Natamycin

Alvarez, F.S. U.S. Patent 3,694/476 September 26,1972 assigned to Syntex Corp., Panama Halpern, 0. U.S. Patent 3,720,708 March 13,1973 

The Fermentation Process The process by which this antifungal substance is produced Is an aerobic fermentation of an aqueous nutrient medium inoculated with a pimaricin-producing strain of Streptomyces gilvosporeus. The nutrient medium contains an assimilable source of carbon such as starch, molasses, or glycerol, an assimilable source of nitrogen such as corn steep liquor and Inorganic cations such as potassium, sodium or calcium, and anions such as sulfate, phosphate or chloride. Trace elements such as boron, molybdenum or copper are supplied as needed in the form of impurities by the other constituents of the medium. 

In more detail the nutrient medium used may contain sources of carbon such as starch, hydrolyzed starch, sugars such as lactose, maltose, dextrose, sucrose, or sugar sources such as molasses alcohols, such as glycerol and mannitol organic acids, such as citric acid and acetic acid and various natural products which may contain other nutrient materials in addition to carbonaceous substances. 

Nitrogen sources include proteins, such as casein, zein, lactalbumin protein hydrolyzates such proteoses, peptones, peptides, and commercially available materials, such as N-Z Amine which is understood to be a casein hydrolyzate also corn steep liquor, soybean meal, gluten, cottonseed meal, fish meal, meat extracts, stick liquor, liver cake, yeast extracts and distillers solubles amino acids, urea, ammonium and nitrate salts. Such inorganic elements as sodium, potassium, calcium and magnesium and chlorides, sulfates, phosphates and combinations of these anions and cations in the form of mineral salts may be advantageously used in the fermentation. 

The so-called trace elements, such as boron, cobalt, iron,copper, zinc, manganese, chromium, molybdenum and still others may also be used to advantage. Generally, these trace elements occur in sufficient quantities in the carbonaceous and nitrogenous constituents of the medium, particularly if derived from natural sources, or in the tap water, and the addition of further quantities of these trace elements may consequently be unnecessary. 

Therapeutic Function Antibacterial (ophthalmic) Chemical Name Sae Structural Formula 

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Natamycin. Natamycin or pimaricin (2) is a polyene with only four conjugated double bonds. This tetraene is obtained from Streptomjces natalensis. Like the other polyenes, pimaricin induces release from cells with membranes containing 20—40 mol % ergosterol. This is also the ergosterol concentration in the membrane of Saccharomjces cerevisiae. 

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. 

Narcotan - Halothane Narco26p Flunitrazepam Nardeizine Phenelzine sulfate Nardil - Phenelzine sulfate Narest Valethamate bromide Narigix Nalidixic acid Narsis - Medazepam Nasafarma - Oxymetazoline HCI Nazalide Flunisolide Nasal Yer Naphazoline Nasin Tetrahydrozoline HCI Nasivin - Oxymetazoline HCI Nasky Inositol niacinate Nasmil - Cromolyn sodium Nasophen - Phenylephrine HCI Natacillin - Hetacillln potassium Natacyn - Natamycin Natam - Flurazepam... 

Natamycin is the only ophthalmic antifungal in use This drug possesses antifungal activity against a variety of yeast and fungi. 

Natamycin is a fungicide used to keep cheese from getting moldy. It works by making holes in the cell membranes of fungi, so their insides leak out. It is produced by Streptomyces natalensis bacteria. 

Suloff, E. C Comparative study of semisynthetic derivative of natamycin and the parent antibiotic on the spoilage of shredded cheddar cheese. Thesis, Virginia Polytechnic Institute and State University, Blacksburg, VA, 1999, http // scholar. lib. vt.edu/theses/available/etd-... 

NASA LaRC-TOR series polyimides, 20 282 Nasal drug deUvery, 9 48-49 Nasal impact frequency (NIF), 11 520-521 Nasal sprays, 7 273t Nasicon compounds, 18 841 NaSPS ionomers, 14 469, 471, 480 melt viscosity of, 14 473 Nata di Coco, 5 364 Natamycin, 12 59 National Aeronautics and Space... 

Monoammonium glutamate Monocalcium citrate Monocalcium phosphate Monomagnesium phosphate Monopotassium citrate Monopotassium glutamate Monopotassium phosphate Monosodium citrate Monosodium glutamate Monosodium phosphate Montan acid esters Na, K and Ca salts of fatty acids Natamycin (pimaricin)... 

Natamycin (Pimaricin) has been approved for use on the surface of cheese and cheese slices for mold inhibition (47). 

Shahani (48) found that natamycin treated cheeses inoculated with toxigenic molds effectively prolonged the shelf life. 

Drugs included in this group—amphotericin B, nystatin, natamycin, are used for treating systemic and snperficial infections. Natamycin is used only for ophthalmologic superficial infection pnrposes. 

Natamycin Natamycin, a mixture of stereoisomeric 22-[(3-amino-3,6-dideoxy-p-D-mannopyranosyl)oxy]-1,3,26-trihydroxy-12-methyl- lO-oxo-6,11,28-trioxatricy-clo[22.3.1.0. ]-octacosa-8,14,16,18,20,penten-25-carboxylic acid (35.1.3), like amphotericin and nystatin, is a polyene antibiotic that is isolated from the products of the vital activity of the actinomycete Streptomyces natalensis [15-17]. 

The spectrum of its activity is somewhat narrower than that of amphotericin and nystatin, but at the same time, it is less toxic. It exhibits especially pronounced activity against a few strains of Fusarium and Cefalosporium. Natamycin is a drug for treating superficial fungal infections, and it is used only for ophthalmologic purposes. Synonyms of this drug are pimafucin, pimaricin, tennecetin, and others. 

Fungal infections Fungal blepharitis, conjunctivitis, and keratitis caused by susceptible organisms. Natamycin is the initial drug of choice in Fusarium solani keratitis. 

Pharmacology Natamycin, a tetraene polyene antibiotic, is derived from Streptomyces natalensis. 

Fungal endophthalmitis The effectiveness of topical natamycin as a single agent in fungal endophthalmitis has not been established. 

Resistance Failure of keratitis to improve following 7 to 10 days of administration suggests that the infection may be caused by a microorganism not susceptible to natamycin. Base continuation of therapy on clinical reevaluation and additional laboratory studies. 

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