JPS62167331A - Chitosan sponge - Google Patents

Abstract

PURPOSE:Sponge useful for protecting wounds or for surgical hemostasis in medical fields, having smooth and improved hemostasis action, comprising a specific chitosan. CONSTITUTION:The titled sponage comprising a chitosan which is insoluble in water and soluble in a dilute aqueous solution of acetic acid. The sponge has >=80% porosity. The sponge is obtained by dissolving the chitosan in <=20v/v%, preferably 1-5v/v% dilute acetic acid solution in <=30% concentration, preferably 1-10% chitosan concentration to give a transparent, uniform solution, expanding the solution and coagulating the foam or by adding a powdered solid substance to the solution, dispersing the substance well, coagulating the dispersion and removing the solid substance.

Description

Detailed Description of the Invention (Field of Industrial Application) The present invention relates to a new and useful chitosan sponge, and more specifically, to a chitosan sponge useful as a sponge for wound protection or external hemostasis, particularly in the medical field. It's about sponges.

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

As a chitin sponge, for example, the 1st International Chitin Sponge
Proceedings of Chitosan Conference
he Ftrst International
Conference on Chitin/C
hitosan) page 300, lines 16-24,
A sponge manufacturing method is described in which sodium sulfate is mixed with a chitin solution obtained by a process similar to the cellulose viscose method, the solution is coagulated, and the sodium sulfate is eluted. Also.

The present inventors have developed a chitin sponge with high wet strength, which involves adding and mixing a water-soluble polymer substance to a chitin solution, coagulating the mixture, and eluting and removing the water-soluble polymer substance from the obtained chitin molded body. Established a manufacturing method (patent application 1983-
No. 176952).

Regarding the molding technology of chitosan, see 2, for example, Japanese Patent Application Laid-open No. 1983-
Japanese Patent Publication No. 116418 describes a method for producing chitosan fibers and films, and Japanese Patent Publication No. 59-30722 describes a method for producing porous chitosan powder. However, nothing is written about chitosan sponge.

(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 robust hemostatic sponge that can hold blood has been eagerly awaited. On the other hand, chitin sponge has high strength when wet and has advantages such as the effect of promoting wound healing, but its hemostatic effect is not significant.

Therefore, there has been a strong desire to develop a sponge for external use that has both wet strength and hemostatic effect.

(Means for Solving the Problems) As a result of intensive studies to obtain a novel and useful external sponge with wet strength and hemostatic effect, the present inventors found that they were satisfied by molding chitosan into a sponge shape. The present invention was completed based on the discovery that a sponge for external use with such properties could be obtained.

That is, the gist of the present invention is a chitosan sponge that is made of chitosan that is insoluble in water and soluble in a dilute aqueous acetic acid solution, and has a porosity of 80% or more.

Chitosan in the present invention is a polymer compound made of glucosamine or glucosamine and a small amount of N-acetylglucosamine, which is insoluble in water but soluble in a dilute acetic acid aqueous solution. What is the preferred concentration of dilute acetic acid aqueous solution?

It is 0.1 to 10 v/v%, particularly preferably 2 v/v%. Chitosan in the present invention is 9, for example, 0.5 g
100mj! 2 v/v% acetic acid aqueous solution.

It has the property of becoming a homogeneous and viscous liquid when stirred at room temperature for at least 3 hours. Industrially, it mainly demineralizes the exoskeletons of crabs, shrimp, etc.

It is obtained by further subjecting the chitin obtained by deproteinization to a de-N-acetyl treatment.

The chitosan sponge of the present invention can be manufactured by the following method.

First, chitosan powder is dissolved in a dilute acetic acid aqueous solution.

The concentration of the dilute acetic acid aqueous solution used is preferably 20v/v% or less, more preferably 10v/v% or less, and optimally 1 to 5%.
It is in the range of v/v%. The concentration of chitosan dissolved in the dilute acetic acid aqueous solution varies depending on the degree of polymerization of the chitosan used, but is preferably 30% or less, more preferably 20% or less, and optimally in the range of 1 to 10%. A specific method for dissolving the chitosan powder is to thoroughly disperse chitosan powder in water and then add a predetermined amount of acetic acid while stirring to obtain a uniform chitosan solution. If there is undissolved bone, it can be removed by filtration to obtain a transparent and uniform chitosan solution.

The chitosan solution thus obtained was coagulated.

