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WO1997026367A1 - Antibiotiques tkr 400-a et tkr 400-b et procedes de production de ces antibiotiques - Google Patents

Antibiotiques tkr 400-a et tkr 400-b et procedes de production de ces antibiotiques Download PDF

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Publication number
WO1997026367A1
WO1997026367A1 PCT/JP1997/000094 JP9700094W WO9726367A1 WO 1997026367 A1 WO1997026367 A1 WO 1997026367A1 JP 9700094 W JP9700094 W JP 9700094W WO 9726367 A1 WO9726367 A1 WO 9726367A1
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Prior art keywords
tkr
tkr400
antibiotic
strain
methanol
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PCT/JP1997/000094
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English (en)
Japanese (ja)
Inventor
Kazutoh Takesako
Katsushige Ikai
Tomoko Iwasaki
Masanobu Kuroda
Ikunoshin Kato
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Takara Shuzo Co., Ltd.
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Priority to AU13996/97A priority Critical patent/AU1399697A/en
Publication of WO1997026367A1 publication Critical patent/WO1997026367A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P1/00—Preparation of compounds or compositions, not provided for in groups C12P3/00 - C12P39/00, by using microorganisms or enzymes
    • C12P1/02—Preparation of compounds or compositions, not provided for in groups C12P3/00 - C12P39/00, by using microorganisms or enzymes by using fungi
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/14—Fungi; Culture media therefor
    • C12N1/145—Fungal isolates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00—Microorganisms ; Processes using microorganisms
    • C12R2001/645—Fungi ; Processes using fungi

Definitions

  • the present invention relates to antibiotics TKR 400-A and TKR 400-B useful as therapeutic agents for fungal infections, a method for producing them, and microorganisms producing them.
  • Fungi are known to infect humans, animals, plants and the like and cause various diseases. For example, it causes superficial mycosis in the skin and oral cavity of humans, systemic mycosis in the internal organs, brain, etc., and the same infectious disease in dead animals such as pets and livestock. In addition, it causes various diseases on plants such as fruit trees and vegetables.
  • Candida and Cryptococcus> Aspergillicus the main fungi that cause human infection and cause systemic mycosis. It is known that superficial mycosis is mainly caused by Candida, which infects the skin, oral cavity, vagina, etc., and Bacillus bacillus, which infects the skin of hands and feet. Various other fungi exist in the living environment and are thought to cause animal and plant contamination.
  • An object of the present invention is to provide a novel antibiotic which is useful as a therapeutic agent for fungal infections in view of the above situation.
  • the present inventors for the purpose of searching for new antibiotics, isolated a large number of microorganisms from nature, isolated the antibiotics produced by them, and examined their biological properties.
  • Aureobasidium Aureo b_a sidium
  • the present inventors isolated this antibiotic and examined its physicochemical properties.As a result, the present inventors confirmed that the two novel substances had unique physicochemical properties and were not described in the literature.
  • the antibiotics were named TKR400-A and TKR400-B.
  • the present invention provides the above antibiotics TKR400-A and TKR400-B, and methods for producing them. Brief description of the drawing
  • FIG. 1 is a diagram showing an ultraviolet absorption spectrum of the antifungal substance TKR 400-A.
  • the horizontal axis shows the wavelength (nm).
  • FIG. 2 is a diagram showing an infrared absorption spectrum of the antifungal substance TKR 400-A.
  • the horizontal axis shows the wave number (cm- 1 ).
  • FIG. 3 shows the 'H-NMR spectrum of the antifungal TKR 400—A.
  • FIG. The horizontal axis shows the chemical shift value (ppm).
  • FIG. 4 is a diagram showing a ' 3 C-NMR spectrum of the antifungal substance TKR 400-A.
  • the horizontal axis shows the chemical shift value (ppm).
  • FIG. 5 is a diagram showing the elution positions of the antifungal substance TKR 400-A in HPLC.
  • the vertical axis indicates the relative ultraviolet absorption intensity, and the horizontal axis indicates the retention time (minutes).
  • FIG. 6 is a diagram showing an ultraviolet absorption spectrum of the antifungal substance TKR400-B.
  • the horizontal axis shows the wavelength (nm).
  • FIG. 7 is a diagram showing an infrared absorption vector of a fungal substance TKR 400-1B.
