BE1021242B1 - TEICOPLANINE LYOFILIZATES - Google Patents

Abstract

TEICOPLANZNE LYOPHILIZATES. The present invention relates to a method for making a powdered Teicoplanin composition for injection, which ensures the stability of Teicoplanin in the composition as best as possible, and further relates to a method for making an injectable Teicoplanin preparation using the powdery composition, which injectable Teicoplanin formulation can be used in the treatment of infections caused by aerobic and / or anaerobic gram positive bacteria. The invention further relates to Teicoplanin compositions and injectable preparations obtained by a method according to the invention.

Description

TEICOPLANINE LYOFILIZATES

TECHNICAL DOMAIN

The invention relates to a method for making a powdered Teicoplanin composition for injection. The present invention further relates to a method for the preparation of an injectable Teicoplanin preparation, which method uses the powdered composition. Finally, the present invention relates to powdered Teicoplanin compositions and injectable Teicoplanin preparation obtained according to a method of the invention. Furthermore, the invention provides that the aforementioned compositions are used in the treatment of infections caused by aerobic and / or anaerobic gram-positive bacteria. The invention is advantageous in the field of pharmaceutical preparations.

BACKGROUND ART

Teicoplanin is a glycopeptide antibiotic produced by Actinoplanes teichomyceticus as a fermentation product, and is a complex of three main components, namely A1, A2 and A3. The factor A2 represents the component that is present in the largest amount in the fermentation brew of Actinoplanes teichomyceticus and is also the factor with the most important antibacterial activity. Factor A2, in turn, also consists of a complex of 5 components, all of which are closely related. The structure of Teicoplanin has already been described and reported in detail, for example in the Merck Index, 11th edition, 1989, page 1438, reference 9062, and also in the Journal of Hospital Infections, (1986) Vol.7, supplement A, page. 79-83.

Since the end of the 1980s, Teicoplanin has been used as a medicine and has been used as an antibiotic against gram-positive bacteria that cause serious infections, such as endocarditis or peritonitis associated dialysis. It is also active against bacteria that are resistant to other types of antibiotics. Teicoplanin is widely used against infections of Staphylococcus aureus, a type of bacterium that is responsible for, among other things, blood poisoning and pneumonia, and that is common in hospital environments. S. aureus is the most aggressive of staphylococcal bacteria and the species developed the first penicillin-resistant strains as early as the 1940s. The bacterium has proven over the years that it is able to very quickly develop new resistant strains, resulting in the production of mutants that are difficult to control by the medical world.

Meticillin-resistant strains of S. aureus (MRSA, meticillin-resistant S. aureus) are more common nowadays and in some countries represent more than 50% of the isolated strains of S. aureus. Infections related to such pathogens are common in hospital environments, with the widespread use of antibiotics leading to the selection of resistant strains. The first infections of these MRSA bacteria were recently discovered, which has greatly disrupted the medical world.

Recently described cases have shown that S. aureus exhibits resistance to Vancomycin, a glycopeptide antibiotic that is similar to Teicoplanin and is also widely used in the treatment of the above-described gram-positive infections. However, teicoplanin has a much more favorable pharmacokinetics compared to Vancomycin and can be administered in a single daily dose.

All these elements clearly show the importance of Teicoplanin as an antibiotic.

Regarding the administration of Teicoplanin, it can be administered by both intramuscular and intravenous injection, while it is not bioavailable when administered orally. In order to be able to inject Teicoplanin intramuscularly or intravenously, it is important to make an injectable preparation of Teicoplanin that not only has the correct physiological properties, but is also sterile and free from particles that can influence the injection. This injectable preparation is typically made just prior to injection by dissolving a powdered composition of Teicoplanin in, for example, water for injection, which solution can then be injected. This method is necessary because Teicoplanin does not remain stable in an aqueous environment for long. The preparation should preferably be made in the shortest possible time, since Teicoplanin must be used for often life-threatening infections.

