JPH02268766A - Chitosan porous laminated material and preparation thereof - Google Patents

Abstract

PURPOSE:To obtain a laminated material with non-porous properties and porous properties by constituting it of a porous layer consisting of chitosan and constituted of a three dimensional network structure with three dimensional network open-cell and a non-porous thin film layer consisting of chitosan. CONSTITUTION:A chitosan acidic aq. soln. is prepd. by dissolving chitosan in an acid aq. soln. and a part of said chitosan acidic aq. soln. is extended into a sheet, which is freeze-dried to form a porous sheet of a chitosan salt. Separately, the remaining part of the chitosan acidic aq. soln. is extended into a thin film, which is dried by evaporation to form a non-porous chitosan salt thin film. While the non-porous chitosan salt thin film is not completely dried or after one face of the dried thin film is made damp with water and it is laminated and adhered on one face of the porous sheet of chitosan salt. The laminated body is neutralized by treating it with an alkali aq. soln. to insolubilize thereby the laminated body in water and the obtd. water-insoluble chitosan laminated body is dried. The chitosan laminated material consists of the non-porous thin film layer and the porous sheet layer and is useful for a covering material of a wound and can be also used for such applications as a water retention agent and a filtering material.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to a chitosan porous laminate material, a method for producing the same, and a living body wound dressing obtained using this laminate material.

[Conventional technology]

Chitin is obtained by treating the outer skin of shellfish such as shrimp and crabs, insects, etc. with hydrochloric acid and hydrochloric acid to separate and purify the calcium content and protein.
It is a polymeric substance consisting of a 1.4β-conjugate of acetyl-D-glucosamine.

Chitin is broken down and absorbed by enzymes such as lysozyme that exist in living bodies, and is known to have functions such as promoting wound healing.

Generally, wound dressings are used to safely cover and protect the wound surfaces of burns and physical and surgical skin defects for a certain period of time.

For example, various wound dressings are currently used to treat burns, but a wound dressing that can effectively prevent infection in extensive burns has not yet been developed.

The most common cause of death from burns is sepsis caused by bacterial infection. Therefore, it prevents the invasion of bacteria from the outside,
The development of a wound dressing material that can suppress the growth of bacteria already present on the wound surface is strongly desired by the three-bed hospital.

In order to meet these demands, it is important for the wound dressing to have the following properties.

That is, it must be a non-irritating material that does not cause a significant foreign body reaction on the wound surface, and it must have good adhesion to the wound surface. If good adhesion is not achieved, exudate will accumulate and the growth of bacteria will be promoted. In order to obtain reliable contact with the wound surface, it is preferable to use a porous structure. However, on the other hand, a uniform non-porous membrane seems to be suitable for preventing the invasion of bacteria from the outside.

A chitin derivative material having both tissue structures as described above is not yet known. This is because the technology for arbitrarily producing porous structures and non-porous homogeneous structures from chitin and its derivatives, such as chitosan, has not been sufficiently developed.

[Problem to be solved by the invention]

The present invention aims to provide a laminate material made of chitosan and having both non-porous and porous properties, a method for producing the same, and a wound dressing comprising this laminate.

[Means and actions to solve the problem]

The chitosan porous laminate material of the present invention consists of chitosan,
and a porous layer composed of a three-dimensional linear structure having continuous pores in a three-dimensional network, and a non-porous thin film layer formed on at least one surface of the porous layer and made of chitosan. It is characterized by:

The method of the present invention for producing the above laminated material includes dissolving chitosan in an acid aqueous solution to prepare an acidic chitosan aqueous solution,
A part of this chitosan acidic aqueous solution is spread into a sheet shape,
This was freeze-dried to form a chitosan salt porous sheet, and separately, the remaining part of the chitosan acidic aqueous solution was spread into a thin film, and this was evaporated and dried to create a non-porous chitosan salt thin film. , laminating and pasting the non-porous chitosan salt thin film on one side of the chitosan salt porous sheet before it is completely dry, or by moistening one side of the dry body with water; The method is characterized in that the laminate is treated with an alkaline aqueous solution to neutralize it, thereby making the laminate water-insoluble, and the obtained water-insoluble chitosan laminate is dried.