  • the horizontal axis shows the wave number (cm- 1 ).
  • FIG. 8 is a diagram showing a ' ⁇ -NMR spectrum of the antifungal substance KR400-B.
  • the horizontal axis shows the chemical shift value (ppm).
  • FIG. 9 is a diagram showing a ' 3 C-NMR spectrum of the antifungal substance TKR 400 -B.
  • the horizontal axis shows the chemical shift value (ppm).
  • FIG. 10 is a diagram showing the elution position of the antifungal substance TKR 400-B in HPLC.
  • the vertical axis indicates the relative ultraviolet absorption intensity, and the horizontal axis indicates the retention time (minutes).
  • the antibiotic TKR400-A has the following physicochemical properties (1), (2), (3), (4) and (5).
  • Mass spectrum by FAB-MS method has a peak of mZz 127 3 [M + H] +
  • the major absorption wavelength (nm) of the ultraviolet absorption spectrum in methanol is 250 s sh 294, and their E ' c 9 are 96 and 20.
  • the main absorption wave numbers of the infrared absorption spectrum by the KBr method are 3450 cm- ', 2970 cm-', 1680 cm- ', 1640 c nT !, 1 5 3 0 cm - ', 1 4 1 0 cm one', is 1 2 2 0 cm- 1 1 5 0 cm _ l
  • Threonine, alanine, phosphoric acid, and isoleucine are detected in aminoacid analysis by ninhydrin reaction
  • the antibiotic TKR400-B has the following physicochemical properties (6), (7), (8), (9) and (10).
  • the main absorption wave numbers of the infrared absorption spectrum according to the KBr method are 3450 cm- ', 3350 cm-', 297 cm-168 cm- ' , 1640 cm _ ⁇ 1530 cm " 1 .1470 cm-', 1 4 1 0 c ⁇ ', 1 2 1 0 cm-', 1 1 4 0 cm-'
  • the antibiotic TKR 4 0 0 - A is the show 'H- NMR-spectrum Le 3 has a 1 3 C-NMR spectrum shown in Figure 4, the reversed-phase high performance liquid chroma preparative chromatography, It has the property of being eluted at the position shown in Fig. 5.
  • antibiotic TKR 4 0 0- B is shown in FIG. 8 'H- NMR scan Bae-vector, shown in Figure 9' has a 3 C-NMR spectrum, reversed-phase high performance liquid body chromatography It has the characteristic of being eluted at the position S shown in FIG.
  • the TKR 400-A belongs to the genus Aureobasidium, and the strain producing the TKR 400-A is cultured, and then isolated from the culture of the strain. O
  • the strain used in the present invention is not particularly limited as long as it belongs to the genus Aureobasidium and produces the TKR400-A.
  • the strain Aureobasidium SP (Aureobasidium sp.) TKR 400 strain (hereinafter referred to as “TKR 400 strain”) and the like.
  • the TKR400-B belongs to the genus Aureobasidium and is used to culture the strain that produces the TKR400-B. Thereafter, the TKR400-B is isolated from a culture of the strain. Can be manufactured by 0
  • the strain to be used in the present invention is not particularly limited as long as it is a strain belonging to the genus Au-reobasidium and produces the TKR400-B.
  • TKR 400 strains and the like can be mentioned.
  • the strain producing TKR400-A and the strain producing TKR400-B produce only one of TKR400-A and TKR400-B. It may be one that produces both TKR 400 -A and TKR 400 -B. Using the latter strain If used, both TKR 400-A and TKR 400-B can be manufactured.
  • the TKR400 strain is one of strains capable of producing both TKR400-A and TKR400-B.
  • TKR 400 strain is a new strain not described in the literature, and was first isolated and identified by the present inventors from a sample collected from Crystal Beach, Fukui Prefecture. It has the property of producing 1 ⁇ 400-B in an advantageous manner.
  • mycological properties of the TKR400 strain will be described in detail.
  • the TKR400 strain has the color tone of colonies (hereinafter also referred to as “populations”) in various media as shown in Table 1.
  • the color tone in the table is based on the color name according to the Japanese Industrial Standard JISZ 8102 (1989) .
  • JISZ 8102 (1989) After inoculating the culture medium, culture at 25 ° C, and after 4 days, 7 days and This is shown by the results observed 14 days later. The diameter of the settlement was measured 14 days later.
