JP2007001963A - Method for producing chitosan sponge having high water absorption property - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a chitosan sponge being useable for applications such as cosmetics, medical materials, and industrial materials, excellent in water-absorbing characteristics, especially water-absorbing rate, water-absorbing magnification and having high flexibility. <P>SOLUTION: The method for producing the chitosan sponge comprises adding polyethylene glycol or polypropylene glycol having 1,500-8,000 molecular weight when producing the porous chitosan sponge from a chitosan solution. Thereby, water absorbing characteristics are remarkably improved. The chitosan sponge is used for application such as cosmetics, e.g. pack materials for the faces and the skins and medical materials, e.g. wound-covering materials. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

Detailed Description of the Invention

  The present invention mainly relates to a method for producing a chitosan sponge with high water absorption, which can be used in applications such as cosmetics, medical materials, and industrial materials.

  Chitosan is widely used in the cosmetics field, the medical field, the food field, and the like, and is preferably used as a natural material in the same manner as the collagen material. Chitosan, which is a natural polymer and is an aminopolysaccharide, is generally easily dissolved in an aqueous solution of acetic acid, so that various molded articles such as films, fibers, and sponges can be prepared from the solution. However, with regard to its practical application, there has been little success in the past. The reason is that the performance of the molded body was not sufficient to withstand practical use.

  On the other hand, regarding collagen, which is a protein obtained from cow skin, tendon, and the like, many molded bodies such as nonwoven fabrics and porous sponges have been put into practical use and are currently widely used in various fields. In particular, bovine collagen sponge, which is a porous sponge, has been developed with good quality from German companies such as Zuverac, and is now widely used in the cosmetics and medical fields all over the world and widely in Japan. . In particular, it has excellent performance with respect to water absorption characteristics, i.e., water absorption speed, water absorption ratio, especially when it is impregnated with lotion in cosmetics and other fields, and used for facial and skin packs. In use, a lotion or the like is quickly and sufficiently absorbed, so that it has high flexibility and is very preferably used.

Problems to be solved by the invention

  However, since bovine collagen sponge is derived from protein, and in particular, the raw material is obtained from bovine skin and tendon, there are concerns about safety due to problems such as mad cow disease in recent years. In particular, in the medical supplies and cosmetics fields, products made of collagen are often withdrawn, and other materials that have performance comparable to existing bovine collagen sponges, that is, high water absorption characteristics and flexibility, and no safety problems. Sponges are widely demanded.

  On the other hand, with regard to the aminopolysaccharide chitosan, many proposals have been made in the past regarding the production method of the sponge shape, and the present has been reached. However, a chitosan sponge, which is a porous body made of chitosan prepared by a conventional method, has not been able to beat a bovine collagen sponge. In particular, a rapid water absorption rate, a high water absorption ratio, and high flexibility associated therewith do not reach the performance of bovine collagen sponge. An object of the present invention is to develop a chitosan sponge having water absorption characteristics, that is, a water absorption speed, a water absorption magnification, and a flexibility equal to or higher than those of these bovine collagen sponges.

Means for solving the problem

      Conventionally, many applications have been filed for a method for producing a chitosan sponge, but no method has been proposed in the past that can achieve performance comparable to that of a collagen sponge. Chitosan is obtained by chemically treating chitin, which is a naturally occurring amino polysaccharide, and deacetylating the aminoacetyl group. In general, chitin is insoluble in most solvents, but chitosan is dissolved in an aqueous solution of an acid such as acetic acid. However, since the amino group generated by deacetylation increases the hydrophobicity, chitosan essentially has a hydrophobic property compared with chitin having a very high hydrophilicity. Therefore, even with porous chitosan sponges, even if the raw material type, manufacturing method, manufacturing conditions are changed and the sponge structure is improved, it is not possible to obtain a past water absorption property, particularly a high water absorption rate, and a high water absorption rate. It was. In other words, regarding the production method of chitosan sponge, no matter how the production conditions related to freeze-vacuum drying, such as various types of porous production, molecular weight, degree of deacetylation, freezing temperature, drying time, etc. are devised, chitosan It is difficult to break through the highly hydrophobic walls, and this is the main reason why chitosan sponges cannot enter the field of practical use of chitosan, that is, cosmetics such as esthetics.

      As a result of diligent efforts by the inventor to improve the water absorption characteristics of the chitosan sponge, which is a high water absorption rate and a high water absorption capacity, to the same or better than that of bovine collagen sponge, It has come. That is, the gist of the present invention is a method for producing a chitosan sponge having high water absorption, wherein polyethylene glycol or polypropylene glycol having a molecular weight of 1500 to 8,000 is added in the production of a porous chitosan sponge. Is.

