GB2053895A - Aminoglycoside antibiotics and their production - Google Patents
Aminoglycoside antibiotics and their production Download PDFInfo
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- GB2053895A GB2053895A GB8011265A GB8011265A GB2053895A GB 2053895 A GB2053895 A GB 2053895A GB 8011265 A GB8011265 A GB 8011265A GB 8011265 A GB8011265 A GB 8011265A GB 2053895 A GB2053895 A GB 2053895A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/22—Cyclohexane rings, substituted by nitrogen atoms
- C07H15/222—Cyclohexane rings substituted by at least two nitrogen atoms
- C07H15/226—Cyclohexane rings substituted by at least two nitrogen atoms with at least two saccharide radicals directly attached to the cyclohexane rings
- C07H15/234—Cyclohexane rings substituted by at least two nitrogen atoms with at least two saccharide radicals directly attached to the cyclohexane rings attached to non-adjacent ring carbon atoms of the cyclohexane rings, e.g. kanamycins, tobramycin, nebramycin, gentamicin A2
- C07H15/236—Cyclohexane rings substituted by at least two nitrogen atoms with at least two saccharide radicals directly attached to the cyclohexane rings attached to non-adjacent ring carbon atoms of the cyclohexane rings, e.g. kanamycins, tobramycin, nebramycin, gentamicin A2 a saccharide radical being substituted by an alkylamino radical in position 3 and by two substituents different from hydrogen in position 4, e.g. gentamicin complex, sisomicin, verdamycin
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- 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
- C12N1/20—Bacteria; Culture media therefor
- C12N1/205—Bacterial isolates
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- 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
- C12P19/00—Preparation of compounds containing saccharide radicals
- C12P19/44—Preparation of O-glycosides, e.g. glucosides
- C12P19/46—Preparation of O-glycosides, e.g. glucosides having an oxygen atom of the saccharide radical bound to a cyclohexyl radical, e.g. kasugamycin
- C12P19/48—Preparation of O-glycosides, e.g. glucosides having an oxygen atom of the saccharide radical bound to a cyclohexyl radical, e.g. kasugamycin the cyclohexyl radical being substituted by two or more nitrogen atoms, e.g. destomycin, neamin
- C12P19/485—Having two saccharide radicals bound through only oxygen to non-adjacent ring carbons of the cyclohexyl radical, e.g. gentamycin, kanamycin, sisomycin, verdamycin, mutamycin, tobramycin, nebramycin, antibiotics 66-40B, 66-40D, XK-62-2, 66-40, G-418, G-52
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- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
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Abstract
Aminoglycoside antibiotics are produced by culturing a strain of Dactylosporangium thailandense in a suitable nutrient medium and isolating the thus-produced antibiotics as such or as a non-toxic acid addition salt. The antibiotics are effective against Gram negative bacteria. They are believed to have the following structure: <IMAGE>
Description
SPECIFICATION
Aminoglycoside antibiotics and their production
This invention relates to aminoglycoside antibiotics and their production using a strain of
Dactylosporangium thallandense.
According to the present invention there are provided aminoglycoside antibiotics G-367-1 (hereinafter called G-367-1) and G-367-2 (hereinafter called G-367-2) and non-toxic acid addition salts thereof; the antibiotic G-367-1 having the following properties:
melting point: 130 to 1330C., [24: +188.90 (c = 1.0, H20),
Elemental analysis: Found:C% = 50.14, H% = 7.60, N% = 14.42
Calculated: C% = 50.51, H% = 7.84, N% = 14.73,
Molecular weight: 475 (measured by mass spectrum),
Molecular formula: C20H37N508, Ultraviolet absorption spectrum: no characteristic maximum absorption peak at 220-360 nm, showing
only end absorption,
Infrared absorption spectrum (KBr): substantially as shown in Figure 1,
NMR spectrum (hydrogen nucleus): substantially as shown in Figure 2. (D20, 100 MHz, inner standard:
DSS),
Solubility: soluble in: water, methanol
insoluble in: acetone, benzene, ethyl acetate, chloroform,
Color reaction: positive: ninhydrin, decolorization of potassium permanganate,
negative:Elson-Morgan, Biuret,
Color: white powder, and
Nature: basic; and the antibiotic G-367-2 having the following properties:
melting point: 151 to 155 C., [α]D24: + 159.8 (c = 1.0, H2O),
Elemental analysis: Found: C% = 50.41, H% = 7.92, N% = 15.16,
Calculated: C% = 50.99, H% = 8.33, N% = 15.64, Molecular weight: 447 (measured by mass spectrum),
Molecular formula: C19H37N507, Ultraviolet absorption spectrum: no characteristic maximum absorption peak in water at 220360 nm, showing only end absorption.
