WO2003055533A1

WO2003055533A1 - Compositions for eliminating endotoxin and elimination method

Info

Publication number: WO2003055533A1
Application number: PCT/JP2002/012768
Authority: WO
Inventors: Kenji Kamimura; Minako Toda
Original assignee: Nihon Medi-Physics Co., Ltd.
Priority date: 2001-12-26
Filing date: 2002-12-05
Publication date: 2003-07-10
Also published as: NO20033772L; JP5296016B2; AU2002349439A1; JPWO2003055533A1; JP2010284535A; TW200301142A; NO20033772D0; JP4647911B2

Abstract

It is intended to provide a technique of eliminating endotoxins, which are attached or adsorbed on the surface of solid articles such as medical instruments or instruments and apparatuses for producing medicines, by using a non-biological origin and sterilizable chemical reagent so as to eliminate the endotoxins at a high efficiency compared with the case of using water or physiological saline. Namely, compositions for eliminating endotoxins attached or adsorbed on solid surface characterized by containing as the active ingredient saccharides selected from the group consisting of monosaccharides, oligosaccharides, derivatives thereof and hydrates and salts of the same; and a method of eliminating endotoxins from solid surface by bringing a solution of the composition as described above with the solid surface.

Description

Specification

TECHNICAL FIELD The present invention relates to a composition for removing endotoxin and a method for removing endotoxin.

The present invention relates to a technique for removing endotoxin using a saccharide, and more particularly to a composition for removing endotoxin containing a saccharide, and a method for removing and extracting endotoxin using the composition, and relates to a medical device and a pharmaceutical manufacturing method. The present invention relates to a technique useful for removing endotoxin from a solid surface such as a device or a pharmaceutical manufacturing device. Background art

Endotoxin is a type of lipopolysaccharide that mainly exists in the outer membrane of the cell wall of Gram-negative bacteria, and is a substance generally well known as a pyrogen (Pyrogen).

If pyrogenic substances enter the body due to endotoxin contamination of injections and catheters, fever, shock, and extensive intravascular coagulation (DIC: Disintegrated Intravaginal Coagulation) Severe control of endotoxin in pharmaceuticals such as injections, medical devices such as syringes and catheters, and endotoxin contamination in drug manufacturing equipment and devices is required.

Many medical tools and pharmaceutical manufacturing tools and devices are composed of various synthetic resins, glass, metals, natural fibers, and the like, and are highly contaminated by the attachment or adsorption of endotoxin.

In general, endotoxin can be inactivated by heat treatment at 250 ° C for 30 minutes or more or at 100 ° C for 120 minutes or more, so that glass and metals are decontaminated by such heat treatment. it can. In addition, endotoxin is inactivated at 30 ° C in an organic solvent such as ethanol containing sodium hydroxide or dimethyl sulfoxide, so that glass and the like can also be washed by washing with such a medium. Can be removed. However, medical tools and pharmaceutical manufacturing instruments and devices made of materials to which such heat treatment or organic solvent treatment cannot be applied, or medical tools and pharmaceutical manufacturing instruments and devices having such a structure that cannot be heated. Etc. must be based on other decontamination methods.

To remove endotoxin contained in these medical devices, pharmaceutical manufacturing tools and equipment, etc., for example, a method of washing with water or physiological saline not containing endotoxin can be considered. There was a concern that a large amount of physiological saline was required, and that the removal of endotoxin adhering or adsorbed to medical equipment and pharmaceutical manufacturing equipment and equipment could be incomplete.

Japanese Patent No. 2884975 discloses a method for efficiently extracting endotoxin adhering or adsorbed on a solid surface of a container, device, or the like, in place of water or saline, instead of albumin, human serum albumin, globulin, and other proteins. A method for extracting endotoxin into a solution by washing a container, equipment, and the like using the solution is described.

However, blood proteins are biological components and are therefore not desirable for washing to remove endotoxin present in medical devices, pharmaceutical manufacturing tools and equipment, and the like. For such uses, it is desirable to use a composition that is easier to prepare and use, rather than using a solution containing a biological component as described above.