In addition, in another method of the present invention for producing the above-mentioned laminated material, chitosan is dissolved in an acid aqueous solution to prepare an acidic chitosan aqueous solution, and this acidic chitosan aqueous solution is spread into a sheet shape, and this sheet-like layer is The surface of this sheet-like layer is neutralized by contacting the surface with a gas stream or a spray stream of a basic substance.
Solidify to form a non-porous chitosan salt thin film, and freeze-dry the sheet-like layer with the thin film to form a porous sheet from the remaining chitosan acidic aqueous solution, thereby forming the chitosan salt non-porous thin film layer and the porous forming a laminate with a porous sheet layer, and treating the laminate with an alkaline aqueous solution to neutralize it, thereby making the porous sheet layer water-insoluble, the obtained water-insoluble chitosan laminate It is characterized by drying.

Additionally, the chitosan porous laminate material of the present invention can be utilized in the formation of wound dressings.

In view of the state of the prior art as described above, the present inventors
As a result of extensive research into the development of materials with a porous/non-porous composite structure that utilize chitin derivatives, especially chitosan, we found that chitosan dissolves in an acidic aqueous solution to form an acidic aqueous solution. When the formed chitosan salt molded article is neutralized with an alkaline aqueous solution, it returns to chitosan and becomes water-insoluble. Also, when this acidic chitosan aqueous solution is freeze-dried, the chitosan salt separates and precipitates from the acid aqueous solution, forming a chitosan salt porous body. The present invention was completed by utilizing these characteristics of chitosan.

The chitosan laminate material of the present invention consists of a chitosan porous layer and a non-porous chitosan thin film layer formed and bound on at least one surface of the chitosan porous layer.

The chitosan porous layer has three-dimensional linear continuous pores, and the chitosan substance (matrix) surrounding these complex-shaped continuous pores also has a three-dimensional network-like continuous complex shape. It has a structure. Further, the non-porous overlapping layer made of chitosan is a homogeneous layer having substantially no or few continuous pores, and its density is higher than that of the porous layer.

The thickness and density of the porous layer and the thickness and density of the non-porous thin film are appropriately determined depending on the use and required performance of the chitosan laminate material, and there are no particular limitations thereon. However, in -i, the porous layer is 0.1 to 50
Preferably, the non-porous thin film has a thickness of 0.005 to 0.15 mm and a density of 0.005 to 0.15 g/C[11].
．． Preferably, it has a thickness of 3 to 100 tones and a density of 0.8 to 1.2 g/ad.

The chitosan laminate material of the present invention can be produced by the method of the present invention described below.

The chitosan used in the present invention may be obtained from a commercially available product, or chitosan obtained by separating and purifying the shells of crustaceans such as crabs and shrimps by a conventional method and heating it with a concentrated alkali. It may also be obtained by de-N-acetylation.

The chitosan used in the method of the present invention generally has 50 to 1
It is preferable to have a degree of de-N-acetylation of 00%,
The degree of N-acetylation is more preferably 50 to 99%.

In the method of the present invention, chitosan is dissolved in an acid aqueous solution,
Prepare an acidic aqueous solution. The type of acid used in this step is not particularly limited as long as it does not decompose or alter chitosan, and is selected from, for example, acetic acid, lactic acid, and hydrochloric acid. The acid concentration of the acid aqueous solution used at this time is not particularly limited as long as it can dissolve chitosan, but generally 0.5 to 15% acetic acid aqueous solution,
A 1-20% lactic acid aqueous solution and a 0.5-8% hydrochloric acid aqueous solution are used. In addition, the concentration of chitosan dissolved in such an acid aqueous solution can be arbitrarily set as long as the solution obtained therefrom has the desired fluidity, but it is generally 0.5 to 15% (by weight). ) is preferably within the range.

