JPH09124503A - Antimicrobial composition for injection of amythiamicins - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a new antimicrobial composition for an injection containing a slightly water-soluble amythiamicin, useful as an antimicrobial agent, as an antimicrobial active ingredient. SOLUTION: This antimicrobial composition is obtained by emulsifying fine fatty particles containing an amythiamicin and oils and fats in an aqueous phase and is in a form of a stably dispersed emulsion. The composition, for example, has 1-30 (weight/volume) concentration of oils and fats, can contain a phospholipid as an emulsifying agent, optionally an emulsion stabilizer such as a higher fatty acid or an acidic phospholipid and, if necessary, a dissolution auxiliary for amythiamicin in oils and fats, a buffering agent, a disinfectant, an osmotic pressure adjustor, etc. The emulsion can be dehydrated by freeze-drying method into a form of powder. The powder is redissolved in water and pharmaceutically manufactured into an injection.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a highly stable antibacterial composition for injection, which is in the form of an oil-in-water emulsion containing amithiamycins as an antibacterial active ingredient. The composition of the invention can be used as an injectable antimicrobial formulation.

Amythiamicin A, B,
C and D are MI481-42F4 belonging to the genus Amycolatopsis
It is an antibacterial antibiotic produced by culturing a strain (deposited as FERM P-12739) and is a cyclic peptide that is sparingly soluble in water ("Journal of Antibiotics").
Volume 47, No. 6, 668-674 (1994), No. 10, 1145-
1159 (1994) and 48, No. 2, 182-184 (1995),). Amitiamycin A is disclosed in
-310766 is described in the name of antibiotic MI481-42F4-A. As an antibacterial substance obtained by decomposing this MI481-42F4-A substance in dilute hydrochloric acid, etc., an antibacterial substance MI481-42F4-
A1, -A2 and -A3, or salts thereof are disclosed in JP-A-6-26.
It is described in Japanese Patent No. 3784. In addition, the above-mentioned MI481-42F4-A
The antibacterial substance MI is obtained by subjecting the substance to decomposition such as methanolysis and further esterification if desired.
481-42F4-B1, -B2 and -B3 are described in JP-A-7-215989.

Amitiamycins A to D, as well as the above
MI481-42F4-A1-A3 and -B1-B3 substances are all cyclic peptides that are sparingly soluble in water and have antibacterial activity, and are collectively referred to as "amithiamycins" in the present specification. Amitiamycins are expected to be useful as medical antibacterial agents, particularly as effective antibacterial agents against drug-resistant Staphylococcus aureus (MRSA). However, amithiamycins
Since it is sparingly soluble in water, it was difficult to formulate it as an antibacterial agent composition that can contain amithiamycins at an antibacterial effective concentration and can be used in medicine.

On the other hand, fat-soluble vitamins and peptide drugs,
For example, various formulation ideas for formulating a poorly soluble drug such as cyclosporin A into an aqueous solution have been studied. For example, a liposome preparation is known in which a drug is contained in a liposome prepared from a lipid containing a phospholipid as a main component. A formulation method using a fat emulsion is also useful.

Further, in order to prepare a poorly water-soluble drug as an injectable preparation, a method of solubilizing the poorly water-soluble drug in water by incorporating a nonionic surfactant is generally used. For example, fat-soluble vitamins are widely formulated in injectable formulations as an aqueous solution solubilized in water by blending a surfactant. In this case, as the surfactant to be added to the injection, a polyoxyethylene castor oil derivative, a polyoxyethylene hydrogenated castor oil derivative, which is a nonionic surfactant having low hemolytic and tissue damage properties,
Polyoxyethylene sorbitan fatty acid esters or polyoxyethylene polyoxypropylene glycols are commonly used. Of these surfactants,
Since polyoxyethylene castor oil derivatives and polyoxyethylene hydrogenated castor oil derivatives are known to cause anaphylactic shock upon injection in some patients, it is desirable to avoid their use. In addition, amitiamycin is a substance that is very difficult to solubilize as a micelle in water even in the presence of a surfactant, and when mixed with polyoxyethylene sorbitan fatty acid esters and polyoxyethylene polyoxypropylene glycols, it does not dissolve in water. Cannot be solubilized.