Techniques for washing or removing endotoxins using compositions that are easier to prepare and use include, for example, drugs that have a short shelf life and require frequent production on demand, such as a short half-life It is suitable for producing radiopharmaceuticals using radionuclides. In particular, the manufacture of drugs used in diagnostic methods for positron emission tomography (hereinafter referred to as PET) using ultrashort half-life positron-emitting nuclides with a half-life of several hours or less is more important. It is a suitable technique. The present invention is intended to adhere to or adsorb to solid surfaces To provide a method for removing endotoxin, which is a non-living chemical reagent that can be sterilized, and that can remove endotoxin more efficiently than water or saline. Aim.

Disclosure of the invention

2- [18 F] -Fluoro-2-deoxy-D-glucose (hereinafter referred to as 18 F-FDG), which is a representative drug for PET diagnosis, is based on the method of Hamacher et al. (Hamacher, K. eta 1., J Nucle ar Medicine, 27: 235-238, 1986) The present inventors have developed a method for removing endotoxin adhering or adsorbing to ion-retardant resin often used in this production method. As a result of intensive research on endotoxin, endotoxin, which is not normally removed with water or saline, is very efficiently removed by elution or extraction with a solution containing saccharides as a component. The present inventors have found that the present invention can be used for removing endotoxin adhering or adsorbed on a solid surface, and have completed the present invention.

Thus, according to one aspect of the present invention, there is provided a composition for removing endotoxin adhered or adsorbed on a solid surface, comprising a saccharide as an active ingredient.

Therefore, endotoxin can be effectively removed by bringing the solution of the removing composition of the present invention into contact with and recovering various solid surfaces, in addition to medical tools and pharmaceutical manufacturing equipment and devices that require endotoxin removal. Can be removed.

Therefore, according to another aspect of the present invention, a solid surface from which endotoxin is to be removed is brought into contact with a solution of the composition to remove endotoxin attached or adsorbed on the solid surface. A method for removing endotoxin is provided. The method for bringing the solution of the removing composition of the present invention into contact with the solid surface may be appropriately selected according to the type of the solid surface. For example, a solid surface may be immersed in the solution, the solid surface may be washed with the solution, or the solution may be impregnated in a sterilized cloth with an appropriate method, and the solid surface may be wiped with the cloth. In addition, the endotoxin adhering or adsorbed to the solid surface of a medical device, a pharmaceutical manufacturing tool or device, etc., by performing the above-described immersion, washing, wiping operations, etc. using the solution of the composition of the present invention, Since the endotoxin can be transferred into a solution and the endotoxin can be eluted or extracted into the solution, the composition of the present invention is useful for obtaining a detection liquid when detecting and measuring the degree of endotoxin contamination on the solid surface. is there.

Therefore, according to still another aspect of the present invention, a solid surface to which endotoxin is attached or adsorbed is brought into contact with a solution of the composition, and the endotoxin containing endotoxin detached or desorbed from the solid surface is contained. There is provided a method for extracting endotoxin, which comprises obtaining a composition.

Hereinafter, embodiments of the present invention will be described.

The saccharide used in the composition of the present invention includes a monosaccharide or an oligosaccharide or a derivative thereof. These saccharides may be salts or hydrates thereof. The saccharide may be either the D-form or the L-form. Specifically, the monosaccharide is generally preferably hexose. For example, in addition to glucose, galactose, mannose, fructose, etc., glucosamine, galactosamine, glucosamine hydrochloride, galactosamine hydrochloride, N— Amino sugars such as acetylglycosamine and N-acetylgalactosamine, derivatives and salts thereof. Oligosaccharides include disaccharides to hexasaccharides in size, preferably disaccharides such as maltose, sucrose and lactose. Of these, particularly preferred saccharides are glucose, glucosamine hydrochloride, N-acetyl-D-galactosamine and maltose, most preferably glucose.