The properties of the powdered composition of Teicoplanin will largely determine the final properties of the injectable preparation. It is therefore extremely important that this powdered composition is made under optimum conditions. Thus it is crucial that the stability of

Teicoplanin remains guaranteed during the preparation of the powdered composition, since this may otherwise lead to the inactivity of this component or the formation of by-products that can lead to undesirable side effects.

There is a need for an improved method for making powdered compositions comprising Teicoplanin. The stability of Teicoplanin should be monitored and guaranteed as well as possible. The compositions should lead to the rapid synthesis of injectable preparations with the correct physiological properties. The preparations must be sterile. Preparation for injection should be clear and substantially free of particles.

It is an object of the present invention to find a solution to at least one of the aforementioned problems.

SUMMARY OF THE INVENTION

The present invention provides improved methods and compositions for this purpose.

The invention relates to a method for making a powdered Teicoplanin composition for injection, as defined in claim 1.

The temperature conditions and pH conditions used in the method according to the present invention allow to control and guarantee the stability of Teicoplanin as well as possible, resulting in an optimum quality of the powdered Teicoplanin composition.

In a second aspect the invention relates to a powdered Teicoplanin composition for injection as defined in claim 9, preferably a composition made according to a method as defined in claim 1. This powdered composition can dissolve in water for injection in a very short time such that an injectable preparation can be made of the composition in a rapid manner.

In a further aspect, the invention relates to a method for making an injectable Teicoplanin preparation, as defined in claim 11, using a powdered Teicoplanin composition for injection as defined in claim 9.

The invention further relates to an injectable Teicoplanin preparation according to claim 13, preferably an injectable preparation made according to a method as described in claim 11.

Finally, the present invention relates to an injectable Teicoplanin preparation for use in the treatment of infections caused by aerobic and / or anaerobic gram-positive bacteria, preferably an injectable Teicoplanin preparation according to claim 13.

DETAILED DESCRIPTION

The invention relates to a method for making a powdered Teicoplanin composition for injection, the stability of Teicoplanin of which can be controlled and guaranteed as well as possible. The present invention further relates to an injectable preparation which can be made in a rapid manner from the powdered composition, which has the correct physiological properties, and which is sterile and substantially free from particles.

Unless defined otherwise, all terms used in the description of the invention, including technical and scientific terms, have the meaning as generally understood by those skilled in the art of the invention. For a better assessment of the description of the invention, the following terms are explicitly explained. "A", "de" and "het" in this document refer to both the singular and the plural unless the context clearly assumes otherwise. For example, "a base" means one or more than one base.

When "about" or "round" is used in this document for a measurable quantity, a parameter, a duration or moment, and the like, variations are meant of +/- 20% or less, preferably +/- 10% or less, more preferably +/- 5% or less, even more preferably +/- 1% or less, and even more preferably +/- 0.1% or less than and of the quoted value, insofar as such variations of are applicable in the described invention. However, it must be understood here that the value of the quantity at which the term "about" or "round" is used is itself specifically disclosed.

The terms "include", "comprising", "consist of", "consisting of", "provided with", "contain", "containing", "include", "including", "contents", "contents" are synonyms and are inclusive or open terms indicating the presence of what follows, and which do not preclude or preclude the presence of other components, features, elements, members, steps, known from or described in the prior art.

The citation of numerical intervals by the end points includes all integers, fractions and / or real numbers between the end points, including these end points.

In a first aspect, the invention relates to a method for making a powdered Teicoplanin composition for injection, which composition comprises the following components: - 86-96 weight percent of Teicoplanin; - 4-13 weight percent of a salt; - 0-1 weight percent of a base; wherein the weight percent of each component is expressed relative to the total weight of the composition. The method of the present invention comprises the steps of: a) providing a first amount of a solvent with a temperature below 25 ° C; b) adding Teicoplanin to the solvent; c) adding the salt to the Teicoplanin solution; d) adding a second amount of said solvent with a temperature below 25 ° C to the salted Teicoplanin solution; e) optionally adding the base; resulting in a solution with pH 6.5-7.5. The resulting solution is then lyophilized at a temperature equal to or lower than 40 ° C, until the powdered composition is obtained.