[0006] Recently, resistant Staphylococcus aureus (MRSA) infection, which has recently become a problem, is a fatal disease for patients with weakened immunity caused by nosocomial infection, and is used for treatment of these severely ill patients. Therefore, there has been a demand for a preparation capable of administering an antibacterial agent effective against MRSA by injection. Therefore, a bactericidal composition of amithiamycins, which can contain amithiamycins as an antibacterial active ingredient at a sufficiently high concentration effective for MRSA, has high safety for administration to patients, and can be administered by injection, is created. Is desired.

[0007]

Means for Solving the Problems The present invention has been earnestly studied in order to provide a novel antibacterial composition for injection which is highly safe and can contain amitiamycins, which are poorly soluble in water, as an active ingredient in a sufficient concentration. The result is a homogeneous mixture of amithiamycins, pharmaceutically acceptable liquid oils and fats such as triglycerides, and pharmaceutically acceptable emulsifiers such as egg yolk lecithin, which is then added to water in the form of fine particles. If amythiamycins are prepared in the form of an oil-in-water emulsion prepared by emulsification and dispersion and having the emulsifier dissolved in water, the amythiamycins can be contained at a sufficient concentration. It has been found that an antibacterial composition in the form of an oil-in-water emulsion, which has good stability of mycins and can be safely administered by injection, can be obtained. The present invention has been completed based on these findings.

[0008] Therefore, according to the present invention, in the form of an emulsion in which fat fine particles consisting of a homogeneous mixture of amythiamycins, a liquid oil and fat and an emulsifier as an antibacterial active ingredient are dispersed in an aqueous phase, Also provided is an antibacterial composition for injection of amitiamycins in the form of an emulsion, characterized in that an emulsifier having a function of stably dispersing the fat fine particles is dissolved in the aqueous phase. To be done.

The preparation of the antibacterial composition in the form of an emulsion according to the invention generally involves the required amount of amitiamycins being well mixed or dissolved in a pharmaceutically acceptable liquid oil and fat, and then , To the oily mixture obtained by adding a pharmaceutically acceptable emulsifier having the action of dispersing oil particles in the aqueous phase, and further uniformly dispersing in oils and fats well mixed amythiamycins And a fat and an emulsifier and a homogeneous mixture is prepared, and the homogeneous mixture is emulsified and dispersed in an appropriate amount of water to form an oil-in-water emulsion, which is simply carried out. it can.

The amithiamycins to be added to the composition of the present invention are the above-mentioned amithiamycins A to D, the above-mentioned antibacterial substances MI481-42F4-A1 to A3, and the antibacterial substance MI48.
It can be a substance of any one of 1-42F4-B1 to B3 or salts thereof, or a mixture of two or more thereof.

The fats or oils in which amithiamycins are dissolved or mixed therewith can be vegetable oils such as soybean oil, safflower oil, corn oil, olive oil, sesame oil, peanut oil, cottonseed oil, rapeseed oil and coconut oil, and also caprin. It is possible to use synthetic fatty acid triglycerides such as medium chain fatty acid triglycerides such as acid triglycerides and caprylic acid triglycerides. From the viewpoint of the solubility or miscibility of fats and oils with amithiamycins, it is preferable to use a glyceride of a medium-chain fatty acid having 8 to 12 carbon atoms. Further, two or more kinds of fats and oils may be mixed and used for the purpose of improving solubility or miscibility of fats and oils with amithiamycins. These fats and oils used for mixing are preferably liquid at room temperature (about 10 to 30 ° C.), for example, triglycerides of saturated or unsaturated fatty acids having 9 to 75 carbon atoms. The amount of the oil / fat used varies depending on the type of the oil / fat, but is usually 1 part by weight or more, preferably 5 parts to 2 parts, relative to 1 part by weight of the amithiamycins.
It is 00 parts (weight). The amount of fats and oils in the emulsion forming the composition of the present invention is 1 to 30% based on the volume of the entire composition.
It can be in the range of (weight / volume).

The emulsifier to be blended with fats and oils together with amithiamycins is an emulsifier having a function of dispersing and emulsifying fat and oil particles in an aqueous phase, and any emulsifier that can be used for medicine can be used. However, the emulsifier is usually a naturally-occurring phospholipid whose main component is phosphatidylcholine. As the phospholipid, a naturally-derived phospholipid such as egg yolk phospholipid or soybean phospholipid purified for injection, or a hydrogenated phospholipid or a synthetic phospholipid thereof is used.
The emulsifier is preferably egg yolk lecithin. The addition amount of these phospholipids is 0.01 to 2 parts by weight with respect to 1 part by weight of oil and fat,
It is preferably 0.1 to 1.5 parts by weight.

