JPH09278803A - Medical treatment material - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an alginic acid gel having a low calcium content, a low cytotoxicity, a high physiological saline absorption rate, and excellent body fluid absorbency, softness, transparency and mechanical properties, and a medical treatment material comprising the same. SOLUTION: This material mainly comprises an alginic acid gel having a calcium content of not higher than 2.5wt.% and is prepared by the gelation conducted without resort to the calcium content. This material is preferably prepared from (A) an alganic acid gel comprising a reaction product between alginic acid and/or a water-soluble salt thereof and a diamine and/or a polyamine and (B) an alginic acid gel comprising a product obtained by converting at least a part of the hydroxyl groups and/or the carboxyl groups of alginic acid into hydrophobic groups.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a medical dressing material mainly composed of alginic acid gel, and an alginic acid gel suitable for use in the medical dressing material. More specifically, the present invention has excellent safety because it is derived from a natural product, low cytotoxicity due to low calcium content, high physiological saline absorption rate, excellent absorbability of body fluid, and flexibility. , Alginic acid gel with excellent transparency and mechanical properties,
The present invention relates to a medical dressing material comprising the alginic acid gel. And, the alginic acid gel of the present invention and the medical dressing made of the same have the above-mentioned characteristics, so that the pain of the patient, the labor of nursing, and the damage to the affected part can be reduced because the number of times of replacement is small. It is possible to adhere well to the affected area, the physical irritation to the affected area is small, and it is easy to observe the affected area from the outside, and while maintaining good healing promoting factors in the exudate from the affected area, such as wounds. The affected area can be healed.

[0002]

2. Description of the Related Art Gauze and ointments have been widely used for the treatment of wounds such as trauma, burns, ulcers and pressure ulcers, which absorb exudate and prevent bacteria from entering from the outside. Have an effect. Recently, various growth factors (eg, bFG) that promote healing in exudate from wounds.
F, TGFβ, etc.) became clear [How
ell, JM, Currentand Future Trends in Wound
Healing, Emerg. Med. Clin. North Amer., 10 ,
655-663 (1992), etc.], and a wound dressing material that has an occlusive property and has an effect of promoting the healing of the wound site by retaining these growth factors in the wound site has been attracting attention []. Eaglel, WE, Experience with biosynthe
tic dressings, J. Am. Acad. Dermatol., 12 , 434
-440 (1985)]. And as such a occlusive wound dressing material, a polyurethane film, a hydrocolloid, an alginate, a polyvinyl alcohol sponge,
Wound dressings made of polyvinyl alcohol hydrogel, polyethylene glycol hydrogel, polyacrylamide hydrogel, etc. are known.

Among the above-mentioned wound dressings, the wound dressing made of polyurethane film is satisfactory in terms of transparency and occlusivity, but it cannot be used in a wound area having a lot of exudate because it does not absorb water. There are drawbacks. Further, some of the hydrocolloid-based wound dressing and the polyvinyl alcohol sponge wound dressing have a physiological saline absorption rate of about 10 g / g, but they have the drawback that the wound cannot be observed because they are opaque. is there. Moreover, it has been reported that the main component of hydrocolloid-based wound dressing remains in living tissues for a long time to cause chronic inflammation [Young, SR et a.
l., Comparison of the effect of semi-occlusive po
lyurethane dressings and hydrocolloid dressings on
dermal repair: 1. Cellular changes, J. Inves
t. Dermatol., 97 , 586-592 (1991)]. Although some polyethylene glycol hydrogels and polyacrylamide hydrogels are transparent, they have almost no water absorption, and like the hydrocolloid wound dressing,
There is a concern that they may remain in the wound site and cause a chronic inflammatory reaction, and that both raw material monomers are highly toxic, and there is a concern that the residual monomers and decomposing components contained in the hydrous gel may cause toxicity. In addition, when these wound dressings are used, once a bacterial infection occurs, the moist environment becomes a suitable medium for the bacteria, and there is a risk that the bacteria will rapidly multiply and develop into a severe infection.

As the above-mentioned alginate-based wound dressing material, (i) a gel of calcium alginate is processed into a spherical shape, a film shape, a fibrous shape or a gauze shape and used for treatment of burns (G. Blainne). , Ann. Surg., 125 , 102-114 (1
974)]; (ii) A gauze-like surgical dressing (Wa comprising a calcium alginate gel treated with an acid such as hydrochloric acid or sulfuric acid to reduce its calcium content to 3 to 5% by weight.
lles Camcron, GB1231506); (iii) Surgical dressing in which the calcium alginate gel is treated with a salt such as sodium acetate or ammonium acetate to reduce its calcium content to 3-5% by weight. (Medical Alginates, British Patent Nos. 13944741 and 1394742); (iv) 40:60 to 90:10 cations such as calcium that form insoluble alginate and cations such as sodium that form soluble alginate. Wound dressing having a backing material contained in the ratio of
67); (v) Wound dressing in the form of fibrous pasta containing 2 to 11% by weight of alginate as alginic acid (JP-A-6-1819787); (vi) Absorption rate of physiological saline solution. A coating material for medical use consisting of calcium alginate fibers having a content of 20 to 50 g / g (JP-A-5-209318); and the like are known.

In the above-mentioned alginate-based wound dressing materials (i) to (vi), there are those with high calcium content and those with low calcium content. In both cases, alginic acid gel formation depends on calcium. Therefore, it has more or less the problem of cytotoxicity due to calcium (A.
Sank, M .; Chi et al, Surgery, 106 , 1141-1148.
(1989)]. In particular, those having a high calcium content as in (i) and (iv) above and those containing calcium and sodium alginate salts have a low physiological saline absorption rate (10 g / g or less). It has poor absorbency of body fluids and poor adhesion to the affected area, and it is opaque and cannot be observed from the outside. It is taken up into tissues and causes chronic inflammation (SE Barnett and SI Valley, Ann. . Royal
Coll. Surg. Eng., 69 , 153-155 (1987)]. Although the above problems can be solved by reducing the calcium content in the alginate gel, calcium alginate gel having a calcium content of 2.5% by weight or less has a very low gel strength as a wound dressing material. Is not practical. For example, in the medical coating material of (vi) above, gelation is performed using a coagulation bath having a low calcium concentration to increase the physiological saline absorption rate of the alginate gel to form an alginate gel having a low calcium content. However, as a result, the degree of cross-linking of the gel is lowered and the mechanical strength is reduced.