Because the temperature in the various steps of the method according to the present invention is optimally adapted to the thermostability of Teicoplanin, ie the temperature of the solvent for dissolving the component, as well as the temperature for freeze-drying the solution, combined with the favorable pH of the solution leads to the optimum control of the stability of this component in the production process of the powdered composition. This ensures that undesired phenomena such as the inactivation of Teicoplanin or the formation of undesired by-products due to too high a temperature and / or too high (> 7.5) or too low (<6.5) pH can be avoided. In this way the final quality of the powdered composition can be checked as well as possible.

In a preferred embodiment, the composition comprises 88-94.5 weight percent of Teicoplanin, 5.5-11.5 weight percent of a salt and 0.0-0.5 weight percent of a base. In another preferred embodiment, the composition comprises 93-94.5 weight percent of Teicoplanin, 5.5-6.5 weight percent of a salt and 0.0-0.5 weight percent of a base. In yet another preferred embodiment, the composition comprises 88-90.5 weight percent of Teicoplanin, 10.5-11.5 weight percent of a salt and 0.0-0.5 weight percent of a base. In all of these embodiments, the weight percent of each component is expressed relative to the total weight of the composition.

The powdered Teicoplanin composition for injection according to the present invention may also comprise other pharmacologically acceptable components, such as, for example, antifoaming agents. The term "antifoam agent" in the present invention is intended to mean an agent, often a surfactant component such as a surfactant, that prevents or counteracts the formation of foam in a solution. This antifoaming agent is primarily important in making, for example, an injectable preparation of the powdered Teicoplanin composition, since foaming greatly impedes the administration of the injectable preparation to a patient, for example by injection. Examples of suitable antifoaming agents include sodium carboxymethylcellulose, sorbitol, mannitol, polyvinylpyrrolidone (PVP), polyoxyethylene sorbitan monolaurate or monooleate, polysorbates or Tween 20 and 80, polyoxyethylene / polyoxypropylene / polyoxyethylene copolymer (e.g., Pluronic ric-poly-glycol ethylene glycol) Cremophor EL), silicone-based antifoaming agents (Dimethicon), sorbitan monooleate or monolaurate (e.g. Span 20 and 80), propylene glycol; polyethylene glycol 300 (PEG), ethanol, dimethylacetamide (DMA), glycerol, A / methyl 2-pyrrolidone (e.g. Pharmasolve) or monothioglycerol.

In a preferred embodiment, after adding each component to the solvent, there will be stirred such that each component completely dissolves in the solvent.

Preferably stirring will take place at a stirring speed between 50 and 150 revolutions per minute, more preferably between 75 and 125 revolutions per minute, even more preferably between 90 and 110 revolutions per minute, most preferably about 100 revolutions per minute.

According to a preferred embodiment, said first amount of the solvent comprises between 70 and 90 weight percent of the total weight of the solvent in the resulting solution, more preferably between 75 and 85 weight percent, even more preferably between 78 and 82%, most preferably preferably about 80 weight percent of the total weight of the solvent in the resulting solution. In this preferred embodiment, in other words, when adding the first amount of the solvent, between 70 and 90 percent by weight of the final amount (by weight) of the solvent in the resulting solution will be added. When adding the second amount of the solvent and, optionally, when adding the base, the remaining 10 to 30 weight percent of the total weight of the solvent will be added in the resulting solution. This administration of the solvent in two steps ensures that the various components of the solution, i.e. Teicoplanin, the salt and optionally the base, can dissolve in the solvent under optimum conditions.

The salt added during the method of the present invention provides the injectable preparation made from the powdered composition obtained by this method with the proper physiological properties to enable it to be injected intramuscularly or intravenously. The salt is preferably sodium chloride, more preferably sodium chloride according to European Pharmacopoeia, chapter 0193.

