関: pimaricin

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/03/27 02:11:10」(JST)

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Natamycin (INN), also known as pimaricin and sometimes sold as Natacyn, is a naturally occurring antifungal agent produced during fermentation by the bacterium Streptomyces natalensis, commonly found in soil. Natamycin has a very low solubility in water; however, natamycin is effective at very low levels. There is an MIC (minimum inhibitory concentration) of less than 10 ppm for most molds. Natamycin is classified as a macrolide polyene antifungal and, as a drug, is used to treat fungal keratitis, an infection of the eye. It is especially effective against Aspergillus and Fusarium corneal infections. Other common members of the polyene macrolide antifungal family are amphotericin B, nystatin, and filipin. Natamycin is also used in the food industry as a natural preservative.

Uses

In foods

Natamycin has been used for decades in the food industry as a hurdle to fungal outgrowth in dairy products, meats, and other foods. Potential advantages for the usage of natamycin might include the replacement of traditional chemical preservatives, a neutral flavor impact, and less dependence on pH for efficacy, as is common with chemical preservatives. It can be applied in a variety of ways: as an aqueous suspension (such as mixed into a brine) that is sprayed on the product or that the product is dipped into, or in powdered form (along with an anticaking agent such as cellulose) sprinkled on or mixed into the product. While not currently approved for use on meats in the United States, some countries allow natamycin to be applied to the surface of dry and fermented sausages to prevent mold growth on the casing. Also, natamycin is approved for various dairy applications in the United States. More specifically, natamycin is commonly used in products such as cottage cheese, sour cream, yogurt, shredded cheeses, cheese slices and packaged salad mixes. One of the reasons for food producers to use natamycin is to replace the artificial preservative sorbic acid.^[1]

As a food additive, it has E number E235. Throughout the European Union, it is only approved as a surface preservative for certain cheese and dried sausage products. It must not be detectable 5 mm below the rind. While natamycin is approved in different applications with different level in the world, it is approved in over 150 countries worldwide.^[2]

The European Food Safety Authority (EFSA) panel took over the responsibilities of providing scientific food safety advice to the EU from the Scientific Committee on Food (SCF) in 2002.^[3] In 2009 the (EFSA) European Food Safety Authority considered that the proposed use levels of natamycin are safe if it is used for the surface treatment for these cheese and sausages types.^[4]

Medical

Natamycin is used to treat fungal infections, including Candida, Aspergillus, Cephalosporium, Fusarium and Penicillium. It is applied topically as a cream, in eye drops, or (for oral infections) in a lozenge. Natamycin shows negligible absorption into the body when administered in these ways. When taken orally, little or none is absorbed from the gastrointestinal tract, making it inappropriate for systemic infections.^[5]

Safety

Natamycin does not have acute toxicity. In animal studies, the lowest LD₅₀ found was 2.5-4.5 mg/kg.^[6] In rats, the LD₅₀ is ≥2300 mg/kg, and doses of 500 mg/kg/day over 2 years caused no detectable differences in survival rate, growth, or incidence of tumors. The metabolites of natamycin also lack toxicity. The breakdown products of natamycin under various storage conditions may have a lower LD₅₀ than natamycin, but in all cases the numbers are quite high. In humans, a dose of 500 mg/kg/day repeated over multiple days caused nausea, vomiting, and diarrhea.^[7]

There is no evidence that natamycin, at either pharmacological levels or levels encountered as a food additive, can harm normal intestinal flora, but definitive research may not be available.^[7]

The European Food Safety Authority (EFSA) has concluded that the use of natamycin as a food additive has no relevant risk for the development of resistant fungi.

External links

Natamycin Articles

References

^ Kraft cheese singles ditch artificial preservatives
^ Regulatory information: www.natamycin.com
^ Safety and regulation: the formal process for analyzing the test data on food additives
^ Scientific Opinion on the use of natamycin (E 235) as a food additive
^ Sweetman, S. (2004). Martindale: The Complete Drug Reference
^ Oostendorp, J.G. (1981). "Natamysin(R)". Antonie van Leeuwenhoek 47: 170–1.
^ ^a ^b Mattia, A. et al. Safety evaluation of certain food additives and contaminants: natamicin (pimaricin). WHO Food Additives Series #48.

UpToDate Contents

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1. フサリウム感染症の治療および予防 treatment and prevention of fusarium infection
2. スケドスポリウム感染の診断および治療 diagnosis and treatment of scedosporium infection

English Journal

Detection method optimization, content analysis and stability exploration of natamycin in wine.

Sun X1, Li X1, Wang P2, Ma T3, Huang W1, Han S4, Zhan J5.
Food chemistry.Food Chem.2016 Mar 1;194:928-37. doi: 10.1016/j.foodchem.2015.08.116. Epub 2015 Sep 2.
A new detection method of natamycin via HPLC-MS/MS was developed that uses an Agilent 6460 HPLC-MS/MS instrument and an Agilent RP18 (2.1mm×50mm, 1.8μm); the LOD was 1μg/L, the LOQ was 3.34μg/L, the recovery was 70-94%, the RSD was approximately 2-4%, and the total run time was 5min. In the new
PMID 26471636

Heterologous coexpression of Vitreoscilla hemoglobin and Bacillus megaterium glucanase in Streptomyces lydicus A02 enhanced its production of antifungal metabolites.

