JPS6253661A - Chitin molded body - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] (Industrial application field) The present invention relates to a novel porous chitin molded article.

The present invention relates to a porous chitin molded body that is useful as a cosmetic tool, a medical tool, etc., and is useful as an external hemostatic sponge because it has a particularly high protein adsorption ability compared to conventional chitin sponges and has a hemostatic effect. .

(Prior Art) Gelatin sponges have been put into practical use as external hemostatic sponges. Since gelatin is originally water-soluble, it quickly dissolves when wetted with blood or body fluids, so gelatin sponges modified with protein denaturants such as formaldehyde, diacetyl, and glyoxal are commercially available.

As a conventionally known chitin sponge.

For example, the Proceedings of the 1st International Chitin and Chitosan Conference (Pr.
oceeding of the First Int.
annual conference on
Chitin/Chitosan) page 300, No. 1
Lines 6 to 24 describe a sponge manufacturing method in which sodium sulfate is mixed with a chitin solution obtained in a process similar to the cellulose viscose method, and then the sodium sulfate is eluted.

In addition, the present inventors have developed a method for achieving high wet strength by adding and mixing a water-soluble polymer substance to a chitin solution, coagulating the mixed liquid, and eluting and removing the water-soluble polymer substance from the obtained chitin molded body. A method for producing chitin sponge was established and previously proposed (Japanese Patent Application No. 176952/1983).

(Problems to be solved by the invention) Gelatin sponges for hemostasis currently in practical use have the disadvantages of low strength and poor shape retention when wet, and do not retain their shape even when wet with blood or body fluids. The development of a hemostasis sponge with a robust structure capable of holding blood has been eagerly awaited.

On the other hand, the chitin sponge previously proposed by the present inventors has high strength when wet and has advantages such as a wound healing promoting effect, but its hemostatic effect was not significant. Therefore, two objects of the present invention are to provide a chitin sponge that has a hemostatic effect without impairing the robust structure and the effect of promoting wound healing.

(Means for Solving the Problems) As a result of extensive research in order to obtain a new and useful chitin sponge that also has a hemostatic effect, the present inventors found that by subjecting a porous chitin molded body to an alkali treatment, protein It was discovered that a hemostatic effect appears as the adsorption capacity increases significantly.

The invention has been completed.

That is, the present invention is a porous molded article made of water-insoluble chitin, which is characterized in that the amount of protein adsorbed per gram of the dry molded article is 0.5 mg or more.

In the present invention, water-insoluble chitin refers to crustaceans.

It refers to poly(N-acetyl-D-glycosamine) obtained by treating insects with hydrochloric acid and soda to remove protein and calcium, or derivatives thereof that do not dissolve in water. As such a chitin derivative.

For example, chitin with some of its acetylamino groups deacetylated, etherified products, and esterified products.

Examples include hydroxyethylated products, 0-ethylated products, etc.
A specific example is poly [N-acetyl-6-0-(2-hydroxyethyl)-D-glycosamine].

Examples include poly[N-acetyl-6-0-(ethyl)-D-glucosamine].

The chitin molded article of the present invention having excellent protein adsorption ability can be produced by first molding chitin into a porous form and then subjecting the molded article to an alkali treatment.

In the present invention, porous specifically refers to spongy or spongy, and the porosity (B/
AX100: B: volume of pores contained in porous molded body per unit weight, A: volume of porous molded body per unit weight) is preferably 80% or more.

More preferably, it is 85% or more, optimally 90% or more. In order to obtain a porous molded body made of chitin, for example, the following method can be adopted.

That is, first, chitin is dissolved in a solvent to obtain a chitin dope. Here, the solvent is a known chitin solvent 2, for example, a mixture of trichloroacetic acid and a halogenated hydrocarbon, a mixture of lithium chloride and N-methylpyrrolidone, or a mixture of lithium chloride and dimethylacetamide. The concentration of chitin in the chitin dope varies depending on the degree of polymerization of chitin used, but is preferably 0.05 to 5.
0°, more preferably 0.1-25. Optimally 0.3~
The range is 10W/%.

Next, a water-soluble polymer substance is added to the chitin dope and dispersed. What is a water-soluble polymer substance here?

A natural or synthetic polymeric substance that is solid at room temperature and soluble in water. For example, polyvinyl alcohol, polyethylene glycol, polypropylene glycol, agar, soluble starch, etc. are preferably used, but polyvinyl Alcohol and agar are preferably used. As the polyvinyl alcohol, one preferably used is one that is soluble in water at low or high temperatures, has a degree of saponification of 60 mol% or more, and a degree of bipolymerization of 50 to 2000.
Furthermore, those which can be dissolved in water at a high temperature, for example, 60° C. or higher, and have a saponification degree of 95 mol % or higher are preferably used.

