JPH02268765A - Hyaluronate sheet and preparation thereof - Google Patents

Abstract

PURPOSE:To obtain an excellent covering and protecting material for skin damage by introducing a hyaluronic acid aq. soln. in a solvent in such a way that the final concn. of a water-soluble org. solvent is a specified value to coagulate and deposit a fibrous hyaluronate, grinding it in the liq. into single fibers, making them into a sheet and drying it. CONSTITUTION:A hyaluronate aq. soln. is introduced in a solvent ao as to obtain the final concn. of a water-soluble org. solvent of 50v/v% or higher and a fibrous hyaluronate is coagulated and deposited. The fibrous hyaluronate is ground in a liq. into single fibers, which are then made in a sheet and the sheet is dried to obtain a sheet. If the final concn. of the water-soluble org. solvent is not kept at 50v/v% or higher, the hyaluronate is not deposited into a fibrous state and it is not pref. As the hyaluronate fiber has self-adhesive characteristics, the hyaluronate fibers adhere and bind each other and the hyaluronate fibers sheet exhibits excellent strength, excellent water absorption proparties, water retention and moisture retention as well as excellent biocompatibility. When the sheet is used as a covering and protecting material for skin damage, it absorbs and holds rapidly. a liq. oozing out of the diseased part to accelerate a skin formation and the condition of the skin after curing is smooth to obtain a good effect.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a hyaluronate sheet, a method for producing the same, and uses thereof.

[Prior art] For the treatment of skin defects such as skin grafts made for shaping scars such as tragic injuries, or skin harvesting parts that occur as a result,
Conventionally, protective coatings have been used. Among them, medical gauze and medical nonwoven fabric have been the most common since ancient times, but these have the problem that they tend to adhere to the wound area and if they are forcibly removed, they will cause further damage.

Therefore, in order to provide a better covering and protecting material for skin defects/wounds that does not have these problems, a protecting material made of a material derived from a natural product with excellent biocompatibility has been developed. For example, nonwoven fabrics made of fibers of chitin, which is a type of amine polysaccharide contained in the exoskeletons of crustaceans, ragun nonwoven fabrics,
Or frozen pork skin etc.

However, all of these have the problem of insufficient adhesion to the wound surface, which tends to cause exudate to accumulate in the affected area, and the condition of the skin after healing is also poor.In addition, sufficient mass production is not possible due to resource constraints. It had the problem of being stiff.

On the other hand, hyaluronic acid is distributed in animal tissues such as the vitreous body, umbilical cord, skin, and chicken crest! It is a polysaccharide with five types of fibers, and in recent years it has been used in cosmetics, medicine, etc. by taking advantage of its properties, and in particular, since the development of a fermentation method for hyaluronic acid, the use of hyaluronic acid has been developed. It is something that is becoming more and more popular.

However, there has been no attempt to directly use this hyaluronic acid and its salt itself in the above-mentioned covering and protecting material for skin defects and injuries. Incidentally, as a technology similar to this, Japanese Patent Application Laid-open No. 187866/1986 describes a technique in which hyaluronic acid or its salts are applied to medical garpi or medical nonwoven fabric.
, 0% by weight has been disclosed, but this is also not a wound dressing protection material made of hyaluronate itself.

[Problem to be solved by the invention]

In view of the above circumstances, the present invention is biocompatible, has excellent adhesion to affected parts of the human body surface such as skin defects or wounds, has good moisturizing properties, and has the following properties: This work was done with the aim of developing an excellent covering and protecting material for skin defects and injuries that would smooth the skin's condition.

(Means for Solving the Problems) The present inventors have focused on the inherent moisturizing properties, water-retaining properties, and affinity for living organisms of hyaluronate, which has been studied for ωI for some time. The present invention was achieved by obtaining the knowledge that the present invention can be used as a covering and protecting material for skin defects and injuries, and by developing a technology for converting hyaluronate into a 1-layer material.

That is, the present invention provides a sheet made of fibers of hyal monophosphate, and in order to produce the sheet, an aqueous hyaluronic acid solution is added to the water-soluble organic solvent so that the final concentration is 50 v/v% or more. After introducing the fibrous hyaluronate and coagulating and precipitating the fibrous hyaluronate, the fibrous hyaluronate is crushed into single fibers in the liquid.
The present invention provides a method for producing the sheet, which is characterized by forming the sheet into paper and drying it.