Wu H1, Li J1, Dong D1, Liu T1, Zhang T1, Zhang D1, Liu W2.
Enzyme and microbial technology.Enzyme Microb Technol.2015 Dec;81:80-7. doi: 10.1016/j.enzmictec.2015.08.003. Epub 2015 Aug 12.
Streptomyces lydicus A02 is a novel producer of commercially important polyene macrocyclic antibiotic natamycin and a potential biocontrol agent to several plant fungal diseases, including wilt caused by Fusarium oxysporum f. spp. To improve the natamycin production and the antifungal activity of S.
PMID 26453475

Study of Pathogens of Fungal Keratitis and the Sensitivity of Pathogenic Fungi to Therapeutic Agents with the Disk Diffusion Method.

Wang L1, Wang L1, Han L1, Yin W1.
Current eye research.Curr Eye Res.2015 Nov;40(11):1095-101. Epub 2015 Aug 13.
Purpose/aim of the study: To identify the causative fungi of fungal keratitis, test their susceptibility to antifungal agents with the disk diffusion method and study the relationship between the organisms, the inhibition zones and the clinical outcomes.MATERIALS AND METHODS: 535 patients with funga
PMID 26268399

Japanese Journal

Predictive genomic biomarkers for drug-induced nephrotoxicity in mice

Journal of toxicological sciences 37(4), 723-737, 2012-08-01
NAID 10030502220

高速液体クロマトグラフィーによるワイン中のナタマイシン分析法について

国立医薬品食品衛生研究所報告 -(129), 100-104, 2011
NAID 40019156861

Determination of free and liposomal Amphotericin B in human plasma by liquid chromatography-mass spectroscopy with solid phase extraction and protein precipitation techniques

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 878(3), 315-326, 2010-02-01
NAID 10028032030

「ピマリシン」

Natamycin
Names
	IUPAC name (1R,3S,5R,7R,8E,12R,14E,16E,18E,20E,22R,24S,25R,26S)-22-[(3-amino-3,6-dideoxy-D-mannopyranosyl)oxy]-1,3,26-trihydroxy-12-methyl-10-oxo-6,11,28-trioxatricyclo[22.3.1.05,7]octacosa-8,14,16,18,20-pentaene-25-carboxylic acid
Identifiers
CAS Number	7681-93-8
ChEMBL	ChEMBL1200656
ChemSpider	10468784
DrugBank	DB00826
Jmol interactive 3D	Image
KEGG	C08073
PubChem	441382
UNII	8O0C852CPO
	InChI InChI=1S/C33H47NO13/c1-18-10-8-6-4-3-5-7-9-11-21(45-32-30(39)28(34)29(38)19(2)44-32)15-25-27(31(40)41)22(36)17-33(42,47-25)16-20(35)14-24-23(46-24)12-13-26(37)43-18/h3-9,11-13,18-25,27-30,32,35-36,38-39,42H,10,14-17,34H2,1-2H3,(H,40,41)/b4-3+,7-5+,8-6+,11-9+,13-12+/t18-,19-,20+,21+,22+,23-,24-,25+,27-,28+,29-,30+,32+,33-/m1/s1 Key: NCXMLFZGDNKEPB-FFPOYIOWSA-N ; InChI=1/C33H47NO13/c1-18-10-8-6-4-3-5-7-9-11-21(45-32-30(39)28(34)29(38)19(2)44-32)15-25-27(31(40)41)22(36)17-33(42,47-25)16-20(35)14-24-23(46-24)12-13-26(37)43-18/h3-9,11-13,18-25,27-30,32,35-36,38-39,42H,10,14-17,34H2,1-2H3,(H,40,41)/b4-3+,7-5+,8-6+,11-9+,13-12+/t18-,19-,20+,21+,22+,23-,24-,25+,27-,28+,29-,30+,32+,33-/m1/s1 Key: NCXMLFZGDNKEPB-FFPOYIOWBQ ;
	SMILES OC(=O)[C@@H]3[C@@H](O)C[C@@]2(O)C[C@@H](O)C[C@H]4O[C@@H]4/C=C/C(=O)O[C@H](C)C\C=C\C=C\C=C\C=C\[C@H](O[C@@H]1O[C@H](C)[C@@H](O)[C@H](N)[C@@H]1O)C[C@@H]3O2 ;
Properties
Chemical formula	C33H47NO13
Molar mass	665.725 g/mol
Appearance	White to cream-colored crystalline powder
Density	1.35 g/ml
Melting point	Darkens at ±200 °C with vigorous decomposition at 280-300 °C
Solubility in water	0.39 mg/ml
Pharmacology
ATC code	A01AB10; A07AA03, D01AA02, G01AA02, S01AA10
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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	Infobox references