Chemical Properties
White to Off-White Solid
Usage
analgesic, antimigraine
Usage
Pimaricin is a macrocyclic tetraene originally isolated from Streptomyces natalensis in 1957. Pimaricin exhibits broad spectrum antifungal activity against yeast and filamentous fungi by binding specifically to ergosterol to block fungal growth. Unlike the related polyenes, nystatin and filipin, pimaricin does not change the permeability of the plasma membrane. Pimaricin is used in the food industry for surface treatment of cheeses as a mould inhibitor.
Usage
Polyene antifungal antibiotic
Originator
Pimafucine,Beytout,France,1964
Manufacturing Process
The Fermentation Process: The process by which this antifungal substance is
produced is an aerobic fermentation of an aqueous nutrient medium The Fermentation Process: The process by which this antifungal substance is
produced is an aerobic fermentation of an aqueous nutrient 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.
The fermentation liquor is aerated in the customary manner by forcing sterile
air through the fermenting mixture usually at the rate of about 1 volume of
air per volume of fermentation medium per minute. To minimize
contamination with foreign microorganisms, the fermentation vessels should
be closed and a pressure of 2 to 15 pounds above atmospheric pressure
maintained in the vessel. In addition to the agitation provided by aeration,
mechanical agitation is generally desirable. Antifoaming agents, such as 1%
octadecanol in lard oil, may be added from time to time as required to
prevent excessive foaming. Fermentation is conducted at a temperature
preferably on the order of 26°C to 30°C but may be as low as 17°C or as high
as 42°C.
The time required for maximum production of the antifungal substance will
vary considerably depending upon other conditions of the fermentation.
Generally, about 48 hours is required before appreciable quantities of the
antifungal substance are detected in the medium. The production of the
antifungal substance increases with time, and the fermentation may run as
long as 120 hours. The hydrogen ion conditions normally vary from about pH
6 to pH 8.0, although deviations from these values are permissible, according
to British Patent 846,933. The reader is referred to the patents cited for detals
of pimaricin purification.
Brand name
Natacyn (Alcon).
Therapeutic Function
Antibacterial (ophthalmic)
Biological Functions
Natamycin, also known as pimaracin, belongs to the polyene family of antibiotics; (a group of antifungal agents which target and bind to eukaryotic sterols and specifically ergosterol), and it is a secondary metabolite of Streptomyces natalensis . Very low levels (10–20 ppm) are needed to inhibit almost all yeasts and molds, while no amount of natamycin is sufficient to inhibit most bacteria, as they lack the sterol targeted by natamycin (some gram-positive types may be susceptible). Thus, natamycin may be used to retard the growth of fungi in meat products to which fermentative cultures are added, and is typically applied as a surface treatment (i.e., dip or spray). Resistant organisms are not typically encountered even though natamycin has been used as a food preservative for more than three decades. Unlike most bacteriocins, natamycin is toxic to eukaryotes. Acceptable daily intake of natamycin for humans is 0–0.3 mg/kg of body weight.
Antimicrobial activity
The spectrum of Natamycin's 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.
General Description
Natamycin (pimaricin; Natacyn) is a polyene antibiotic obtainedfrom cultures of Streptomyces natalensis.The natamycin structure consists of a 26-membered lactonering containing a tetraene chromophore, an α,β-unsaturatedlactone carbonyl group, three hydroxyl groups, a carboxyl group, a trans epoxide, and a glycosidically joined mycosamine.Like the other polyene antibiotics, natamycin isamphoteric.The smaller polyenes are fungistatic and fungicidal within thesame concentration range.Natamycin possesses in vitro activity against severalyeasts and filamentous fungi, including Candida,Aspergillus, Cephalosporium, Penicillium, and Fusariumspp. The drug is supplied as a 5% ophthalmic suspension intendedfor the treatment of fungal conjunctivitis, blepharitis,and keratitis.
Pharmacokinetics
The LC-MS-MS methods allowed Natamycin (Nat) quantification as low as 2.0ng/ml (R>0.99), respectively, for up to 90mins after a single administration of Nat to the eye.
After a single topical instillation, Nat reached the highest concentration in cornea at 10mins (Cmax:299.3ng/g). Nat was detected at all selected time points in the aqueous humor, and the highest was 27.03ng/ml at 30mins. The repeated dosing group, the concentrations in cornea and aqueous humor for Nat were 10569ng/g and 54.4ng/ml, respectively.
Side effects
Side effects that you should report to doctor as soon as possible:
allergic reactions like skin rash, itching or hives, swelling of the face, lips or tongue
changes in vision
eye pain
severe burning, stinging, or swelling of the eyelids
Side effects that usually do not require medical attention:
blurred vision for a few moments after application
temporary redness or stinging for a few moments after application
temporary watering of eyes
Synthesis
Natamycin, a mixture of stereoisomeric 22-[(3-amino-3,6-dideoxy-β-Dmannopyranosyl)oxy]-1,3,26-trihydroxy-12-methyl-10-oxo-6,11,28-trioxatricyclo[22.3.1.0.5,7]-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.
Veterinary Drugs and Treatments
Natamycin is a semisynthetic polyene antibiotic. Natamycin is
poorly water-soluble and will not penetrate the intact corneal epithelium.
Natamycin is the only antifungal agent approved for use
on the eye and the only commercially available eye drug for treatment
of fungal keratitis.
target
NADPH-oxidase | Antifection