The present invention will be explained in detail below.

Hyaluronic acid is a type of glycoliminoglycan contained in the vitreous body, umbilical cord, skin, chickens, etc.

In the present invention, this hyaluronate is used as a raw material. The hyaluronate is preferably a sodium, potassium or calcium salt, and particularly preferably a sodium salt.

To produce hyaluronate, animal tissues such as chicken crests and umbilical cords are crushed, and impurities such as proteins are removed by prodiaepidermy or solvent treatment, followed by fractional precipitation with ammonium sulfate. It can be produced by a fermentation method using acid-producing bacteria.

Regardless of the method used, the hyaluronate used must be sufficiently purified and of high purity.

This hyaluronate is made into a fiber by the following method.

That is, first, a hyaluronate, such as sodium hyal[1 phosphate, etc., is dissolved in water, and the solution is 0.1 to 2. It is made into an aqueous solution of OW/V%. 81 times of the hyaluronate aqueous solution is 0.
If it is less than 1 W/V%, it is not preferable because it becomes powder and filtering and dehydration becomes difficult. If the OW/V% is exceeded, the precipitate will form, but the internal fluidity will become uniform, which is not preferable.

The viscosity of this aqueous solution is 200CI' when it is 0.1Δ/V%
However, in the case of 1.0W/V %), 25,000CP
Tel)'Q, 2.0ill/v% Noteha 250,0OO
CP toiuka becomes a viscous liquid.

Next, when this hyaluronate aqueous solution is placed in a water-soluble organic solvent, it coagulates to form IIi filaments. The structure of the fibrous material is such that thinner vIA particles of hyaluronate are intertwined with each other.

Preferred water-soluble organic solvents are methanol, ethanol, acetone, n-propanol, isopropanol, or acetonyl-l-lyl.

In addition, the final m degree of the water-soluble organic solvent is 50 v/v% or more,
Preferably 60-80 v/v%, particularly preferably 70
~75 v/v%. That is, the concentration of the solvent decreases due to water added from the hyaluronate aqueous solution, but unless the concentration is maintained at 50 v/v% or more, the hyaluronate will not precipitate in the form of fibers, which is not preferable.

A method for introducing hyaluronate (dope) into a water-soluble organic solvent, which is a coagulating liquid, is to naturally drip a viscous hyaluronate aqueous solution directly from a container into a water-soluble organic solvent in the form of starch syrup. Although a method of introducing the dope into the coagulation liquid can also be used, industrially it is preferable to discharge the above-mentioned dope into the coagulation liquid from a nozzle with a diameter of about 0.01 to 0.5M using a gear pump or the like.

The I fibrous material obtained above is not in a state suitable for sheeting as it is, so the fine fibers are loosened to form a thick thread, and the quality is 2 to 5M, which is suitable for sheeting. It is necessary to make the NM relatively short. If the length of the fibers is too short outside the above range, the fibers will become fluffy and difficult to form into a sheet, while if the fibers are too long, the fibers will form lumps in the dispersion medium, making uniform dispersion difficult, which is not preferable. On the other hand, when the length is about 2 to 5 mm, the entanglement of the fibers within the sheet becomes appropriate, and the self-adhesive property, which is a characteristic of hyaluronate fibers, works effectively, resulting in good adhesive bonding between 14M. This effect can be obtained.

As a method for forming Class 1 fibers, known shortening techniques can be used;
A method of finely pulverizing the Ii fibrous material is simple. In this case, the rotation speed of the mixer is 2000 to 5000 r.
PM! ! i! The time is preferably about 10 to 30 seconds. Further, when forming short LLI fibers, the solvent used is preferably the water-soluble organic solvent used for spinning, and the amount of water is preferably 90 to 99 v/v%.

C.I. can be produced from the short fibers of hyaluronate obtained in the above manner by a method similar to that used for making Japanese paper.

First, the short fibers are stirred in a dispersion of a water-soluble organic solvent or the like so that they are uniformly softened, and then the solid-liquid content is passed through the dispersion but not the short fibers. 1ift device, for example, pour the necessary amount onto various filter media.

At this time, it is preferable to pour the material so that it has an average thickness, and if a suction filtration method is used, the production time can be shortened.