When used, the removal composition of the present invention is prepared as a solution dissolved in an appropriate solvent. However, it may be provided in the form of a solution previously dissolved in a solvent, or may be provided in a lyophilized form so that it can be used after being dissolved in a solvent at the time of use. Further, the composition of the present invention may be provided as a kit in which a freeze-dried product and a solvent are combined.

The solvent is not particularly limited as long as it is physiologically, pharmaceutically or chemically acceptable. For example, water, physiological saline, electrolyte compositions such as Ringer's solution, injection solutions, and various buffer solutions Is mentioned. Buffers include phosphate buffer, citrate buffer, etc., as well as fluoric acid, phosphoric acid, boric acid, citric acid, succinic acid, tartaric acid, lactic acid, acetic acid, ammonium chloride, carbonic acid, tris (hydroxymethyl ) Buffers composed of aminomethane and their salts.

Further, the composition of the present invention can contain various physiologically, pharmaceutically or chemically acceptable additives as necessary. Examples of additives include various pH adjusting agents such as acids and bases, various buffer solutions, dextran 10 and dextran 40, dextrin, cyclodextrin, sodium lactate, various amino acids, methanol, ethanol, dimethyl sulfoxide, N, N-dimethylformamide, acetonitrile, tetrahydrofuran and the like can be mentioned.

In the present invention, the concentration of the saccharide in the solution depends on the type of the saccharide and the solvent, etc., or the degree of endotoxin attachment or adsorption on the solid surface, and cannot be necessarily constant. It is about 1 to 15 g / 100 ml (hereinafter referred to as w / v%), preferably about 0.5 to 10 w / v%. If the concentration is too low, the effect of removing endotoxin decreases, and if the concentration is too high, a large amount of washing solution is required to wash saccharides remaining after the removal operation, and the operation becomes complicated.

The solution of the composition of the present invention can be prepared by dissolving a saccharide together with an additive as necessary in a solvent. However, due to its properties, it must be prepared without endotoxin or inactivated. Endotoxin is removed from the composition of the present invention. Examples of the method include removing endotoxin from a saccharide solution using an ultrafiltration membrane or endotoxin adsorbent, or preparing a saccharide solution using water from which endotoxin has been removed in advance using an ultrafiltration membrane. And the like. Alternatively, a sterilized commercially available saccharide solution, for example, Japanese Pharmacopoeia Glucose Injection (5 w / v%, 10 w / v%, etc.) can be used as it is, in which case special preparation is required. Not convenient. Further, such a commercially available saccharide solution may be appropriately aseptically diluted using the above-mentioned solvent and used.

Thus, by immersing a suitable solid in the solution of the composition of the present invention or washing the surface of the solid with the solution, endotoxin adhering to or adsorbing to the surface of the solid is desorbed from the surface. Alternatively, it is desorbed and moves into the solution, so that it is effectively removed. Also, by collecting the solution used for immersion or washing, the amount of endotoxin adhering to the solid surface can be detected or measured. That is, the composition of the present invention can also be used as an endotoxin detection solution.

The solution recovered as described above is used as a sample for measurement by a per se known endotoxin measurement method, for example, the Limulustest method using a blood cell component extract of Limulus aegypti (hereinafter abbreviated as AL solution). By doing so, the degree of contamination of the solid surface by endotoxin can be accurately measured. Examples of the AL solution include those extracted from the blood cells of the genus Butogani, such as the genus Limulus (Limus 1 us) and the genus Tachypleus, and are endotoxin or / 1,3-glucan. Those which cause coagulation due to the reaction with can be used. Generally, those prepared from freeze-dried products commercially available from Seikagaku Corporation and Wako Pure Chemical Industries, Ltd. can be used. As a method for measuring the endotoxin concentration in a sample by the Limulus test method, any method commonly used as described in the Japanese Pharmacopoeia can be used without any particular limitation.