In the method of the present invention, a portion of the chitosan acidic aqueous solution is
Spread it in a sheet shape in a specified container or on a base (e.g. glass plate or polytetrafluoroethylene resin plate), and pre-freeze it at -10 to -80°C (after JI freezing). dry.

Then, the chitosan precipitates and solidifies from the acidic aqueous solution to form a three-dimensional network-like continuous structure, and within it, three-dimensional network-like continuous pores are formed. Sublimation and volatilization. A porous sheet is thus obtained.

The above-mentioned freeze-drying can be easily performed using a normal freeze-drying machine. Methanol, ethanol, N
- A viscosity modifier containing at least one of propatool and isoproptool may be added in an amount of, for example, 0.5 to 50%.

Separately, a non-porous chitosan salt thin film can be obtained by spreading the other part of the chitosan acidic aqueous solution into a thin film on a container or a base and drying this thin film liquid layer by an evaporative drying method. Although there are no particular limitations on the evaporative drying conditions at this time, it is generally sufficient to gradually evaporate and dry at a temperature of 5 to 110°C.

This chitosan salt non-porous thin film is wetted with water (liquid water, water vapor, steam, etc.) before it is completely dry (while it is still slightly wet), or one side of the dry body is wetted with water (liquid water, water vapor, steam, etc.). This is laminated and adhered to one surface of the chitosan salt porous sheet to form a precursor laminate.

In the method of the present invention, the precursor laminate may be created as follows. That is, an acidic chitosan aqueous solution is spread in a sheet shape in a container or on a base, and a gas stream or a spray stream of a basic substance is brought into contact with the surface of this sheet layer. Then, the surface portion of the sheet-like layer is neutralized. Therefore, the chitosan present in this surface portion is precipitated and solidified, and a non-porous thin film of chitosan is formed on the surface of the sheet-like layer.

Neutralizing agents used in this step include, for example, a gas stream containing gaseous ammonia, or finely sprayed particles of an aqueous solution of other alkaline substances, such as sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate. A gas flow containing a gas can be used.

This sheet-like layer is then freeze-dried to precipitate and solidify the chitosan salt from the remaining unsolidified chitosan acidic aqueous solution to form a porous sheet layer.

The second porous sheet layer has a three-dimensional network of continuous pores, as described above. In this way, a precursor laminate consisting of a non-porous thin film and a porous sheet layer continuous thereto is obtained.

The step of forming a non-porous thin film layer and the step of forming a porous sheet layer by freeze-drying may be performed separately in the above order, or the step of forming a non-porous thin film may be performed by forming a porous sheet layer by freeze-drying. It may also be carried out to overlap with the early stages of nest building.

The precursor laminate obtained as described above is treated with an alkaline aqueous solution. The precursor laminate is then neutralized, thereby rendering the entire laminate insoluble in water.

The alkali used in this step is selected from sodium ammonia hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, and the like. Further, although there is no particular limitation on the alkali concentration of the alkaline aqueous solution, it is generally preferably 1 to IO% by weight.

Next, the resulting water-insoluble laminate is thoroughly washed and dried. The drying method can be selected as appropriate, but generally hot air drying at 5°C to 110°C, dehydration using a hydrophilic organic solvent, etc. , freeze-drying, etc. can be used.

The chitosan porous laminate material of the present invention can be subjected to necessary treatments such as sterilization, and then prepared into a wound dressing having a predetermined size and shape.

〔Example〕

The invention will be further illustrated by examples.

1. Heat chitin powder to 110°C with 45% aqueous sodium chloride solution.
was treated for 2 hours to produce powdered chitosan. This powdered chitosan was sufficiently washed with water and dried, and then dissolved in a 2% acetic acid aqueous solution to prepare an acidic aqueous chitosan solution having a concentration of 2% by weight. A portion of this chitosan acidic aqueous solution was poured into a mold of 5×5 CI11 and 1 cylinder thick, and freeze-dried to produce a porous sheet-like body. Separately, the remaining portion of the chitosan acidic aqueous solution was thinly spread on a glass plate and air-dried to produce a non-porous thin film. One side of this thin film was held over a hot water bath to make it wet, and then the porous sheet obtained by freeze-drying was stacked on top of the other, and the thin film and the porous sheet were bonded together. This precursor laminate is
% sodium hydroxide aqueous solution to neutralize it, thoroughly washed with water, and freeze-dried to obtain a chitosan porous laminate material. This laminated material has a thickness of approximately 3-1 and a density of 1.1 g/c
a non-porous thin film of i and a thickness of about 1III bound thereto.
11. Density 0.02g/co! The continuous pores had a non-uniform diameter of 50 to 1100 u.