[0006]

DISCLOSURE OF THE INVENTION An object of the present invention is to eliminate the cytotoxicity caused by calcium alginate and to provide a medical dressing material comprising an alginic acid gel containing no calcium or having a reduced calcium content, and the same. The purpose is to provide a suitable alginate gel. Furthermore, the purpose of the present invention is a high physiological saline absorption rate, excellent absorbency of the exudate from the affected area such as a wound and the adhesion to the affected area, the number of times of replacement is small, the patient's pain, By providing an alginate gel-based medical treatment material that can reduce nursing trouble and wound damage, prevent bacterial infection and reproduction, and heal wounds smoothly, and an alginate gel suitable for it. is there. Furthermore, the object of the present invention is excellent in flexibility and less irritation to the affected area,
It is intended to provide an alginic acid gel-based medical dressing material having excellent transparency, capable of observing an affected area from the outside, excellent in mechanical properties, and excellent in handleability and shape retention property, and an alginic acid gel suitable therefor. The present invention can be effectively used for general wounds such as abrasions, cuts, and contusions; surgical wounds such as skin-collecting wounds and dermabrasion wounds; burns; ulcers; pressure ulcers; The object is to provide an alginic acid gel-based medical dressing material and an alginic acid gel suitable for the same.

[0007]

Means for Solving the Problems The present inventors have conducted extensive studies in order to achieve the above object. As a result, the gelation of alginic acid is not performed with the calcium content as in the above-mentioned prior art, but by performing in another form, an alginic acid gel with a reduced calcium content can be obtained.
The present inventors have completed the present invention by discovering that the alginic acid gel having a reduced calcium content is extremely suitable as a medical dressing material and can achieve the above-mentioned various purposes.

[0008] That is, the present invention is a medical dressing material characterized in that it mainly comprises an alginic acid gel having a calcium content of 2.5% by weight or less and the gelation is not dependent on the calcium content. is there.

The present invention provides (A) an alginic acid gel comprising a reaction product of alginic acid and / or a water-soluble salt thereof and a diamine and / or polyamine; and (B) a hydroxyl group and / or a carboxyl group in alginic acid. The medical dressing material is mainly composed of at least one of alginic acid gel comprising a product obtained by modifying at least a part of groups into a hydrophobic group.

The present invention further comprises: -an alginic acid gel comprising a reaction product of alginic acid and / or a water-soluble salt thereof and a diamine and / or polyamine; and-a part of a hydroxyl group and / or a carboxyl group in alginic acid. An alginate gel comprising a product modified with a hydrophobic group.

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be described in detail below. The medical dressing material of the present invention is mainly composed of alginic acid gel having a calcium content of 2.5% by weight or less, preferably 1.7% by weight or less and gelling without depending on calcium. Any substance may be used as long as it is safe for the living body in that it is used for medical purposes. The "alginic acid gel in which gelation is not dependent on calcium content" in the present invention means an alginic acid gel in which gelation of alginic acid is mainly performed by factors other than calcium content or by factors other than calcium content. Say.

The term "medical dressing material" as used in the present invention refers to general external wounds such as scratches, cuts and contusions; surgical wounds such as skin-cutting wounds and dermabrasion wounds; burns; ulcers; pressure ulcers; By applying it to the affected part due to various wounds (using it in contact with the affected part), absorption of exudate from the affected part, retention of the exudate, prevention of fungal infection and proliferation of the affected part, promotion of healing of the affected part, etc. Refers to the generic name of the material for measuring, medical dressing material of the present invention, even if it consists of alginic acid gel only,
It may be a composite material of an alginic acid gel and another material.

Alginic acid, which is the basis of the medical dressing material and alginic acid gel of the present invention, is a polysaccharide obtained from brown algae such as kelp which is a kind of seaweed. For alginic acid, its molecular weight, properties, composition (for example, the ratio of mannuronic acid residues to guluronic acid residues), etc. are determined by the preparation method (extraction method, etc.)
The alginic acid gel and medical dressing of the present invention may be based on any alginic acid, although this may vary depending on the case. Among them, from the viewpoint of strength of alginic acid gel, when it is made into a 1% by weight aqueous solution of sodium alginate, its viscosity at 20 ° C. is 100 cp.
Those based on alginic acid having a (centipoise) or more are preferable, and those based on alginic acid having a viscosity of 300 cp or more are more preferable. However, if the viscosity is too high (generally, more than 1000 cp), it becomes difficult to produce the alginic acid gel of the present invention. Therefore, it is preferable that the viscosity is based on alginic acid having a viscosity of 1000 cp or less.

Further, the molar ratio (M / G) of the mannuronic acid residue (M) and the guluronic acid residue (G) constituting the alginic acid.
The larger the value is, the higher the physiological saline absorption rate of the alginic acid gel (medical dressing material) obtained therefrom is, but if it is too large, the strength of the alginic acid gel is lowered and the practicality is likely to be lowered. On the other hand, the smaller the M / G value, the higher the strength of the alginic acid gel, but if it is too small, the physiological saline absorption rate will be low, and when used as a medical dressing material, the absorbability of exudate from a wound or the like and the affected area will be low. The adhesiveness to Therefore, taking these points into consideration, the alginic acid gel of the present invention and the alginic acid that forms the basis of the medical dressing preferably have an M / G value in the range of 0.6 to 1.5. More preferably, it is in the range of 8 to 1.2.

The medical dressing material of the present invention having a calcium content of 2.5% by weight or less is particularly a reaction product of (A) alginic acid and / or a water-soluble salt thereof and a diamine and / or polyamine. The alginic acid gel of the present invention consisting of [hereinafter referred to as "alginic acid gel (A)"]; and (B) the present invention consisting of a product obtained by modifying at least a part of the hydroxyl groups and / or carboxyl groups in alginic acid into hydrophobic groups. Alginic acid gel (hereinafter referred to as "alginic acid gel (B)");

The diamine and / or polyamine used for forming the alginic acid gel (A) (hereinafter collectively referred to as "polyamines") may be low molecular weight polyamines or high molecular weight polyamines, Alternatively, both may be used in combination. In the alginic acid gel (A), a gel composed of a reaction product of alginic acid or a water-soluble salt thereof and a low molecular weight polyamine [hereinafter, referred to as "alginic acid gel (A ₁ )]" is alginic acid or its water-soluble salt. It is preferable that the product obtained by mainly performing the dehydration condensation reaction between the salt and the polyamines is not limited thereto, but is not limited thereto, and in some cases, between the alginic acid and the low molecular weight polyamines. The ionic reaction (ionic bond) of the alginic acid gel (A) may partially occur, and the alginic acid gel (A) is a gel composed of a reaction product of alginic acid or a water-soluble salt thereof and a high-molecular polyamine. “May be called alginate gel (A ₂ )]
May be a product of an ionic reaction (ionic bond) between alginic acid and a high molecular weight polyamine and / or a product of a dehydration condensation reaction between the two.
Therefore, the "alginic acid gel (A)" of the present invention is a gel-like product obtained by a dehydration condensation reaction of alginic acid or a water-soluble salt thereof with a diamine and / or polyamine,
It may be either a gel-like product by an ionic reaction (ionic bond) or a gel-like product by both reactions.

