Water-insoluble inhibitor

A novel approach to study of action of water-insoluble inhibitors of enzyme reactions. ). Biochem. Biophys. 

Chemical Reactivity - Reactivity with Water No reaction Reactivity with Common Materials No reactions Stability During Transport The product darkens and forms water insoluble material on exposure to air or acids. This reaction is accelerated at elevated temperatures Neutralizing Agents for Acids and Caustics Not pertinent Polymerization Not pertinent Inhibitor of Polymerization Not pertinent. 

Thus, the effects of glycosylation inhibitors on intact cells may also be studied best with virus-infected cells. Before release of virus, the glycoproteins are detected in the water-insoluble, membranous fraction. Furthermore, the lipid-linked oligosaccharides may be rather specifically extracted from whole cells, and monosaccharide-lipids may also be determined.3-116 It is thus seen that the various tools of virology and of lipid and carbohydrate biochemistry have proved productive in establishing the mode of action of inhibitors of lipid-depen-dent glycosylation of proteins. 

Fig. 10.7 Principle of affinity adsorption. The specific ligand (L), such as enzyme inhibitor and antigen, is immobilized on a water-insoluble carrier (C). A solute (S) can react selectively with the affinity ligand.

The micelle-forming molecule TPGS is an effective vehicle for lipid-based drug delivery, and is also a water-soluble source of the water-insoluble oil Vitamin [16] jjjY protease inhibitor, amprenavir,... 

Ritonavir, an HIV protease inhibitor with peptidelike structure, has an intrinsic water solubility of l.Opg/ml. Norvir is a thermodynamically stable solution formulation containing 100 mg of ritonavir dissolved in a mixture of oleic acid, Cremophor EL, ethanol, and the antioxidant butylated hydroxytoluene (BHT), and filled into soft gelatin capsules. However, Norvir is being replaced by Kaletra oral solution and soft gelatin capsule, which is a combination of 133.3 mg of lopinavir and 33.3 mg ritonavir dissolved in a mixture of oleic acid, polyoxyl 35 castor oil (Cremophor EL), and propylene glycol. The water-insoluble HIV protease inhibitor, saquinavir, is solubilized by a mixture of Vitamin E and medium-chain mono- and diglycerides in 200 mg Fortovase soft gelatin capsules. 

Ritonavir is solubilized in a cosolvent mixture of propylene glycol, ethanol, water, the surfactant Cremophor EL, and peppermint oil to 80 mg/ml in the Norvir oral solution. A similar cosolvent mixture of propylene glycol, 42% ethanol, water, glycerin, the surfactant Cremophor RH 40, and peppermint oil is used to cosolubilize ritonavir to 20 mg/ml and lopinavir, a non-ionizable water-insoluble HIV protease inhibitor, to 80 mg/ml in the Kaletra oral solution. The dose of Kaletra Oral Solution is up to 5 ml twice daily, which is 2.1 ml of ethanol per dose representing the estimated maximum amount of ethanol administered orally per dose. 

Efavirenz is a water-insoluble non-nucleoside reverse transcriptase inhibitor widely used as Sustiva tablets in the treatment of HIV infection, and is also available as an oral solution in which 30 mg/ml is dissolved in medium-chain triglycerides along with benzoic acid and strawberry/mint flavor. The daily dose of Efavirenz is 600 mg (20 ml) for adults and for pediatrics is 270-600 mg (9-20 ml) and these dosing regimens delivers the maximum amount of medium-chain triglycerides per unit dose of any currently marketed oral lipid-based formulation. Calcitrol is formulated in a fractionated triglyceride of palm seed oil in the 1 pg/ml Rocaltrol oral solution. The daily dose of calcitrol is 1 pg, which is only 1 ml of the oral solution. 