The solvent according to the present invention can be any solvent that is suitable for removal via lyophilization. Preferably the solvent is water for injection and / or ethanol, more preferably the solvent is water for injection. The term "water for injection" denotes a certain quality of water, such as sterile, pyrogen-free and distilled water, which is suitable for, for example, dissolving components intended for pharmaceutical applications, such as, for example, Teicoplanin. This term is known in the art. Most preferably the solvent is water for injection according to European Pharmacopoeia, chapter 0169.

The administration of the base can optionally take place if, after the addition of the salt and Teicopianin, the solution does not have the desired pH between 6.5 and 7.5, but has a too low pH (<6.5), for example. The base is preferably sodium hydroxide or sodium bicarbonate. A combination of sodium hydroxide and sodium bicarbonate can also be used. The base is preferably first dissolved in a solvent, such as water for injection, before the base is administered to the container. More preferably, a 0.1 M aqueous sodium hydroxide solution is made, with water for injection as a solvent, and this solution is added in such amounts to the salted Teicopianin solution to achieve the correct pH between 6.5 and 7.5. Preferably the sodium hydroxide used is sodium hydroxide according to European Pharmacopoeia, chapter 0677.

Freeze-drying preferably takes place in a number of consecutive steps. The solution is preferably first cooled, preferably to a temperature between -50 and -40 ° C, more preferably to a temperature between -48 and -42 ° C, most preferably to a temperature of approximately -45 ° C . Preferably the frozen solution is then placed under vacuum conditions, preferably at a pressure between 0.1 and 0.3 mbar, more preferably at a pressure between 1.5 and 2.5 mbar, most preferably at a pressure of about 0.2 mbar, after which the solution in a first drying step is preferably heated to a temperature between 0 and 15 ° C, more preferably between 5 and 10 ° C. The temperature is then preferably further increased in a second drying step to a temperature between 20 and 40 ° C. Finally, the solution which has been transformed by this freeze-drying process into a powdered composition is brought to a temperature between 15 and 25 ° C, more preferably a temperature of approximately 20 ° C and a pressure between 850 and 1000 mbar, more at preferably a pressure between 875 and 975 mbar, most preferably a pressure between 900 and 950 mbar. The powdered composition is preferably at this pressure under an inert atmosphere, for example a nitrogen atmosphere. The total freeze-drying process preferably lasts between 36 and 72 hours, more preferably between 40 and 60 hours, most preferably about 48 hours.

According to an embodiment, the solution for freeze-drying is filtered at least once, i.e. the solution is passed through at least one filter to sterilize the solution, and clear and substantially free of particles. In a preferred embodiment, the solution is filtered twice. Preferably, the filter used for filtering the solution has a filter size between 0.15 and 0.25 µm, i.e. the pores of the filter have a size between 0.15 and 0.25 µm. More preferably, the filter has a filter size between 0.17 and 0.23 µm, most preferably of about 0.22 µm. Preferably the filter comprises a cellulose acetate membrane.

In a preferred embodiment, before freeze-drying the solution and preferably after filtering the solution, the solution is added in a vial in which the solution is freeze-dried. In this way the powdered composition is formed in the bottle. The bottle preferably has a volume content between 5 and 30 ml, more preferably between 10 and 25 ml. In a preferred embodiment, the vial has a volume content of approximately 10 ml. In another preferred embodiment, the vial has a volume content of approximately 25 ml. Preferably, the volume content of the vial is dependent on the amount of Teicoplanin in the powdered composition. In a powdered composition with 200 mg of Teicoplanin, a bottle with a volume content of approximately 10 ml is preferably used. For a powdered composition with 400 mg of Teicoplanin, a bottle with a volume content of approximately 25 ml is preferably used. The bottle is preferably a glass bottle. More preferably, the glass bottle is a transparent colorless glass bottle that meets the criteria of the Type I glass containers for pharmaceutical use according to the European Pharmacopoeia (Ph. Eur.), Chapter 3.2.1. Preferably, the vial is sterilized prior to adding the solution to the vial.