As the low molecular weight polyamines used for forming the alginic acid gel (A ₁ ), in particular, the following general formula (I);

[0018]

Embedded image R ¹ HN- (CH ₂ ) m-NHR ² (I) [wherein, R ¹ and R ² are each independently hydrogen or a formula; —COCH (NH ₂ )-(CH ₂ ) n- A group represented by NH ₂ (wherein n is an integer of 2 to 8), and m is 1 to 18
Represents an integer], that is, the following general formulas (Ia) to (Ic);

[0019]

Embedded image H ₂ N- (CH ₂ ) m-NH ₂ (Ia) H ₂ N- (CH ₂ ) m-NH-COCH (NH ₂ )-(CH ₂ ) n-NH ₂ (Ib) H _{2 N- (CH 2) n- (NH} 2) CHCO-NH- (CH 2) m-NH-COCH (NH 2) - (CH 2) n-NH 2 (Ic) ( wherein, m and n are the The same as the above) is preferably used. The above general formulas (Ia) to (I
In c), m is an integer of 2 to 12 and n is an integer of 3 to 6 so that the reaction between the alginic acid and the polyamines can be carried out smoothly, and the desired alginic acid gel can be obtained smoothly. It is more preferable because it can be generated.
The greater the number of amino groups in the low molecular weight polyamines,
The reaction with alginic acid is strong, but if it is too large, the proportion of amino groups that do not participate in the reaction increases and the degree of cross-linking decreases, and moreover, it becomes easy to cause coagulation and precipitation before forming a gel. The number of amino groups in the molecular polyamines is preferably 2 to 4 as in the compound represented by the above general formula (I).

Specific examples of the low molecular weight polyamines represented by the above general formula (I) include diaminoethane, diaminopropane, diaminobutane, diaminopentane, diaminohexane, diaminoheptane, diaminooctane, diaminononane, diaminodecane, Diaminoalkanes such as diaminododecane and diaminooctadecane; N-
(Lysyl) -diaminoethane, N, N '-(dilysyl)
-Diaminoethane, N- (lysyl) -diaminohexane, N, N '-(dilysyl) -diaminohexane, and other mono- or dilysyldiaminoalkanes can be mentioned, and these low-molecular polyamines can be used alone. Alternatively, two or more kinds may be used in combination. Of which
Diaminoethane, diaminohexane, N, N '-(dilysyl) -diaminoethane and N- (lysyl) diaminohexane are preferably used.

The above-mentioned diaminoalkanes are easily available as commercial reagents. Further, the above-mentioned mono- or dilysylaminoalkanes may be commercially available ones or may be synthesized and used. When synthesizing, it may be carried out according to a usual organic synthesizing method. The method for producing mono- or dilysylaminoalkanes includes, but is not limited to, for example, (1) a dehydration-condensing agent such as carbodiimide in a state in which the α-amino group and ε-amino group of lysine are protected. A method of reacting with a carboxyl group of lysine and an amino group of diaminoalkane in the presence thereof, and then removing the protective groups of α-amino group and ε-amino group; (2) α-amino group and ε-amino group Protect and N-
A method in which a lysine salt forming a salt with hydroxysuccinimide or the like is used as an active ester, which is then reacted with a diaminoalkane, and then the protecting groups for the α-amino group and the ε-amino group are removed; be able to.

In the above synthetic methods (1) and (2), if the molar ratio of [lysine or salt thereof protected with amino group]: [diaminoalkane] is set to 1: 1, the above general formula (Ib) is obtained. The compound represented can be obtained, and the compound represented by the above general formula (Ic) can be obtained by setting the above molar ratio to 2: 1. In the synthetic methods (1) and (2), a t-butyloxycarbonyl group, a fluorenylmethyloxycarbonyl group, or the like is used as a protecting group for the α-amino group and ε-amino group of lysine. The former protecting group can be removed by treatment with trifluoroacetic acid or dioxane in which hydrogen chloride is dissolved, and the latter protecting group can be removed by treating with piperidine in dimethylformamide. Removal of protecting groups is possible.

[0023] Then, since in forming the alginate gel (A ₁₎ using a low-molecular polyamines represented by the above general formula (I) can be smoothly formed in a short period of time the alginate gel (A ₁₎ First, make alginic acid in the form of a water-soluble salt such as sodium alginate,
Further, it is preferable that the low-molecular weight polyamines are also in the form of water-soluble salts and the dehydration condensation reaction is carried out between the alginic acid and the low-molecular weight polyamines in the aqueous solution because the reaction can be carried out rapidly. In converting the low molecular weight polyamines into the salt form, when the salt form of N-hydroxysuccinimide is used, the N-hydroxysuccinimide acts as a dehydration condensation auxiliary agent, and alginic acid and the low molecular weight polyamines are used. The dehydration condensation reaction with can be carried out more smoothly, and the desired alginic acid gel can be rapidly formed. When the low-molecular-weight polyamines are in the form of N-hydroxysuccinimide salt, it is preferable that all the amino groups contained in the low-molecular-weight polyamines be in the form of N-hydroxysuccinimide salt. It is more preferable in terms of accelerating the condensation reaction. The method of converting the low molecular weight polyamines into the salt form of N-hydroxysuccinimide is not particularly limited, but for example, the low molecular weight polyamines are reacted with N-hydroxysuccinimide using ethyl acetate as a solvent, or the low molecular weight polyamines are reacted. Examples of the method include converting an aqueous solution of the hydrochloride or trifluoroacetic acid salt of 1) into an anion exchange resin column equilibrated with N-hydroxysuccinimide to convert it into a salt form of N-hydroxysuccinimide.

The reaction for forming the alginic acid gel (A ₁ ) in an aqueous solution using the water-soluble salt of alginic acid and the water-soluble salt of low molecular weight polyamines can be carried out in the presence of a dehydration condensation agent. In that case, as the dehydration condensation agent,
For example, a water-soluble carbodiimide such as 2-ethyl-3- (3-dimethylaminopropyl) -carbodiimide hydrochloride is preferably used. The dehydrating condensing agent is generally about 100-200 based on the weight of the water-soluble salt of alginic acid.
It may be used at a ratio of about wt%. Alginate gel (A
The reaction conditions for producing ₁ ) are not particularly limited,
Generally, the temperature of the aqueous solution is set to about 20 to 30 ° C., and it is good to carry out under normal pressure.

