KR100987819B1 - Hydrocolloid Pressure Sensitive Adhesive Coated Alginate Sponge And Method For Preparing Thereof - Google Patents

Abstract

The present invention relates to an alginate sponge coated with a hydrocolloid pressure-sensitive adhesive composition and a method for manufacturing the same, and more specifically, to an alginic acid sponge having physical properties usable for medical use, a thin coating of the hydrocolloid pressure-sensitive adhesive composition having adhesiveness and wound protection is performed. It relates to an alginic acid sponge and a method for producing the same greatly improved.

Hydrocolloid, Alginate Sponge

Description

Hydrocolloid Pressure Sensitive Adhesive Alginate Sponge Coated and Method for Manufacturing the Same {Hydrocolloid Pressure Sensitive Adhesive Coated Alginate Sponge And Method For Preparing Thereof}

The present invention relates to an alginate sponge coated with a hydrocolloid pressure-sensitive adhesive composition and a method for manufacturing the same, and more specifically, to an alginic acid sponge having physical properties usable for medical use, a thin coating of the hydrocolloid pressure-sensitive adhesive composition having adhesiveness and wound protection is performed. It relates to an alginic acid sponge and a method for producing the same greatly improved.

Alginic acid is a polysaccharide of marine plants that is equivalent to cellulose of land plants. It is a linear copolymer composed of α- (1 → 4) -L-gluronic acid and β- (1 → 4) -D-mannuronic acid.

Alginic acid is widely used in the field of medical wound coating materials, topical hemostatic agents, etc. by utilizing properties such as biodegradability, hygroscopicity, hemostatic action, biocompatibility, etc. The alginic acid wound coating material is used in a coagulation bath consisting of aqueous sodium alginate solution in aqueous calcium chloride solution. The nonwoven fabric of calcium alginate fiber produced by spinning is most widely used. However, the alginate wound coating material in the form of the nonwoven fabric has a problem in that short fibers separated from the nonwoven fabric remain after being attached to the skin damage site and are difficult to be transformed into various forms. There is a problem that it is not suitable to use.

In order to solve the problems of the alginic acid nonwoven fabric in the wound coating material, topical hemostatic agent, and tissue engineering polymer support using alginic acid as described above, US Patent No. 3,653,383, US Patent No. 5,718,916, US Patent No. 4,948,575, etc. The preparation of the alginic acid cross-linked gel by adding a crosslinking agent to the composition of the aqueous alginic acid solution at the time of preparation, and then molding and lyophilizing to provide a method for producing the alginic acid sponge. However, the method has a disadvantage in that the surface of the alginic acid sponge is rough and the attachment feeling is bad, and the structure of the sponge is not dense so that the same wound exudates can be absorbed to increase the thickness or to be replaced frequently compared to the sponge having a dense structure. In addition, the sponge's structure is low, which is low in flexibility, poor adhesion to the wound, and brittle and difficult to handle. Compared to the current situation is almost not commercialized.

In order to solve the above problems, the present inventors prepare an alginic acid sponge intermediate by molding and freeze-drying an aqueous alginic acid solution, and then immersing the alginic acid sponge intermediate in an aqueous solution of a crosslinking agent and crosslinking, followed by washing and drying for medical and tissue engineering. Alginate sponges of excellent physical properties usable have been prepared (Korean Patent Application No. 2003-0016849).

However, since the alginic acid sponge itself is not tacky, in order to continuously apply the alginic acid sponge to the wound site of the skin, a separate adhesive dressing material has to be applied on the sponge.

The hydrocolloid adhesive composition is a wound coating material in which a hydrophilic hydrocolloid polymer is dispersed in a hydrophobic rubbery matrix having adhesive force. Hydrocolloid pressure-sensitive adhesive composition has a wound protection ability and excellent adhesion due to the hygroscopicity and the maintenance of a wet environment, and is widely used in wounds, wounds, burns, bedsores, etc., which have a light leakage of exudate. However, the hydrocolloid adhesive composition described above is not suitable for wounds showing a large amount of exudate leakage because only the hydrophilic hydrocolloid polymer dispersed in the matrix is involved in the absorption of the exudate, and is applied to a wound showing a large amount of exudate leakage. If this is the case, the outflow of exudate or the disintegration of dressings may appear, so the application of a wide range of wounds is restricted.

Thus, the present inventors have studied in order to solve all the problems of the alginic acid sponge and the hydrocolloid pressure-sensitive adhesive composition as described above, hydrocolloid adhesive having adhesiveness and wound protection after the alginate sponge of the patent application No. 2003-0016849 The present invention has been completed by developing an alginate sponge having a thin coating of the composition, which greatly improves absorption and durability.