If the solution is added in a bottle, before freezing the solution, the bottle is preferably partially closed by a stopper. This stop is preferably a rubber stop. 'Rubber' can be understood to mean any kind of rubber that is suitable for pharmaceutical applications, such as natural rubber, polyisoprene-based rubber, styrene-butadiene-based rubber, nitrile-butadiene-based rubber, EPDM (ethylene-propylene-diene monomer) -based rubber, silicone based rubber, chlorobutyl based rubber or bromobutyl based rubber, or any possible combination of these types of rubber. Preferably, the stopper is a bromobutyl-based rubber stopper. The rubber stopper is furthermore preferably free of mercaptobenzothiozole (MBT) and / or preferably contains an inorganic dirt remover such as aluminum silicate, magnesium silicate, silica, calcium carbonate or a combination of these fillers. Such fillers provide the rubber stopper with its mechanical properties by, for example, influencing the hardness or the moisture absorption / desorption properties of the rubber. Furthermore, the rubber stopper preferably also contains a dye, such as for example carbon black or an inorganic dye, such as titanium oxide or iron oxides. An example of a rubber stopper that can be used according to the present invention is a dark gray bromobutyl-based rubber stopper according to European Pharmacopoeia (Ph. Eur.), Chapter 3.2.9, which is free of MBT and which contains aluminum silicate and / or magnesium silicate as a refuse .

Preferably the stop is a freeze-drying stop. A freeze-drying plug means according to the present invention a plug which, when partially placed on a vial, allows to dry a frozen solution in the vial in a vacuum chamber. Such freeze-drying plugs are preferably partially placed on the vial after filling the vial with the solution, channels, slits, or other suitable means being provided for allowing sublimation under vacuum. At the end of the drying process, the vial with the freeze-dried solution can be completely sealed by the stopper, for example by hydraulic or mechanical means within the vacuum chamber. In other words, the freeze-drying stopper is provided with channels, slits or other suitable means which, when the stopper is partially placed on the bottle, allow the sublimation under vacuum, but which completely seals the bottle when the stopper is completely placed on the bottle. Such types of plugs are available, for example, from The Datwyler Group, such as a freeze-drying plug with product number 5252.

Preferably, after freeze drying of the solution, whereby the powdered composition is obtained, the vial is completely closed by the stopper. This means that it is prevented that contaminants can get into the bottle or that the powdered composition can escape from the bottle. Preferably, the plug is hereby additionally sealed by an aluminum sealing envelope. Such aluminum closure casing is typically "clamped" around the opening of the bottle where the stopper closes the bottle. It is preferably possible to penetrate the stopper with a needle in order to get into the bottle up to the powdered composition. Preferably, upon removal of the needle again, the stopper will completely close the contents of the vial. This guarantees the shelf life of the powdered composition such that Teicoplanin can remain stable under these optimum conditions.

In a second aspect, the invention relates to a powdered Teicoplanin composition for injection obtained by a method as described above, which composition comprises the following components: - 86-96% by weight of Teicoplanin; - 4-13 weight percent of a salt; - 0-1 weight percent of a base; wherein the weight percent of each component is expressed relative to the total weight of the composition. In particular, the composition dissolves in less than 6 minutes when to a composition containing at most 400 mg of Teicoplanin, 3.2 ml of water for injection is added at 25 ° C. Since Teicoplanin must be administered as an antibiotic in patients with often life-threatening infections, it is extremely important that the powdered composition with Teicoplanin dissolves as quickly as possible in water for injection in order to be able to administer it.

In a preferred embodiment, the composition comprises 88-94.5 weight percent of Teicoplanin, 5.5-11.5 weight percent of a salt and 0.0-0.5 weight percent of a base. In another preferred embodiment, the composition comprises 93-94.5 weight percent of Teicoplanin, 5.5-6.5 weight percent of a salt and 0.0-0.5 weight percent of a base. In yet another preferred embodiment, the composition comprises 88-90.5 weight percent of Teicoplanin, 10.5-11.5 weight percent of a salt and 0.0-0.5 weight percent of a base. In all of these embodiments, the weight percent of each component is expressed relative to the total weight of the composition.

