JP2884975B2 - Endotoxin extraction method - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for extracting endotoxin adhered or adsorbed on a solid surface.

[0002]

BACKGROUND OF THE INVENTION Endotoxin is a type of lipopolysaccharide mainly present in the cell surface of Gram-negative bacteria and is a substance generally well known as a pyrogen (Pyrogen). Therefore, knowing the degree of endotoxin contamination of a sample has become one of the important things in the fields of medicine, pharmacy and microbiology.

[0003] Regarding medical devices such as syringes and catheters, it is necessary to control the contamination with endotoxin strictly in order to prevent the incorporation of pyrogenic substances into the body.
Many medical devices are composed of various synthetic resins, glass, metals, natural fibers, and the like, and some of them are known to adsorb endotoxin. In order to measure the degree of contamination of these materials by endotoxin, endotoxin adhering to the surface is usually extracted by leaching with water or saline that does not contain endotoxin, and A method for measuring the amount of endotoxin has been used.

However, in this extraction method, it is considered that endotoxin adhering or adsorbed on a solid surface may not be completely extracted, and endotoxin that cannot be extracted with water or physiological saline is exposed to blood, medicine, or the like. It was feared that it would be extracted. Therefore, there is a need for a method for efficiently extracting endotoxin from the surface of a solid and measuring the degree of contamination of the substance with endotoxin more accurately, and at the same time, the effects of containers and instruments contaminated with endotoxin. At present, there is a long-awaited desire for a more efficient cleaning method.

[0005]

An object of the present invention is to provide a method for efficiently extracting endotoxin which is adhered to or adsorbed on a solid surface and which cannot be extracted with water or physiological saline in view of the above situation. With the goal.

[0006]

The present invention relates to a method for extracting endotoxin adhering or adsorbed on a solid surface, characterized in that extraction is carried out using a solution containing albumin and / or globulin as a component.

[0007] The present invention is also an invention of an endotoxin extraction reagent adhering or adsorbed on a solid surface, characterized by comprising albumin and / or globulin as a component.

Further, the present invention is an invention of a method for cleaning a container or an instrument contaminated with endotoxin, which comprises cleaning using a solution containing albumin and / or globulin as a component.

Furthermore, the present invention relates to a cleaning agent for a container or device contaminated with endotoxin, characterized in that it comprises albumin and / or globulin as a component.

That is, the inventors of the present invention have intensively studied a method for efficiently extracting endotoxin adhering or adsorbed on the surface of a solid. The present inventors have found that the adsorbed endotoxin can be extracted very efficiently by using a solution containing albumin and / or globulin as a component, particularly a solution containing albumin as a component, and have completed the present invention.

Examples of the solution containing albumin and / or globulin as a component used in the present invention include, for example, aqueous solutions of albumin and / or globulin and various buffer solutions, as well as plasma and serum containing albumin and / or globulin as a main protein component. Can also be mentioned.

The plasma or serum used in the present invention includes, without limitation, any plasma or serum derived from vertebrates.

As the albumin and / or globulin used in the present invention, albumin and / or globulin obtained by purifying or partially purifying protein components in plasma or serum can be mentioned as typical examples.

The solution containing albumin and / or globulin as a component (hereinafter abbreviated as "albumin solution etc.") used in the present invention does not necessarily have to be specially prepared for that purpose. Fresh liquid plasma and fresh frozen human plasma commercially available from Red Cross, etc., or from Nippon Pharmaceutical Co., Ltd., Roller Company, Armor Company, Cutter Company, Baxter Company, Midori Cross Company, Ltd. Commercially available heated human plasma protein and human serum albumin preparations, and also Takeda Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd.,
Human immunoglobulin preparations commercially available from Midori Cross, Hoechst, Japanese Red Cross and Fujirebio Co., Ltd., as well as commercially available from Whittaker, Hycron, Gibco, Boehringer Mannheim, etc. Naturally, those prepared using a calf fetal serum or the like can also be used.

Among these albumin solutions used in the present invention, the most preferable is an aqueous solution containing human serum albumin (hereinafter abbreviated as HSA solution).

The amount of endotoxin adhering or adsorbed on the solid surface extracted by the extraction method of the present invention using the extraction solution of the present invention can be determined by a known endotoxin measuring method.
For example, if the measurement is performed by a so-called Limulus test method or the like using a horseshoe crab blood cell component extract (hereinafter abbreviated as AL solution), the degree of endotoxin contamination of containers and instruments can be more accurately measured.