Accordingly, the present invention is coated with a hydrocolloid pressure-sensitive adhesive composition excellent in flexibility, structural density, absorbency and processability, which can impart tackiness to alginic acid sponges that can be used for medical and tissue engineering. Eggplant is an object to provide a alginate sponge coated with a hydrocolloid adhesive composition and a method for producing the same.

The present invention features an alginate sponge coated with a hydrocolloid adhesive composition and a method for preparing the same.

Hereinafter, the present invention will be described in detail.

The present invention relates to an alginic acid sponge and a method for preparing the alginic acid sponge having a physical property usable for medical use and a thin coating of the hydrocolloid pressure-sensitive adhesive composition having adhesiveness and wound protection greatly improved functionality.

In particular, the alginate sponge coated with the hydrocolloid pressure-sensitive adhesive composition prepared according to the present invention has a maximum bending angle (flexibility) of 90 ° or more, saline absorption rate of 150 to 7,000%, and provides adhesion of 50 to 1,000 g / 12 mm.

Hereinafter, the present invention will be described in detail.

The manufacturing method of the present invention will be described in detail as follows.                     

a) preparation of alginic acid sponge

This step is the same as the manufacturing method of the alginate sponge of the patent application No. 2003-0016849, but a detailed description thereof is as follows.

The alginate aqueous solution is molded and lyophilized to prepare an alginate sponge intermediate, which is then crosslinked, washed with water, and lyophilized to prepare an alginate sponge.

The aqueous alginic acid solution used in the present invention is prepared by dissolving alginic acid in pure water. The alginic acid is an alginic acid or an alginic acid alkali metal salt, and it is particularly preferable to use sodium alginate salt, potassium alginate salt, or ammonium alginate salt having excellent water solubility.

The aqueous alginic acid solution further includes an alkali metal salt of group 1A of the periodic table, polyethylene oxide, polyvinyl alcohol, carboxymethyl cellulose, carboxylated styrene butadiene latex, polyvinylpyrrolidone, coconut oil, glycerin, or a surfactant. The mechanical properties of the alginic acid sponge can be improved by controlling the external or internal pores of the alginic acid sponge.

In addition, the aqueous alginic acid solution is fibronectin, vitronectin, acidic fibroblast growth factor FGF, basic FGF, KGF, VEGF, EGF, PDFG-AA, PDGF-AB, PDGF-BB, TGF-α, TGF-β, IGF, TNF Bioactive factors such as GM-CSF, NGF, heparin-binding EGF, interferon, erythrocyte hematopoietic factor, 1L-1 (interleukin-1), IL-2, IL-6, IL-8, or tissue activating peptide It may include. The production activating factor may be used alone or in combination of two or more thereof.

The aqueous alginic acid solution composed of the above components can be molded into a mold, as well as by coating, die casting, extrusion, or the like. Preferably, the aqueous alginic acid solution is defoamed and molded. The aqueous alginic acid solution molded as described above is rapidly frozen at a temperature of −10 ° C. or lower and lyophilized to prepare an alginic acid sponge intermediate.

The prepared alginic acid sponge intermediate is crosslinked by dipping in an aqueous solution of a crosslinking agent, followed by washing and drying the excess crosslinking agent component to prepare an alginic acid sponge.

The crosslinking agent contained in the aqueous solution of the crosslinking agent may be a divalent metal salt or an organic crosslinking agent having a covalent binding ability. Specifically, as the divalent metal salt, calcium chloride, zinc chloride, or the like may be used, and an organic crosslinking agent having a covalent bond may be glutaaldehyde, dicyclohexyl carbodiimide, hexamethylene diisocyanate, or the like.

The concentration of the crosslinking agent contained in the aqueous solution of the crosslinking agent is not particularly limited, and may be used in various concentrations depending on the required performance and appearance of the alginate sponge as the final product.

In addition, the aqueous solution of the crosslinking agent may further include the same bioactive factor, water-soluble chitosan, hyaluronic acid, pectin, or gelatin as described in the alginate sponge intermediate preparation step, thereby promoting antimicrobial activity on the wound healing material and promoting skin regeneration. Additional performances, such as these, can be provided.                     

After immersing and crosslinking the alginate sponge intermediate material in the aqueous solution of the crosslinking agent as described above, the crosslinking alginic acid has excellent molding processability by washing and removing excess crosslinking agent component and drying, and is flexible and uniform in the inner and outer layers of the sponge. Sponges can be prepared.

b) preparing a hydrocolloid adhesive composition

This step is to prepare a hydrocolloid pressure-sensitive adhesive composition of a type in which hydrophilic hydrocolloid polymer is dispersed in a rubbery elastomer matrix having adhesive force.