After sterilizing this chitosan porous PA layer material with ethylene oxide gas, a 2x3
It was attached to the wound surface with a size of 11 cm and a depth of 1 ffiI, and fixed using gauze and a bandage. When the gauze and bandage were removed two weeks after the surgery, the wound had healed with only a scab about 5 mm in diameter remaining.

1/1 The same operation as in Example 1 was performed. However, the chitosan acidic aqueous solution was cast in the form of a sheet on the mold, and the surface thereof was sprayed with an ammonia gas stream for 2 minutes. Then, a non-porous chitosan thin film was formed on the surface of the sheet. When this sheet-like body was placed in a freeze dryer, pre-frozen at -30°C, and then freeze-dried, a porous chitosan salt sheet layer was formed from the remaining chitosan acidic aqueous solution.

This precursor laminate was subjected to the same alkaline aqueous solution treatment as in Example 1.

The obtained chitosan laminated material consists of a non-porous thin film with a thickness of about IOμ and a porous sheet layer with a thickness of about 1 mm continuous with the non-porous thin film.The porous layer has non-uniform pore sizes. A three-dimensional network of continuous pores was formed.

This chitosan laminate material showed the same wound coverage effect as Example 1.

〔Effect of the invention〕

The chitosan laminated material of the present invention is composed of an extremely thin non-porous thin film layer and a porous sheet-like layer attached to or continuous with it, and is useful as a wound dressing material. It can be used for applications such as agents and filter media. Furthermore, the method of the present invention has made it possible to efficiently produce such a chitosan laminated material.

Claims (1)

[Scope of Claims] 1. A porous layer composed of a three-dimensional network structure made of chitosan and having three-dimensional network continuous pores, and formed on at least one surface of this porous layer, and A non-porous thin film layer made of chitosan, and a chitosan porous laminate material made of chitosan. 2. Dissolve chitosan in an acid aqueous solution to prepare an acidic chitosan aqueous solution, spread a portion of this chitosan acidic aqueous solution into a sheet,
This was freeze-dried to form a chitosan salt porous sheet. Separately, a portion of the remaining acidic chitosan aqueous solution was spread into a thin film, and this was evaporated and dried to create a non-porous chitosan salt thin film. , laminating and pasting the non-porous chitosan salt thin film on one side of the chitosan salt porous sheet before it is completely dry, or by moistening one side of the dry body with water; A chitosan porous material characterized in that the laminate is treated with an alkaline aqueous solution to neutralize it, thereby making the laminate water-insoluble, and the obtained water-insoluble chitosan laminate is dried. Production method. 3. Dissolve chitosan in an acid aqueous solution to prepare an acidic chitosan aqueous solution, spread this chitosan acidic aqueous solution into a sheet shape, and contact the surface of this sheet-like layer with a gas stream or a spray stream of a basic substance. Then, the surface portion of this sheet-like layer is neutralized and solidified to form a non-porous chitosan thin film, and this sheet-like layer with the thin film is freeze-dried to form a porous sheet from the remaining chitosan acidic aqueous solution. , thereby forming a laminate with a chitosan non-porous thin film layer and a porous sheet layer, and treating said laminate with an aqueous alkaline solution to neutralize it, thereby rendering said porous sheet layer hydrated. A method for producing a chitosan porous laminate material, which comprises making the chitosan insoluble and drying the obtained water-insoluble chitosan laminate. 4. A wound dressing comprising the chitosan porous laminate material according to claim 1 as a main component.