When the extraction method of the present invention is applied to such a purpose, the albumin solution and the like used for the extraction must not contain endotoxin in an amount that affects the measurement.

For this purpose, an albumin solution or the like of a lot having a low endotoxin content is selected, or when an albumin solution containing endotoxin is used, the endotoxin is previously purified using an autoclave or an endotoxin adsorbent. Need to be removed.

The conditions of the autoclave in this case include, for example, a temperature usually used (about 121 ° C.) of 15 to 120 ° C.
Minutes.

Examples of the endotoxin adsorbent include a carrier on which polymyxin B is immobilized, a carrier on which histidine is immobilized via a spacer, and the like. Specific trade names include detox gel (manufactured by Pierce). Examples include Affiprep polymyxin (manufactured by Bio-Rad) and Pyrosep (manufactured by Tanabe Seiyaku Co., Ltd.), but are not limited thereto.

The concentration of the albumin solution or the like in the extraction solution of the present invention used in the present invention may vary depending on the type or lot of the albumin solution or the like used, or the adhesion or adsorption of endotoxin to containers or instruments. Although it varies depending on the degree and is not necessarily constant, it is usually 0.0001 as the protein concentration in the solution.
mg / ml or more, preferably about 0.0001 to 6.00 mg / ml, more preferably about 0.02 to 3.00 mg / ml. When the albumin solution or the like is a human serum albumin solution, it is usually 0.0001% or more, preferably 0.0001 to 0.5%.
(Protein amount 0.001 to 6.00 mg / ml), more preferably 0.00
When the albumin solution is, for example, a human plasma solution, the protein concentration is usually 0.0001 mg / ml or more, preferably 0.0001 to 1.0%.
It is about mg / ml, more preferably about 0.1 to 0.5 mg / ml.

When the extract obtained by the extraction method of the present invention is subjected to a so-called Limulus test using an AL solution to measure its endotoxin concentration, there is no hindrance to the measurement, and an accurate measured value can be obtained. It is desirable that

On the other hand, albumin solutions and the like used in the present invention, that is, human serum albumin (HSA) solution, human plasma solution, human serum solution, fetal bovine serum solution, bovine serum albumin (BSA) solution, globulin solution, etc. In any case, when the protein concentration becomes high, an inhibitory action occurs in the measurement of endotoxin by the Limulus test method after extraction, and a value lower than the actual value is obtained. Therefore, when it is intended to measure the amount of endotoxin adhered or adsorbed on a solid surface such as a container or device, such a high concentration is not preferable. Therefore, the preferable concentration range of the albumin solution and the like according to the present invention, particularly the upper limit value is in consideration of such points, and is high when only used for washing or extraction. Concentrations can be used at all.
Note that the concentration of an albumin solution or the like that causes inhibition at the time of measurement by the Limulus test method differs significantly depending on the type of the albumin solution or the like. That is, for example, in the case of an HSA solution, inhibition occurs at a protein concentration of about 6.0 mg / ml, whereas in the case of a human plasma solution, inhibition occurs at a protein concentration of about 1 mg / ml.

The AL solution used for measuring the amount of endotoxin in the extract obtained by the extraction method of the present invention using a Limulus test is, for example, Limulus, Tachypleus or Carcinosco. It is not particularly limited as long as it is extracted from the blood cells of horseshoe crab belonging to the genus Pius (Carcinoscorpius) and coagulates by reaction with endotoxin or β-1,3-glucan.

For example, ACC (Associates of Cape)
Cod), Whitaker Bioproducts, In
c.), Endosafe, Inc., Seikagaku Corporation
Naturally, those prepared from freeze-dried AL solutions commercially available from Wako Pure Chemical Industries, Ltd. or the like can also be used.

The method of the Limulus test for measuring the amount of endotoxin in the extract obtained by the extraction method of the present invention using the Limulus test is not particularly limited as long as it is a commonly used method. is there.

A commonly used technique is, for example, the FDA guideline (Guidelineon validation of
the Limulus amebocyte lysate test as an end-pro
ductendotoxin test for human and animal paren
teral drugs, biologicalproducts, and medical devi
ces, Food and Drug Adm. (1987)), a gel inversion method, a synthetic substrate method, a turbidimetric time analysis method, and the like.