In more detail, the adhesive rubbery elastomer matrix is isobutylene rubber which gives elasticity and adhesion to the matrix, styrene-isoprene-styrene copolymer polymer and tackifier, oil for imparting flexibility of the matrix, and antioxidant Consists of

Isobutylene rubber, which can impart adhesion to the hydrophobic rubbery matrix, is generally used due to its excellent performance as a pressure-sensitive adhesive having a polymer having a viscosity average molecular weight of 36,000 to 58,000.

The styrene-isoprene-styrene copolymer polymer imparts excellent elasticity as well as adhesion to the matrix, and the tackifier plays a role of imparting adhesiveness to the rubbery elastomer.

In addition, oils give the matrix flexibility and use antioxidants to prevent tack oxidation at high temperatures.                     

A rubbery elastomer matrix having the above composition is generally prepared by uniformly mixing the above components at a high temperature in a Z blast mixer, and after obtaining a uniform rubbery elastomer matrix, by mixing hydrophilic hydrocolloid components A uniformly mixed hydrocolloid adhesive composition is prepared.

Suitable hydrocolloids capable of imparting absorbency to the hydrocolloid agents include natural gums such as gum arabic and karaya gum guar gum, algae extracts such as alginic acid and carrageenan, dextran, xanthan gum, hydroxymethylcellulose, carboxy It includes methyl cellulose, pectin, gelatin, chitosan, water-soluble chitosan, and the like. Particularly, alginic acid or carboxymethyl cellulose, which is the same as the sponge material, is preferred because it can contribute to the initial absorption of the wound coating with high absorption. 10-50 weight% is preferable with respect to an adhesive composition. If the hydrocolloid is less than 10% by weight, the exudate is not absorbed and delivered to the alginic acid sponge smoothly. If the hydrocolloid is more than 50% by weight, it is difficult to disintegrate the structure due to the excessive amount of hydrocolloid and to secure proper adhesive force. There is this.

Hydrocolloid pressure-sensitive adhesive composition prepared by the above method is a thin coating on the alginic acid sponge by the method of pressing (Pressing), coating, laminating. In contrast to the conventional hydrocolloid adhesive composition, most of the dressing structure is composed of the hydrocolloid adhesive composition, and the alginate sponge coated with the hydrocolloid adhesive composition of the present invention delivers the exudates of the hydrocolloid adhesive composition to which the adhesive force is absorbed and absorbed by the alginate sponge. Since it only serves to serve as a thin coating on the alginic acid sponge, the preferred thickness is 1 to 1000 ㎛, more preferably 5 to 20 ㎛. In this case, when the coating thickness is less than 1 μm, there is a problem in that it is difficult to obtain a suitable adhesive force, and when it exceeds 1000 μm, the exudate cannot be effectively delivered to the alginic acid sponge, and thus it is difficult to absorb a large amount of exudate.

The alginate sponge coated with the hydrocolloid adhesive composition thus prepared has a maximum possible bending angle of 90 ° or more, in which the structure of the material is not broken, and exhibits an adhesive force of 50 to 1,000 g / 12 mm. If the maximum bending angle appears less than 90 ° it does not serve as a dressing material that can be effectively applied to the curved body. If the adhesive strength is less than 50g / 12mm does not exhibit the proper adhesion to the wound site, if it is higher than 1,000g / 12mm it can cause a large pain and secondary wounds when peeling from the wound site with more adhesive force than necessary. In addition, the alginate sponge coated with the hydrocolloid pressure-sensitive adhesive composition prepared according to the present invention can effectively absorb the exudates without disrupting the structure, compared to the existing hydrocolloid pressure-sensitive adhesive composition dressings whose structure is collapsed, and absorbed exudates The amount also shows a saline absorption rate of 150 to 7,000%, which is significantly higher than that of conventional products. If the absorption rate is less than 150%, the effective exudate can not be absorbed, so that it does not function as a dressing agent, and if the absorption rate is higher than 7000%, it is difficult to form a wetting environment of the wound due to excessive exudate absorption.

Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the scope of the present invention is not limited to the following examples.

Examples 1-6

a) alginate sponge manufacture

Sodium alginate [SIGMA] was dissolved in pure water at a concentration of 1% by weight to prepare an aqueous alginic acid solution. After removing the bubble completely by depressurizing it, it was placed in a plastic culture dish with a diameter of 100 mm, frozen at -40 ° C, and lyophilized to prepare a sodium alginate sponge intermediate.

