JPS62116511A - Pharmaceutical composition - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention is directed to bacterial and/or mycoplasma
The present invention relates to novel compositions for the treatment of plasma) infections.

[Summary of the invention]

Tyrosin (tylosln) is well known as an antibacterial/antimycoplasmal agent used in the treatment of bacterial and mycoplasmal infections in animals.

The inventors have discovered a composition with improved antibacterial and antimycoplasma properties.

According to the present invention, there is provided a pharmaceutical composition comprising tyrosine or a pharmaceutically acceptable salt thereof and a β-lactam antibiotic.

Preferably the β-lactam antibiotic is amoxicillin.

Advantageously, the pharmaceutically acceptable salt of tyrosine is tyrosine tartrate.

The composition is preferably provided to provide for simultaneous administration of Telo-7 or a salt thereof and the beta-lactam antibiotic.

For example, tyrosine tartrate may be provided with a β-lactam antibiotic in a form suitable for administration in an aqueous solution, eg, animal drinking water.

When the beta-lactam antibiotic is amoxicillin, suitable formulations include those which are well known to be administered by injection, such as those described in GB 157,833 and GB 1,532,993.

Tyrosine tartrate, unlike tyrosine itself, is bath-compatible. However, the solubility properties of tartrate are rather low.

The inventors have discovered that combining tyrosine tartrate and an acidifying agent produces a composition that has a substantially improved dissolution rate compared to tyrosine tartrate alone.

The tyrosine tartrate/acidifying agent composition is suitably in the form of a concentrated aqueous dispersion, such as a solution, or a dry powder for solution in drinking water. When the composition is in dry powder form, a concentrated dispersion is suitably prepared therefrom before being added to potable water.

The concentrated dispersion suitably has a volume of 20,011 t to 2
It is t.

Suitably the composition is supplied in the form of a dry powder in a container whose volume is larger than the concentrated dispersion produced. A concentrated dispersion is then prepared by filling the desired level of water with water and shaking for, for example, 2 minutes. Once complete dispersion, eg, dissolution, has occurred, the contents of the container are poured into a conventional animal drinking water tank.

The amount of acidifying agent present should preferably be sufficient to bring the pH of the concentrated dispersion to between 2 and 6.

Suitable acidifying agents include acid salts such as potassium dihydrogen phosphate and acids such as citric acid. Alkali metal acid salts are preferred. The anion may be inorganic, such as phosphate, or organic, such as citrate. The acidifying agent may be anhydrous or it may be a hydrate.

One suitable acidifying agent is airtrium hydrogen citrate. In this case, the weight ratio of tyrosine tartrate to airtrium hydrogen citrate is suitably between 1:1 and 100:1, for example about 2
The ratio is 3 to 1.

Another suitable acidifying agent is citric acid. In this case, the weight ratio of tyrosine tartrate to citric acid in the composition is suitably 1.
1:1 to 125:1, for example about 30:1 or 7:3.

The amount of tyrosine tartrate present is the concentration of tyrosine in the final solution that is conventionally used in therapy. For example, for use in drinking water for animals, 100 to 1000 pp.
m (or 8-80q/4 weight).

More preferably a concentration of tyrosine of approximately 200-1000 Pp''% and most preferably about 500 ppm is used.

The tyrosine tartrate composition described above forms a completely clear solution of tyrosine at a rapid rate. No precipitation is seen even if hard water is used to form the solution.

The ratio of tyrosine tartrate to β-lactam antibiotic in the compositions of the invention will depend on the particular β-lactam antibiotic used. Suitably the beta-lactam antibiotic is present in a solution for conventional administration. When the antibiotic is 7 moxicillin, the ratio of tyrosine tartrate to β-lactam antibiotic is suitably 10:1 to 0.1:1, more suitably 10:1 to 0.5.
It is 1 to 1.

Many β-lactam antibiotics, including amoxicillin, require high pH to increase their solubility in water.

The inventors have discovered that by combining amoxicillin with a basic salt such as trisodium sulfate, a composition with advantageous solubility properties is produced.

Suitable basic salts include sodium glycine carbonate and trisodium phosphate. Basic salts of alkali metals are preferred. The anion may be inorganic, such as phosphate or carbonate, or it may be organic.

The amoxicillin/basic salt composition is suitably in the form of a concentrated aqueous solution or a dry powder for potable water solution. When the composition is in dry powder form, a concentrated solution is suitably prepared therefrom before being added to potable water. Typically, a volume of the concentrated solution, suitably 60-lt, will be added to the potable water at the same time as the concentrated dispersion of tyrosine tartrate.

Suitably the composition is supplied in the form of a dry powder in a container whose volume is larger than the concentrated solution produced. A concentrated solution may then be prepared by filling a container with the desired level of launch and shaking for, for example, 2 minutes. Once dissolution has occurred, the contents of the container are poured into a conventional animal drinking water tank.

The amount of basic salt present should preferably be sufficient to bring the pH of the concentrated solution to at least about 9, preferably 9.5. Suitably the composition contains 1 part by weight of υ
It consists of about 1 part by weight of amoxicillin.

Small amounts of sequestering agents, such as ethylenediaminetetraacetic acid or its salts, such as its disodium salt and sodium nibbutate, may also be included in the Amoxicilly 7 composition.

A particularly preferred composition comprises about 11 parts amoxicillin trihydrate, 10 parts trisodium phosphate, and 1 part disodium edetate.