Different types of serum have been used to supplement media with various necessary growth factors and hormones that cells need for their growth. Serum also contains various adhesion factors and antitrypsin activity, which promotes cell attachment. Serum components can act as buffers and as chelators for labile or water insoluble nutrients, bind and neutralize toxins, and provide protease inhibitors. Serum can also reduce oxidative injury to cells caused by ferrous ions. Reduced serum conditions have also been reported to increase the susceptibility of cells to apoptosis. ... 

This method (Fig. 9.5 B) was designed to test whether any inhibition reaction occurred in the presence of a water-insoluble substrate during lipase hydrolysis. Lipase was injected into the reaction vessel of a pH-stat containing the emulsified substrate maintained under vigorous stirring. The inhibitor was injected a few minutes after lipase addition. Lipase activity was then continuously recorded (Fig. 9.5 B). 

Verger, R. and de Haas, G.H. (1990) Competitive inhibition of lipolytic enzymes. I. A kinetic model applicable to water-insoluble competitive inhibitors. 

A mixture of oleic add, cremophor EL and propylene glycol solubilizes 133.3 mg of lopinavir and 33.3 mg of ritonavir, which are water-insoluble HIV protease inhibitors used in the treatment of HIV infection, in the hxed-dose combination Kaletra soft gelatin capsules. The dose of Kaletra is three capsules twice daily and the product must be stored refrigerated at 2—8°C or at controlled room temperature for no more than two months. Kaletra has been available in the UK since 2001, and is also available in the USA. 

Efavirenz is a water-insoluble non-nucleoside reverse transcriptase inhibitor widely used in the treatment of HIV infection. Efavirenz is available as Sustiva 600 mg tablets in both the UK... 

Two examples of radical inhibitors that are present in biological systems are vitamin C and vitamin E. Like hydroquinone, they form relatively stable radicals. Vitamin C (also called ascorbic acid) is a water-soluble compound that traps radicals formed in the aqueous environment of the cell and in blood plasma. Vitamin E (also called a-tocopherol) is a water-insoluble (hence fat-soluble) compound that traps radicals formed in nonpolar membranes. Why one vitamin functions in aqueous environments and the other in nonaqueous environments should be apparent from their structures and electrostatic potential maps, which show that vitamin C is a relatively polar compound, whereas vitamin E is nonpolar. 

Silicone oils are particularly effective antifoaming agents because of their low surface tension, thermal stability, chemical inertness, and total water insolubility. However, on their own they show little or no foam inhibiting properties. It is only when they are combined with finely divided silica particles that an effective foam inhibitor is produced. Traditional silicone anti foam compounds are proprietary combinations of... 

Hirudin (lepirudin). Protein from the head and gullet rings of the medicinal leech (Hirudo medicinalis) (ca. 3 mg/leech). H is a heparinoid that delays blood coagulation (thrombin inhibitor). The Mr of H. is ca. 9060 (other reports 10800), it has a high content of acidic amino acid residues. H. is a colorless powder, soluble in water, insoluble in ethanol. The anticoagu-lati ve activity of H. is based on the formation of a compound with Aromhin, so that the latter cannot exert its catalytic effect Commercially available for use in the treatment of thrombosis, hematomas, etc. In Europe, recombinant H. (Refludan ) is marketed for heparin-associated thrombocytopenia. 

The most common acid solvent is inhibited muriatic acid. It is inhibited, as all acids solvents must be, to reduce chemical attack on metal surfaces to an acceptable level. Muriatic acid is cheap and effective. It forms reaction products that are generally water-soluble and so are removed in the used solvent. Sulfuric acid is seldom used because of its insoluble reaction products. Nitric acid cannot be prevented from attacking carbon steels or copper alloys. It has certain special applications where the substrate metal is stainless steel or aluminum. Of special interest for small-scale maintenance cleaning by plant personnel is sulfamic acid, mainly because it is a dry solid product that is safely to handle. It has acid properties only after it is dissolved in water. Solid inhibitors and wetting additives can be premixed into the packaged product. 

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