Infrared absorption spectrum (KBr): substantially as shown in Figure 3,
NMR spectrum (hydrogen nucleus): substantially as shown in Figure 4. (D20, 100MHz, inner standard:
DSS),
Solubility: soluble in: water, methanol,
insoluble in: acetone, benzene, ethyl acetate, chloroform,
Color reaction: positive: ninhydrin, decolorization of potassium permanganate,
Negative: Elson-Morgan, Biuret,
Color: white powder, and
Nature: basic.
The present invention further provides a process for the production of the aminoglycoside antibiotics G-367-1 or G-367-2 or a non-toxic acid addition salt thereof, which process comprises culturing Dactylosporangium thailandense G-367 (FERM-P No. 4840) in a nutrient medium therefor and isolating the thus-produced antibiotic G-367-1 or G-367-2 as such or as a non-toxic acid addition salt.
G-367-1 is estimated to have the following formula:
As can be seen from Figure 1, G-367-1 has infrared absorption bands at 3350, 2920, 1660, 1590, 1380, 1140, 1100, 1050, 1000, 950 cm-1. Its NMR spectrum (carbon nucleus) (D20, 25 MHz, inner standard: dioxane) shows the following resonance positions:
No. p.p.m. No. p.p.m.
1 164.8 11 68.6
2 150.6 12 67.4 (dioxane)
3 101.4 13 64.2
4 98.1 14 51.7
5 96.3 15 50.1
6 87.8 16 45.5
7 85.3 17 43.3
8 75.3 18 37.8
9 73.2 19 36.3
10 70.2 20 23.4
21 22.5
When subjected to thin layer chromatography (silicagel), G-367-1 exhibits the following Rf values: lower layer of chloroform:methanol: 28% aq. ammonia (1 :1:1) Rf=0.36, 10% ammonium acetate: methanol (1 :1), Rf = 0.13.
G-367-2 is estimated to have the following formula:
G-367-2 has infrared absorption bands at 3350, 2920, 1650, 1540, 1470, 1350, 1140, 1100, 1050, 1020, 950 cm-l as shown in Figure 3. Its NMR spectrum (carbon nucleus) (D20, 25 MHz, inner standard: dioxane) shows the following resonance positions:
No. p.p.m. No. p.p.m.
1 149.5 11 67.4 (dioxane)
2 101.4 12 64.2
3 98.7 13 51.6
4 97.5 14 50.1
5 87.9 15 47.2
6 85.1 16 43.0
7 75.2 17 37.7
8 73.1 18 36.2
9 70.0 19 23.9
10 68.6 20 22.5
When subjected to thin layer chromatography (silica-gel): lower layer of chloroform:methanol:28% aq.
ammonia (1:1:1), Rf = 0.28, 10% ammonium acetate:methanol (1 :1), Rf = 0.10.
Certain of the physico-chemical properties of G-367-2, such as elemental analysis, molecular weight and molecular formula, resemble those of the known antibiotic sisomicin. However the Rf value of sisomicin on thin layer chromatography of chloroform:methanol:28% aq. ammonia (1:1:1) is 0.38, which is different from that of G-367-2.