  • the TKR400 strain grows moderately on a malt extract agar medium, a YpSS agar medium, etc., and the center of the colony is glossy and usually exhibits a viscosity or a paste. However, it may become leathery as the culture days elapse.
  • the periphery of the colony shows a remarkable root-like shape.
  • the color of the colony is white in the early stage of the culture, and then gradually changes from light grayish yellow to peach to dark grayish yellow, but gradually changes from dull reddish yellow to brownish brown. As the days elapse, the color of the colony changes from brown to dark brown. Dyes are insoluble.
  • Hyphae are 2-4 m ⁇ and develop well, but do not form aerial hyphae and extend into the agar. From the tip or side of the hypha, budding conidia of 2 to 4 ⁇ 4 to 8 / m are often formed in the shape of a fingertip, and some are grown to a ball-like mass. Young vegetative cells are yeast-like, measuring 3-7 X 6-14 / m, their shape is oval or lemon-shaped, multipolar Propagate by budding. It forms arthropod spores with a size of 4 to 6 x 8 to 18 m, thick membrane spores with a size of 4 to 8 x 8 to 16 um, and no ascospores.
  • the growth temperature range is 10 to 25, and the optimum growth temperature is around 20 ° C.
  • Growth pH range The pH range at which growth is possible is pH 3 to pH 9, and the optimal growth pH is pH 4 to pH 8.
  • BP-5780 (May 17, 1995) (deposited in the present invention, in addition to the above-mentioned TKR400 strain, the TKR400 natural strain)
  • an artificial mutant a strain belonging to Aureobasidium, and a strain (microorganism) capable of producing TKR400-A can be used.
  • TKR400 strain in addition to the above-mentioned TKR400 strain, natural or artificial mutant strains of TKR400 strain, other strains belonging to the genus Aureobasidium, etc.
  • a strain (microorganism) capable of producing TKR400-B can be used.
  • TKR 400-A and TKR 400-B are the above-mentioned TKR 400-A producing strain and TKR 400-B producing strain in a nutrient source-containing medium.
  • examples of carbon sources include glucose, fructose, saccharose, starch, dextrin, glycerin, molasses, starch syrup, oils and fats, and the like.
  • Organic acids and the like can be mentioned.
  • nitrogen sources include, for example, organic nitrogen compounds such as soybean flour, cottonseed flour, corn steep liquor, casein, peptone, yeast extract, meat extract, germ, urea, amino acids, ammonium salts, and inorganic salts.
  • nitrogen compounds include, for example, sodium salt, potassium salt, calcium salt, magnesium salt, and phosphate salt. And the like inorganic salts. Each of these may be used alone or in combination as appropriate.
  • the nutrient-containing medium may further contain, if necessary, heavy metals such as iron salts, copper salts, zinc salts, and cobalt salts; vitamins such as biotin and vitamin B; Organic substances, inorganic substances, and the like that promote the production of TKR400-A and TKR400-B can be appropriately added.
  • heavy metals such as iron salts, copper salts, zinc salts, and cobalt salts
  • vitamins such as biotin and vitamin B
  • Organic substances, inorganic substances, and the like that promote the production of TKR400-A and TKR400-B can be appropriately added.
  • an antifoaming agent such as silicone oil or polyalkylene glycol ether, a surfactant, or the like can be added to the above-mentioned medium containing the nutrients, if necessary.
  • the above culture is preferably performed at 15 to 25 ° C., and the pH of the medium is usually pH 3 to 8, but is preferably around pH 5. A sufficient production amount can be obtained usually in a culture period of 3 to 15 days.
  • TKR400-A and TKR400-B are contained in the culture solution and the cells and accumulate in the culture.
  • TKR 400-A and TKR 400-B accumulated in the culture are separated from the culture using the physicochemical properties of these antifungal substances, and It can be further purified and obtained as needed.
  • the above separation can be performed by extracting the whole culture with a non-hydrophilic organic solvent such as ethyl acetate, butyl acetate, chloroform, butanol, and methyl isobutyl ketone. Separate the culture into culture solution and cells by filtration or centrifugation, and then separate from the culture solution and cells. You can also.
  • a non-hydrophilic organic solvent such as ethyl acetate, butyl acetate, chloroform, butanol, and methyl isobutyl ketone.