The filter medium may be appropriately selected from among known filter paper, wire mesh, filter cloth, ceramic or plastic filters, and the like.

In addition, the dispersion liquid in which the short fibers are dispersed dissolves or changes the short fibers.14 t! Although any solvent can be used as long as it does not cause sulfur, it is preferable to use the same water-soluble organic solvent used during spinning and short fiber formation because it is more economical for recovery and reuse.

In this way, the jq-dareda hyaluronate fiber sheet is in the state of a so-called wet paper. In terms of moisture contained in the sheet, the solvent used during short fiber formation is 90 to 99 v.
/v% is usually 1.0 to 11. Ov/v% is preferred, and a particularly preferred moisture content is 5 to 6 v/v% in order to obtain a good sheet.

The desired sheet is obtained by drying this wet paper-like sheet using an ordinary dryer or the like. In this case, the drying temperature of the drying strip f1 is usually 50 to 90°C, preferably 60 to 80°C,
Drying time is 30 minutes to 60 minutes.

〔Effect of the invention〕

In the hyaluronate Ili fiber sheet of the present invention, the hyaluronate fibers have self-adhesive properties, so each fiber is adhesively bonded to each other and has excellent strength, even though it does not use an adhesive that is essential for general nonwoven fabrics. have. In addition, this sheet is safe for the human body because the hyaluronic acid is derived from natural products and does not use adhesives as mentioned above.
It has the following effects: excellent absorption, water retention, and moisturizing properties, as well as excellent compatibility with living organisms.

Therefore, when the sheet of the present invention is used as a covering material for damaged skin by utilizing these effects and characteristics, it quickly absorbs and retains the liquid exuding from the affected area, promotes epidermis formation, and improves the epidermis after healing. The effect is that the condition is smooth and good.

(Example) The present invention will be explained below with reference to Examples.

Example 1 95% methanol 1000 rn with slow stirring
I W/V% of viscous hyaluronate notorium in l
Aqueous solution 300! When Ill is gradually introduced while dripping,
It solidifies immediately to form a fibrous material. The final a degree of methanol in this case was approximately 73% v/v.

The fibrous material was taken out of the liquid, the liquid was sufficiently squeezed by filtration, and then placed in 500 d of 95% methanol and vigorously stirred for about 20 seconds at 4130 rpm using a commercially available Juice Mikili, the fibrous material was crushed. This resulted in short fibers with a length of 2 to 5 cm.

Next, this is stirred properly to prepare a dispersion (dope) in which the short fibers are uniformly dispersed, and poured onto a circular filter paper with a diameter of 150 # installed in a suction filtration device, resulting in a wet paper-like material. A sheet was obtained.

This sheet was placed in an electric dryer and dried at 60° C. for 30 minutes to obtain a circular sodium hyaluronate fiber sheet I- with a diameter of 150#. This sheet was white and had the appearance of filter paper, and was a uniform sheet with a thickness of about 0.5#.

A 1.5 CIi test piece was cut from this sheet, and the weight increase after leaving it for 24 hours in a relative humidity of 81% was measured, and its hygroscopicity was determined to be 18.7%.

In addition, a strip sample with a width of 2# was cut, both ends were fixed, a weight was added to one end, and the strength was measured by the amount of load at the cut end. It was found that the sample had a strength of 41.59 g.

Patent applicant: Kibun Co., Ltd.

Claims (1)

[Claims] 1. A sheet made of hyaluronate fibers. 2. The sheet according to claim 1, wherein the hyaluronate is one or more selected from sodium hyaluronate, potassium hyaluronate, and calcium hyaluronate. 3. Introduce an aqueous hyaluronate solution into the water-soluble organic solvent so that the final concentration is 50 v/v% or more, coagulate and precipitate the fibrous hyaluronate, and then add it to the solution. A method for producing a sheet made of hyaluronate fibers, which comprises crushing the fibers into short fibers, forming the fibers into paper, and drying the fibers. 4. The production method according to claim 3, wherein the water-soluble organic solvent is one or more solvents selected from methanol, ethanol, acetone, n-propanol, iso-propanol, and acetonitrile. 5. The manufacturing method according to claim 3, wherein the hyaluronate is one or more selected from sodium hyaluronate, potassium hyaluronate, and calcium hyaluronate. 6. Covering and protecting material for skin defects made of hyaluronate fiber sheet.