It is considered that the alginic acid gel (A ₁ ) is formed by cross-linking alginic acid with the low molecular weight polyamines by the above-mentioned dehydration condensation reaction between the alginic acid and the low molecular weight polyamines. However, in some cases, an ionic reaction (ionic bond) may partially occur between the alginic acid and the low molecular weight polyamines. In the alginic acid gel (A ₁ ), when the amount of the low molecular weight polyamines is increased to increase the degree of crosslinking, a strong gel having a low water content is obtained, while the amount of the low molecular weight polyamines is decreased to reduce the degree of crosslinking. Lowering the value gives a gel that is flexible and has a high physiological saline absorption rate. Therefore, the amount of the low molecular weight polyamines to be used may be adjusted depending on the use of the alginic acid gel (A ₁ ) and the mode of use as a medical dressing. Generally, 1 to 50 mol% of all carboxyl groups of alginic acid,
Preferably, the low molecular weight polyamines are used in an amount such that 10 to 40 mol% participate in the reaction with the amino groups of the low molecular weight polyamines. The ratio of the carboxyl group reacted with the amino group is determined by, for example, elemental analysis of nitrogen atoms in the alginic acid gel (A), signals of methine protons of alginic acid and methylene protons in low molecular weight polyamines in proton NMR of the alginic acid gel (A). It can be examined by intensity ratio.

In addition, in the alginic acid gel (A ₂ ) of the present invention comprising a reaction product of alginic acid or a water-soluble salt thereof and high molecular weight polyamines, the high molecular weight polyamines include two or more amino groups and / or imino groups. Various polymeric polyamines having a group can be used, and examples thereof include polylysine, polyethyleneimine, chitosan, and homopolymers or copolymers of allylamine.
These high molecular weight polyamines may be used alone or in combination of two or more kinds.

As mentioned above, alginic acid gel (A ₂ )
Can be formed by an ionic reaction (ionic bond) between the alginic acid and the polymeric polyamines, a dehydration condensation reaction, or both reactions. In general, by adding a polymeric polyamine to an aqueous solution of a water-soluble salt of alginic acid such as sodium alginate, an ion is formed between the carboxyl group of alginic acid and the amino group and / or imino group of the polymeric polyamine. A reaction (ionic bond) occurs, and a gel can be formed as it is. The reaction temperature and reaction pressure at that time are not particularly limited, but generally, the temperature of the aqueous solution may be set to about 0 to 30 ° C. and the reaction may be performed under normal pressure.

Also in the case of the alginic acid gel (A ₂ ), the bond between the alginic acid and the high molecular weight polyamines, which increase the amount of the high molecular weight polyamines used, becomes tight and a strong gel having a low water content is obtained. On the other hand, when the amount of the high molecular weight polyamines is reduced, the binding between the alginic acid and the high molecular weight polyamines becomes sparse, and a flexible gel having a high physiological saline absorption rate can be obtained. Therefore, the amount of the high molecular weight polyamines to be used may be adjusted depending on the use of the alginic acid gel (A ₂ ), the mode of use as a medical dressing material, and the like. The strength of the alginate gel (A ₂ ) and the absorption rate of physiological saline solution are
Since it is also affected by the type and molecular weight (viscosity) of the high molecular weight polyamines, the type and molecular weight of the high molecular weight polyamines to be used may be selected according to the application of the alginic acid gel (A ₂ ). Although it may vary depending on the type and molecular weight of the high molecular weight polyamines, in general, 1 to 100 mol%, preferably 10 to 90 mol% of the carboxyl groups of the alginic acid are combined with the amino groups and / or imino groups of the high molecular weight polyamines. It is preferable to use the high molecular weight polyamines in such an amount that they participate in the reaction. Also in the case of alginic acid gel (A ₂ ), the proportion of carboxyl groups reacted with amino groups and / or imino groups is
It can be examined in the same manner as described above for ₁ ).

The alginic acid gel (B) of the present invention comprising a product obtained by modifying at least a part of the hydroxyl group and / or the carboxyl group in alginic acid into a hydrophobic group.
Is a gel formed by introducing a hydrophobic group into a portion of a hydroxyl group and / or a carboxyl group in alginic acid to hydrophobize it. As the hydrophobic group used for modifying the hydroxyl group and / or the carboxyl group of alginic acid, various hydrophobic groups can be mentioned, and a hydrophobic group having a hydrocarbon group in some form is particularly preferable.

The compound capable of modifying the hydroxyl group and / or the carboxyl group in alginic acid to a hydrophobic group is not limited, and examples thereof include amines, alcohols and halides having a hydrophobic group such as a hydrocarbon group. Examples thereof include carboxylic acids, carboxylic acids, and carboxylic acid esters. More specifically, for example, alkylamines such as butylamine, hexylamine, octylamine, decylamine, and laurylamine; aromatic amines such as benzylamine and naphthylethylamine; leucine methyl ester, glycine benzyl ester, phenylalanine butyl ester, etc. Amino acid alkyl esters; phospholipid amine derivatives such as phosphatidylethanolamine; aliphatic alcohols such as butyl alcohol, hexyl alcohol, octyl alcohol, decyl alcohol, lauryl alcohol; aromatic alcohols such as benzyl alcohol and naphthyl ethanol ;
Alcohol derivatives of phospholipids such as phosphatidylglycerol; butyl chloride, hexyl bromide, octyl bromide, decyl iodide, lauryl bromide and other aliphatic halides; benzyl chloride and other aromatic halides; butyric acid, pivalic acid, butylacetic acid, capron Acids, aliphatic carboxylic acids such as lauric acid; aromatic carboxylic acids such as phenylacetic acid and naphthylacetic acid; N-substituted amino acids such as t-Boc-leucine and benzoylglycine; the aforementioned aliphatic carboxylic acids and aromatic carboxylic acids; Examples thereof include acid anhydrides and acid halides of N-substituted amino acids. In modifying the hydroxyl group and / or carboxyl group in alginic acid into a hydrophobic group, one type of the above-mentioned compounds may be used, or two or more types may be used in combination.