  • TKR 400-A and TKR 400-B The method of extracting with the above non-hydrophilic organic solvent can also be adopted.
  • a method may be employed in which TKR400-A and TKR400-B in the culture solution are adsorbed on a carrier and then eluted with a solvent.
  • the carrier include activated carbon, powdered cellulose, and adsorbent resin.
  • the solvent may be used singly or in combination of two or more depending on the type and properties of the carrier.For example, an aqueous solution of a water-soluble organic solvent such as aqueous acetate or aqueous alcohol may be used. Appropriate combinations can be given.
  • a method of extracting with a hydrophilic organic solvent such as acetone can be adopted.
  • the crude extracts of TKR400-A and TKR400-B thus separated from the culture may be subjected to a step of further purification, if necessary. it can.
  • the above-mentioned purification can be carried out by a method usually used for separation and purification of fat-soluble antibiotics. Examples of such a method include silica gel, activated alumina, activated carbon, and adsorbent resin. Column chromatography using a solid, high-performance liquid mouth chromatography, and the like. When column chromatography using silica gel as a carrier is adopted, examples of the eluting solvent include chromatographic form, ethyl acetate, methanol, acetone, and water. Can be used together.
  • examples of the carrier include a chemically bonded silica gel having an octadecyl group, an octyl group, a fuunyl group, etc. bonded thereto; a polystyrene-based porous polymer gel, and the like.
  • the mobile phase for example, hydrated methanol, hydrated acetonitrile
  • an aqueous solution of a water-soluble organic solvent such as toluene can be used.
  • the TKR 400 -A and TKR 400 -B of the present invention can be used in medicine as they are or as pharmacologically acceptable salts thereof.
  • the salt is not particularly limited as long as it is pharmacologically acceptable.
  • salts of mineral acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrofluoric acid, and hydrobromic acid
  • Salts of organic acids such as acetic acid, tartaric acid, lactic acid, citric acid, fumaric acid, maleic acid, succinic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, toluenesulfonic acid, naphthalenesulfonic acid, camphorsulfonic acid, etc.
  • Alkali metals such as sodium, potassium and calcium or salts of alkaline earth metals and the like.
  • the TKR400-A, TKR400-B of the present invention or a pharmacologically acceptable salt thereof is administered as a medicament
  • the TKR400-A, TKR400-B of the present invention is administered.
  • a pharmaceutically acceptable salt thereof, as it is, or in a pharmaceutically acceptable non-toxic and inert carrier, for example, 0.1 to 99.5%, preferably 0.5 to It is administered to animals containing humans as a pharmaceutical composition containing 90%.
  • the carrier examples include solid, semi-solid or liquid diluents, fillers, and other prescription auxiliaries. One or more of these can be used.
  • the pharmaceutical composition is preferably administered in the form of a dosage unit, and can be administered orally, intrathecally, topically (eg, transdermally), or rectally. Naturally, the above pharmaceutical composition is administered in a dosage form suitable for these administration methods.
  • the dose as an antifungal agent depends on the condition of the patient such as age and weight. , Administration route, the nature and extent of the disease, etc. It is desirable to adjust the above, but usually, for humans, the amount of the active ingredient of the present invention for adults is in the range of 1 to 200 mg per day. Dosages below the above range may be sufficient, while conversely, doses above the above range may be required. When administering large amounts, it is preferable to divide the dose into several doses. In addition, depending on the formulation, it is desirable to administer it once a week or once a week.
  • the above-mentioned oral administration can be carried out in solid, powder or liquid dosage units, for example, powders, powders, tablets, dragees, capsules, drops, sublinguals, other dosage forms, etc. .
  • Parenteral administration can be accomplished, for example, by using liquid dosage unit forms for subcutaneous, intramuscular, or intravenous injection, such as solutions and suspensions.
  • liquid dosage unit forms for subcutaneous, intramuscular, or intravenous injection such as solutions and suspensions.
  • These can be used for the TKR400-A, TKR400-B or a pharmacologically acceptable salt thereof according to the present invention, for example, in an aqueous or oily medium, for example, mineral oil ( It is manufactured by suspending or dissolving in a non-toxic liquid carrier suitable for the purpose of injection, such as incomplete Freund's adjuvant.
  • the above-mentioned topical administration can be carried out, for example, by using external preparations such as liquids, creams, powders, bases, gels, and ointments.