The chitosan sponge of the present invention can be obtained by making it porous, for example, the following two methods can be used. The first method is to mix the chitosan solution with 2 surfactants, for example.

This is a method of foaming using some method, such as a chemical foaming agent or gas suction, and then solidifying it.

The second method is to add a powdery solid material to a chitosan solution, disperse it well, solidify it, and then remove the powdery solid material.

In the first method, foaming agents used for foaming the chitosan solution include, for example, soap (higher fatty acid salt, general formula: RCOO-Ma, sulfate (half-sulfate ester of higher fatty acid alcohol).

General formula: RCHzO3O□OM", sodium lauryl sulfate, etc.), sulfonated product (RS020-M") + alkyl sulfonated product, alkylaryl sulfonated product, amide sulfonated product, ester sulfonated product, and anionic interface such as nitrosyl sulfonated product Active agents and various cationic surfactants, as well as Span (product name) type, Tween (product name) type, Sea! Examples include nonionic and amphoteric surfactants such as fatty acid esters of sugars, polyhydric alcohol esters of fatty acids, and fatty acid esters of polyethylene glycol. In addition, a substance that reacts with the acetic acid aqueous solution and foams, such as calcium carbonate, may be added, as well as air and nitrogen.

Gas such as carbon dioxide gas may be directly blown into the chitosan solution to cause foaming. The amount of foaming agent added may be any amount that causes the chitosan solution to foam, and is preferably 50% or less, more preferably 10% or less, and most preferably in the range of 0.01 to 5% by weight of the chitosan solution. .

To solidify the chitosan solution foamed by the method described above or a combination thereof.

It may be brought into contact with a coagulating liquid. As the coagulating liquid, an alcohol solution such as methanol, ethanol, isopropanol, or an alkaline solution is preferably used. Specific examples include water or alcohol solutions containing sodium hydroxide, potassium hydroxide, or ammonia. 2 For example, when an aqueous sodium hydroxide solution is used as the coagulating liquid, its concentration is preferably 40 w/v% or less, more preferably 20 w/v% or less, and optimally 1 to 10 w/v%.
/v% range. After solidification, it can be washed with water or various solvents to obtain a wet chitosan sponge.

In the second method for producing the chitosan sponge of the present invention, a powdery solid substance is added to the chitosan solution, and the substance is preferably water-soluble, and more preferably insoluble in water at room temperature. However, it has the property of being soluble in hot water. Examples of such substances include:

Examples of water-soluble polymeric substances include polyvinyl alcohol, polyethylene glycol, polypropylene glycol, agar powder, and soluble starch. These powders are added at a weight ratio of 0.2 to 5 times the weight of the chitosan solution, mixed uniformly, and then brought into contact with a coagulating liquid to coagulate. After solidification, a wet chitosan sponge can be obtained by repeating hot water treatment, preferably at 80° C. or higher, in order to dissolve and remove the water-soluble polymeric substance. This second method is advantageous over the first method in that a chitosan sponge with high wet strength can be obtained.

General drying methods can be used to dry the chitosan sponge obtained by the two methods described above, but a freeze-drying method is especially preferred as a method for drying without impairing porosity.

The chitosan sponge of the present invention obtained by the method described above is characterized by high porosity. Here, the porosity is the ratio of the pore volume contained per unit weight of the chitosan sponge to the total volume of the sponge, expressed as a percentage. For example, the volume of the sponge is A
cd and the pore volume inside the sponge is Ba&, the porosity is B/AX 100 (%). The chitosan sponge of the present invention preferably has a porosity of 80%.
It is more preferably 90% or more, most preferably 95% or more.

(Example) Next, the present invention will be described in more detail with reference to Examples.

Example 1 Chitosan powder (manufactured by Shin Nippon Chemical Co., Ltd.) Log was suspended in 970 ml of distilled water, stirred at room temperature for about 30 minutes, and then
mf of glacial acetic acid was added, and the mixture was further stirred at room temperature for 2 hours. The obtained highly viscous chitosan solution was filtered using a 1480 mesh stainless steel net to obtain a transparent chitosan solution.

Take 100 g of chitosan solution in a beaker, add 0.5 g of sodium dodecyl sulfate powder, stir vigorously to foam the chitosan solution, and then pour it into a cylinder with a diameter of 1.51 containing sodium hydroxide at a concentration of 4-/v%. The chitosan solution was extruded into methanol to solidify it into a cylindrical shape. Next, the mixture was repeatedly washed with water and then freeze-dried to obtain a nine-cylindrical chitosan sponge.