Agar is a mucilage substance that exists as a cell membrane component of Agaricaceae such as Amanita, or it is frozen and dehydrated and dried.
and agarose, agaropectin and derivatives thereof separated therefrom. For polypropylene glycol and polyethylene glycol, the molecular weight of 2 is 1.
000 or more is preferably used. All of these water-soluble polymeric substances are preferably used in the form of a dispersed powder. These water-soluble polymer substances are mixed with the chitin dope.

Generally, the water-soluble polymeric substance is not dissolved in the chitin dope but is present in a monodispersed state. What is the mixing ratio?

Weight ratio of chitin dope/water-soluble polymer = 115 to 5/1
A range of is preferred.

The chitin dope in which the water-soluble polymer substance obtained as described above is dispersed is immersed in a coagulation solution to form and coagulate, and then treated with an aqueous solution to elute and remove the water-soluble polymer substance to make it porous. A molded body is obtained.

The coagulating liquid is water or alcohols such as methanol, ethanol, propatool, butanol, etc.

Ketones such as acetone are preferably used.

The aqueous solution used to treat the solidified molded article means water or water containing a small amount of salt, etc., and the treatment temperature and time are selected depending on the solubility of the water-soluble polymer substance in water. Generally, a method of treating at a high temperature of 80 to 125°C for a long time of one hour or more is preferably used.

If the porous molded article thus obtained is treated with an alkali, the two chitin molded articles of the present invention can be obtained.

The alkali treatment in the present invention includes any method in which a porous molded article made of chitin is brought into contact with an alkaline solution. As the alkaline solution, a sodium hydroxide aqueous solution is practical, and its concentration is preferably 0.1 w
/v% or more, more preferably 10 w/v% or more, optimally in the range of 30 to 60 w/v%, and the preferable treatment temperature is 10°C or more, more preferably 40°C or more, optimally 60 to 120°C. It is sufficient if it is within the range of . The treatment time varies depending on the alkali concentration and treatment temperature, but is preferably 1 minute to 24 hours, more preferably 15 minutes to 12 hours.

The optimum time is about 1 to 6 hours. The bath ratio is preferably 25 parts by weight or more, more preferably 50 parts by weight or more of an alkaline solution per 1 part by weight of the dry chitin molded body.
Optimally, the amount may be 100 parts by weight or more. The alkaline solution may be stirred if necessary, and after the treatment, when removing the alkali, operations such as neutralization and water washing may be performed, and organic solvent treatment and drying may be performed. Natural drying is the drying method.

Methods such as blow drying and vacuum drying can be used.

In order to prevent shrinkage of the porous chitin molded article due to drying, freeze-drying is preferably used.

The porous molded body obtained by such a method preferably has a protein adsorption amount of 0.5 mg or more, more preferably 1 g of protein adsorption per gram of dried porous chitin molded body.
It has the ability to adsorb proteins of more than mg, optimally 2 to 100 μg.

The protein adsorption amount referred to herein can be measured by the following method.

Prepare diluted serum by diluting the rejuvenating serum for cell culture 500 times with Fujidame water, and prepare 1 sample per 20 ml of this diluted serum.
The protein concentration in the diluted serum after adding 00■ and stirring gently for 10 minutes at 37°C is A■/ml, and the protein concentration when the same procedure is performed without adding the sample is B.
If it is 1/ml, then (B-A) x 20 2 proteins are adsorbed to 100 2 samples.

Protein concentration was determined using the phenol reagent method (published by the University of Tokyo Press, Biochemistry Experimental Method Series A-3. Protein Quantification Method,
(pages 86 to 103).

(Example) The present invention will be described in more detail with reference to two examples below.

Example 1 Chitin powder (Shin Nippon Kagaku type) was ground into 100 meshes and treated with IN-HCl at 4°C for 1 hour.

Further, ash and protein were removed by treatment with a 3% NaoH aqueous solution at 90 to 100°C for 3 hours.

After repeated washing with water and drying, purified chitin powder was obtained.

2 g of purified chitin powder was dissolved in 98 g of dimethylacetamide containing 18 w/-% LiCff at room temperature to obtain a transparent chitin dope. To this chitin dope.