  The chitosan referred to in the present invention is a deacetylated product of the aminopolysaccharide chitin contained in the exoskeleton of crustaceans such as crabs and shrimps, and the chemical structure is a repeating unit of glucosamine or glucosamine and a small amount of N-acetylglucosamine. It is a natural polymer. In general, chitosan refers to chitin obtained by deproteinizing a crustacean exoskeleton with an alkaline aqueous solution and decalcifying with a hydrochloric acid aqueous solution, and further deacetylating with a high concentration alkaline aqueous solution such as caustic soda. In general, a chitosan having a degree of deacetylation of 70% or more is called chitosan. However, chitosan which is usually marketed and used for food or industrial use is deacetylated by 80% or more. The most special property of chitosan is that it does not dissolve in water alone but dissolves in an acetic acid aqueous solution.

  For example, chitosan can be produced by deproteinizing fresh red snow crab shells with a dilute alkaline aqueous solution such as caustic soda and decalcifying with a dilute aqueous acid such as hydrochloric acid. This is a method of treating for about 5 to 20 hours while maintaining a temperature of about 90 ° C. or higher in a concentrated alkaline aqueous solution. What is obtained by this production is usually in the form of solid flakes, and is generally dried and used as a powder. The obtained chitosan is a polymer and has a high molecular weight after purification, but is generally about 100,000 to 3 million. Usually, the molecular weight can be controlled by dissolving in a certain aqueous acetic acid solution and measuring the solution viscosity. In the standard viscosity measurement, 0.5 wt% chitosan is usually dissolved in an acetic acid aqueous solution, and the viscosity is measured with a B-type viscometer at 20 ° C. The viscosity of ordinary chitosan is 3 to 500 mPa · s, and generally 10 to 250 mPa · s, as described above. For example, the solution viscosity of chitosan having a molecular weight of about 300,000 is about 10 mPa · s.

  The chitosan sponge is composed of a homogeneous porous structure of chitosan, and the average pore size is generally 10 to 200 μm in diameter and the density is generally 0.05 or less. Therefore, if it can be immersed in water and sufficiently impregnated with water, the water absorption ratio may be increased. The present invention is not particularly limited to these sponge structures, and any shape can be applied as long as it is porous. Further, the present invention does not particularly limit the method for producing chitosan sponge. However, as a method of producing a sponge, it is common to start by first dissolving chitosan in an acetic acid aqueous solution to prepare a solution. The amount of chitosan added is usually about 0.3 to 2 wt%. In general, chitosan has a viscosity suitable for production in many cases, but the concentration is decreased for those having a high molecular weight, and the concentration is increased for those having a low molecular weight, thereby adjusting to an appropriate viscosity. When using acids other than acetic acid such as hydrochloric acid, chitosan dissolves only at a high concentration, so it is relatively difficult to create an aqueous solution from other than acetic acid, but it is possible to create a solution using a combination of strong and weak acids. It is.

A sponge can be produced from this aqueous acetic acid solution by various methods. However, the present invention is not limited to a specific manufacturing method, and can be applied to any manufacturing method.
Conventional methods for producing chitosan sponges include foaming a chitosan aqueous solution with a surfactant, chemical foaming agent, gas blowing, etc., then solidifying, or adding a powdered solid substance to the chitosan solution and dispersing well. And then lyophilizing them after removing the powdered solid material with hot water, etc. However, as a commonly used method, the chitosan aqueous solution is frozen as it is and frozen. A method of removing moisture contained by vacuum drying is performed, and this method is the simplest method for producing a chitosan sponge. For example, this method is disclosed in the example of the production of chitosan sponge in JP 2005-503197 (a wound dressing and a method for controlling severe and life-threatening bleeding). The present invention is particularly preferably applicable to this manufacturing method.

  The polyethylene glycol referred to in the present invention refers to a polyether having a structure that is considered to be produced by dehydration polycondensation of ethylene glycol, and both terminals are hydroxyl groups. Polypropylene glycol refers to a polyether having a structure in which propylene glycol is considered to be produced by dehydration polycondensation, and both terminals are hydroxyl groups. Both substances have molecular weights of several hundred to tens of thousands. In general, 200-600 are viscous and transparent liquids. In addition, when the molecular weight is 1000 or more, it is an individual at room temperature. Usually, those having a molecular weight of 1000 or less are used as lubricants and surfactants, and those having a molecular weight of 1000 or more are used as glycol components in the production of polyurethane. In the present invention, this molecular weight is very important. That is, the molecular weight is in the range of 1500 to 8000. Preferably, it is 2000-7000. More preferably, it is 3000-6000. Most preferably, it is 3500-5000. At other molecular weights, the effect of the present invention cannot be exhibited at all. For example, the effect of the present invention is not seen at all in the case of a molecular weight of 600 to 1000 which is usually used as a surfactant. For example, in Japanese Patent Laid-Open No. 2003-292501 (chitosan sponge and method for producing the same), polyethylene glycol 400 is disclosed in order to maintain flexibility, but with such a thing, the object of the present invention cannot be achieved at all. . Molecular weight is extremely important.

