JPH1180021A - Vancomycin injection - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a vancomycin injection suppressed in discoloration, having excellent action on Staphylococcus aureus with multiple drug resistance, and useful for dealing with e.g. MRSA infectious diseases, by including water, vancomycin and an amino acid. SOLUTION: This injection is obtained by including (A) water, (B) 80-99.9 pts.wt., pref. 85-99.5 pts.wt., more pref. 90-99 pts.wt., based on the whole injection except the water, of vancomycin (pref. its hydrochloride), and (C) 0.1-20 pts.wt., pref. 0.5-15 pts.wt., more pref. 1-10 pts.wt., based on the whole injection except the water, of an amino acid (esp. glycine) in a weight ratio C/B of 0.01-0.1. Furthermore, for example, this injection can also be made into a lyophilized preparation by substituting the gas in its container with pref. an inert gas (e.g. nitrogen, helium, argon) followed by lyophilization.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to an injection of vancomycin, which is an antibiotic.

[0002]

2. Description of the Related Art Vancomycin is a glycopeptide antibiotic which has an excellent action against multidrug-resistant Staphylococcus aureus and is one of the few effective against MRSA infection which is now a social problem. It is one of the antibiotics, and it is expected that the demand will increase further in the future. Since vancomycin is a glycopeptide, its bioavailability is not high in oral administration, and therefore it is frequently used in injections. The most problematic problem when preparing an injection is that coloring occurs during a manufacturing process such as freeze-drying. Various studies have been made to solve the coloring problem. For example, metal chlorides or lower alcohols are added, but all have problems in solubility, finished appearance and the like. That is, no suitable solution to this problem has yet been found.

On the other hand, it is common to add an amino acid such as glycine at the time of preparing a lyophilized drug product, but the physical and chemical properties of the obtained drug product depend on the active ingredient,
It greatly differs depending on amino acids, their composition ratio, and the like, and is very difficult to predict. That is, it has never been known or expected that a composition containing water, vancomycin and an amino acid is suppressed in coloration.

[0004]

Accordingly, an object of the present invention is to provide a vancomycin injection with suppressed coloring.

[0005]

Means for Solving the Problems In view of such a situation, the present inventors have made intensive studies, and as a result, have found that the composition containing water, vancomycin and amino acid is suppressed from coloring, and the present invention has been developed. It was completed.

That is, the present invention provides a vancomycin injection containing water, vancomycin and an amino acid.

Further, the present invention provides a freeze-dried preparation of the vancomycin injection. Hereinafter, embodiments of the present invention will be described.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION

<1> Vancomycin used in the present invention Vancomycin is a glycopeptide antibiotic.
It is already commercially available and easily available. In the present invention, a free form may be used or a salt such as hydrochloric acid or nitrate may be used, but the use of a hydrochloride is preferred. This is because the manufacturing cost and stability are excellent.

<2> Amino acid used in the present invention The vancomycin injection of the present invention is characterized by containing an amino acid. The amino acid referred to herein is not particularly limited as long as it is generally used as a pharmaceutical composition, and examples thereof include glycine, alanine, valine, leucine, isoleucine, and optically active and racemic forms thereof. Among them, glycine is particularly preferred. This is because the coloring is particularly excellent. In the present invention, the amino acid may or may not form a salt with another substance. In the injection of the present invention, the amino acid may or may not form a salt with the intramolecular and / or other components.
In the present invention, a single amino acid may be used, or a plurality of amino acids may be used. In the present invention, the amount of the amino acid used is preferably 0.1 to 20 parts by weight, more preferably 0.5 to 15 parts by weight, preferably 1 to 15 parts by weight, based on the total amount of the injection except water.
10 parts by weight is more preferred. This is the effect of suppressing coloring,
This is because the medicinal properties and the like are well balanced.

<3> Vancomycin Injection / Lyophilized Formulation In the vancomycin injection of the present invention, vancomycin is preferably 80 to 99.9 parts by weight, more preferably 85 to 99.5 parts by weight, based on the total amount of the injection except water. Is more preferable,
90-99 parts by weight are more preferred. In addition, the injection of the present invention can contain, in addition to these essential components, optional components usually used in injections, as long as the effects of the invention are not impaired. Examples of such optional components include buffers such as sodium citrate, sodium hydrogen carbonate, sodium hydrogen phosphate, and sodium acetate; isotonic agents such as sodium chloride and potassium chloride; and sugars such as glucose. The dosage form of the injection may be a liquid preparation or a lyophilized preparation, but a lyophilized preparation is preferred. The term “injection” as used in the present invention means a form of administration via a needle into a blood vessel, intramuscularly, subcutaneously, etc., and the pharmaceutical classification means both injection and / or infusion.
The injection of the present invention can be used as it is as an injection, or the injection or lyophilized preparation of the present invention dissolved in an aqueous medium can be added to other infusions and administered. The injection of the present invention is preferably in a dosage form capable of administering 100 to 2000 mg of vancomycin at a time. The method for producing the injection of the present invention may be carried out according to a conventional method.
It may be filled in a vial. Further, in the final step of the production, it is preferable to replace the air in the preparation container with an inert gas such as nitrogen, helium, argon or the like, since coloring is suppressed more. As the inert gas used, nitrogen is particularly preferred. This is because it is advantageous in terms of cost. The freeze-dried preparation of the present invention can be obtained by freeze-drying the injection obtained by the above method. At the time of freeze-drying, it is preferable to replace the air in the preparation container with an inert gas such as nitrogen, helium, argon or the like, since coloring is further suppressed. As the inert gas used, nitrogen is particularly preferred. This is because it is advantageous in terms of cost.

[0011] The vancomycin injection thus obtained has suppressed coloring and is useful as a pharmaceutical composition.