When the hydroxyl group and / or carboxyl group in alginic acid is reacted with the above compound to modify it into a hydrophobic group, the compound having a hydroxyl group and / or carboxyl group is reacted with the above compound for hydrophobization. It may be performed according to a method generally adopted for this purpose. For example, when the carboxyl group of alginic acid is reacted with the above-described amine and / or alcohol having a hydrophobic group, 1-ethyl-3 is added in an aqueous solution of a water-soluble salt of alginic acid such as sodium alginate.
When a dehydration condensation reaction between a carboxyl group of alginic acid and amines and / or alcohols is performed in the presence of a dehydration condensation agent such as-(3-dimethylaminopropyl) -carbodiimide, the carboxyl group of alginic acid becomes a hydrophobic group. It can be modified. Further, for example, when a hydroxyl group of alginic acid is reacted with an aliphatic halide and / or an aromatic halide to be modified into a hydrophobic group, the reaction is performed in an aqueous solution of a water-soluble salt of alginic acid such as sodium alginate in the presence of an alkali. By carrying out, the hydroxyl group of alginic acid can be modified into a hydrophobic group. further,
For example, when a hydroxyl group of alginic acid is reacted with the above-mentioned carboxylic acids to be modified into a hydrophobic group, 1-in an aqueous solution of a water-soluble salt of alginic acid such as sodium alginate,
By carrying out the reaction in the presence of a dehydration condensing agent such as ethyl-3- (3-dimethylaminopropyl) -carbodiimide, the hydroxyl group of alginic acid can be modified to a hydrophobic group.
Further, for example, when the hydroxyl group of alginic acid is reacted with the above-mentioned carboxylic acid anhydride or acid halide to be modified into a hydrophobic group, in the aqueous solution of a water-soluble salt of alginic acid such as sodium alginate, the presence of an alkali is present. By carrying out below, the hydroxyl group of alginic acid can be modified into a hydrophobic group.

In the alginic acid gel (B), the higher the modification ratio of the hydroxyl group and / or the carboxyl group in alginic acid to the hydrophobic group, the lower the physiological saline absorption rate is, and the more the modification ratio to the hydrophobic group is. Since the gel having a higher physiological saline absorption rate is obtained as the content becomes lower, the modification of the hydroxyl group and / or the carboxyl group with the hydrophobic group depending on the use of the alginic acid gel (B) and the usage as a medical dressing material. Adjust the proportion. In addition, the degree of hydrophobization of alginic acid is affected not only by the modification ratio of the hydroxyl group and / or carboxyl group in alginic acid but also by the type of hydrophobic group introduced by modification, etc. It is necessary to select the type of hydrophobic group according to the application. Generally, based on the total number of moles of hydroxyl groups and carboxyl groups in alginic acid, about 1 to 50 mol% of the alginic acid is modified with the hydrophobic group as described above, which is the obtained alginic acid gel (B). Is preferable in terms of strength, physiological saline absorption rate, transparency and the like.

Further, the alginic acid gel of the present invention is formed by using two or more of the above-mentioned reaction with low molecular weight polyamines, reaction with high molecular weight polyamines, and introduction reaction of hydrophobic groups in combination. May be

In the alginic acid gel of the present invention described above, since the gel is formed without using calcium, the calcium content is, of course, extremely low. In particular, the gel formed by the method as described above is preferable. When the alginic acid gel is used as it is without being treated with a solution containing a calcium component, the calcium content in the alginate gel is 0%, so that there is no cytotoxicity due to calcium. Therefore, the alginic acid gel of the present invention can be effectively used for various applications such as medical dressing materials, other than that, for example, drug carriers, bases for external preparations, etc., by utilizing the characteristic that the calcium content is low. be able to.

When the above-mentioned alginic acid gel of the present invention is used as a medical dressing, its water content is 1%.
It is preferably set to 0% by weight or less. When the water content of the alginic acid gel is 10% by weight or less, the physiological saline absorption rate increases, and when used as a medical dressing material, the absorbability and retention of exudate from the affected area are good, and the healing effect is high. It will be even higher. The method for reducing the water content of the alginic acid gel to 10% by weight or less is not particularly limited, and any method can be adopted as long as it does not cause alteration of the gel, for example, a freeze drying method, a solvent displacement drying method, a reduced pressure drying method,
It can be performed by a heating drying method, a warm air drying method, or the like. Here, the “moisture content” of the alginic acid gel or the medical dressing as referred to in the present specification can be determined by a gravimetric method according to the following mathematical formula or a water quantitative method by titration using a Karl Fischer reagent.

[0036]

Moisture content (% by weight) = {(Wa-Wb) / Wa} × 100 (wherein, Wa = weight of alginic acid gel or medical dressing material, Wb = absolute of alginic acid gel or medical dressing material) Represents the dry weight)

When the alginic acid gel of the present invention is used as a medical dressing, its physiological saline absorption rate is 20.
-60 g / g is preferable, and 30-50 g / g
Is more preferable. When the physiological saline absorption rate of the alginic acid gel (medical dressing material) is within the above-mentioned range, the absorbability of the exudate from the affected area, the retention, the blocking ability against bacterial infection, the mechanical properties and the like are improved. If the physiological saline absorption rate is less than 20 g / g, the exudate cannot be sufficiently absorbed when it is used immediately after injury and when it is used on an affected area with a large amount of exudate such as deep wounds such as ulcers and pressure ulcers, and the exudate may leak. Risk of bacterial infection is likely to occur. As a result, when using a medical dressing material with a low physiological saline absorption rate, it is necessary to frequently replace the medical dressing material in order to prevent the leakage of the exudate described above, the burden on the nursing side and the patient, and the affected part. The damage is likely to be large. On the other hand, the physiological saline absorption rate is 60
A medical dressing material (alginic acid gel) exceeding g / g generally has low mechanical strength, and it is difficult for the medical dressing material to have sufficient sealing ability against bacterial infection from the outside. Here, the “physiological saline solution absorption rate” of the alginic acid gel or the medical dressing material as used in the specification of the present application refers to a value obtained according to the following mathematical formula.

[0038]

## EQU00002 ## Absorption rate of physiological saline (g / g) = (Wc-Wd) / Wd (where, Wc = alginic acid gel or medical dressing is 3
Weight after soaking in physiological saline at 7 ° C for a predetermined time, W
d = represents the dry weight of alginic acid gel or medical dressing material)

Wound dressings such as the above-mentioned conventional polyurethane films, hydrocolloids, polyvinyl alcohol sponges, polyvinyl alcohol hydrogels, polyethylene glycol hydrogels, polyacrylamide hydrogels and the above-mentioned conventional wound fabrics of non-woven alginate fibers. Has a physiological saline absorption rate of 20
It is smaller than g / g and cannot be said to have sufficiently good properties as a wound dressing material in this respect, but in the medical dressing material of the present invention, the physiological saline absorption rate is 20 to 60 g as described above. / G makes it possible to promote healing of wounds while sufficiently absorbing exudate from the affected area and preventing bacterial infection while maintaining sufficient strength. It has excellent characteristics compared to.