In a preferred embodiment, the powdered Teicoplanin composition for injection comprises a Teicoplanin dose of 100, 200 or 400 mg. Preferably the powdered Teicoplanin composition for injection is present in a bottle, more preferably a glass bottle, most preferably a glass bottle that meets the Type I criteria according to European Pharmacopoeia (Ph. Eur.), Chapter 3.2.1 , which is preferably completely closed off by a plug and optionally provided with an aluminum closure cover as described above. This stopper is preferably a rubber stopper with similar characteristics as described above, more preferably the stopper is a rubber freeze-drying stopper, most preferably the stopper is a dark gray bromobutyl-based rubber freeze-drying stopper according to European Pharmacopoeia (Ph. Eur.), Chapter 3.2. 9, which is free from MBT and which comprises aluminum silicate and / or magnesium silicate as a refiner. The powdered composition is herein preferably present in the vial under a light vacuum at a pressure between 850 and 1000 mbar, more preferably a pressure between 875 and 975 mbar, most preferably a pressure between 900 and 950 mbar, preferably in a nitrogen atmosphere .

In a following aspect, the invention relates to a method for making an injectable Teicoplanin preparation. This method comprises the step of adding a physiologically tolerable liquid to a powdered composition as described above. Preferably, the aforementioned liquid is water for injection. The solvent can also include an antifoam agent. Possible examples of such anti-foaming agents are described above. In particular, the pH of the preparation is 6.0-8.0 which gives the preparation the correct physiological properties for injection.

Preferably, the powdered composition is contained in a bottle when the preparation is made, completely sealed with a stopper and optionally provided with an aluminum cover as described above, into which the water is injected for injection, for example by injection with a needle through the Stop. Preferably, the water is administered slowly and, after the water is injected, the bottle is preferably gently rolled between the hands to cause the powdered composition to dissolve in the water, thereby preventing foaming. Preferably the composition dissolves in less than 6 minutes when to a composition containing at most 400 mg of Teicoplanin, 3.2 ml of water for injection is added at 25 ° C.

In a fourth aspect, the invention relates to an injectable preparation obtained by a method as described above. In particular, the pH of the preparation is 6.0-8.0. In a final aspect, the invention relates to this injectable preparation for use in the treatment of infections caused by aerobic and / or anaerobic gram-positive bacteria.

In the following, the invention is described a.d.h.v. non-limiting examples illustrating the invention, and which are not intended or may be interpreted to limit the scope of the invention.

EXAMPLES

Examples of solutions for making a powdered Teicoplanin composition for injection, as shown in Table 1:

Table 1

The solutions according to these embodiments were made by the following method:

A first amount of water for injection (80 percent by weight relative to the total amount of water for injection in the solution) with a temperature below 25 ° C was added to a vessel. - Teicoplanin was added to the solvent while stirring. The mixture was stirred for 10 minutes at 100 ± 10 revolutions per minute until Teicoplanin was completely dissolved.

Sodium chloride was added to the Teicoplanin solution while stirring (stirring for 10 minutes).

A second amount of the water for injection was added to the salted Teicoplanin solution to complete the total volume of the solvent.

Optionally, the pH of the solution was adjusted to 6.5-7.5 with a 0.1 M aqueous sodium hydroxide solution.

The resulting solution was then filtered twice through a cellulose acetate membrane filter with a filter size of 0.22 µm and filled into a vial to then be freeze-dried in the vial, which was partially sealed by a freeze-drying plug. This resulted in the following powdered Teicoplanin compositions, as shown in Table 2:

Table 2

The bottle in which the solution was freeze-dried was a glass bottle that meets the criteria of the Type I glass containers for pharmaceutical use according to the European Pharmacopoeia (Ph. Eur.), Chapter 3.2.1. The freeze-drying stopper was a dark gray bromobutyl-based rubber freeze-drying stopper according to European Pharmacopoeia (Ph. Eur.), Chapter 3.2.9, which is free of MBT and which contains aluminum silicate and / or magnesium silicate as a refuse. After freeze-drying, the bottle was completely sealed by the freeze-drying stopper and provided with an aluminum seal that was clamped around the opening of the bottle where the stopper closes the bottle.