Since the endotoxin adhering to or adsorbed on the surface of a solid can be effectively extracted by using the extraction reagent of the present invention, the extract of the present invention can also be used for containers and instruments contaminated with endotoxin. And the like.

In addition, the extraction method of the present invention can inevitably be used as a method for cleaning containers and instruments contaminated with endotoxin.

Examples of containers and instruments to be subjected to the cleaning method of the present invention include disposable syringe needles, disposable syringes, disposable blood transfusion sets and infusion sets, disposable blood sampling instruments, heart-lung disposable blood sets, and medical artificial blood vessels. , Medical devices such as artificial heart valves, cardiac pacemakers, and dialysis type artificial kidney devices, and disposable laboratory instruments (sterile pipettes, sterile test tubes, sterile pipette tips, etc.) used for endotoxin tests, etc. It is not limited.

Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited to these examples.

[0032]

【Example】

Example 1 [Reagents] (1) Endotoxin solution Escherichia coli reference endotoxin (standard endotoxin defined by the Pharmacopoeia, lipopolysaccharide derived from E. coli UKT-B strain, 16,000 endotoxin units per vial (EU / ml))
Endotoxin corresponding to ) Was appropriately diluted with distilled water for injection. (2) AL solution Limulus ES-Test Wako (manufactured by Wako Pure Chemical Industries, Ltd.) was used. (3) HSA solution A 25% HSA solution (manufactured by Cutter Inc. for injection) was diluted to 1% with distilled water for injection, and autoclaved at 121 ° C. for 20 minutes to use after confirming that endotoxin was not detected.

[Operation] Minisart NML which is a filtration unit for syringes with a cellulose acetate membrane set
10 ml of distilled water for injection was filtered using (manufactured by Sartorius). Next, 10 ml of the 1% HSA solution was filtered, and then 10 ml of distilled water for injection was filtered to wash HSA attached to the membrane. The filtrate was fractionated and collected in 2 ml portions. Endotoxin was adsorbed to the membrane by filtering 5 ml of the endotoxin solution (1.0 EU / ml) using the mini-sarts that had been pre-washed. Followed by distilled water for injection 5
0 ml and 25 ml of a 1% HSA solution were filtered. These filtrates were fractionated and collected in 5 ml portions, and the endotoxin concentration in the fractionated filtrate was measured using a toxinometer ET-201 (Wako Pure Chemical Industries, Ltd.).
(Co., Ltd.). The measurement operation was performed as follows according to a standard method. 0.1 ml of the sample is added to 0.1 ml of the AL solution, and after stirring, the time until the amount of transmitted light of the above-mentioned mixture decreases by 5% while keeping the temperature at 37 ° C (hereinafter abbreviated as Tg).
Was measured. Separately, the same measurement was performed using endotoxin solutions of various concentrations prepared using distilled water for injection and a predetermined endotoxin solution as a specimen, and a calibration curve representing the relationship between the endotoxin concentration and Tg was prepared. Based on the calibration curve, the concentration of endotoxin in the sample was calculated.

[Results] FIG. 1 shows the change in the amount of endotoxin in the filtrate. In the filtration of distilled water for injection, a small amount of endotoxin was detected in the initial filtrate, but when the filtration of distilled water for injection was further continued, endotoxin was not detected in the filtrate. When the 1% HSA solution was filtered in this state, endotoxin was detected in the filtrate. This result indicates that endotoxin which was not extracted with distilled water for injection, but extracted with the 1% HSA solution was originally attached or adsorbed to minisart. After this,
When the distilled water for injection was filtered again, endotoxin was detected again in the filtrate. However, the endotoxin that had adhered or was adsorbed to the minisart membrane and became insoluble in distilled water for injection was solubilized by the HSA solution. It is considered to be attached to the membrane surface in a state, and this is dissolved in the distilled water for injection. Then, the endotoxin solution was filtered, and then distilled water for injection was filtered. After the endotoxin was no longer detected in the filtrate, a large amount of endotoxin was detected by filtering the 1% HSA solution. This result indicates that when the endotoxin solution is filtered through the minisart, a part of the endotoxin adheres or is adsorbed to the membrane and is not sufficiently extracted with distilled water for injection.
This indicates that extraction is possible with the SA solution. As is evident from these results, even endotoxin that is adhered or adsorbed to the solid surface and cannot be extracted with distilled water for injection can be solubilized and extracted by using an HSA solution.