Polyvinyl alcohol [Poval UF-170GS, manufactured by Unitika Chemical @1 polymerization degree 170. saponification degree of 95 mol% or more] was added and mixed to uniformly disperse it.

This dispersion was cast onto a glass plate to a size of 5cm square and 5H thick, and immersed in tap water to coagulate into a sheet. After being peeled off from the glass plate, it was immersed in a sufficient amount of water, and the treatment at 100° C. for 2 hours was repeated three times while exchanging the water to obtain 6 sealant-shaped porous chitin molded bodies.

Squeeze out the water from the sheet thus obtained.

No. 11 was immersed in a 40 w/v% NaOH aqueous solution and treated at 80° C. for 5 hours. After cooling, the sheet was transferred to about 11 g of water, neutralized with concentrated hydrochloric acid, washed with running water, further washed with distilled water, and then freeze-dried to obtain a sheet-like chitin molded article of the present invention.

The protein adsorption amount of the obtained chitin molded product per 1 g of dry molded product was 33 μ, and the tensile strength when wet was 13.5.
g/n'', and the porosity was 97%.

Example 2 2 g of purified chitin powder obtained in Example 1.

LiCj! 98g of N-methylpyrrolidone containing 8-8%
A transparent chitin dope was obtained. 50 g of agar powder was added to and mixed with this chitin dope and uniformly dispersed.

This dispersion was extruded into methanol under pressure through a circular nozzle with a diameter of 7 cm, solidified to a length of approximately 5C11, and then immersed in water of 1000ml, and treated at 120°C for 30 minutes while exchanging the water. The process was repeated three times to obtain two cylindrical porous chitin molded bodies.

Squeeze the water out of the chitin molded body obtained in this way,
Immersed in 40 w/v% NaOH aqueous solution at 500 mA,
It was treated at 20°C for 1 hour. After cooling.

The sponge was transferred to about 11 g of water, neutralized with concentrated hydrochloric acid, washed with running water, further washed with distilled water, and then freeze-dried to obtain a cylindrical chitin molded article of the present invention.

The protein adsorption amount of the obtained chitin molded body per gram of dry molded body was 36 μ, and the tensile strength when wet was 12.8 g.
/ms" and the porosity was 98%. Examples 3 to 7. Comparative Example 1 The relationship between the conditions of alkali treatment when obtaining the chitin molded article of the present invention and the amount of protein adsorption was investigated. That is, when the sheet-like porous chitin molded article obtained by the method described in Example 1 was treated with alkali, the temperature was fixed at 120° C. for 9 hours and 60 minutes.

The protein adsorption ability of chitin molded bodies obtained by treatment with varying concentrations of NaOH aqueous solution was measured.

As a result, as shown in Table 1, it can be seen that as the alkali concentration during treatment increases, the amount of protein adsorption also increases.

Reference Examples 1 and 2 The hemostatic effects of a conventional chitin sponge and a porous chitin molded article of the present invention were compared.

As a conventional chitin sponge, the sheet-like porous molded product (protein adsorption amount: 0.3 / g) obtained in Example 1 and not subjected to alkali treatment was used. teeth.

The one obtained in Example 1 was used.

Shave the back hair of a rabbit weighing approximately 2.5 kg and use 10 insect pins.
The surface of the back muscle was opened to a depth of 5 to 6 N to cause bleeding using a puncture device made of books bundled with a diameter of about 8 U+. A conventional chitin sponge and a chitin sponge of the present invention were separately pressed on two such puncture bleeding areas and fixed with adhesive tape, and after about 2 hours, the areas of colored areas due to bleeding were compared. As a result, the conventional chitin sponge was colored in a circle with a diameter of about 35 fins, and the porous chitin of the present invention was only colored in a circular part with a diameter of about 20 fins.

From the above results, it can be seen that the porous chitin molded article of the present invention has an excellent hemostatic effect compared to an untreated molded article.

(Effect of the invention) The porous chitin molded article of the present invention has a robust structure.

It has excellent biocompatibility and a hemostatic effect not found in conventional chitin sponges. The manufacturing method is an extremely convenient operation of creating a chitin sponge and treating it with an alkaline solution, and is also applicable to industrial production.

In addition to the hemostatic effect, the porous chitin molded article of the present invention has a very smooth feel upon contact compared to before treatment, and from this point of view as well, it is suitable as a wound covering material.

Claims (1)

[Claims] (1) A porous molded body made of water-insoluble chitin,
A porous chitin molded article characterized in that the amount of protein adsorption per gram of the dry molded article is 0.5 mg or more.