Active principles

All active principles introduced earlier are per se unidirectional. However, the implementation of feedback loops allows for bioresponsive hydrogels that exhibit a true self-regulation capacity. These next-generation systems can adopt magnitude and direction of the response to the respective stimulus like the concentration of a particular biomolecule in the local enviromnent. This 

FIGURE 6.28 Different types of bioresponsive hydrogels that change properties in response to (I) small molecules via receptor/ligand interactions (II) (ceU-secreted) enzymes via cleavable linkers and (III) small molecules that are convated by immobilized enzymes. The macroscopic response (sweUing/coUapse of the hydrogel) is shown. Source Ulijn et al. [113]. Reproduced with permission of Elsevier. 

Until the end of the 19th century, medicines were natural organic or inorganic products, mostly dried, but also fresh, plants or plant parts. These might contain substances possessing healing (therapeutic) properties, or substances exerting a toxic effect. 

Soaking plants or plant parts in alcohol (ethanol) creates a tincture. In this process, pharmacologically active constituents of the plant are extracted by the alcohol. Tinctures do not contain the complete spectrum of substances that exist in the plant or crude drug, but only those that are soluble in alcohol. In the case of opium tincture, these ingredients are alkaloids (i. e., basic substances of plant origin) including morphine, codeine, narcotine = noscapine, papaverine, narceine, and others. 

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I6I C. Warfarin baits need contain only 0 025% active principle, and rats are killed after ingesting about 5 doses the bait can be left down and the risk of acute toxicity to man or domestic animals is not serious. In common with other coumarin derivatives, warfarin reduces the clotting power of blood and death is caused by haemorrhages initiated by any slight injury. Warfarin is a vitamin K antagonist, and large oral doses of the vitamin can be given as an antidote. 

Sodium Levothyroxine. As one of the active principles of the thyroid gland, sodium levothyroxine [55-03-8] (levothyroxine sodium) can be obtained either from the thyroid glands of domesticated animals (10) or synthetically. It should contain 61.6—65.5% iodine, corresponding to 100 3% of the pure salt calculated on an anhydrous basis. Its chiral purity must also be ascertained because partial racemi2ation may occur during synthesis and because dl-T is available commercially. Sodium levothyroxine melts with decomposition at ca 235°C. It is prepared as pentahydrate [6106-07-6] from... 

Other Lethal Agents. There are a number of substances, many found in nature, which are known to be more toxic than nerve agents (6). None has been weaponized. Examples of these toxic natural products include shellfish poison, isolated from toxic clams puffer fish poison, isolated from the viscera of the puffer fish the active principle of curare "heart poisons" of the digitaUs type the active principle of the sea cucumber active principles of snake venom and the protein ricin, obtained from castor beans (See Castor oil). 

Guaiacols. Cresote, obtained from the pyrolysis of beechwood, and its active principles guaiacol [90-05-1] (1) and cresol [93-51-6] (2) have long been used ia expectorant mixtures. The compounds are usually classed as direct-acting or stimulant expectorants, but their mechanisms of action have not been well studied. Cresol is obtained by the Clemmensen reduction of vanillin (3), whereas guaiacol can be prepared by a number of methods including the mercuric oxide oxidation of lignin (qv) (4), the ziac chloride reduction of acetovanillone (5), and the diazotization and hydrolysis of o-anisidine (6). 

A solvent free, fast and environmentally friendly near infrared-based methodology was developed for the determination and quality control of 11 pesticides in commercially available formulations. This methodology was based on the direct measurement of the diffuse reflectance spectra of solid samples inside glass vials and a multivariate calibration model to determine the active principle concentration in agrochemicals. The proposed PLS model was made using 11 known commercial and 22 doped samples (11 under and 11 over dosed) for calibration and 22 different formulations as the validation set. For Buprofezin, Chlorsulfuron, Cyromazine, Daminozide, Diuron and Iprodione determination, the information in the spectral range between 1618 and 2630 nm of the reflectance spectra was employed. On the other hand, for Bensulfuron, Fenoxycarb, Metalaxyl, Procymidone and Tricyclazole determination, the first order derivative spectra in the range between 1618 and 2630 nm was used. In both cases, a linear remove correction was applied. Mean accuracy errors between 0.5 and 3.1% were obtained for the validation set. 

That the degree of comminution on its own is not the only factor involved in the kinetics-of the release of the active principles, but that evidently the nature and amount of the accompanying substances also play an essential part, has been demonstrated in the case of the sennosides in aqueous preparations (hot extractions and cold macerates) from senna fruits and senna leaves [3],... 

The result of taking into account the three factors mentioned - dose - degree of comminution - method of extraction - should be a tea that has an optimal amount of active constituents. But, at present ihere are very few studies which answer the often posed question What proportion of the active principles in the drug pass over into the tea With a hot-watcr infusion of chopped senna... 

The large influence that the degree of comminution of the drug has on the liberation of active principles during preparation of the tea has been domonstrated in investigations with alder buckthorn bark and cascara bark ... 