The solid surface to be subjected to the endotoxin removal or extraction method of the present invention includes: Examples include surfaces of medical equipment, pharmaceutical manufacturing equipment, and pharmaceutical manufacturing equipment. Examples of medical devices include disposable injection needles, disposable syringes, disposable blood transfusion devices and infusion devices, disposable blood collection devices, cardiopulmonary bypass devices, medical artificial blood vessels, Includes artificial heart valves, cardiac pacemakers, dialysis artificial kidney devices, and disposable laboratory equipment (sterile pipes, sterile test tubes, sterile pipe tips, etc.) used for endotoxin testing. It is. Pharmaceutical manufacturing equipment and equipment include, for example, purification and separation of resins used for purification and separation of ion exchange resins, reverse osmosis membranes, nanofiltration membranes, ultrafiltration membranes, precision filtration membranes, electrodialysis membranes, etc. For example. In addition, the present invention is useful for removing endotoxin from manufacturing equipment and devices for pharmaceuticals requiring short-lived expiration and requiring frequent production according to demand. In particular, 2- [18F] This is convenient for effectively removing endotoxin adhering or adsorbed to a device and / or device for synthesizing fluoro-2-dexoxy-D-glucose. Example

Hereinafter, the present invention will be described more specifically with reference to Examples, but the present invention is not limited to these Examples. In the following examples, unless otherwise specified, the concentration of the saccharide solution is expressed as “w / v%”.

Reagents and equipment used for testing

A commercially available sterilized disposable device was used for the syringe, stopcock and column. After washing, the glassware was passed through water for injection and sterilized by dry heat at 250 ° C for 90 minutes. For the saccharide solution, a commercially available product was appropriately diluted, or a commercially available special-grade reagent was dissolved in water for injection, and used as an endotoxin removal solution to be passed through an ion-retarding resin in the following Examples. All of these solutions were prepared by aseptic operation.

The following endotoxin test reagents based on the Japanese Pharmacopoeia were used. Endotoxin standard solution (1000 EU / ml): Endotoxin 100 0 Endotoxin test solution (10000 EU / ml) was prepared by adding an appropriate amount of water for endotoxin test to a standard product (standard product of the Japanese Pharmacopoeia) and dissolved, and this was used as a stock solution, diluted appropriately, and used. “EU” means endotoxin unit.

Gelling method: Limulus ES-II Test Co. (Wako Pure Chemical Industries)

Turbidimetry: Limulus E S-II Test I Co. or Limulus E S J Test II Co. (Wako Pure Chemical Industries)

The ion retardation resin used was an ion retardation resin AG11A8 manufactured by Bio-Rad.

Example 1

Washing of ion-retardant resin with glucose solution— 1

The column that had been autoclaved (120 ° C, 20 minutes) was aseptically packed with the ion-delay resin. Two columns were created.

Conditioning was performed by passing 10 Oml of water for injection through the two columns. Then, 1 Oml of water for injection is passed through one column (hereinafter referred to as column 1) and 1 Oml of 0.175 w, v% glucose solution is passed through the other column (hereinafter referred to as column 2). did. An endotoxin test (gelation method) was performed on each eluate from each column. The gelation method was performed according to the method of the Japanese Pharmacopoeia. Table 1 shows the results.

From the results of column 2 in Table 1, it was confirmed that endotoxin was eluted by passing a 0.175 w / v% glucose solution through the column. On the other hand, endotoxin was not detected in the eluate of column 1 through the injection water. From this, it can be said that endotoxin which was not eluted from the column in the conditioning using 10 Oml of water for injection was eluted by passing 1 Oml of the 0.175 w / v% glucose solution thereafter. Water for injection, 0.175 w / v% glucose solution in ion-retarding resin

Endotoxin test results for each eluate when passed through

Example 2

Washing of Ion Delayed Resin with Glucose Solution—2

Columns sterilized by autoclave (120 ° (:, 20 minutes)) were aseptically packed with ion-retarding resin.

Water for injection was passed through one column (hereinafter referred to as column 3), and 0.175 wZv% glucose solution was passed through the other column (hereinafter referred to as column 4). Each eluate was sampled when 100 ml, 200 ml, 500 ml and 1000 ml were eluted, and the sampling numbers were 1, 2, 3 and 4, respectively. The endotoxin concentration of the sampled eluate was measured by turbidimetry. Nephelometry was performed according to the method of the Japanese Pharmacopoeia. Table 2 shows the results.