  • external preparations such as liquids, creams, powders, bases, gels, and ointments.
  • These can be used as the TKR400-A, TKR400-B of the present invention, or a certain amount of their pharmacologically acceptable salts, in a fragrance, colorant, or filling suitable for the purpose of the external preparation. It is manufactured by combining with one or more of agents, surfactants, humectants, emollients, gelling agents, carriers, preservatives, stabilizers and the like.
  • Rectal administration is performed by treating a certain amount of TKR 400-A, TKR 400-B or a pharmacologically acceptable salt thereof of the present invention with, for example, higher esters such as myristyl palmitate, Polyethylene glycol, cocoa butter, It can be carried out using a suppository mixed in a low melting point solid such as a mixture thereof.
  • BEST MODE FOR CARRYING OUT THE INVENTION is performed by treating a certain amount of TKR 400-A, TKR 400-B or a pharmacologically acceptable salt thereof of the present invention with, for example, higher esters such as myristyl palmitate, Polyethylene glycol, cocoa butter, It can be carried out using a suppository mixed in a low melting point solid such as a mixture thereof.
  • Example 1 Example 1
  • One platinum loop was obtained from the slant culture of TKR400 strain (FERMP-149927), and 100 ml of a liquid medium (Difcoyce Tonitogen base 0.67% (W / V), glucose 2.0% (W / V)) was inoculated into a 500 ml Erlenmeyer flask, and shaken at 25 ° C for 3 days to obtain a seed culture solution. 1.0 ml of this seed culture solution was inoculated into one 500 ml Erlenmeyer flask containing 100 ml of the above liquid medium, shaken for 25 days, and cultured for 8 days. r pm). The culture solution thus obtained was centrifuged and separated into a supernatant and cells.
  • the obtained supernatant was adsorbed on a Diaion HP20 (manufactured by Mitsubishi Chemical Corporation) column (1 L) which was made into a bite with water, and washed with 50% methanol. This was eluted with 3 L of methanol to obtain an active fraction.
  • a 50-type self-recording spectrophotometer (manufactured by Shimadzu Corporation) was used.
  • a 270-30 type infrared spectrophotometer (manufactured by Hitachi, Ltd.) was used.
  • Amino acid was detected by a ninhydrin reaction using L-850, manufactured by Hitachi, Ltd.
  • 'H- NMR dashed methanol in one le, standard: Te Torame Chirushira down
  • S C-NMR in deutero meta Nord, standard: heavy methanol
  • J NM A 5 A nuclear magnetic resonance apparatus (manufactured by JEOL Ltd.) was used.
  • the physicochemical properties of TKR 400 -A and TKR 400 -B are described below.
  • the ultraviolet absorption spectra of the obtained TKR 400-A and TKR 400-B are shown in FIGS. 1 and 6, respectively.
  • IR cm-R: 3450, 2970, 1680, 1640, 1550 30.14.0.120.20 , 1 1 5 0
  • IR (cnT: 3450, 3350, 2970, 1680, 1640, 1530, 1470, 1 4 1 0, 1 2 1 0, 1 1 4 0
  • the infrared absorption spectra of the obtained TKR400-A and TKR400-B are shown in FIGS. 2 and 7, respectively.
  • the purified TKR400- ⁇ and TKR400-B white powders which were obtained by high-performance liquid chromatography and concentrating the obtained active fractions under reduced pressure, were subjected to 'H-NMR It was subjected to a vector measurement and a 13 C-NMR spectrum measurement.
  • the 'H-NMR spectra of the obtained TKR 400 -8 and 1 ⁇ 1 ⁇ 400 —8 are shown in FIGS. 3 and 8, respectively, and the' 3 C-NMR spectrum is shown in FIG. Figures 4 and 9 show the results.
  • TKR 400-A and TKR 400-B obtained by high-performance liquid chromatography and concentrating the obtained active fractions under reduced pressure were treated with 6N hydrochloric acid. , I 10, for 24 hours. After decomposition, the product was analyzed by an amino acid analyzer. Lanin, balin, and isoleucine were detected in TKR400-B, and parin and isoleucine were detected.
  • TKR 400-A and TKR 400-B substances in various solvents is both soluble in methanol, but slightly soluble in chloroform, water and hexane. Met.