The concentration of amoxicillin in the final solution, e.g. the animal's drinking water, is suitably about 50-500 ppm (or 4-40 ppm).
Kf body weight), most suitably about 250 ppm.

Two such compositions were prepared directly because soluble tyrosine compositions require acidic pH conditions and many beta-lactam antibiotics, including amoxicillin, require high pH to increase solubility. cannot be mixed with.

Further in accordance with the present invention, there is provided a container having two compartments, one of which contains telokone tartrate and an acidifying agent, and the second of which contains β- Lactam antibiotics include, for example, the 7 moxicillin/trisodium phosphate compositions described above.

The present invention also provides an animal drinking water containing tyrosine tartrate and β-2cutam antibiotics.

Advantageously, if the beta-lactam antibiotic is amoxicillin, the pH of the animal's drinking water is in the range of 5.2 to 6.8, preferably about 6.3, to optimize the stability of amoxicillin. To accomplish this, the acidifying agent mentioned above bathes the tyrosine tartrate and corrects the pH in the final solution.
is selected to work to obtain H.

The invention will be described in more detail by way of example with reference to the accompanying drawings, in which: FIG.

FIG. 1 is a schematic A-side view of the container of the present invention, and FIG. 2 is a schematic side view of another embodiment of the container of the present invention.

The container 1 shown in FIG. 1 consists of a container 2 having a capacity of at least 700 cm. A screw cap 4 is provided in the chamber 2, in which there is a mixture 3 consisting of 12Of tyrosine tartrate in dry powder form and 5.26F of airtrium hydrogen citrate.

Also within the container 1 is a chamber 5 having a capacity of at least 120 cm. Inside chamber 5 there are 322 amoxicillin formulations 6 in dry powder form @amoxicillin formulation 6 is 51.
It consists of 0% by weight of amoxicillin trihydrate, 454% by weight of disodium edetate and 44.46% by weight of trisodium phosphate. The chamber 5 is provided with another screw cap 7.

Container 1 suitably consists of a plastics material, such as high density polyethylene or polypropylene. Container 1 is intended to be supplied to farmers.

For use, chambers 2 and 5 are first filled with some water and the contents are gently shaken until they are completely dispersed.

The contents of both presentations 2 and 5 are then placed into the animal's drinking water tank (typically containing about 2001 cups of drinking water). The pH of the diluted solution obtained is 7.8.

In the alternative embodiment shown in FIG. 2, chambers 2, 5 are fat exchanged by first and second bottles 8 and 9, respectively.

Bottles 8, 9 suitably consist of plastic material. They are held together, for example by laces 10 as shown or alternatively by fusion or welding. ! 8. The volume of 9 may vary depending on the amount of composition it contains. For example, the first bottle 8 has a capacity of about 16, while the second bottle 9 has a capacity of about 12.
It is 5-.

In another embodiment of the invention, chamber 5 or bottle 9 has a volume 1 of at least 350 m and contains 98.1 F of amoxicillin formulation 6, while chamber 2 or bottle 8 has a volume of at least 700 m
And 120? Theron tartrate and 50? of citric acid (replacing the airtrium hydrogen citrate of the 1st-1 embodiment). The contents of container 1 are mixed with water as described above and poured into about a zoot of animal drinking water. The pH of the diluted solution obtained is 6.3.

[Brief explanation of drawings]

FIG. 1 is a schematic side view of a container of the present invention, and FIG. 2 is a schematic side view of another embodiment of the container of the present invention. 1... Container 2... Wealth 3... Tyrosine mixture 4... Cap 5... Chamber 6... Amoxicillin prescription Item 7... Cap 8... Bottle 9... - Bottle 10... String agent Patent attorney Masamitsu Akisawa and 1 other personFig, 1 Voluntary procedure amendment Book November 14, 1986

Claims (12)

[Claims] (1) A pharmaceutical composition comprising tyrosine or a pharmaceutically acceptable salt thereof and a β-lactam antibiotic for simultaneous use in the treatment of bacterial and/or mycoplasmal infections. (2) A composition according to claim 1, comprising a β-lactam antibiotic and tyrosine tartrate in water-soluble form. (3) The composition according to claim (2), which is drinking water for animals. (4) A composition according to claim 3, wherein the β-lactam antibiotic is amoxicillin and the animal's drinking water has a pH in the range of 5.2 to 6.8. (5) comprising a first container containing tyrosine tartrate and an acidifying agent and a second container containing a water-soluble form of the β-lactam antibiotic, the contents of each container being in the form of a dry powder or an aqueous dispersion; The composition according to claim 2, which is a liquid. (6) The contents of the one or each container are in the form of a dry powder and the size of the container is sufficient to contain the entire aqueous dispersion of the contents. Composition of. (7) The composition according to claim (5) or (6), wherein the acidifying agent is airtrium hydrogen citrate or citric acid. (8) The composition according to any one of claims (5) to (7), wherein the second container contains amoxicillin and trisodium oxate. (9) The β-lactam antibiotic is amoxicillin and the weight ratio of tyrosine tartrate to amoxicillin is 10.
Claim No. (5) in the range of 1 to 0.1 to 1
The composition according to any one of items 1 to 8. (10) Use of tyrosine or a pharmaceutically acceptable salt thereof and a β-lactam antibiotic for the production of a composition according to any one of claims (1) to (9). (11) A composition comprising tyrosine tartrate and an acidifying agent. (12) A composition comprising amoxicillin and a basic salt.