Example 2 [Reagents] (1) Endotoxin solution Same as that used in Example 1. (2) AL solution Same as that used in Example 1. (3) HSA solution Same as that used in Example 1. (4) NaCl solution Physiological saline for injection (Otsuka Pharmaceutical) was used. (5) Plasmanate solution Plasmanate (manufactured by Cutter Co., heated human plasma) was diluted 10-fold with distilled water for injection and autoclaved at 121 ° C. for 20 minutes. (6) Sodium deoxycholate (hereinafter abbreviated as DOC) solution DOC (manufactured by Wako Pure Chemical Industries, Ltd., for biochemistry) was dissolved in distilled water for injection to prepare a 1% solution. This was autoclaved at 121 ° C. for 20 minutes and diluted to 0.01% before use. (7) Sodium dodecyl sulfate (hereinafter abbreviated as SDS) solution SDS (manufactured by Wako Pure Chemical Industries, Ltd., for biochemistry) was dissolved in distilled water for injection to prepare a 1% solution. This was autoclaved at 121 ° C. for 20 minutes and diluted to 0.01% before use. Each of the reagents (3) to (7) was used after confirming that endotoxin was not detected.

[Operation] After washing Minisart NML (manufactured by Sartorius) with 2 ml of a 1% HSA solution and 10 ml of distilled water for injection, 5 ml of an endotoxin solution (1.0 EU / ml) was added.
Filtered. Furthermore, filtration was performed using distilled water for injection until no endotoxin was detected in the filtrate. Next, filtration was performed using 3 ml each of an HSA solution, a NaCl solution, a plasmanate solution, a DOC solution, and an SDS solution as an extract. The endotoxin concentration in the filtrate of each extract was determined in the same manner as in Example 1.

[Results] Table 1 shows the amount of endotoxin in the filtrate of the extract.

[0038]

[Table 1] * The amount of endotoxin adhering or adsorbed to the membrane (the value obtained by subtracting the amount of endotoxin in the endotoxin solution after filtration from the amount of endotoxin in the endotoxin solution before filtration) was calculated as 100%.

As is clear from Table 1, endotoxin was detected in the filtrates of all the extracts.
It can be seen that the amount of endotoxin detected in the solution and the plasmanate solution is particularly large. From this result, it can be seen that among various endotoxin extracts, the HSA solution and the plasmanate solution according to the present invention have particularly excellent extraction power.

Example 3 [Reagents] (1) Endotoxin solution Same as that used in Example 1. (2) AL solution Same as that used in Example 1. (3) HSA solution A 2% solution of HSA prepared in the same manner as in Example 1 was used.

[Operation] 1.0 ml of distilled water for injection was placed in each of 10 sterilized polypropylene serum tubes (manufactured by Corning Co., Ltd., 2 ml volume), and the mixture was shaken.
0.2 ml was collected and used as a distilled water extract sample for injection. 0.8 ml of a 2% HSA solution was added to each of these serum tubes and shaken to prepare a 1% HSA solution extracted sample. The endotoxin concentration in the extracted specimen was determined by the same operation as in Example 1.

[Results] Table 2 shows the amount of endotoxin in each extract.

[0043]

[Table 2]

As is evident from Table 2, endotoxin is not extracted with distilled water for injection, or even when the amount of extraction is small, a considerable amount of endotoxin is extracted when the HSA solution is used.

Example 4 [Reagents] (1) Endotoxin solution Same as that used in Example 1. (2) AL solution Same as that used in Example 1. (3) HSA solution Same as that used in Example 2.

[Operation] A 0.1 EU / ml aqueous endotoxin solution and a 0.1 EU / ml endotoxin solution were placed in a glass test tube containing six disposable injection needles (manufactured by Nippon Medical Supply Co., size 22G).
10% each 1% HSA solution containing EU / ml endotoxin
Was added and mixed, and the amount of endotoxin in each solution was determined in the same manner as in Example 1. As a negative control, those without an injection needle were each measured, and the percentage of endotoxin when the injection needle was inserted was determined using this as 100%.

[Results] Table 3 shows the endotoxin recovery rate of each solution.

[0048]

[Table 3]

As is clear from Table 3, when no HSA solution was present, the endotoxin recovery rate was greatly reduced to 10% due to the presence of the injection needle. However, when the HSA solution coexisted, almost no influence by the injection needle was recognized. As is clear from these results, the HSA solution is effective for an endotoxin extraction test using an injection needle.