An emulsion stabilizer may be added to the aqueous phase of the emulsion forming the composition of the present invention. The emulsion stabilizer is preferably a middle to higher fatty acid having an action of preventing the aggregation and coalescence of the fatty fine particles dispersed in the aqueous phase, and is not particularly limited as long as it can be used for medicine. . Usually, examples of the emulsion stabilizer include saturated or unsaturated fatty acids having 8 to 24 carbon atoms, preferably 10 to 20 carbon atoms. Examples of these fatty acids include myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, and linolenic acid. These compounds also have the effect of improving the solubility of amythiamycins in fats and oils, and the compounding of these compounds is preferred.

The above-mentioned fatty acid to be incorporated as an emulsion stabilizer can also be incorporated into a uniform mixture of amitiamycins, fats and oils and an emulsifier, in which case the homogeneous mixture is added to the aqueous phase. When it is dispersed as fine particles in, the fine dispersed particles are dissolved in the water phase together with the emulsifier and dissolved in the water phase.

The amount of these fatty acids added as an emulsion stabilizer is 0.1% to 40% (weight / weight), preferably 0.2% to 20% (weight / weight), based on the oil and fat, usually.
It is about 0.3% to 10% (weight / weight).

Acid phospholipids can also be used as an emulsion stabilizer, and naturally occurring acid phospholipids and synthetic phospholipids are used. As acidic phospholipids, phosphatidic acid,
Phosphatidyl glycerol, phosphatidyl serine,
Examples include phosphatidylinositol, which is added in an amount of 0.1% to 50% of the phospholipid used as the emulsifier.
(Weight / weight), preferably 0.5-20% (weight / weight)
Of the degree. The amount of solubilizer and emulsion stabilizer added is
Generally, both combined, 0 to 20% (weight / volume), preferably 0 to 10%, based on the total volume of the composition of the present invention.
The range is (weight / volume).

The amount of water in the composition of the present invention forms a continuous phase of water in which the liquid dispersion particles containing amitiamycins dispersed in the emulsion forming the composition can be stably dispersed therein. The amount may be sufficient, and generally, it may be in the range of 70 to 95% (volume / volume) based on the volume of the entire composition.

In addition to the above components, the composition of the present invention may also contain other medicinal auxiliaries. Examples of these auxiliary additives include solubilizing agents for amythiamycins in fats and oils, pH adjusting agents, pH buffering agents, osmotic pressure adjusting agents, preservatives and the like.

Aromatic carboxylic acids and their esters can be used as solubilizing agents for the amythiamycins in the above oils and fats. For example, benzoic acids (benzoic acid and hydroxybenzoic acid having 1 to 2 hydroxyl groups, etc.)
Further, ester derivatives of their carboxyl groups and lower alcohols (C1-4) and ester derivatives of their hydroxyl groups and lower fatty acids (C1-3) can be used. The addition amount of these is usually 0.05 to 2 parts by weight, preferably 0.1 to 2 parts by weight with respect to 1 part by weight of amitiamycins.
1 part by weight. This amithiamycin-type solubilizing agent can be incorporated in a uniform mixture of amythiamycins, fats and oils and an emulsifier to be dispersed in the aqueous phase of the emulsion forming the composition of the present invention.

As the pH adjusting agent and the pH buffering agent, physiologically safe acids and bases usually used in injections can be used and can be incorporated in the aqueous phase of the emulsion of the present invention. As this example, inorganic acids such as hydrochloric acid, sulfuric acid and phosphoric acid, organic acids such as citric acid and alkali metal salts thereof are used. The pH to be adjusted is not limited as long as it is physiologically acceptable, but it is preferably pH 5 to 9 in order to maintain safety and emulsion stability, and generally p
H6-8.

As the osmotic pressure adjusting agent, physiologically safe salts, sugars and sugar alcohols are used. In order to maintain the stability of the composition of the present invention, sugars such as glucose, sugar alcohols such as mannitol, polyhydric alcohols such as glycerin, and nonionic substances such as C _{2 to} C ₄ lower alcohols are preferable. These may be added in an amount necessary to maintain the osmotic pressure of the composition of the present invention at a physiologically safe osmotic pressure. Usually, when the osmotic pressure of physiological saline is 1, 0.7 or more, preferably Is an amount sufficient to provide the concentration specific to the osmotic pressure adjusting agent required to obtain an osmotic pressure corresponding to 0.7 to 4 values.

