Neomycine

Pharmaceutical. Ion-exchange resins are useful in both the production of pharmaceuticals (qv) and the oral adrninistration of medicine (32). Antibiotics (qv), such as streptomycin [57-92-17, neomycin [1404-04-2] (33), and cephalosporin C [61-24-5] (34), which are produced by fermentation, are recovered, concentrated, and purified by adsorption on ion-exchange resins, or polymeric adsorbents. Impurities are removed from other types of pharmaceutical products in a similar manner. Resins serve as catalysts in the manufacture of intermediate chemicals. 

A Acetylation, O-Phosphorylation, and O-Adenylylation. A/-Acetylation, O-phosphorjiation, and O-adenyljiation provide mechanisms by which therapeutically valuable aminocyclitol antibiotics, eg, kanamycia [8063-07-8] gentamicin [1403-66-3] sisomicin [32385-11-8], streptomycia [57-92-1], neomycin, or spectinomycin are rendered either partially or completely iaactive. Thus, eg, kanamycia B [4696-78-8] (50) can be iaactivated by modification at several sites, as shown. The elucidation of these mechanisms has allowed chemical modification of the sites at which the iaactivation occurs. Several such bioactive analogues, eg, dibekacia and amikacin have been prepared and are not subject to the iaactivation hence, they inhibit those organisms against which the parent antibiotics are iaeffective (96) (see Antibacterial agents, synthetic). 

In 1939 the isolation of a mixture of microbial products named tyrotbricin from a soil bacillus was described. Further investigation showed this material to be a mixture of gramicidin and tyrocidine. In rapid succession the isolation of actinomycin (1940), streptothricin (1942), streptomycin (1943), and neomycin (1949), produced by Streptomjces were reported and in 1942 the word antibiotic was introduced. Chloramphenicol, the first of the so-called broad spectmm antibiotics having a wide range of antimicrobial activity, was discovered in 1947. Aureomycin, the first member of the commercially important tetracycline antibiotics, was discovered in 1948. 

Aminoglycosides. Antibiotics ia the amiaoglycoside group characteristically contain amino sugars and deoxystreptamiae or streptamiae. This family of antibiotics has frequentiy been referred to as aminocyclitol amiaoglycosides. Representative members are streptomycia, neomycin, kanamycia, gentamicin, tobramycia, and amikacin. These antibiotics all inhibit proteia biosynthesis. 

Neomycin [1404-04-1] (33) or neomycin sulfate [1405-10-3], isolated from Streptomjcesfradiae (34—36), is sometimes used for gut sterilisation and other nonsystemic apphcations. Neomycin is a mixture of neomycin B /719-04-0] CggH N Ogg (9)... 

Derivatives Containing a 4,5-Disubstituted-2-deoxystreptamine Moiety. The first of this subclass to be isolated were the neomycins (B (9) and C), followed by paromomycin I [7542-37-2] 023114 X 024, and paromomycin 11 [51795-47-2] C23II43X3O24. The paromomycins are... 

Most polymyxin B sold for human use in the United States is in dermatological, otic, and ophthalmic preparations that usually contain one or more other spectmm extending antibacterials such as bacitracin, neomycin sulfate [1404-04-2], C23H4gNg023, linear gramicidin, oxytetracycline [79-57-2],... 

Although tyrothricia is too toxic for parenteral therapy, it was formerly sold in the United States as oral lo2enges. Modem tyrothricin formulations are composed of 70—80% tyrocidines and 30—20% linear gramicidins. Tyrocidines are not as active as linear gramicidins and are too toxic for any therapeutic use by themselves. The bactericidal linear gramicidins are used in the United States solely as an ophthalmic solution in combination with polymyxin B sulfate and neomycin sulfate. The linear gramicidin is used in this aqueous product as a substitute for bacitracin, which lacks stabiUty under such conditions. 

Nystatin (100,000 lU) is also available in combination with neomycin sulfate [1405-10-3] (35,000 lU), polymyxin B sulfate [1405-20-5] (35,000 lU), acetarsol [97-44-9] (150 mg), and dimethicone [8050-81-5] (2,500 mg). One or two ovules per day are inserted vaginaHy for at least 6—12 days. This combination has an antibacterial, antimycotic, and antitrichomonas action (see also Antibiotics, oligosaccharides Antiparasitic agents, antiprotozoals). 

Combination creams or ointments contain 3.5 mg neomycin base and 10 mg hydrocortisone [50-23-7] per g, in addition to 10 mg natamycin. The combination as a lotion contains 1.75 mg neomycin and 5 mg hydrocortisone/g, in addition to 10 mg natamycin. This combination has an antiinflammatory, antibacterial, and antimycotic action. It is appHed 2—4 times per day. 

Amphotericin B. Amphotericin B (3), an important polyene antibiotic, is administered almost exclusively via the intravenous route and is therefore discussed in more detail under the systemic antimycotics. The vaginal tablets contain 50 mg amphotericin B, and 100 mg tetracycline base per tablet (see also Antibiotics, tetracyclines). The tablets for oral use contain 50 mg amphotericin B, 250 mg tetracycline base, and 125 mg sodium hexametaphosphate. A combination ointment contains 1 mg fludrocortisone acetate, 2.5 mg neomycin, 0.25 mg gramicidin, and 1 g plastibase in addition to 30 mg amphotericin B (see also Antibiotics, peptides). 

Neomycin has been produced by growing the organism, Streptomyces No. 3535, in a suitable nutrient medium under appropriate stationary or submerged aerobic (viz shaken) conditions, and then isolating and purifying the substance, e.g., by procedure of the sort described in the figure including various steps of adsorption, recovery by elution, separation from impurities, and precipitation. 

---