The antimicrobial spectra (minimum inhibitory concentration, MIC) of G-367-1 and G-367-2 by the agar dilution method are as follows:
MIC (mcg/ml)
Test organisms G-367-1 G-367-2
Staphylococcus aureus ATCC 6538P 6.3 12.5
" " MS27 6.3 12.5
" " 0119 12.5 12.5
Staphylococcus epidermidis sp-al-l 1.6 1.6
Streptococcus pyogenes N.Y.5 6.3 6.3
Bacillus subtilus ATCC 6633 0.8 1.6
Escherichia coli NIHJ-JC2 1.6 3.1
" " W3630 1.6 1.6
" " W3630 RGN14 1.6 1.6
Citrobacter freundii GN346 1.6 3.1 Klebsiella pneumonia ATCC 10031 1.6 1.6
Salmonella enteritidis Gartner 1.6 3.1
Shigella sonnei E33 1.6 3.1
Proteus morganii 0239 3.1 6.3
Proteus rettgeri ACR 3.1 3.1
Enterobacter aerogenes 0655 1.6 1.6
Enterobacter cloacae GN336 1.6 1.6
Serratia marcescens 25 50 Pseudomonas aeruginosa IAM 1095 25 25
" " ML4561 25 125
" " ML4561 Rms166 > 100 > 100
ML4561 Rms 164-1 50 50 ML4561 RP4 12.5 6.3
" " 1946 > 100 > 100
" " 2512 > 100 > 100
Pseudomonas putida 1842 > 100 > 100
Pseudomonas maltophilia 1850 > 100 > 100
The antibiotics G-367-1 and G-367-2 have strong antibacterial effect against Gram negative bacteria, and can be used as non-toxic acid addition salts of organic or inorganic acids.
Examples of these salts are the hydrochloride, hydrobromide, sulfate, phosphate, carbonate, acetate, fumarate, malate, citrate, manderate, succinate, ascorbate, aspartate or glutamate.
The antibiotics G-,367-1 or G-367-2, or their non-toxic acid addition salts, may be employed as an active ingredient in pharmaceutical compositions also containing a pharmaceutically acceptable carrier or diluent. Preferably these compositions are injectable preparations, for example in the form of 2040 mg. vial or ampoule.
The G-367-1 and G-367-2 producing streptomyces strain G-367 was isolated from a soil sample obtained in Fuji-shi, Shizuoka-ken, Japan, and has been designated Dactylosporangium thailandense G-367. This strain was deposited at the Institute for Microbial Industry and Technology,
Japan, as FERM-P No. 4840 on 28th February, 1979.
The taxonomical properties of the strain are as follows.
[I] Morphological properties: Observations on calcium-malate agar[Bact. Rev., 21,1 (1957)] at 300C. for 3-7 days cultivation are as follows.
Substrate mycelium is curved or weavy, branched growth, non-fragmentation, 0.5-0.8 in diameter and no formation of aerial hyphae.
Globose or elliptical bodies of 1.5-2.0 x 2.0-2.5 y are formed on the substrate mycelium embedded in the agar medium.
Shortsporangiophore emerge from the substrate mycelium and singular or tuft finger-shaped sporangia are formed on the surface of the agar medium. The size of the sporangia is 1.0-1.5 x 4.6-6.5 y. Each sporangium contains a vertical single row of three to four spores. The spores are motile in water, with a globose, elliptical or pyriform shape, 1.0-1.5 x 1.5-2.5 iu in size, by polytrichous polar fiagella.
[II] Composition of diaminopimelic acid:
Meso-type and lower Rm value than meso-type (slow moving diaminopimelic acid) were detected by whole mycelial analysis.
[III] Growth on various media:
Observations of growth on various media at 30 C for 14 days are illustrated in the following
Table. Aerial mycelia are not formed except in a rudimentary form on oat-meal agar. Formation of sporangia is good on calcium malate agar, medium on soil agar [J. gen. Microbiol., 50, 295 (1968)], with slight or no formation on the other media.
Color indication is based on "Color Harmony Manual, 4th Ed. 1958" (Container Corporation of
America).