As shown in Table 2, the results of column 4 confirmed that endotoxin was eluted in the first fraction (sampling number 1) by flowing the 0.175 w / v% glucose solution. In addition, the extraction of endotoxin from the column was relatively fast, and it was observed that almost no endotoxin concentration was observed in sampling numbers 2 to 4. On the other hand, endotoxin was not eluted when water for injection was used as shown in the results of column 3. Table 2

Water for injection (column 3) and 0.175 w / v% glucose solution (column 4)

Reference example

Preparation of endotoxin-contaminated ion-delay resin column

20 g of the ion-retarding resin (AG11A8) was placed in a beaker, an appropriate amount of water for injection was added to swell, and 0.4 ml of the endotoxin standard solution (10000 EU / ml) prepared as described above was added. This was stored at 4 ° C. with stirring overnight. An appropriate amount of this ion-retarded resin was aseptically packed into a column that had been autoclaved (120 ° C, 20 minutes).

Example 3

Measurement of endotoxin removal effect in ion-retardant resin: Removal of endotoxin from ion-retardant resin 1

Prepare two ion-delay resin columns prepared according to the reference example. One column (hereinafter referred to as column 5) contains 5 ml of water for injection and the other column (hereinafter referred to as column 6). 5 ml of a 1 Ow / v% glucose solution was passed. Each eluate from each column was dispensed in 0.5 ml aliquots into sterile beakers for a total of 10 fractions. These fractions were designated as fraction numbers 1 to 10.

Washing operation to confirm endotoxin remaining in column

Next, 7.5 ml of a 10 w / v% glucose solution was passed through the columns 5 and 6. Add 0.5 ml of each eluate from each column to a sterile tube. A total of 15 fractions were collected. Each of these fractions was designated fraction number 11 to 25.

Endotoxin concentration measurement of each fraction

The endotoxin concentration was measured for the solutions of fraction numbers 4, 5, 6, 7, 10, 13, 16, 19, 22 and 25 obtained from columns 5 and 6 as described above. The endotoxin test was performed by turbidimetry according to the method of the Japanese Pharmacopoeia.

Correction of endotoxin concentration measurement

The measured values of the endotoxin test on the eluate were corrected for inhibition. Inhibition correction was performed as follows. An endotoxin standard solution dilution (0.5 EU / ml) was added to each saccharide solution so that the sample solution became 0.25 EU / ml, and the endotoxin concentration of this solution was measured. On the other hand, an endotoxin standard solution diluent (0.5 EUZml) was similarly added to water for injection, and the endotoxin concentration of this solution was measured. For each endotoxin concentration of each saccharide solution to which the endotoxin standard solution diluent (0.5 EU / ml) was added, add the endotoxin standard solution diluent (0.5 EU / ml) to the injection water. Percentage (%) was calculated assuming the concentration of undotoxin as 100, and this was defined as the inhibition rate (%). The endotoxin concentration of each fraction was corrected for this inhibition rate. No correction was made for endotoxin measurements in water for injection.

Table 3 shows the concentrations (corrected values) of endotoxin contained in fractions 4, 5, 6, 7 and 10 in columns 5 and 6, respectively. Table 3

Changes in endotoxin concentration during removal of endotoxin from an ion lag resin column by 10 w / v% glucose solution and water for injection.

(EU / ml) From Table 3, when 10 w / v% glucose solution was passed through the column, the amount of endotoxin eluted was different for each fraction, as indicated by the change in endotoxin concentration from fractions 4 to 7. It decreased rapidly. From this, 1 0

It was observed that the endotoxin was rapidly removed by the% glucose solution.

From these results, it was confirmed that endotoxin in the column can be eluted more quickly by eluting endotoxin in the column using a 10 w / v% glucose solution than by using water for injection.

To show the presence or absence of endotoxin still remaining in the column, Table 4 lists the endotoxins contained in each of fractions 13, 16, 19, 22, and 25 of columns 5 and 6. Indicates the density (value after correction).