Other medicinal auxiliaries include antioxidants and preservatives. In particular, when fats and oils containing unsaturated bonds are used, fat-soluble antioxidants such as vitamin Es, butylhydroxytoluene, and butylhydroxyanisole can be added as antioxidants for the purpose of preventing the fats and oils from being oxidized. The amount of these antioxidants added is usually 0.0001 to 0.01 part by weight per 1 part by weight of the fat or oil. Further, in order to prevent changes due to oxidation of lipids, the atmosphere in the container containing the composition of the present invention may be replaced with an inert gas such as nitrogen gas.

Since amitiamycins are poorly soluble in water,
During long-term storage, crystals of amitiamycins may precipitate in the aqueous phase of the emulsion forming the composition of the present invention. In order to prevent this crystal precipitation, a physiologically safe polar organic solvent such as ethanol or glycerin can be added to the above aqueous phase. The amount of the polar organic solvent such as ethanol added may be 20% (weight / volume) or less, preferably 1 to 10% (weight / volume) based on the total volume of the composition of the present invention.

Next, the method for producing the composition of the present invention will be described in detail. The step of forming a uniform mixture of amythiamycins, fats and oils and an emulsifier may be carried out at room temperature, but it is usually preferably carried out by heating to about 30 ° C to 80 ° C. In the case of using amithiamycin-type solubilizing agents, emulsion stabilizers, preservatives, etc., it is preferable to preliminarily mix them in the oil or fat, but in some cases, even if they are added later to the above mixture. Good. Alternatively, once these components to be blended are completely mixed with a mixed solvent such as chloroform-methanol (the weight ratio of each solvent is 1: 2 to 10: 1, preferably 1: 1 to 4: 1). After dissolution, the solvent is distilled off to obtain a uniform mixture of the components to be blended.

Usually, amythiamycins are first dissolved in or mixed with fats and oils, and an emulsifier is added to the resulting mixture of amythiamycins and fats (or fat and oil solution), if desired. It is convenient to add, thoroughly mix, and evenly mix with the components to be additionally blended. At this time, the emulsifiers may be mixed at room temperature or warming. A homogeneous mixture of amitiamycins thus prepared, fats and oils and emulsifiers, and optionally other ingredients additionally added, is added to water and emulsified in an emulsifier to obtain an aqueous phase. It can be dispersed as fine fat particles. A homogenizer, a homomixer, etc. are suitable as an emulsifier to be used.

In order to prepare an emulsion that can be administered as an injection, it is necessary that the dispersed particles dispersed in the aqueous phase have a fine particle size. Therefore, Manton Gorin (registered trademark) type homogenizer or micro It is preferable to emulsify using a high-pressure emulsification device such as Fildiizer (registered trademark). When carrying out the emulsification step of dispersing a uniform mixture of amitiamycins, oils and fats and emulsifiers, and other components additionally compounded in the aqueous phase as finely dispersed particles, water is removed from the particles of the mixture. The at least part of the water-soluble emulsifier and other water-soluble components are dissolved and dissolved in the aqueous phase. The particle size of the amythiamycin-containing fatty particles dispersed in the aqueous phase of the obtained emulsion is preferably in the range of 0.01 to 1 μm in order to maintain safety when injected. The average particle size of the particles is particularly preferably in the range of 0.4 μm or less. The obtained emulsified liquid can be used to remove solid foreign matter using a membrane filter. Further, the filtered emulsion may be filled in a sterilized container, sealed, and then sterilized by high-pressure steam.

As mentioned above, a uniform mixture of amitiamycins, fats and oils and emulsifiers and optionally other ingredients additionally compounded is added to water to emulsify and disperse finely divided particles in the aqueous phase. As an oil-in-water type emulsion (emulsion) was prepared by dissolving at least a part of the water-soluble components in the aqueous phase during the emulsification process. Can be formulated into a lyophilized powder by dehydration using a conventional lyophilization method.

Therefore, in another aspect of the present invention, there is provided an emulsion in which fat fine particles composed of a homogeneous mixture of amythiamycins, a liquid oil and fat and an emulsifier as an antibacterial active ingredient are dispersed in an aqueous phase. And a powder obtained by freeze-drying the emulsified liquid in which an emulsifier is dissolved in the aqueous phase of the emulsified liquid, which is redispersed and dissolved in water when used as an injection. An injectable antimicrobial composition of amitiamycins in the form of a lyophilized powder is provided.