An injectable preparation was then made from each of these powdered compositions by injecting an appropriate volume of water for injection with a needle into the vial through the freeze-drying plug. The powdered composition completely dissolved in the water for injection in order to obtain the injectable preparation:

Table 3

The composition of the present invention quickly dissolved in water for injection. For a powdered composition with 200 mg of Teicoplanin (Example 1), the composition dissolved in 3.2 minutes of water for injection in 3 minutes or less than 3 minutes. For a powdered composition with 400 mg of Teicoplanin (Example 2), the composition dissolved in 3.2 ml of water for injection in 5 minutes or less than 5 minutes. The solutions were clear.

The good stability of the powdered Teicoplanin composition was demonstrated for these examples with the following stability test, where an "X" indicates that the composition remained stable. The test was performed according to CPMP / QWP / 122/02 guideline: stability testing guideline: stability testing of existing active substances and related finished products. Sufficient stability is defined as meeting its specifications. The results are summarized in Table 4.

Table 4: stability test results

The vials were turned during this stability test such that the composition was in contact with the stopper of the vial.

It is believed that the present invention is not limited to the embodiments described above and that some modifications or changes can be added to the described examples without re-evaluating the appended claims.

Claims (14)

CONCLUSIONS A method for making a powdered Teicoplanin composition for injection, which composition comprises the following components: - 86-96 weight percent of Teicoplanin; - 4-13 weight percent of a salt; - 0-1 weight percent of a base; wherein the weight percentage of each component is expressed relative to the total weight of the composition, said method comprising the following steps: a) providing a first amount of a solvent with a temperature below 25 ° C; b) adding Teicoplanin to the solvent; c) adding the salt to the Teicoplanin solution; d) adding a second amount of said solvent with a temperature below 25 ° C to the salted Teicoplanin solution; e) optionally adding the base; resulting in a solution with pH 6.5-7.5, which solution is then freeze-dried at a temperature equal to or lower than 40 ° C to the powdered composition. Method according to claim 1, characterized in that the solution for freeze-drying is filtered at least once. Method according to claim 2, characterized in that the solution is filtered using a filter with a filter size between 0.15 and 0.25 µm. Method according to claim 3, characterized in that said filter comprises a cellulose acetate membrane. A method according to any one of the preceding claims, characterized in that said first amount of the solvent comprises between 70 and 90 percent by weight relative to the total weight of the solvent in the solution. Method according to one of the preceding claims, characterized in that the aforementioned salt is sodium chloride. Method according to one of the preceding claims, characterized in that the aforementioned solvent is water for injection or ethanol. Process according to any one of the preceding claims, characterized in that the aforementioned base is sodium hydroxide or sodium bicarbonate. A powdered Teicoplanin composition for injection obtained by a method according to any one of the preceding claims 1-8, which composition comprises the following components: - 86-96% by weight of Teicoplanin; - 4-13 weight percent of a salt; - 0-1 weight percent of a base; wherein the weight percentage of each component is expressed relative to the total weight of the composition, characterized in that the composition dissolves in less than 6 minutes when 3.2 ml of water for injection is added to a composition containing at most 400 mg of Teicoplanin at 25 ° C. A powdered composition according to claim 9, comprising a Teicoplanin dose of 100, 200 or 400 mg. A method for making an injectable Teicoplanin preparation comprising the step of adding a physiologically tolerable liquid to a powdered composition according to claim 9 or 10, characterized in that the pH of the preparation is 6.0-8.0 . The method of claim 11, wherein said fluid is water for injection. An injectable Teicoplanin preparation obtained by a method according to claim 11 or 12, characterized in that the pH of the injectable preparation is 6.0-8.0. An injectable Teicoplanin preparation according to claim 13, for use in the treatment of infections caused by aerobic and / or anaerobic gram-positive bacteria.