The medical dressing material comprising the alginic acid gel of the present invention contains sodium as needed for the purpose of adjusting its physiological saline solution absorption rate (absorption of exudate from the affected area) and imparting adhesiveness. Inorganic ions such as calcium and magnesium; polyhydric alcohols such as ethylene glycol, propylene glycol, glycerin, and polyethylene glycol; polymer compounds such as polyvinyl alcohol and polyacrylic acid may be contained. Further, the medical dressing material of the present invention, promotion of healing of the affected part and its peripheral part,
Antibacterial agents, antibiotics, antibacterial agents, blood circulation improving agents (eg, actin, PGEI, etc.) for the purpose of preventing bacterial infection
It may contain one or more of growth factors (eg PDGF, FGF, etc.), structural proteins (eg fibrin, collagen, etc.), various amino acids, vitamins, and may be pharmacologically acceptable. You may contain the additive of. By including calcium in the medical dressing material of the present invention, a hemostatic effect can be expected, and the physiological saline absorption rate can be adjusted as described above. It is necessary that the content be 2.5% by weight or less as specified in the invention.

The method of incorporating the above-mentioned various agents and components into the medical dressing material of the present invention is not particularly limited, and for example, a method of adding them to the alginic acid gel-forming raw material before forming the alginic acid gel, After forming the alginic acid gel, the gel may be immersed in a liquid containing the above-mentioned agent or component, and dried by a method of supporting the gel on the gel if necessary. A method suitable for each property may be adopted.

The shape, structure, etc. of the medical dressing material of the present invention are not particularly limited, and include, for example, a flat plate shape (film shape, sheet shape, film shape, etc.), woven / knitted shape, non-woven material shape, mesh shape, particle shape,
It can be used in the form of a lump, a sponge, or the like. Further, the medical dressing material of the present invention may be formed only from alginic acid gel or may be formed by combining with other materials, for example, formed by laminating with other materials such as polyurethane film and silicone resin film. Alternatively, a woven or knitted fabric or a non-woven fabric made of another material may be present at the time of forming the alginic acid gel to form a medical dressing material in which the alginic acid gel and these other materials are integrated. The method for sterilizing the medical dressing material of the present invention is not particularly limited, and any method can be adopted as long as it does not cause deterioration of the alginic acid gel,
For example, ethylene oxide gas sterilization, autoclave sterilization (for example, 121 ° C. for 20 minutes), γ-ray sterilization, electron beam sterilization and the like can be mentioned. In particular, the medical dressing of the present invention is excellent in safety because it can be sterilized by moist heat by an autoclave.

[0043]

EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited thereto.

Example 1 (1) 2.3 g (20 m) of N-hydroxysuccinimide [manufactured by Peptide Institute Co., Ltd.] in 150 ml of methanol
mol) was dissolved, and a solution of 0.6 g (10 mmol) of ethylenediamine (manufactured by Wako Pure Chemical Industries, Ltd.) in 10 ml of methanol was added dropwise thereto while stirring at room temperature. After completion of the dropwise addition, stirring was continued for another hour. The precipitated crystals were collected by filtration, dried under reduced pressure and dried with ethylenediamine 2N.
2.6 g of hydroxysuccinimide salt (yield about 90
%) Was obtained. (2) Sodium alginate (manufactured by Funakoshi Co., Ltd.,
1% by weight aqueous solution of M / G value 1.0) (viscosity 550 cp,
(20 ° C) 30 ml, ethylenediamine 2N-hydroxysuccinimide salt 66 mg prepared in the above (1), and 1-ethyl-3- (3-dimethylaminopropyl).
-Carbodiimide hydrochloride [manufactured by Peptide Institute, Inc.]
0.48 g was dissolved and the resulting solution was 10 cm × 10 c
The mixture was cast on a Teflon-coated tray of m, and allowed to stand at 25 ° C. for 48 hours to form an alginic acid gel. (3) First, the alginic acid gel obtained in (2) above is thoroughly washed with water for injection (Otsuka Pharmaceutical Co., Ltd.) in which 2.5 mM calcium chloride and 143 mM sodium chloride are dissolved, and then calcium chloride and sodium chloride are added. It was washed with the above-mentioned water for injection which did not contain it. The washed alginate gel was freeze-dried and then sterilized by gamma ray irradiation of 25 kGy to obtain a medical dressing material. (4) A portion of the medical dressing obtained in (3) above was dry decomposed in a platinum crucible, and then the calcium content determined by atomic absorption spectrometry was 1.6% by weight. It was incorporated into the alginic acid gel in the washing step (3).

(5) 0.31 g of the medical dressing obtained in the above (3) was weighed and dried under reduced pressure in a desiccator for 48 hours, and the weight when dried was 0.30 g. The moisture content of the medical dressing material obtained from the values of 0.31 g of the weight of the medical dressing material before drying and 0.30 g of the weight of the medical dressing material before drying was 3.2 according to the above formula. % By weight. (6) The medical dressing obtained in (3) above was dried under reduced pressure in a desiccator for 48 hours. 0.43 g of this was weighed out, placed on a polyurethane sponge sufficiently filled with physiological saline (manufactured by Otsuka Pharmaceutical Co., Ltd.), and allowed to stand in a constant temperature bath at 37 ° C., and physiological saline for 1 hour at intervals up to the 4th hour. Was absorbed, the amount of absorption was measured, and the physiological saline absorption rate was determined from the above formula. As a result, it was 42 g / g at the first hour, 50 g / g at the second hour, 49 g / g at the third hour, and 48 g / g at the fourth hour.

Example 2 (1) The alginic acid gel obtained in (2) of Example 1 was thoroughly washed with physiological saline (manufactured by Otsuka Pharmaceutical Co., Ltd.) and then washed with water for injection. The washed alginate gel was freeze-dried and then sterilized by gamma ray irradiation of 25 kGy to obtain a medical dressing material. (2) A part of the medical dressing obtained in (1) above was weighed out, and the calcium content thereof was calculated in the same manner as in (4) of Example 1 to find that it was 0%. It was not contained. (3) A portion of the medical dressing material obtained in (1) above is weighed and dried under reduced pressure in the same manner as in (5) of Example 1, and the water content is set to (5) of Example 1. Similarly, it was 4.5% by weight when calculated according to the above-mentioned mathematical formula. (4) Regarding the medical dressing obtained in (1) above,
The physiological saline absorption rate was determined according to the above mathematical formula in the same manner as in (6) of Example 1, and it was 2 at the first hour.
9 g / g, 33 g / g for 2 hours, 41 g / for 3 hours
g, and 45 g / g at the 4th hour.