Table 4

Endotoxin in washing operation of column with 10 w / v% glucose solution

(EU / ml) In column 5 using water for injection as the eluate for fractions 1 to 10, endotoxin was eluted in fractions 1 to 25 using the subsequent 10 w / v% glucose solution as eluent. It can be said that endotoxin removal by ~ 10 water for injection was not sufficient.

On the other hand, in column 6, which used a 10 w / v% glucose solution as the eluate for fractions 1 to 10, almost no endotoxin was eluted after fraction 11 using the subsequent 10 w / v% glucose solution as the eluate. Was.

Thus, it was confirmed that endotoxin could be more effectively eluted by using a 10 w / v% glucose solution as a solution for removing endotoxin in the ion-retardant resin than by using water for injection. Was.

Example 4

Measurement of endotoxin removal effect in ion-retardant resin: Removal of endotoxin from ion-retardant resin— 2

5 ml of an lw / v% glucose solution was passed through the ion retardation resin column (hereinafter referred to as column 7) prepared in the reference example. The eluate from this column was dispensed in 0.5 ml aliquots into sterilized beakers for a total of 10 fractions (fraction numbers 1 to 10) .o

Endotoxin concentration measurement of each fraction

Among the obtained fractions, solutions of fraction numbers 4, 5, 6, 7 and 10 were subjected to measurement of endotoxin concentration. The endotoxin test and the inhibition correction of the measured values were performed in the same manner as in Example 3. Table 5 shows the results. Table 5

End in an ion retarding resin column with lw / v% glucose solution

Changes in endotoxin concentration during toxin removal.

(EU / ml) As shown in Table 5, the endotoxin in the ion-delay resin column was eluted into each fraction by passing the lw / v% glucose solution through the column, and the amount of endotoxin in fractions 4 to 7 was increased. As shown by the change in the concentration, it was observed that the concentration rapidly decreased for each fraction, and endotoxin was rapidly removed and extracted from the ion-lagging resin column.

Example 5

L w / v% to the ion retardation resin column (hereinafter referred to as column 8) created in Reference Example

5 ml of D-(+) darcosamine hydrochloride solution were passed through. The eluate from this column was collected in a sterilized beaker in 0.5 ml portions for a total of 10 fractions (fraction numbers 1 to 10).

Endotoxin concentration measurement of each fraction

Among the obtained fractions, solutions of fraction numbers 4, 5, 6, 7, and 10 were subjected to endotoxin concentration measurement. The endotoxin test and the inhibition correction of the measured values were performed in the same manner as in Example 3. Table 6 shows the results. Table 6

Changes in endotoxin concentration during removal of endotoxin from ion-retarded resin column by lw / v% D-(+)-glucosamine hydrochloride solution.

(EU / ml)

Example 6 Measurement of Endotoxin Removal Effect in Ion-Retardant Resin: Removal Procedure of Endotoxin from Ion-Retardant Resin 1 4 Prepare two ion-retardant resin columns prepared according to Reference Example, and use one column. 5 ml of lw / v% maltose solution for the other column (hereinafter referred to as column 9) and 5 ml of 10 w / v% maltose solution for the other column (hereinafter column 10). Was passed. Each eluate from each column was dispensed in 0.5 ml aliquots into sterile beakers for a total of 10 fractions. Each of these fractions was designated fraction number 1 to 10.

Endotoxin concentration measurement of each fraction Among the obtained fractions, the endotoxin concentration was measured for the solutions of fraction numbers 4, 5, 6, 7, and 10 respectively. The endotoxin test and the inhibition correction of the measured values were performed in the same manner as in Example 3. Table 7 shows the results.

Table 7

Changes in endotoxin concentration during removal of endotoxin from an ion-retarded resin column by lw / v% and 10w / v% maltose solutions.