The prepared sodium alginate sponge intermediate was crosslinked by immersion in 0.2 M aqueous calcium chloride solution for 30 minutes, washed several times with deionized water to remove excess crosslinker components, and then frozen at -40 ° C and freeze-dried to give a thickness of 5 mm. Insoluble crosslinked calcium alginate sponge was prepared.

b) Preparation of Alginate Sponge Coated with Hydrocolloid Adhesive Composition

Z-blade sigma mixer [AMK], which has a temperature of 200 ° C, Katon [Shell], a styrene-isoprene-styrene copolymer, Vistanex [Exxon], isobutylene rubber, Irganox [Ciba] as an antioxidant, and a tackifier Pentalyn [Eastman], Kaydol [Crompton] as an oil and stirred for 40 minutes to prepare a uniform liquid rubber-like elastomer matrix. After the temperature of the mixer was lowered to 100 ° C., hydrocolloid (sodium alginate) [Sigma] in the form of powder was added thereto, followed by stirring for 30 minutes. The well mixed solution was removed from the mixer, placed in a hot press at 80 ° C., and pressed to a thickness of 50 μm, and then adhered to the lower portion of the alginic acid sponge prepared by a) and cooled at room temperature to coat the hydrocolloid adhesive composition. Alginic acid sponge was prepared. The composition of the hydrocolloid pressure-sensitive adhesive composition is shown in Table 1 below.

division
(weight%) Isobutylene Rubber Styrene-isoprene-styrene copolymer Tackifier oil Antioxidant Alginic acid Example 1 8 13 9 26 One 43 Example 2 9 14 10 23 One 43 Example 3 9 16 15 16 One 43 Example 4 9 15 14 18 One 43 Example 5 8 14 20 14 One 43 Example 6 7 13 24 12 One 43

Comparative Examples 1-2

Commercially available hydrocolloid pressure-sensitive adhesive compositions of Duoderm CGF [ConvaTec] and Dermaplast [Hartmann] were compared with Examples 1 to 6 above.

Test Example

The sponges of Examples 1 to 6 and Comparative Examples 1 and 2 were measured for flexibility, water absorption, and adhesiveness by the following methods, and the results are shown in Table 2 below.

1) Flexibility (°): The maximum possible bending angle at which the structure of the material is not broken was measured and evaluated.                     

2) Absorption rate (%): The sample was dried in a dryer at a temperature of 60 ° C. for 24 hours to measure its weight (A), and then immersed in a 0.9% aqueous sodium chloride solution at 25 ° C. for 24 hours, followed by external moisture. After removing the weight (B) was measured by measuring the absorption according to the following equation (1).

[Equation 1]

3) Adhesion (g / 12mm): After making a sample with a width of 12 mm and a length of 250 mm, each sample was prepared by a 180 degree peel adhesion test method of a texture analyzer (CNS Farnell). Adhesion was measured.

division Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Comparative Example 1 Comparative Example 2 flexibility
(°) 162 162 155 160 165 165 180 180 Absorption rate
(%) 3420 3325 3250 3380 3360 3530 181.4 1024.2 adhesiveness
(g / 12mm) 369.11 380.3 401.08 303.5 450.3 400.2 571.78 402.3

Through Table 2, the alginic acid sponge coated with the hydrocolloid pressure-sensitive adhesive composition prepared in Examples 1 to 6 according to the present invention was confirmed to exhibit an excellent water absorption compared to Comparative Examples 1 and 2. In addition, the alginate sponge coated with the hydrocolloid pressure-sensitive adhesive composition of Examples 1 to 6 according to the present invention did not have a change in structure even after absorbing a large amount of water. When the structure of the colloidal pressure-sensitive adhesive composition itself is collapsed and the absorption rate is measured, it was confirmed that the structure was not maintained at all before the water absorption was maintained.

As described above, the present invention can not only prepare an alginate sponge coated with a hydrocolloid pressure-sensitive adhesive composition having physical properties usable as a medical wound coating material, but also coated with an alginate sponge coated with a hydrocolloid pressure-sensitive adhesive composition prepared by the present invention. Is expected to be useful in the use of dressings for wound healing because it has a significantly superior absorption and durability compared to conventional hydrocolloid dressings.

Claims (4)

1) molding the alginic acid aqueous solution and lyophilizing to prepare an alginic acid sponge intermediate; 2) cross-linking the intermediate material in an aqueous solution of a crosslinking agent, and then washing and drying to prepare an alginic acid sponge; And 3) coating a hydrocolloid adhesive composition on the alginic acid sponge to a thickness of 1 ~ 1000 ㎛ The maximum bending angle (flexibility) is characterized in that it comprises more than 90 °, saline water absorption is 150 ~ 7000%, adhesive strength 50 ~ 1000 g / 12mm coated hydrocolloid pressure-sensitive adhesive composition coated alginate sponge manufacturing method. The method of claim 1, wherein the hydrocolloid adhesive composition comprises a hydrophilic hydrocolloid, isobutylene rubber, styrene-isoprene-styrene copolymer polymer, a tackifier, an oil and an antioxidant. Alginate sponge, characterized in that prepared by the method of claim 1. delete