In this antibacterial composition in the form of a lyophilized powder, the amount of water can generally be 0.01% to 5% (weight / volume), based on the volume of the whole composition,
Preferably 0.1-2% (weight / volume), most commonly
It is preferably about 0.2 to 1% (weight / volume).

[0030]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be further described below with reference to examples, but the present invention is not limited to these examples.

Example 1 Amitiamycin A was dissolved in a mixed solvent of chloroform-methanol (2: 1) to a concentration of 10 mg / ml. After taking 2 ml of the obtained solution and distilling off the solvent, 20 g of soybean oil and 2.4 g of egg yolk lecithin were added to the residue.
Was added, and these components were uniformly mixed and homogenized with a homogenizer to obtain a uniform mixture.

150 ml of distilled water for injection and 5 g of glycerin were added to the obtained homogeneous mixture and emulsified with a homogenizer. The obtained emulsion (emulsion) is prepared by adding an appropriate amount of an aqueous solution of hydrochloric acid or sodium hydroxide.
The pH was adjusted to 6.8. Distilled water for injection was added to the obtained emulsion to dilute it to obtain an emulsion having a total volume of 180 ml. Further, the mixture was filtered through a membrane filter (pore size 0.8 μm), the filtered emulsion was placed in a container and the atmosphere was replaced with nitrogen gas, and the container was sealed.

Example 2 Amitiamycin A was dissolved in a mixed solvent of chloroform-methanol (2: 1) to a concentration of 10 mg / ml. After taking 2 ml of the obtained solution and distilling off the solvent, 20 g of soybean oil and 2.4 g of egg yolk lecithin were added to the residue.
Further, 0.25 g of oleic acid was added, and these components were uniformly mixed and homogenized with a homogenizer to obtain a uniform mixture.

170 ml of distilled water for injection and 5 g of glycerin were added to the obtained homogeneous mixture, and the mixture was subjected to primary emulsification with a homogenizer. The obtained emulsion was further subjected to secondary emulsification with a high pressure emulsifying device. The pH of the emulsion obtained here is adjusted by adding an appropriate amount of an aqueous solution of hydrochloric acid or sodium hydroxide.
Adjusted to 6.7. Distilled water for injection was added to the obtained emulsion to dilute it to give an emulsion having a total volume of 180 ml. Further, the mixture was filtered through a membrane filter (pore size 0.8 μm), and the filtered emulsion was placed in a container and replaced with nitrogen gas and sealed.

Example 3 Amitiamycin A was dissolved in a mixed solvent of chloroform-methanol (2: 1) to a concentration of 10 mg / ml. After taking 2 ml of the obtained solution and distilling off the solvent, 20 g of soybean oil and 2.4 g of egg yolk lecithin were added to the residue.
Was added, and these components were uniformly mixed and homogenized with a homogenizer to obtain a uniform mixture.

170 ml of distilled water for injection was added to the obtained homogeneous mixture.
ml and 5 g of glycerin were added, and the mixture was further emulsified with a homogenizer. The obtained emulsion was further subjected to secondary emulsification with a high pressure emulsifying device. The emulsion was adjusted to pH 6.8 by adding an appropriate amount of an aqueous solution of hydrochloric acid or sodium hydroxide, and the obtained emulsion was diluted with distilled water for injection to make an emulsion having a total volume of 180 ml. Further, it was filtered with a membrane filter (pore size 0.8 μm). The filtered emulsion was placed in a sterilized container for injection, which was replaced with nitrogen gas and sealed.

Example 4 Amitiamycin A was dissolved in a mixed solvent of chloroform-methanol (2: 1) to a concentration of 10 mg / ml. After taking 2 ml of the obtained solution and distilling off the solvent, 20 g of soybean oil and 2.4 g of egg yolk lecithin were added to the residue.
Was added, and these components were uniformly mixed with a homogenizer to obtain a uniform mixture.