Example 5 [Reagents] (1) Endotoxin solution Same as that used in Example 1. (2) AL solution Limulus amoebocyte lysate extract (manufactured by Wako Pure Chemical Industries, Ltd., gelation sensitivity: 0.25 EU / ml, for 5 ml) was dissolved in Limulus ES Test Wako Lysis Buffer (Wako Pure Chemical Industries, Ltd.) Was dissolved in 5 ml and used as an AL solution. (3) Globulin solution Human immunoglobulin for injection (gamma globulin-Nichiyaku, containing 15% of IgG) is diluted to 0.5%,
The one heated for 0 minutes was used. The human immunoglobulin for injection was selected from lots in which endotoxin was not detected.

[Operation] In the same manner as in Example 1, endotoxin was attached to or adsorbed to Minisart NML (manufactured by Sartorius). Subsequently, the distilled water for injection was filtered until no endotoxin was detected in the filtrate, and then 5 ml of a 0.5% globulin solution was filtered. The amount of endotoxin in the filtrate was measured with a toxinometer ET-201 (manufactured by Wako Pure Chemical Industries, Ltd.). The measurement was performed in the same manner as in Example 1.

[Results] Table 4 shows the endotoxin concentration of the globulin filtrate.

[0053]

[Table 4]

As is clear from Table 4, some of the endotoxins adhering or adsorbed to the minisart were not extracted with distilled water for injection, but were extracted with some globulin solutions. It is found to be effective.

Example 6 [Reagents] (1) Endotoxin solution Same as that used in Example 1. (2) AL solution Limulus aegypti blood cell extract (manufactured by Wako Pure Chemical Industries, Ltd., gelation sensitivity: 0.06 EU / ml) was added to endotoxin test water 2.0 ml.
And used as an AL solution. (3) HSA solution A 25% HSA solution (manufactured by Cutter Inc. for injection) was diluted to 1% with distilled water for injection, and autoclaved at 121 ° C. for 20 minutes, and used after confirming that endotoxin was not detected. (4) Fetal bovine serum FETAL BOVINE SERUM (Whittaker Bioproduct, Inc.) 5
After 0 ml was diluted 10-fold with water, it was heated at 100 ° C. for 10 minutes on a water bath before use. (5) Human plasma Human pool plasma diluted 10-fold with water was heated at 100 ° C. for 10 minutes on a water bath before use. (6) Globulin solution 5 g of γ-GLOBULINS (Bovine cohn Fraction II, III)
It was adjusted to 2% and autoclaved at 120 ° C. for 20 minutes, and diluted with water for endotoxin test to 0.1% before use.

[Operation] To a disposable sterilized polypropylene test tube (FALCON 2059), 20 μl of a 25 EU / ml endotoxin solution (containing 6.25% ethanol) was added, and dried overnight (15 hours). Produced. Test samples (HSA, fetal bovine serum, human plasma, globulin solution) were diluted to appropriate concentrations, added to endotoxin-loaded test tubes in 1 ml portions, and extracted for 1 hour with occasional stirring. The endotoxin concentration in each extract was determined in the same manner as in Example 1.

[Results] Table 5 shows the endotoxin recovery rate of each solution.

[0058]

[Table 5]

As is clear from Table 5, the recoveries of three extracts of a 0.1% HSA solution, a 32.5-fold diluted bovine serum albumin and a 60.8-fold diluted human plasma at the same protein concentration (1.20 mg / ml). Are 109%, 71% and 57%, respectively, indicating that the HSA solution is most effective for endotoxin extraction at this protein concentration. A 0.1% HSA solution extracted with the same amount of albumin (1.20 mg / ml), 2
In comparison of 2.8-fold diluted bovine serum albumin and 42.6-fold diluted human plasma, the recoveries were 109%, 59% and 54%, respectively.
At this albumin concentration, both the bovine serum solution and the human plasma solution showed lower values than the HSA solution. On the other hand, H
In comparison of SA solution and globulin solution, 0.0096% HSA
HSA was clearly more effective than globulin at this protein concentration, with 106% for the solution (protein concentration 0.115mg / ml) and 51% for the 0.1% chlorophyllin solution (protein concentration 0.115mg / ml). .

Example 7 Examination of HSA Solution Concentration [Reagents] (1) Endotoxin solution Same as that used in Example 1. (2) AL solution Same as that used in Example 6. (3) HSA solution An HSA 25% solution (manufactured by Cutter Inc. for injection) was diluted to 1% with distilled water for injection, and autoclaved at 121 ° C. for 20 minutes to confirm that endotoxin was not detected. It was used after being diluted with water to a predetermined concentration.