TABLE
Growth on various media
Medium growth Color of substrate mycelium Soluble pigment Sucrose-nitrate agar moderate to poor Apricot (4ia) to (Waksmann medium No. 1)* Dasty orange (4ic) None Glucose-asparagine agar poor Brite Melon Yellow " (Waksmann medium No. 2)* (3ia) to Apricot (4ia) Glycerin-asparagin agar little to poor colorless to Light Melon " (ISP medium No. 5) * Yellow (3ea) Starch-inorganic agar moderate to good Russet Orange (4nc) " (ISP medium No. 4) ** Dasty orange to (4ic) Tyrosine agar little to poor Apricot (4ga) to (ISP medium No. 7 ) ** Pale Paster Orange (4ic) " Oat meal agar moderate to good Orange Rust (4pe) to " (ISP medium No. 3) ** Russet orange (4pc) Yeast extract-malt extract agar " Maple (4ie) to Maple (4ie) (ISP medium No. 2) ** Luggage Tan (4ne) to Light Brown (4ng) Calcium-malate agar poor colorless none Nutrient agar little (Waksmann medium No. 14) * " " Benett agar moderate to good Maple (4ie) to Luggage Maple (4ie) to (Waksmann medium No. 30) * Tan (4ne) Light Brown (4ng) Emarson agar moderate Pastel Orange (4ic) to Maple Maple (4ie) Waksmann medium No. 28) * (4ie) TABLE (continued)
Medium Growth Color of substrate mycellium Soluble pigment Hickey and Tresner agar moderate to good Cinnamon (3ie) to Maple (4ie) Maple (4ie) to (Waksmann medium No. 32 * Light Spice Brown (4ig) Glucose-yeast extract agar melon yellow (3ga) none (Waksmann medium No. 29) * moderate Peptone-yeast extractferrous agar (IPS medium No. 6) ** colorless " Soil agar little to poor " " Potato stabb Red (5ne) to (Waksmann medium No. 40) * moderate Copper (5ic) " Potato stabb + calcium carbonate " " " Carrot stabb little colorless " * Waksmann. S.A. "The Actinomycetes" Vol. 12, 1961, p. 327-334 Williams & Wilkins Co.
** Inter. J. Syst. Bact. 16:313-340 (1966) *** Antimicrob. Agents and Chemother. 1963 p. 116-124.
1) Utilization of carbon sources:
Carbon source P @ G* Lm**
D-arabinose + +
L-arabinose + +
D-fructose + +
D-galactose + +
D-glucose + +
glycerol - - i-inositole - - D-mannose + +
D-mannitol + + α-melibiose + +
ss-lactose + # dulcitol -
D-toreharose + +
D-cellobiose + +
meleditose + +
raffinose +
L-rhamnose + +
D-ribose -
L-sorbose - D-sorbitol - - sucrose + +
D-xylose + +
adonitol -
salicin + to + + to +
starch + +
maltose + +
dextrin + +
inulin - +: positive +: weakly positive -: negative
*Pridham-Gotlieb inorganic medium **Inter. J. Syst.Bact., 21,240-247 (1971)
2) Growth temperature: 2O-400C 3) Peptonization and coagulation of skim milk: positive
4) Formation of melanin-like pigment: negative on tyrosine and peptone-yeast extract-ferrous agar.
5) Starch hydrolysis: positive 6' Cellulose decomposition: negative 7) Casein decomposition: positive
8) Tyrosine decomposition: negative
9) Gelatin liquefaction: positive 10) H2S formation: weakly positive 11) Nitrate reduction: positive 12) Growth pH: 5.5-9.0 As illustrated above, the characteristics of strain G-367 are finger-shaped sporangia grown on substrate mycelium, a vertical single row of spores for each sporangium, and polytrichous polar flagella on each spore. Sporangia containing polytrichous flagella belong to the genusActinoplanaceae, and among them, finger-shaped sporangia having a vertical single row of spores belong to the genus
Dactylosporangium.As the strain G-367 shows orange-brown to brown colored substrate mycelium and brown soluble pigment, the strain is referred to Dactylosporangium thailandense [Ach. Microbial., 58, 42-52 (1967)]. Therefore the strain is designated as Dactylosporangium thallandense G-367.
The antibiotics G-367-1 and G-367-2 can be produced by aerobically cultivating a G-367-1 or G-367-2 producing strain belonging to genus Dactylosporangium in a conventional medium. Solid or liquid media can be used, and for large scale production liquid medium is preferable.
Conventional nutrient medium for microorganisms can be used, containing assimilable carbon sources such as glucose, sucrose, maltose, starch, dextrin or molasses and assimilable nitrogen sources such as corn steep liquor, soy bean powder, cotton seed powder, wheat gluten, peptone, meat extract, yeast extract, casein hydrolysate, ammonium salt or nitrate. Phosphate and salts of magnesium, calcium, potassium, sodium, cobalt, ferrous or manganese can be added to the medium as required.
The cultivation temperature depends on the growth of the microorganisms and production of antibiotics. Preferably the temperature is from 25 to 350C. Cultivation time depends on the conditions and usually from 100 to 200 hours. Cultivation is terminated when the maximum potency of the antibiotics in the medium has been reached.