(EU / ml) Example 7

Prepare two ion-delay resin columns prepared according to the reference example. One column (hereinafter referred to as column 11) contains 5 ml of 1 w / v% N-acetyl-D-galactosamine solution and another column. A column (hereinafter referred to as column 12) was passed with 5 ml of a 10 w / v% N-acetyl-D-galactosamine solution. Each eluate from each column was dispensed in 0.5 ml aliquots into a sterilized beaker for a total of 10 fractions. These fractions were designated as fraction numbers 1 to 10. Endotoxin concentration measurement of each fraction Among the obtained fractions, the endotoxin concentration was measured for the solutions of fraction numbers 4, 5, 6, 7, and 10, respectively. The endotoxin test and the inhibition correction of the measured values were performed in the same manner as in Example 3. Table 8 shows the results.

Table 8

Ion delay due to lw / v% and 10 w / v% N-acetyl-D-galactosamine solutions Changes in endotoxin concentration during endotoxin removal from resin columns.

(EU / ml)

From Table 6, Table 7 and Table 8, lw / v% D — (+) — glucosamine hydrochloride solution, 1 w / v% maltose solution, 10 w / v% maltose solution, lw / v% N— Cetyl-D-galactosamine solution and 10 w / v% N-acetyl-D-galactosa When the min solution was used as the endotoxin removing solution, the same results as those of the glucose solutions shown in Tables 1 to 5 were obtained. That is, by flowing these solutions through the column, the endotoxin in the ion-retarding resin column is eluted into each fraction, and the amount of endotoxin varies with the fraction as indicated by the change in endotoxin concentration from fraction 4 to Ί. The endotoxin was rapidly removed from the ion-lagging resin column and extracted.

In addition, 1 O w / v% maltose solution was added over 1 w / v% maltose solution, and 1 O w / v% N-acetil was added over 1 w / v% N-acetyl-D-galactosamine solution. When 1-D-galactosamine solution was used as the endotoxin removal solution, the appearance of endotoxin elution was rapid, and it was also observed that the higher the concentration, the faster the rate of reduction.

Industrial applicability

According to the present invention, it has been clarified that endotoxin adhering or adsorbing to a solid surface can be removed using a saccharide solution. Therefore, the endotoxin adhering or adsorbed to the surface can be efficiently removed by bringing the sterilized saccharide solution into contact with the surface of a medical device, a pharmaceutical manufacturing device, or a device. ADVANTAGE OF THE INVENTION According to this invention, it can remove effectively and easily what was difficult to elute or extract with the conventional removal method, Furthermore, complicated post-processing after removal is unnecessary. Useful in the field.

Claims

The scope of the claims

1. A composition for removing endotoxin adhered or adsorbed on a solid surface, comprising a saccharide as an active ingredient.

2. The composition according to claim 1, wherein the saccharide is at least one selected from the group consisting of monosaccharides, oligosaccharides and derivatives thereof, and hydrates and salts thereof.

3. The composition according to claim 2, wherein the monosaccharide is hexose.

4. The composition according to claim 2, wherein the saccharide is glucose, glucosamine hydrochloride, N-acetyl-D-galactosamine or maltose.

5. The composition according to claim 1, wherein the composition is in the form of a solution, and the concentration of the saccharide is 0.1 to 15 g / 100 ml.

6. The solid surface from which endotoxin is to be removed is brought into contact with a solution of the composition according to any one of claims 1 to 5 to adhere or adsorb to the solid surface. A method for removing endotoxin, which comprises removing endotoxin.

7. The method according to claim 6, wherein the solid surface is a surface of a medical device, a pharmaceutical manufacturing tool or a pharmaceutical manufacturing device.

8. The method according to claim 7, wherein the pharmaceutical manufacturing equipment or the pharmaceutical manufacturing equipment is a radiopharmaceutical manufacturing equipment or manufacturing equipment.

9. The method according to claim 8, wherein the radiopharmaceutical production apparatus or apparatus is a 2- [18 F] monofluoro-2-dexoxy-D-glucose production apparatus or apparatus.

10. The solid surface to which endotoxin is adhered or adsorbed is brought into contact with the solution of the composition according to any one of claims 1 to 5 to remove the endotoxin desorbed or desorbed from the solid surface. A method for removing endotoxin, comprising obtaining the composition containing the endotoxin.