[Operation] According to the sixth embodiment.

[Results] Table 6 shows the endotoxin recovery rates with various concentrations of the HSA solution.

[0063]

[Table 6]

As is clear from Table 6, the HSA solution was 0.1%.
It can be seen that even a low concentration of about 0001% is effective for endotoxin extraction. It should be noted that the recovery rate seems to be lower as the HSA concentration is higher. However, as described above, when the HSA concentration is higher, the inhibitory effect is lower in the endotoxin measurement of the extract by the Limulus test method. This is because it occurs and the extraction power itself is not low.

Example 8 Examination of concentration of human plasma solution [Reagents] (1) Endotoxin solution Same as that used in Example 1. (2) AL solution Same as that used in Example 6. (3) Human Plasma Solution Human pooled plasma was diluted 10-fold with water, heated at 100 ° C. for 10 minutes in a water bath, and diluted with water for endotoxin test to a predetermined concentration before use.

[Operation] According to the sixth embodiment.

[Results] Table 7 shows the endotoxin recovery rate in human plasma solutions of various concentrations.

[0068]

[Table 7]

As is evident from Table 7, in the case of human plasma, a 320-fold dilution is most effective for endotoxin extraction, and the extraction power gradually decreases as the concentration decreases. I understand. In the case of human plasma concentration, the higher the concentration, the lower the value of the recovery rate because an inhibition reaction occurs when measuring the endotoxin content of the extract,
The recovery itself is not actually decreasing.

[0070]

According to the present invention, there is provided a method for efficiently extracting endotoxin adhering to or adsorbed on a solid surface of a container, a device or the like. The present invention has a remarkable effect in that simple and effective extraction can be performed even for difficult ones, and this is a great invention that contributes to the industry.

[0071]

[Brief description of the drawings]

FIG. 1 shows a change in the amount of endotoxin in a filtrate obtained in Example 1.

[Explanation of symbols]

 Each abbreviation in FIG. 1 has the following meaning. WFI: distilled water for injection HSA: 1% human serum albumin solution RSE: endotoxin solution (1.0 EU / ml)

Continuation of front page (58) Field surveyed (Int.Cl. ⁶ , DB name) C08B 37/00 A61K 31/715

Claims (20)

(57) [Claims] 1. A method for extracting endotoxin adhering or adsorbed on a solid surface, comprising extracting using a solution containing albumin and / or globulin as a component. 2. The extraction method according to claim 1, wherein the extraction is performed using a solution containing albumin as a component. 3. The albumin is human serum albumin,
The extraction method according to claim 1. 4. The concentration of human serum albumin is 0.0001 to 0.5.
%. 5. The extraction method according to claim 1, wherein the solution containing albumin is a plasma solution or a serum solution. 6. An endotoxin extraction reagent adhered or adsorbed on a solid surface, characterized by comprising albumin and / or globulin as a component. 7. The extraction reagent according to claim 6, comprising albumin as a component. 8. The albumin is human serum albumin,
The extraction reagent according to claim 6. 9. A human serum albumin concentration of 0.0001 to 0.5.
%. 10. The test solution for extraction according to claim 6, wherein the solution containing albumin is a plasma solution or a serum solution. 11. A method for cleaning a container or device contaminated with endotoxin, comprising cleaning using a solution containing albumin and / or globulin as a component. 12. The cleaning method according to claim 11, wherein a solution containing albumin as a component is used. 13. The albumin is human serum albumin,
13. The cleaning method according to claim 11 or 12. 14. The human serum albumin concentration of 0.0001 to 0.5.
14. The cleaning method according to claim 13, wherein the percentage is%. 15. The washing method according to claim 11, wherein the solution containing albumin is a plasma solution or a serum solution. 16. A cleaning agent for containers or instruments contaminated with endotoxins, characterized in that it comprises albumin and / or globulin as a component. 17. The cleaning agent according to claim 16, comprising albumin as a component. 18. The albumin is human serum albumin.
18. The cleaning agent according to claim 16 or 17. 19. The method according to claim 19, wherein the concentration of human serum albumin is 0.0001 to 0.5.
19. The cleaning agent according to claim 18, which is% by weight. 20. The detergent according to claim 16, wherein the solution containing albumin is a plasma solution or a serum solution. [0001]