  The chitosan aqueous solution to which the present invention is applied is generally obtained by dissolving chitosan of about 0.3 to 3 wt% in an acetic acid aqueous solution of about 0.3 to 2 wt% of acetic acid. The resulting aqueous solution is usually a viscous and transparent solution, and can be prepared by selecting the molecular weight and concentration of chitosan with the aim of a normally fluid solution. The polyethylene glycol or polypropylene glycol of the present invention can be added as it is at the time of preparation of the aqueous chitosan solution or after the preparation of the aqueous solution and mixed with sufficient stirring. The addition amount is preferably 5 to 40 wt%, more preferably 10 to 30 wt%, based on the weight of the finished dry chitosan sponge. Most preferably, it is 15-25 wt%.

In order to produce chitosan sponge from this solution, a general method can be adopted. For example, there is a method in which this chitosan aqueous solution is frozen and freeze-dried. Various shapes of chitosan sponge can be prepared depending on the purpose of use, such as a sheet shape, a block shape, and a cocoon shape, and the present invention can be applied to any shape.
For example, in order to create a sheet with a certain thickness, it is preferable to first put the chitosan solution in a tray with a certain depth and freeze it as it is or in a bag made of polyethylene, polypropylene, etc. Can be used. When putting into a bag, in order to make thickness uniform, putting a bag into a tray and applying a weight with a weight etc. to an upper part etc. can use preferably. Freezing includes freezing with a freezing gas such as liquid nitrogen, freezing in a refrigerant such as ethanol, or freezing as a tray with a freeze-drying facility. In general, it is preferable to sufficiently freeze with a refrigerant before entering the freeze dryer. The freezing temperature is preferably −15 ° C. to −80 ° C., more preferably −20 ° C. to −50 ° C.

  The freeze-drying time is usually performed under conditions used for cosmetics, foods, and the like. Although it varies depending on the set temperature, it is preferably 10 to 48 hours, preferably 15 to 24 hours. After completion of lyophilization, hot air drying or the like is performed at a temperature of 50 ° C. or higher in order to remove the remaining acetic acid.

  Sheets or other shaped bodies that are created usually have a smooth white surface. Usually, when observed with an electron microscope or the like, the average pore size is a porous body of about 20 to 100 μmφ. This shape does not change much regardless of whether or not the polyethylene glycol or polypropylene glycol of the present invention is added. However, there are significant differences in water absorption characteristics. That is, when the chitosan sponge of the present invention is used to measure the water absorption rate by measuring the time for moisture to enter the sponge when the sponge is put on the surface of the water, the time for completely absorbing water is not used when the present invention is not adopted. However, it takes 30 seconds or more, or 60 seconds or more, whereas when the method of the present invention is used, water enters the sponge in an instant and is completely within 10 seconds or less than 1 second. There is a marked improvement over chitosan sponges that absorb water and usually have poor water absorption.

  In the case of the present invention, when the present invention is not adopted, water absorption is 20 times or less with respect to the weight of the dried chitosan sponge, whereas in the present invention, a high water absorption ratio of 40 times or more is obtained. In the present invention, the flexibility after water absorption is very high. That is, it is equal to or greater than bovine collagen sponge. That is, in the present invention, a high-performance chitosan sponge that can be used as a cosmetic or medical product can be obtained.

Comparative Examples 2 and 3

  Red snow crab shells were pulverized, deproteinized at 5% caustic soda solution at 90 ° C. for 4 hours, and decalcified with 2N hydrochloric acid for 3 hours to obtain chitin. Further, this chitin was treated in a 50 wt% alkaline solution at a temperature of 90 to 100 ° C. for 20 hours to obtain flaky chitosan. This was pulverized to prepare a powder of 100 mesh pass. The degree of deacetylation of this chitosan was measured by a colloid titration method (chitin, chitosan experiment manual, pages 51-52, chitin, chitosan research edition, Gihodo Shuppan), and was 90.3%. Moreover, the viscosity measured with a B-type viscometer at 20 ° C. of a solution obtained by dissolving 0.5 wt% chitosan in 0.5 wt% acetic acid aqueous solution was 48 mPa · s. In addition, the molecular weight of this chitosan was measured using a GPC measurement device (system: manufactured by JASCO, column: ShodexOHpak SB-805, SB-806, mobile phase: 0.5 M acetate buffer, column temperature: 40 ° C., flow rate: 1 (0.0 ml / min), a calibration curve was prepared and measured based on the pullulan sample, and was found to be about 1 million. This chitosan was dissolved in a 0.75 wt% acetic acid aqueous solution to obtain a 1.5 wt% solution.