The antibiotics are produced in the culture filtrate. Isolation of G-367-1 and G-367-2 can be by conventional isolation methods for water-soluble basic aminosugar antibiotics.
G-367-1 and G-367-2 can be assayed on agar plate using Bacillus subtilis as test organisms.
One technique of isolating and purifying G-367-1 and G-367-2 is as follows:
A filtrate is obtained by adjusting the culture medium to an acidic pH, neutralizing the medium and then filtering. The filtrate is charged on a column of a cation exchange resin, such as Amberlite lRC-50 (NH+4 type) [AMBERLITE is a Registered Trade Mark], to absorb active substance. The active substance is eluted by 2 N aqueous ammonia and concentrated. The pH of the eluafe is adjusted. The concentrate is charged on a column of a cation exchange resin, such as CM-Sephadex C-..25 (NH+ type) [SEPHADEX is a Registered Trade Mark], eluted with aqueous ammonia having a concentration varying from 0 to 0.35 N to obtain active fractions.Each active fraction was concentrated and lyophylized to obtain G-367-1 and G-367-2 as purified white powder, free base. The thus-obtained G-367-1 and G-367-2 showed a single spot when subjected to thin layer chromatography.
The following Examples illustrate the invention. Throughout the description and claims, percentages are by weight.
EXAMPLE 1
A medium (pH 7.0, 100 ml) containing dextrin 1%, glucose 1%, casein hydrolysate 0.5%, yeast extract 0.5% and calcium carbonate 0.1% in 500 ml-Erlenmeyer flask was sterilized at 1 2O0C for 20 minutes. One loopful of Dactylosporangium thailandense G-367 in agar slant medium was inoculated in to this sterilized medium and shake cultured at 300C for 120 hours. This seed culture was inoculated in to a sterilized medium of the same composition (20 1.) in a 30 1. Jar-fermenter and cultured at 30 C for 72 hours at 300 r.p.m., 20 1./min. aeration.The said cultured medium (10 1.) was inoculated in to a sterilized medium containing dextrin 5%, defatted soy bean powder 3%, glucose 0.5% calcium carbonate 0.7% and cobalt chloride 1.3 ppm (pH 7.2, 200 1.) in a 250 1. tank and cultured at 300C for 120 hours at 250 r.p.m., aeration rate 1001./mien. to obtain 190 I. of cultured medium.
EXAMPLE 2
Cultured medium obtained in Example 1 was adjusted to pH 2 by adding 1 2 N sulfuric acid and stirred for 30 minutes. The stirred medium was adjusted to pH 7.0 by adding concentrated aqueous ammonia and filtered after the addition of the filter-aid "Perlite" (4 kg). The filtrate was charged on a column of Amberlite lRC-50 (Rohm and Haas Co:) (NH+4 type, 10 1.), and eluted with 2 N aqueous ammonia (20 1.) after washing with water. The eluate was concentrated in vacuo to 100 ml Volume.
The concentrate was adjusted to pH 7.0 by adding 6 N sulfuric acid and was charged on a column of CM-Sephadex G-25 (Pharmacia Fine Chem. Co.) NH+4 type, 500 ml, diameter 4 cm). After washing with water, the active substances were eluted by gradient elution with aqueous ammonia (5 1.) of 0--0.35 N concentration gradient. Each fraction was checked by thin layer chromatography using a lower layer of chloroform:methanol:28% aqueous ammonia (1 :1:1). The presence of an active substance was confirmed by ninhydrin coloring. G-367-1 was found in fractions no. 1 75 to 185.
These fractions were combined, concentrated in vacuo and freeze dried to obtain a white powder. This powder was dried at 40 C for 48 hours over phosphorus pentoxide under reduced pressure to yield purified G-367-1 as a white powder (free base, 750 mg).
G-367-2 was found in fractions no. 190 to 205. These fractions were combined, concentrated in vacuo and freeze dried to obtain a white powder. The powder was dried at 400C for 48 hours under reduced pressure to yield purified G-367-2 as a white powder (free base, 680 mg).
