JPH07136507A - Endotoxin adsorbent - Google Patents

Abstract

PURPOSE:To obtain an adsorbent having excellent adsorption performance for endotoxin by dispersing or dissolving paraffin having specified mol.wt. in an org. solvent and depositing the liquid on the surface of an inorg. material to constitute a composite material. CONSTITUTION:Endotoxin is a lipopolysaccharide and is a typical exothermic matter. When blood contaminated with endotoxin is introduced into a human body, endotoxin causes side-effect such as fever. Therefore, contamination of medicine with endotoxin is severely inspected. By providing a composite material having excellent adsorption performance for endotoxin, endotoxin-free water can be efficiently produced at a low cost and endotoxin in proteins can be removed at a low cost. Namely, paraffin having >=250mol.wt. is dispersed or dissolved in an org. solvent and deposited on the surface of an inorg. material to constitute the composite material.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an endotoxin adsorbent comprising a novel composite material.

[0002]

2. Description of the Related Art Endotoxin is a lipopolysaccharide and is a typical pyrogenic substance. When blood, infusions, or injections contaminated with endotoxin enter the body, side effects such as fever and shock are caused, and thus endotoxin contamination of pharmaceuticals is strictly examined. Therefore, pharmaceutical water, water used to wash syringes, water used in operating rooms, etc., have been produced by distilling ion-exchanged water, sterilizing it, and sealing it. The water was wasteful and costly to dispose of. Therefore, at present, the development of a system that can easily obtain endotoxin-free water is awaited.

Conventionally, as a means for removing endotoxin, a method using a reverse osmosis membrane or a filtration membrane, or Japanese Patent Laid-Open No.
There is known a method for removing a polymethylmethacrylate resin with a porous body as described in Japanese Patent Publication No. 242105. However, even by these methods, the former cannot be applied to blood and the like, and the latter cannot remove endotoxin in a protein.

[0004]

An object of the present invention is to provide a composite material having excellent endotoxin adsorption performance, thereby making it possible to efficiently produce endotoxin-free water at low cost, and It is intended to enable low-cost removal of endotoxins of.

[0005]

DISCLOSURE OF THE INVENTION The present invention is an endotoxin adsorption comprising a composite material in which a paraffin oil or wax represented by the following formula is dispersed or dissolved in an organic solvent and adhered to various inorganic substances having an appropriate particle diameter. It is in wood.

The present invention will be specifically described below. The paraffin used in the present invention is a paraffin oil or wax represented by the following general formula.

[0007]

[Chemical 2]

The paraffin represented by the above general formula is R in the formula.
₁ , R ₂ and R ₃ may be any of a methyl group, an ethyl group, a propyl group, a butyl group, a heptyl group and a phenyl group, but a methyl group is preferable.

The paraffin used in the present invention is paraffin oil or paraffin wax having a molecular weight of 25.
Those of 0 or more are preferable.

The inorganic material used in the present invention may be any one having an average particle size of 5 to 500 μm, preferably 20 to 300 μm. Examples of such inorganic materials include silica gel, alumina, titanium oxide, aluminum hydroxide, talc and the like. Of these, silica gel and alumina are preferably used. These inorganic substances may be used alone or as a mixture.

The composite material of the present invention can be obtained by dispersing paraffin in ethyl alcohol or by dissolving it in an organic solvent such as a halogenated hydrocarbon or hexane, mixing it with an inorganic substance, adhering it, and drying it.

The mixing ratio of both components in the composite material of the endotoxin adsorbent of the present invention, paraffin and inorganic material, is such that paraffin / inorganic material = 0.05 to 50 / 99.95 to 50 parts by weight, preferably 0. 1 to 30 / 99.9 to 70 weight ratio. If the amount of paraffin is less than 0.05% by weight, the adsorptivity is not sufficient, and if it exceeds 50% by weight, the composite material becomes difficult to handle, which is not suitable for the purpose of the present invention.

[0013]

EXAMPLES The present invention will be specifically described below with reference to examples. Adsorption amount of endotoxin (ng / g paraffin)
(Hereinafter, abbreviated as ng / g paraffin) is a silica gel having an average particle size of 50 μm coated with paraffin or wax, which is filled in a glass tube for column chromatography and passed through water containing 1000 to 2000 pg of endotoxin. After watering, the amount of endotoxin was determined for the water at the column inlet and outlet at regular time intervals, and the total adsorption amount was determined. The amount of endotoxin is Limulus HSJ- manufactured by Wako Pure Chemical Industries, Ltd.
It was quantified by the turbidimetric method using II Test Wako.

Example 1 2 g of liquid paraffin was dissolved in hexane, mixed with 100 g of silica gel having an average particle size of 50 μm, heated to 60 ° C. in a separable flask with stirring to remove hexane, and dried. 20 g of the dried silica gel composite material was packed in a glass chromatography tube having a diameter of 2 cm, and water containing 1000 to 2000 pg of endotoxin was passed through to obtain a total adsorption amount of 6 μg / g paraffin.

Example 2 An experiment was conducted in the same manner as in Example 1, except that the mixing ratio of liquid paraffin and silica gel was changed as shown in Table 1. The results are shown in Table 1. It was found that when the amount of liquid paraffin in the composite material was 0.05% by weight or less, the total amount of adsorption was small, and when it exceeded 20% by weight, it was saturated.

[0016]

[Table 1]

[Example 3] The same procedure as in Example 1 was carried out, except that the kinds of inorganic substances were changed as shown in Table 2. The results are summarized in Table 2. All showed the same level of adsorption capacity.

[0018]

[Table 2]

Example 4 The procedure of Example 1 was repeated, except that paraffins having various melting points were used. The results are summarized in Table 3. Those having a molecular weight of 150 or less were not usable because they were evaporated during drying.

[0020]

[Table 3]

[Example 5] A bovine serum albumin (5 wt / vol%) aqueous solution (pH = 4.0) as a protein,
Collagen 0.3 wt% / vol aqueous solution (pH 3.0)
After passing water, the removal ability was examined. The amount of endotoxin in the protein was 200 ng / ml of bovine serum albumin,
The collagen contained 50 ng / ml. It has been found that a paraffin amount of 0.1 g can remove up to 30 ml of albumin and up to 120 ml of collagen. More than 98% of the protein was recovered. The results are shown in Table 4.

[0022]

[Table 4]

Claims (5)

[Claims] 1. An endotoxin adsorbent characterized by comprising a composite material in which paraffin having a molecular weight of 250 or more is dispersed or dissolved in an organic solvent and attached to an inorganic substance. 2. The endotoxin adsorbent according to claim 1, wherein the paraffin is a compound having a main structure represented by the following formula. [Chemical 1] 3. The endotoxin adsorbent according to claim 1, wherein the inorganic particles have an average particle size of 5 to 500 μm. 4. The endotoxin adsorbent according to claim 1, 2 or 3, wherein the adhering ratio of paraffin to the inorganic substance is 0.05 to 50% by weight. 5. The endotoxin adsorbent according to claim 3, wherein the inorganic substance is at least one of silica gel, alumina, titanium oxide, aluminum hydroxide and talc.