  In this transparent viscous solution, 0.45 wt% of polyethylene glycol having a molecular weight of 4000 was dissolved and mixed well to prepare a solution. For comparison, a solution in which the production conditions were the same and only polyethylene glycol having a molecular weight of 4000 was removed was also prepared (Comparative Example 1). This solution was filled in a polyethylene bag so as to have a thickness of 2 mm, placed in an aluminum tray, an aluminum plate placed on top, and immersed in an ethanol refrigerant bath at -30 ° C. for 1 minute to freeze. After freezing, the polyethylene bag was removed, and frozen ice (thickness: about 2 mm) was placed in a tray (preliminary freezing temperature −45 ° C.) of a freeze vacuum dryer, and freeze vacuum drying was performed. Depressurization was performed at about 100 mTorr, the temperature was increased from −45 ° C. to −15 ° C. over 5 hours, and then freeze-drying was performed up to 20 ° C. over 18 hours.

  The obtained product had already shown a sponge shape, but was dried with hot air at 70 ° C. for about 10 hours for the purpose of removing the remaining acetic acid. As a result, the obtained chitosan sponge had a thickness of 1.9 mm, showed a uniform porous structure as a whole, and had continuous pores with a diameter of 30 to 80 μm. The water absorption characteristics of this chitosan sponge were measured. Water absorption speed is 20cm in length, 30cm in width, 5cm in depth. Put enough water into a 5cm × 5cm chitosan sponge piece on the water surface and measure the time for the sponge to absorb water completely. did. In addition, the water absorption ratio is obtained by sucking the water, and taking out the chitosan sponge while still containing water with a clip, leaving it for about 10 seconds, removing excess water, measuring its weight, The water absorption ratio was expressed as the sponge weight after water immersion / sponge weight before water immersion.

  As a result, a sponge containing a polyethylene glycol having a molecular weight of 4000 has an average of 5 measurements, a water absorption rate of 0.9 seconds, and a water absorption rate of 42.5 times. The chitosan sponge of the present invention exhibited outstanding water absorption characteristics compared to the comparative example at a second (however, some of the sponge did not absorb water) and the water content was 19 times. The same measurement was performed on bovine collagen sponge (manufactured by Zverac, Germany, thickness 1.2 mm), and the same water absorption characteristics as described above were measured (Comparative Example 2). The water absorption rate was 1.1 seconds and the water absorption magnification. Was 39.4 times, and the method of the present invention showed the same water absorption property as that of bovine collagen sponge. When this chitosan sponge was used as a face or skin pack material, the water absorption was high and it could be preferably used.

Examples 2-14

Comparative Example 3

  Chitosan powder (93% deacetylation, solution viscosity of 58 mPa · s: both measurement methods are the same as the method described in Example 1) is dissolved in 0.75 wt% acetic acid aqueous solution to 1.5 wt% chitosan aqueous solution. Created. To this solution, 0.5 wt% of polyethylene glycol having various molecular weights was added. The molecular weight of the polyethylene glycol used was 400, 600, 800, 1000, 1500, 2000, 3000, 4000, 5000, 6000, 8000, 10000, 20000 (hereinafter referred to as PEG400, PEG600, respectively). These solutions were placed in a tray and frozen at −40 ° C., and then freeze-dried at a reduced pressure of about 100 mTorr to 20 ° C. for 24 hours, followed by hot-air drying at 70 ° C. for 12 hours.

以上のとおり、本発明の分子量のポリエチレングリコールを添加したキトサンスポンジは、優れた吸水特性、すなわち良好な吸水速度および吸水倍率を示していた。As a result, a sponge having a thickness of about 1.4 mm could be obtained. About these, the water absorption characteristic was measured by the method similar to Example 1. FIG. The measurement was performed for each of five samples, and the average value was calculated. The results are shown in Table 1.

As described above, the chitosan sponge to which the polyethylene glycol having the molecular weight of the present invention was added exhibited excellent water absorption characteristics, that is, good water absorption speed and water absorption capacity.

Claims (1)

A method for producing a chitosan sponge with high water absorption, wherein polyethylene glycol or polypropylene glycol having a molecular weight of 1500 to 8,000 is added in producing a porous chitosan sponge.