[0012]

EXAMPLES The present invention will be described in more detail with reference to the following examples, but it goes without saying that the present invention is not limited thereto.

Example 1 A freeze-dried preparation was prepared according to the following formulation. That is, the formulation components were dissolved, sterilized by filtration through a 0.2 μm filter, filled in two vials, freeze-dried, and sealed to obtain a freeze-dried preparation. The appearance of the freeze-dried product was clean and white. Addition of 10 ml of water for injection to one of the two vials dissolved easily. (Prescription) Vancomycin hydrochloride 500 mg (96 parts by weight) Glycine 20 mg (4 parts by weight) 5 ml of distilled water for injection

Example 2 A freeze-dried preparation was prepared according to the following formulation. That is, the formulation components were dissolved, sterilized by filtration through a 0.2 μm filter, filled in two vials, lyophilized, replaced with nitrogen, and sealed to obtain a lyophilized preparation. The appearance of the freeze-dried product was clean and white. Addition of 10 ml of water for injection to one of the two vials dissolved easily. (Prescription) Vancomycin hydrochloride 500 mg (96 parts by weight) Glycine 20 mg (4 parts by weight) 5 ml of distilled water for injection

Comparative Example 1 A freeze-dried preparation was prepared according to the following formulation. That is, the formulation components were dissolved, sterilized by filtration through a 0.2 μm filter, filled in two vials, freeze-dried, and sealed to obtain a freeze-dried preparation. (Prescription) Vancomycin hydrochloride 500mg Distilled water for injection 5ml

Comparative Example 2 A freeze-dried preparation was prepared according to the following formulation. That is, the formulation components were dissolved, sterilized by filtration through a 0.2 μm filter, filled in two vials, lyophilized, replaced with nitrogen, and sealed to obtain a lyophilized preparation. (Prescription) Vancomycin hydrochloride 500mg Distilled water for injection 5ml

Example 3 The preparations of Examples 1 and 2 were subjected to a severe test together with the preparations of Comparative Examples to confirm the stability. That is, 50
At 16 ° C. for 16 days, and dissolved by adding 10 ml of water.
Spectrophotometry was performed at 65 nm to examine the degree of coloring. Table 1 shows the results. From this table, it can be seen that the injection of the present invention has a suppressed degree of coloring. It is also found that the degree of coloration of the freeze-dried preparation of the present invention can be further suppressed by nitrogen substitution during freeze-drying.

[0018]

[Table 1]

Example 4 An injection was prepared according to the following formulation. That is, dissolve the prescription components, filter sterilize with a 0.2μm filter,
Two vials were filled. (Prescription) Vancomycin hydrochloride 500 mg (96 parts by weight) L-alanine 20 mg (4 parts by weight) 10 ml of distilled water for injection

Example 5 An injection was prepared according to the following formulation. That is, dissolve the prescription components, sterilize by filtration through a 0.2 μm filter,
Two vials were filled. (Prescription) Vancomycin hydrochloride 500 mg (98 parts by weight) L-alanine 10 mg (2 parts by weight) Distilled water for injection 10 ml

Example 6 An injection was prepared according to the following formulation. That is, dissolve the prescription components, sterilize by filtration through a 0.2 μm filter,
Two vials were filled. (Prescription) Vancomycin hydrochloride 500 mg (96 parts by weight) L-valine 20 mg (4 parts by weight) 10 ml of distilled water for injection

Example 7 An injection was prepared according to the following formulation. That is, dissolve the prescription components, sterilize by filtration through a 0.2 μm filter,
Two vials were filled. (Prescription) Vancomycin hydrochloride 500 mg (98 parts by weight) L-valine 10 mg (2 parts by weight) Distilled water for injection 10 ml

Example 8 Injections were prepared according to the following formulation. That is, dissolve the prescription components, filter sterilize with a 0.2μm filter,
Two vials were filled. (Prescription) Vancomycin hydrochloride 500 mg (96 parts by weight) L-leucine 20 mg (4 parts by weight) 10 ml of distilled water for injection

Example 9 An injection was prepared according to the following formulation. That is, dissolve the prescription components, sterilize by filtration through a 0.2 μm filter,
Two vials were filled. (Prescription) Vancomycin hydrochloride 500 mg (98 parts by weight) L-leucine 10 mg (2 parts by weight) Distilled water for injection 10 ml

Example 10 An injection was prepared according to the following formulation. That is, dissolve the prescription components, sterilize by filtration through a 0.2 μm filter,
Two vials were filled. (Prescription) Vancomycin hydrochloride 500 mg (96 parts by weight) L-isoleucine 20 mg (4 parts by weight) 10 ml of distilled water for injection

Example 11 An injection was prepared according to the following formulation. That is, dissolve the prescription components, sterilize by filtration through a 0.2 μm filter,
Two vials were filled. (Prescription) Vancomycin hydrochloride 500 mg (98 parts by weight) L-isoleucine 10 mg (2 parts by weight) Distilled water for injection 10 ml

[0027]

According to the present invention, it is possible to provide vancomycin injection with suppressed coloring.

Continuation of front page (72) Inventor Ryuji Strashina 1130-4 Kamekubo, Oi-machi, Iruma-gun, Saitama Pref.

Claims (5)

[Claims] 1. An injectable vancomycin containing water, vancomycin and an amino acid. 2. The vancomycin injection according to claim 1, wherein the amino acid is glycine. 3. The vancomycin injection according to claim 1, wherein the weight ratio of the amino acid to vancomycin is 0.1 to 10%. 4. A freeze-dried preparation of vancomycin injection according to any one of claims 1 to 3. 5. The lyophilized preparation according to claim 4, wherein the lyophilized preparation is substituted with nitrogen during lyophilization.