Example 3 (1) Sodium alginate (manufactured by Funakoshi Co., Ltd.,
1% by weight aqueous solution of M / G value 1.0) (viscosity 550 cp,
20 ° C.) 30 ml, leucine benzyl ester tosylate [manufactured by Peptide Research Institute Co., Ltd.] 0.2 g, and 1-ethyl-3- (3-dimethylaminopropyl) -carbodiimide hydrochloride [manufactured by Peptide Research Laboratories Co., Ltd.] ] 0.11 g was dissolved, and the obtained solution was cast on a 10 cm x 10 cm Teflon-coated tray and allowed to stand at 25 ° C for 48 hours to form an alginic acid gel. (2) First, the alginic acid gel obtained in (1) above is thoroughly washed with water for injection (manufactured by Otsuka Pharmaceutical Co., Ltd.) in which 2.5 mM calcium chloride and 143 mM sodium chloride are dissolved, and then calcium chloride and sodium chloride are added. It was washed with the above-mentioned water for injection which did not contain it. The washed alginate gel was freeze-dried and then sterilized by gamma ray irradiation of 25 kGy to obtain a medical dressing material. (3) A portion of the medical dressing material obtained in (2) above was weighed out, and the calcium content thereof was determined in the same manner as in (4) of Example 1 to be 1.5%. The amount was incorporated into the alginic acid gel in the washing step (2). (4) A portion of the medical dressing obtained in (2) above is weighed and dried under reduced pressure in the same manner as in (5) of Example 1, and the water content is set to (5) of Example 1. Similarly, it was 3.8% by weight as determined according to the above-mentioned mathematical formula. (5) Regarding the medical dressing obtained in (2) above,
The physiological saline absorption rate was determined according to the above mathematical formula in the same manner as in (6) of Example 1, and it was 2 at the first hour.
3 g / g, 27 g / g for 2 hours, 25 g / for 3 hours
g and at the 4th hour was 24 g / g.

Example 4 (1) Sodium alginate (manufactured by Funakoshi Co., Ltd.,
1% by weight aqueous solution of M / G value 1.0) (viscosity 550 cp,
20 ml) and 1% by weight of chitosan dissolved 2
10 cm immediately after mixing with 30% aqueous acetic acid solution
Cast on a Teflon-coated tray of × 10 cm and pour 48 at 25 ° C.
Allowed to stand for a time to form an alginate gel. After drying this alginic acid gel with hot air at 60 ° C for 48 hours,
It was sterilized by γ-ray irradiation of Gy to obtain a medical dressing material. (2) A portion of the medical dressing material obtained in (1) above was weighed out, and the calcium content was determined in the same manner as in (4) of Example 1 to find that it was 0% by weight. It did not contain at all. (3) A portion of the medical dressing material obtained in (1) above is weighed and dried under reduced pressure in the same manner as in (5) of Example 1, and the water content is set to (5) of Example 1. Similarly, it was 8.6% by weight when calculated according to the above-mentioned mathematical formula. (4) Regarding the medical dressing obtained in (1) above,
The physiological saline absorption rate was calculated according to the above mathematical formula in the same manner as in (6) of Example 1, and it was 4 at the first hour.
5 g / g, 2 hours 60 g / g, 3 hours 61 g / g
g, and 63 g / g at 4th hour.

Comparative Example 1 (1) Calcium content of commercially available alginate-based wound dressing (medical dressing) (Bristol-Myers Squibb's "cultstat")
It was 6.5% by weight as determined in the same manner as in (4). (2) The moisture content of this commercially available wound dressing was 3.5% by weight as determined by the above-mentioned mathematical formula in the same manner as in (5) of Example 1. (3) Further, the physiological saline absorption rate of this commercially available wound dressing was determined according to the above mathematical formula in the same manner as in (6) of Example 1, and it was 13 g at the first hour.
/ G, 2 hours 12 g / g, 3 hours 12 g / g,
And it was 12 g / g in the 4th hour.

Comparative Example 2 (1) Commercially available polyurethane foam wound dressing (medical dressing) (Smith &Nehu's"Alevin")
The calcium content was determined in the same manner as in (4) of Example 1, and it was 0% by weight. (2) The moisture content of this commercially available wound dressing was 0.5% by weight as determined by the above-mentioned mathematical formula in the same manner as in (5) of Example 1. (3) Further, the physiological saline absorption rate of the commercially available wound dressing was determined according to the above mathematical formula in the same manner as in (6) of Example 1, and 2.4 at the first hour.
g / g, 2.6 g / g for the second hour, 2.8 g for the third hour
/ G, and 3.0 g / g at 4th hour.

<< Test Example 1 >> (1) Medical dressing material of Example 1 [Medical dressing material obtained in (3) of Example 1; the same applies below], Medical dressing material of Example 2 [Implementation] 0.2 g of the medical dressing obtained in (1) of Example 2; the same applies hereinafter] and the commercially available medical dressing of Comparative Example 1 were weighed in an amount of 0.2 g each, and 10% by weight of fetal bovine serum was used for each.
Eagle's minimum essential medium containing 10% FC
S-MEM) (Nissui Pharmaceutical Co., Ltd.) 40 ml and put 5
The mixture was allowed to stand at a temperature of 37 ° C. for 24 hours in the presence of% carbon dioxide gas.
After that, the supernatant was filtered through a 5 μm filter (“Millex SV” manufactured by Millipore) and the filtrate was collected as a test solution. In addition, 10% FCS described above without adding medical dressing
-The same treatment was performed using MEM to obtain a blank test solution. (2) L9 that has been subcultured with 10% FCS-MEM
29 cells (“NCTC obtained from Dainippon Pharmaceutical Co., Ltd.
CLONE 929 ") with 0.25% trypsin (D
IFCO, 1: 250) ・ Phosphate buffer (0.1
10 mM phosphate buffer containing 4 M sodium chloride; pH 7.
4) and 0.02% EDTA / phosphate buffer were dispersed, and the number of viable cells was counted by a phase contrast microscope. 10% F
The cells were serially diluted with CS-MEM and adjusted to a final concentration of 2 × 10 ² cells / ml. Add this to 10% FCS-MEM
Add 1 ml each to a 6 cm diameter petri dish ("3002" manufactured by Falcon) using 10 ml petri dishes for both test solution and blank test solution, and in the presence of 5% carbon dioxide gas at 37 ° C for 7 days. Cultured.

