Chitosan microflake and method of manufacturing the same

Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives

Reexamination Certificate

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C536S055000, C536S055100

Reexamination Certificate

active

06444797

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to chitosan microflakes which are greatly improved in coatability onto the skin. Also, the present invention is concerned with a method for preparing such a chitosan microflake.
2. Description of the Prior Art
Chitin is quantitatively found in the shells of crustaceans, such as crabs and shrimps, and insects, and in the cell walls of fungi, mushrooms and bacteria, and along with potassium carbonate, proteins, lipids, and pigments, serves to support the main structure of the shells and exoskeletons of various animals. Next to cellulose, chitin is the polysaccharide most produced in the world, with as much as ten billion tons of chitin and its derivatives estimated to be produced from living organisms each year.
Despite its abundance in nature, chitin has not been effectively utilized because of its low solubility in aqueous solutions. Owing to this problem, chitin is difficult to form into fibers or films and thus, has found limited applications. In an effort to overcome this problem, chitin was converted into chitosan which is soluble in aqueous acid solutions. A deacetylation technique is generally used for the conversion of chitin into chitosan. Industrially, chitosan, which is water-soluble, is more extensively used than chitin, which is non-water soluble.
Derived from chitin, chitosan, which is an aminopolysaccharide, is known as being bio-friendly, i.e., non-toxic and biodegradable. In addition, chitosan was found to have effective biological activities for use in, for example, cell fusing, tissue culturing and hemorrhage stopping, and biological properties such as antibacterial activity and biocompatibility.
At first, chitin and chitosan were used as coagulants to recover useful materials from the wastewater of food factories. In recent, numerous applications of chitin and chitosan have been found in a broad spectrum of industries, including food, medical and medicine, bioengineering, cosmetic, agricultural, chemical engineering, and environmental industries.
Thus far, wastes from crustaceans, such as crabs and shrimps, have been used as main sources for chitin. In the future, chitin is expected to be obtained from krill. With respect to the production of chitosan, particular attention is paid to fungi because they are found to contain chitosan as well as chitin in their cell walls. Thus, if culture and extraction methods from fungi are developed to ensure the production of the useful polysaccharides, their sources will be expanded.
Typically, chitin is used in an unrefined form for the treatment of wastewater; while refined, high quality chitosan is applied for high value-added fields such as clinical medicine fields and cosmetic fields. Accordingly, there is a strong requirement to develop a method for preparing refined, high quality chitosan at low cost.
U.S. Pat. No. 3,533,940 discloses a method for preparing chitosan from chitin, along with its application to fibers and films. For possible applications, the prepared chitosan is dissolved in aqueous organic solutions. In U.S. Pat. No. 4,699,135, it is disclosed that chitin is dissolved in polar solvents such as lithium chloride-containing dimethyl acetate amide to produce chitin fibers. Also, disclosed is the production of chitosan staples from a solution of chitosan in an aqueous acetic acid solution. U.S. Pat. No. 5,900,479 describes the production of films and fibers of water-insoluble chitin using an aqueous organic acid solution of chitosan.
In addition to these, many other techniques for utilizing chitin or chitosan as raw materials in producing films and fibers are disclosed. In addition, active research has been directed to the production of biocompatible, hygienic products suitable for use in clinical medicine fields and to their possible applications. As a result, various relevant techniques are developed and disclosed at present.
For example, the applicability and superior functionalities of chitin, chitosan and derivatives thereof as materials for use in wound healing agents, artificial skins, pharmaceuticals, blood coagulants, artificial kidney membranes, biodegradable sutures, antibacterial agents, etc. are described in Dynesh et al (Rev. Macromol. Chem. Phys., C40(1), 69-83 (2000)). Another research result can be referred to Maryefan et al (ILEE Engineering In Medicine and Biology November/December, 1999), reporting that bedcovers with a coating of chitosan have the medicinal effects of preventing the formation of cicatrices and facilitating wound healing.
Recently, there have been reported various research results concerning chitosan's activities against tumors and cancers. In addition, chitosan has been, in a variety of routes, examined for the mechanism for improving the wound healing capability of the body. According to a generalized hypothesis, positively charged ions of chitosan are combined with negatively charged ions of bacteria to agglutinate the bacterial cells to inhibit them from transferring into other tissues or regions than the original lesions, thereby improving the wound healing capability of the body. Chitosan is slowly hydrolyzed by enzymes in vivo, but easily degraded into oligomers and dimmers by lysozyme, which exists in abundance at wound sites of the skin. These hydrolysates are known to continuously exert medicinally healing actions on the wounds for a long period of time.
Known as the first patents concerning use of chitin and chitosan in wound healing agents, Germany Pat. Nos. DE 1906155 and DE 1906159 disclose the medicinal efficacy of chitin or chitosan powder on wound healing. A similar content can be found in British Pat. No. GB1252373.
U.S. Pat. Nos. 3,632,754 and 3,914,413 teach that chitin has the effect of facilitating wound healing and can be physiologically solubilized by virtue of its hydrolysis by lysozyme.
In both European Pat. No. EP0089152 and Japanese Pat. No. 86141373, there is disclosed that composite films prepared from chitin and keratin or collagen are used as wound protectives.
As described above, there are many techniques for applying chitin and chitosan for medicinal purposes. However, most of the conventional techniques only suggest the availability of chitin or chitosan as biocompatible materials, but failed in their commercialization. Further, nowhere is mentioned the preparation of chitin and chitosan into forms which can be properly applied for various clinical-pathological treatments with maximal functionality.
Skins of the body assume various forms, depending on body regions. With exercise, skin differs from one body region to another in physical properties such as extension and contraction extent. For these reasons, there is a strong requirement for a novel form of chitosan, which is greatly improved in coatability. Because conventional chitosan applications for skins are in the form of powders, films, sponge or sheets, an extreme limitation is imposed on their uses.
For instance, chitosan powders are difficult to uniformly apply onto a dermal wounded region. To this end, a large quantity of chitosan powder is required. Another disadvantage of chitosan powder is that chitosan powder is too small in contact area with the dermal region to sufficiently exert its medicinal effect. Also, chitosan powder is poor in close adherence. As for chitosan films, sponge or sheets, they suffer from disadvantages of having difficulty in closely adhering to skins and being extremely limited in size. Furthermore, it is expected that they are not able to maintain close adherence to the skin, which continuously conducts movements such as extension and contraction.
SUMMARY OF THE INVENTION
Therefore, it is an object of the present invention to overcome the above problems encountered in prior arts and to provide a method for preparing chitosan into microflake forms which are exceptionally improved in coatability to the skin.
It is another object of the present invention to provide chitosan microflakes which have very high coatability onto the skin, thereby improving the medicin

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