To the above-obtained homogeneous mixture, 150 ml of distilled water for injection and 5 g of glycerin were added, and the mixture was subjected to primary emulsification with a homogenizer. The obtained emulsion was further subjected to secondary emulsification with a high pressure emulsifying device. This secondary emulsified emulsion is prepared by adding an appropriate amount of aqueous hydrochloric acid or sodium hydroxide solution.
The pH was adjusted to 6.7. Distilled water for injection was added to the obtained emulsion to dilute it to make a total volume of 180 ml. Further, it was filtered with a membrane filter (pore size 0.8 μm). The filtered emulsified liquid was placed in a container, which was replaced with nitrogen gas and sealed.

Test Example 1 (MRSA Infection Treatment Test) The composition of the present invention, which is an emulsion containing amythiamycin A prepared in Example 1, is effective for treating mice infected with MRSA. It has an effect in the following test. That is, 5 male ICR mice per group were treated with methicillin-resistant Staphylococcus aureus (Saureus MS15031), 4 × 10 5.
A mixture of equal amounts of CFU / ml and 5% mucin solution,
The mice were inoculated intraperitoneally with a dose of 2 × 10 CFU per mouse for infection. One hour after infection, the emulsion preparation of Example 1 was added.
0.3 ml was administered through the tail vein. Life and death were observed 2 days after the administration. In the emulsion administration group, 5 out of 8 mice survived, and in the untreated infected mouse group (control group), all died within 2 days of infection. The effect was demonstrated.

[0040]

EFFECT OF THE INVENTION A homogeneous mixture of poorly water-soluble amythiamycins, liquid fats and oils and emulsifiers (preferably naturally-derived phospholipids), and other components additionally added as desired is dispersed in a fine fat. INDUSTRIAL APPLICABILITY The antibacterial composition of the present invention, which is in the form of an emulsion dispersed as particles in an aqueous phase, can be safely administered by injection as an injection, and exhibits an excellent antibacterial action. Further, the emulsion-type composition of the present invention can be subjected to high-pressure steam sterilization without causing separation of an oil layer and increase in dispersed particle size even when subjected to high-pressure steam sterilization. Therefore, it is easy to guarantee sterility in the preparation of injections, and it is possible to obtain an antibacterial agent preparation excellent in antibacterial action and stability.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Tomio Takeuchi 5-11, Higashigotanda, Shinagawa-ku, Tokyo 701 Nyufuji Mansion 701 (72) Inventor Minako Araaki 760 Meijioka, Kohoku-ku, Yokohama-shi, Kanagawa Prefecture Meiji Confectionery Co., Ltd., Pharmaceutical Research Institute

Claims (8)

[Claims] 1. A form of an emulsion in which fine fat particles comprising a uniform mixture of amithiamycins, a liquid oil and fat and an emulsifier as an antibacterial active ingredient are dispersed in an aqueous phase,
An antibacterial composition for injection of amitiamycins in the form of an emulsion, characterized in that an emulsifier is dissolved in the aqueous phase. 2. The composition according to claim 1, wherein the amount of fats and oils in the emulsion is 1 to 30% (weight / volume) based on the volume of the entire composition. 3. The composition according to claim 1, wherein the emulsifier is a phospholipid, and the amount of the phospholipid is 0.1 to 2 parts by weight with respect to 1 part by weight of the fat or oil in the emulsion. 4. The composition according to claim 1, which also contains a higher fatty acid or an acidic phospholipid as an emulsion stabilizer. 5. A method for assisting the dissolution of amithiamycins in fats and oils, wherein a homogeneous mixture of liquid particles dispersed in the aqueous phase of an emulsion comprises a compound selected from aromatic carboxylic acids and their esters. The composition according to claim 1, which is contained as an agent. 6. Amythiamycins are contained in a proportion of 0.01 to 2% (weight / volume), fats and oils are contained in a proportion of 1 to 20% (weight / volume), and an emulsifier is 1 based on the total volume of the composition. ~
The composition according to claim 1, wherein the composition comprises 10% (weight / volume), the other medicinal auxiliaries comprise 1 to 10% (weight / volume), and the balance is water. 7. The amount of water is 70 based on the total volume of the composition.
7. The composition of claim 6 which is ˜95% (weight / volume). 8. An emulsion in which fine fat particles comprising a uniform mixture of amithiamycins as an antibacterial active ingredient, a liquid oil and fat and an emulsifier are dispersed in an aqueous phase, and the aqueous phase of the emulsion. The emulsion in which the emulsifier is dissolved in
An antibacterial composition for injection of amythiamycins in the form of a freeze-dried powder that is redispersed and dissolved in water when used as an injection, which is a powder obtained by freeze-drying.