Claims (8)
1. Aminoglycoside antibiotics referred to herein as G-367-1 and G-367-2, and non-toxic acid addition salts thereof;
the antibiotic G-367-1 having the following properties:
melting point: 130 to 1 330C., [(t]D4 +188.90 (e = 1.0,H20) Elemental analysis: Found: C% = 50.14, H% = 7.60, N% = 14.42
Calculated:C% = 50.51, H% = 7.84, N% = 14.73,
Molecular weight: 475 (measured by mass spectrum),
Molecular formula: C20H3,NsOyl Ultraviolet absorption spectrum: no characteristic maximum absorption peak at 220-360 nm, showing
only end absorption,
Infrared absorption spectrum (KBr): substantially as shown in Figure 1,
NMR spectrum (hydrogen nucleus): substantially as shown in Figure 2. (D20, 100 MHz, standard: DSS),
Solubility: soluble in: water, methanol,
insoluble in: acetone, benzene, ethyl acetate, chloroform,
Color reaction: positive: ninhydrin, decolourization of potassium permanganate,
negative:Elson-Morgan, Biuret,
Color: white, and
Nature: basic; and
the antibiotic G-367-2 having the following properties:
melting point: 151 to 1 550C., [α]D24: + 1 59.80 (c = 1.0, H20),
Elemental analysis: Found: C% = 50.41, H% = 7.92, N% = 15.16,
Calculated: C% = 50.99, H% = 8.33, N% = 15.64,
Molecular weight: 447 (measured by mass spectrum),
Molecular formula: C1gH3,NsO" Ultraviolet absorption spectrum: no characteristic maximum absorption peak at 220-360 nm, showing
only end absorption,
Infrared absorption spectrum (KBr): substantially as shown in Figure 3,
NMR spectrum (hydrogen nucleus): substantially as shown in Figure 4 (D20, 100 MHz, standard:DSS)
Solubility: soluble in: water, methanol,
insoluble in: acetone, benzene, ethyl acetate, chloroform,
Color reaction: positive: ninhydrin, decolorization of potassium permanganate,
negative: Elson-Morgan, Biuret,
Color: white, and
Nature: basic.
2. A process for the production of the aminoglycoside antibiotics G-367-1 or G-367-2 as defined in claim 1 or a non-toxic acid addition salt thereof, comprising culturing Dactylosporangium thailandense G-367(FERM-P No. 4840) in a nutrient medium therefor and isolating the thusproduced antibiotic G-367-1 or G-367-2 as such or as a non-toxic acid addition salt.
3. A process according to claim 2 substantially as hereinbefore described with reference to
Examples 1 and 2.
4. A pharmaceutical composition comprising, as active ingredient, antibiotic G-367-1 or G-367-2 as defined in claim 1 or a non-toxic addition salt thereof, together with a pharmaceutically acceptable carrier or diluent.
5. A pharmaceutical composition according to claim 4 which is in the form of an injectable preparation.
6. A culture of the microorganism Dactylosporangium thailandense G-367(FERM-P No. 4840) in a culture medium containing a source of assimilable carbon, a source of assimilable nitrogen and, as appropriate, mineral elements, and substantially free from other microorganisms.
7. A process for the growth of the microorganism Dactylosporangium thailandense G-367(FERM-P No. 4840), which process comprises culturing said microorganism in a nutrient medium therefor.
8. Dactylosporangium thailandense G-367(FERM-P No.4840).
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4127479A JPS55133394A (en) | 1979-04-04 | 1979-04-04 | Novel aminosaccharide antibiotic g-367-1 and its preparation |
| JP10514079A JPS5629598A (en) | 1979-08-18 | 1979-08-18 | Novel amino sugar antibiotic g-367-2 and its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB2053895A true GB2053895A (en) | 1981-02-11 |
| GB2053895B GB2053895B (en) | 1983-03-16 |
Family
ID=26380841
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB8011265A Expired GB2053895B (en) | 1979-04-04 | 1980-04-03 | Aminoglycoside antibiotics and their production |
Country Status (2)
| Country | Link |
|---|---|
| CA (1) | CA1140877A (en) |
| GB (1) | GB2053895B (en) |
-
1980
- 1980-04-03 CA CA000349243A patent/CA1140877A/en not_active Expired
- 1980-04-03 GB GB8011265A patent/GB2053895B/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| GB2053895B (en) | 1983-03-16 |
| CA1140877A (en) | 1983-02-08 |
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