37 is even more polar than dopamine 33, it is orally active and crosses the blood-brain barrier by active transport mediated by the amino acid transporter.

In a chemically similar application, phthalic anhydride was reacted with the naturally occurring polymer chitosan, a polyaminosugar. Reaction with the amino groups gave a polymer with half phthalamide residues. This substance shows promise as a matrix for colon-specific, orally administered drugs which must survive the acidic conditions of the stomach <1999MI103>. 

Great attention has been paid to HAS and their safety application in plastics and coatings. The 4-unsubstituted 2,2,6,6-tetramethylpiperidine is considered as relatively toxic, the acute oral toxicity being about 1 g/kg. The substitution in position 4 (i.e. the general mode in the synthesis of HAS for polymer purposes) dramatically improves the situation. Therefore, commercial HAS like 28 (R = H), 34,35a or 35b were approved for stabilization of packaging materials in contact with food [307]. Some data are available on properties of TEMPO (2,2,6,6-tetramethylpiperidinyl-l-oxyl) and its 4-amino or 4-hydroxy derivatives. They were found to act as weak intrinsic direct mutagens in Salmonella typhimurium. TEMPO increases intracellular hydroperoxide concentration. This may indicate its pro-oxidative effect which does not result, however, in cellular toxicity [314]. 

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