When used at room temperature in the presence of an active platinum catalyst in an inert solvent, e.g., acetone or ethyl acetate, oxygen will oxidize nonhindered, saturated hydroxyl groups and exposed allylic alcohols. This reagent has found extensive use in sugar chemistry and is particularly suited for the selective oxidation of either 3a- or 3j -alcohols of steroids. Other hydroxyl groups on the steroid skeleton are much less sensitive to oxidation. As a result, this reaction has been used extensively in research on polyhydroxy cardiac-active principles, e.g., the cardenolides and bufadienolides, where the 3-hydroxyl group is easily oxidized without extensive oxidation or dehydration of other hydroxyl groups. The ordinarily difficult selective oxidation of the... 

The active principle of the autumn crocus (Colchicum autumnale), colchicine (48), is one of the very few drugs that have remained in reputable medical use since ancient times. This drug was the only useful treatment available for the excruciating pain associated with crystallization of uric acid in the joints characteristic of gout until the advent of allopurinol. Although the precise mechanism by which colchicine gives this dramatic relief remains undefined, the antimitotic activity of this agent is... 

It was known for some time that even after the corticoids had been separated from crude extracts of the adrenal cortex, the remaining material, the so-called "amorphous fraction" still possessed considerable mineralocorticoid activity. Aldosterone (250), one of the last steroids to be isolated from this fraction, proved to be the active principle. This compound proved to be an extremely potent agent for the retention of salt, and thus water, in body fluids. An antagonist would be expected to act as a diuretic in those edematous states caused by excess sodium retention. Although aldosterone has been prepared by both total and partial synthesis, the complexity of the molecule discouraged attempts to prepare antagonists based directly on the parent compound. 

A culture of Bacillus polymyxa in a tube with Trypticase soybean broth was incubated overnight at 25°C. 5 ml of this culture was transferred to 100 ml of the tank medium in a 500 ml Erlenmeyer flask which was incubated for 48 hours at room temperature. This 100 ml culture served as inoculum for one tank. During the course of fermentation the medium was aerated at the rate of 0.3 volume of air per volume of mash per minute. The temperature was maintained at about 27 C. Samples of mash were taken every 8 hours in order to determine pH and the presence of contaminants and spores. After 88 hours of fermentation the pH was about 6.3 and an assay using Escherichia coll showed the presence of 1,200 units of polymyxin per cubic centimeter. The polymyxin was extracted and purified by removing the mycelia, adsorbing the active principle on charcoal and eluting with acidic methanol. 

Unfortunately, nicandrenone is typical of many instances in the field of natural pesticides where elucidation of chemical structure has not previously received the attention it deserves. However, with the increased availability of powerful instrumental techniques, considerable progress has been made during the past decade. Since the last general review (14), active principles from several more of the time-honored insecticidal plants have yielded to structure elucidation (Table I). 

Despite the recent efforts of Beroza (3), the insecticidal alkaloids of the thunder-god vine (Tripterygium ivilfordii) remain only partially characterized. A structure has been proposed for anhydrory-anodine (VIII), a major degradation product of the active principle (ryanodine) of the commercial insecticide ryania (34), and a structure for the parent compound will be proposed soon by Rapoport and his coworkers (27). This again illustrates the importance of collaboration between physical and biological scientists and the intriguing research which each can reveal to the other. 

Dronabinol (tetrahydrocannabinol), the active principle from cannabis and synthetic cannabinoids, nabilone and levonantradol are effective in treating nausea and vomiting in cancer chemotherapy. The mode of action is unclear but appears to involve cannabinoid CBi receptors. Cannabinoids have been shown to reduce acetylcholine release in the cortex and hippocampus, and have been suggested to inhibit medullary activity by a cortical action. Inhibition of prostaglandin synthesis and release of endorphins may also be involved in the antiemetic effect. A review of trials of dronabinol, nabilone or levonantradol concluded that while the cannabinoids were superior to placebo or dopamine receptor antagonists in controlling emesis... 

These polymers generally comprise a hydrophilic substituent in a ratio corresponding to the required hydrophilicity, and an active principle either grafted or merely trapped in the polymeric... 

Subcase b2 This case, called the paired f-test , is often done when two test procedures, such as methods A and B, are applied to the same samples, for instance when validating a proposed procedure with respect to the accepted one. In practicular, an official content uniformity" 5 assay might prescribe a photometric measurement (extract the active principle from a tablet... 

Since full analyses are carried out, a lot of data are generated. Every parameter is reviewed for trends that signal product aging or outright decomposition of the active principle this can be as cosmetic in nature as discoloration or as potentially hazardous as buildup of toxic derivatives. If the drug substance is an ester, for example, hydrolysis, particularly if moisture penetrates the primary packaging material, will decompose the compound into its acid and alcohol components. From a pharmaceutical or medical viewpoint, even if there is no toxicity issue involved, this will result in a loss of bioavailability. Even this is to be avoided because subpotency introduces therapeutic uncertainty and can go as far as lethal undertreatment. 

Pernicious anaemia was a fatal disease first reported in 1880. It was not until 1926 that it was discovered that eating raw liver effected a remission. The active principle was later isolated and called vitamin B or cyanocobalamin. It was initially obtained... 

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