(3) After culturing, the supernatant was gently removed,
5 ml of methanol (manufactured by Wako Pure Chemical Industries, Ltd .; special grade)
Each was dispensed gently. The cells were fixed by allowing them to stand at room temperature for 30 minutes. The methanol is discarded and the phosphate buffer (pH 7.
5 ml each of Giemsa stain solution (manufactured by Merck) diluted 10 times in 4) was dispensed. After leaving it at room temperature for 30 minutes, it was washed several times with purified water and then dried, and the number of colonies consisting of 50 or more cells was counted. (4) As a result, the number of colonies in the blank test solution was 10
When set to 0, the number of colonies of the test solution containing the medical dressing of Example 1 was 99.7, and the number of colonies of the test solution containing the medical dressing of Example 2 was 94.7. On the other hand, the number of colonies in the test solution containing the medical dressing of Comparative Example 1 was 0.0. (5) From the result of the above (4), the medical dressing materials of Example 1 and Example 2 show almost no cytotoxicity to L929 cells and can smoothly grow L929 cells. It can be seen that the medical dressing of Comparative Example 1 is highly cytotoxic to L292 cells and inhibits the growth of L929 cells.

<< Test Example 2 >> (1) Nine circular full-thickness defect wounds each having a diameter of 2.5 cm were prepared on the backs of two domestic boars, and each of the defect wounds had a side of 2.5 cm. Each of the three square-shaped medical dressing materials of Example 1, the medical dressing material of Example 2, and the commercially available medical dressing material of Comparative Example 1 were applied for 18 days over 18 days. (2) When 18 days after application, the medical dressing was peeled off and the healing state of the wound was visually observed, the wound closure rate of the wound to which the medical dressing of Example 1 was applied was 100% (6/6). ),
The wound closure rate of the wound to which the medical dressing of Example 2 was attached was 67.
% (4/6), and the wound closure rate of the wound with the medical dressing of Comparative Example 1 attached was 50% (3/6). (3) Further, when the tissue of each wound after peeling the medical dressing 18 days after application was observed with a microscope after fixing and staining, foreign matters were found in the place where the medical dressing of Example 1 and Example 2 was applied. No residual or foreign body giant cells were observed. On the other hand, alginate fibers were taken into the wound tissue at the location where the medical dressing material of Comparative Example 1 was applied, and many foreign body giant cells were present. (4) Therefore, from the results of this Test Example 2, the medical dressing material of the present invention of Example 1 and Example 2, compared to the conventional commercially available alginate-based medical dressing material (wound dressing material), It can be seen that the wound-healing promoting effect is significantly superior.

[0054]

INDUSTRIAL APPLICABILITY The alginic acid gel of the present invention does not undergo gelation with a calcium component, and has a calcium content of zero or very low. Therefore, the medical allowance of the present invention mainly composed of such alginic acid gel. The material has low cytotoxicity and can smoothly grow normal cells when applied to an affected area, and has an extremely high healing effect on wounds and the like. In particular, the medical dressing material and physiological saline absorption rate of the present invention having a water content of 10% by weight or less are 20 to 6
The medical dressing material of the present invention, which is 0 g / g, has excellent absorbency and retention of exudate from a wound or the like, so the number of times of medical dressing material replacement is small, and replacement of the medical dressing material is possible. It is possible to reduce the patient's pain, labor for nursing, the damage to the affected area, the prevention of bacterial infection, etc., and the healing promoting factors contained in the exudate from the affected area can be used in the medical material. The healing of the affected area can be promoted while maintaining good retention inside.

Furthermore, the medical dressing material of the present invention is flexible,
Since it is excellent in transparency and mechanical properties, it has little physical irritation to the affected area, can be closely adhered to the affected area, the state of the affected area can be easily observed from the outside, and is excellent in handleability. Further, the medical dressing material of the present invention can be subjected to wet heat steam sterilization by an autoclave or the like, and in that case, a highly safe medical dressing material can be provided. The medical dressing material of the present invention is used for general wounds such as abrasions, incisions and contusions; surgical wounds such as skin-collecting wounds and dermabrasion wounds; burns; ulcers; pressure ulcers; It can be effectively used for treatment.

Claims (11)

[Claims] 1. A medical dressing material which is mainly composed of an alginic acid gel having a calcium content of 2.5% by weight or less and gelling without depending on the calcium content. 2. The medical dressing material according to claim 1, wherein the calcium content of the alginate gel is 1.7% by weight or less. 3. An alginic acid gel comprising (A) a reaction product of alginic acid and / or a water-soluble salt thereof and a diamine and / or a polyamine; and (B) at least one of a hydroxyl group and / or a carboxyl group in the alginic acid. A medical dressing material, which is mainly composed of at least one of alginic acid gel consisting of a product whose part is modified with a hydrophobic group. 4. An alginic acid gel (A) comprises (A ₁ ) alginic acid and / or a water-soluble salt thereof, and a compound represented by the following general formula (I): embedded image R ¹ HN- (CH ₂ ) m-NHR ² (I) [wherein, R ¹ and R ² are each independently hydrogen or a formula; —COCH (NH ₂ ) — (CH ₂ ) n—NH ₂ (where n is an integer of 2 to 8) Group, and m is 1-18
A gel comprising a reaction product with a compound represented by the formula; and (A ₂ ) alginic acid and / or a water-soluble salt thereof, and a polymer having two or more amino groups and / or imino groups. A medical dressing material according to claim 3, which is at least one of a gel consisting of a reaction product of 5. The medical dressing material according to claim 3, wherein the alginic acid gel (B) is obtained by modifying at least a part of the hydroxyl group and / or the carboxyl group in alginic acid into a hydrophobic group having a hydrocarbon group. 6. The medical dressing material according to claim 1, wherein the water content of the alginic acid gel is 10% by weight or less. 7. The medical dressing material according to claim 1, which has a physiological saline absorption rate of 20 to 60 g / g. 8. An alginic acid gel comprising a reaction product of alginic acid and / or a water-soluble salt thereof and diamine and / or polyamine. 9. The diamine and / or polyamine is
(A ₁ ) The following general formula (I); embedded image R ¹ HN- (CH ₂ ) m-NHR ² (I) [wherein, R ¹ and R ² are each independently hydrogen or a formula; _{COCH (NH 2) - (CH} 2) n-NH 2 groups (n in the formula is an integer of 2-8) is represented by and m is 1 to 18,
Represents an integer of], and (a ₂ ) 2
The alginic acid gel according to claim 8, which is at least one kind of polymer having one or more amino groups and / or imino groups. 10. An alginic acid gel comprising a product obtained by modifying a part of a hydroxyl group and / or a carboxyl group in alginic acid into a hydrophobic group. 11. The alginic acid gel according to claim 10, wherein a part of the hydroxyl group and / or the carboxyl group in alginic acid is modified to a hydrophobic group having a hydrocarbon group.