The porosity of the chitosan sponge thus obtained was 9
7%, and the wet strength was 2.5 g/m*''.Also, although this chitosan sponge did not dissolve in water,
It was dissolved in a 2v/V% acetic acid aqueous solution at room temperature.

Example 2 25 g of chitosan powder was suspended in 955 ml of distilled water and stirred at room temperature for about 30 minutes, then 2 Q ml of glacial acetic acid was added and further stirred at room temperature for about 3 hours.

The obtained chitosan solution was filtered using a 1480 mesh stainless steel net to obtain a transparent chitosan solution.

Take 100 g of chitosan solution in a beaker and add 50 g of polyvinyl alcohol [Poval UF-170GS, manufactured by Unitika Chemical: degree of polymerization 170. Saponification degree of 95 mol% or more] was added and stirred to uniformly disperse. Then, after degassing under reduced pressure.

It was cast onto a glass plate to a thickness of about 5 mm, and solidified by immersing it in a 4 w/v % aqueous sodium hydroxide solution. It was peeled off from the glass plate, repeatedly treated with hot water at 115°C to elute and remove polyvinyl alcohol, and then freeze-dried to obtain a sheet-like chitosan sponge.

The porosity of the chitosan sponge thus obtained was 9
8%, and the wet strength was 3.2 g/m''.Also, this chitosan sponge did not dissolve in water, but
It was dissolved in a v/v% acetic acid aqueous solution at room temperature.

Comparative example 1. Reference Example 1 The hemostatic effects of a chitin sponge and a chitosan sponge of the present invention were compared.

As the chitosan sponge, a sheet sponge obtained by the method described in Example 2 was used, and as the chitin sponge, one manufactured by the following method was used.

Grind chitin powder (Kyowa oil layer) into 100 mesh pieces,
Treated with 1N-HCl at 4°C for 1 hour.

Further, the powder was heated at 90 to 100° C. for 3 hours in a 3% NaOH solution to remove calcium and protein contained in the chitin powder, and then washed with water repeatedly and dried. The chitin thus obtained was dissolved in a dimethylacetamide solvent containing 8% by weight of lithium chloride at room temperature to a concentration of 2% by weight to obtain a transparent liquid, and then poured into a 1480 mesh stainless steel net. The mixture was filtered under pressure and defoamed under reduced pressure while stirring to obtain a chitin dope.

Add 1100g of this chitindo to polyvinyl alcohol [Poval UP-17003. Manufactured by Unitika Chemical ■: Degree of polymerization 170. Add 50g of saponification degree of 95 mol% or more,
A uniform dispersion was prepared by stirring in a beaker for 1 hour.

This dispersion was cast onto glass to a thickness of 0.5 cm, and then immersed in water at about 25° C. to sufficiently coagulate and wash to obtain a sheet. Next, the sheet was immersed in a sufficient amount of water, boiled for 5 hours, and freeze-dried to obtain a sheet-like chitin sponge.

The back hair of a domestic rabbit weighing approximately 2.5 kg was shaved, and the surface of the back muscle was incised to a depth of 5 to 6 fl to cause bleeding using a puncture device containing 10 insect pins bundled to a diameter of approximately 8 fl. The above-mentioned chitin sponge and the chitosan sponge of the present invention were separately crimped onto two such puncture bleeding areas and fixed with adhesive tape.
The colored area of the sheet sponge due to bleeding after a period of time was compared. the result.

The chitin sponge is colored into a circle with a diameter of about 35 cranes.

Only a portion of the chitosan sponge with a diameter of approximately 20 m was colored.

From the above results, the chitosan sponge of the present invention.

It can be seen that it has superior hemostatic effect compared to chitin sponge.

(Effects of the Invention) The chitosan sponge of the present invention is a completely new form of chitosan molded product, and also has new functions not found in sponges made of chitin, which has a chemical structure very similar to chitosan. be.

In other words, the high porosity chitosan sponge of the present invention has many advantages as a wound protection material, in that it is particularly smooth to the touch and can also be expected to have a hemostatic effect.

Claims (1)

[Claims] (1) A chitosan sponge that is made of chitosan that is insoluble in water and soluble in a dilute acetic acid aqueous solution, and has a porosity of 80% or more.