  • the purified white powder obtained by subjecting the obtained active fraction to high-performance liquid chromatography under reduced pressure is TKR400-A and TKR400-B. It has been found.
  • TKR400-A and TKR400-B were converted to reversed-phase high-performance liquid chromatograph (HPLC) using LC-10A type high-performance liquid chromatograph (manufactured by Shimadzu Corporation). Analysis.
  • HPLC reversed-phase high-performance liquid chromatograph
  • LC-10A type high-performance liquid chromatograph manufactured by Shimadzu Corporation.
  • the conditions for high performance liquid chromatography were as follows.
  • TKR400-A and TKR400-B antibacterial spectrum against various microorganisms was examined.
  • concentration that almost completely inhibited the growth of the bacteria was determined as the minimum growth inhibitory concentration (/ z gZml) by the liquid culture medium dilution method.
  • Table 2 shows the results.
  • the minimum concentration that partially inhibits bacterial growth was determined as the half-inhibitory concentration (gZml).
  • YNBG represents a medium containing 0.67% of yeast tonite trogen base (manufactured by Difco) and 1.0% of glucose.
  • the antifungal substances TKR 400-A and TKR 400-B of the present invention are antibacterial against pathogenic fungi such as Candida albicans, Candida kefir, and Cryptococcus neoformans. It was found to have activity.
  • TKR 400-A has a therapeutic effect on Aspergillus infection.
  • TKR 400-B A 10% solution of TKR 400-B in ethanol was thoroughly mixed with an equal volume of incomplete adjuvant adjuvant to give a water-in-oil formulation of 3.715 mg MgZkg.
  • C57BLZ6 mice female, 7-week-old, 5 mice per group, but only 6 mice in the control group
  • the mixture with Freund's adjuvant was similarly administered subcutaneously.
  • 1 ⁇ 10 s cells obtained by culturing Candida albicans TIMM1768 strain in a Sabouraud. Dextros liquid medium were inoculated into the tail vein of each mouse.
  • mice Seven days after the inoculation, the mice were dissected on the 7th day, both of the kidneys were aseptically removed, homogenized, and the viable cell count was determined using Sabouraud's dextrose agar medium. Table 4 shows the results. Table 4
  • TKR-400 OA and TKR-400B were administered intraperitoneally to ICR mice at 5 O mg / kg, respectively, but no toxicity was observed.
  • TKR400-A and TKR400-B which are useful as clinical drugs such as therapeutic agents for mycosis, and methods for producing them.

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Abstract

Cette invention se rapporte à de nouveaux antibiotiques utiles comme remèdes contre les infections fongiques, ainsi qu'à un procédé pour produire l'antibiotique TKR 400-A ou des sels de celui-ci pharmacologiquement acceptables, cet antibiotique ayant les propriétés physicochimiques suivantes: (1) il produit un spectre de masse ayant une crête de m/z 1273 [M+H]+ selon FAB-MS; (2) il produit dans le méthanol un spectre d'absorption des ultraviolets ayant des crêtes maximales aux longueurs d'ondes (nm) de 250 sh et 294, dont les valeurs de E1%1cm sont 96 et 20, respectivement; (3) il produit un spectre d'absorption des infrarouges par la méthode KBr qui possède des crêtes maximales aux nombres d'ondes de 3450, 2970, 1680, 1640, 1530, 1410, 1220 et 1150 cm-1; (4) la thréonine, l'alanine, la valine et l'isoleucine sont détectées lors de l'analyse de détection des acides aminés par la réaction de ninhydrine; et (5) il est soluble dans le méthanol mais il n'est guère soluble dans le chloroforme, l'eau et l'hexane.
PCT/JP1997/000094 1996-01-19 1997-01-20 Antibiotiques tkr 400-a et tkr 400-b et procedes de production de ces antibiotiques WO1997026367A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102012365A (zh) * 2010-10-27 2011-04-13 河北大学 一种基于红外光谱的茶叶发酵度识别方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH02138296A (ja) * 1988-07-19 1990-05-28 Takara Shuzo Co Ltd 新規抗生物質ｒ１０６及びその製造法並びに用途
JPH0445792A (ja) * 1990-06-11 1992-02-14 Takara Shuzo Co Ltd 新規抗性物質ｒ１９３０及びその製造方法

Patent Citations (2)

* Cited by examiner, † Cited by third party
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