KR102621083B1 - Biodegradable film for skin regeneration function and method for preparing thereof - Google Patents

Abstract

The present invention relates to a biodegradable film having a skin regeneration function and a method for manufacturing the same. According to the present invention, the polymer itself promotes skin regeneration or improves skin wounds, and at the same time, it has the property of dissolving without the need to be separately removed from the skin. It has the effect of representing .

Description

Biodegradable film with skin regeneration function and manufacturing method thereof {BIODEGRADABLE FILM FOR SKIN REGENERATION FUNCTION AND METHOD FOR PREPARING THEREOF}

The examples below relate to a biodegradable film with skin regeneration function and a method of manufacturing the same.

Skin is a membrane that covers the outside of the body and performs various physiological functions to protect the body from environmental factors such as various external stimuli, obstacles, and dryness, and plays a role in protecting and regulating internal organs and other organs of the body. do. However, as we age, the secretion of various hormones that internally regulate metabolism decreases, and the function and activity of immune cells decrease. In addition, externally, the content of ultraviolet rays in the sun increases due to the destruction of the ozone layer, and as environmental pollution becomes more severe, excessive physical and chemical stimulation and stress caused by the increase in free radicals and active harmful oxygen, etc., affect the skin's normal function. It damages the skin by promoting the formation of spots and freckles due to melanin deposition and skin aging. In order to maintain healthier and more beautiful skin by preventing skin aging and damage caused by internal and external factors, physiologically active substances obtained from various animals, plants, and microorganisms are added to cosmetics to maintain the skin's inherent functions. Efforts to maintain skin health by activating cells and promoting skin metabolism are continuing, and cosmetics and external skin preparations are being developed accordingly. The most representative changes in human skin are deterioration of skin function and visual beauty due to aging. Final skin appearance phenomena that occur as a result of skin aging include the formation of wrinkles, decreased skin elasticity, and formation of senile spots, and the formation of wrinkles and decreased elasticity are accepted as the most representative phenomena. Recently, a lot of physiological research has been conducted on the causes of skin wrinkles and loss of elasticity. To prevent this, methods such as maintaining moisture in the stratum corneum with moisturizers, protecting the skin from ultraviolet rays or the environment, and promoting new cell activity are being applied. .

Accordingly, Republic of Korea Patent Publication No. 10-1221472 is an enzyme for exfoliating skin that can naturally remove dead skin cells and sebum from pores through the action of proteolytic enzymes and lipolytic enzymes when applying a mask pack without having to rub the skin with a scrub. A mask pack containing is disclosed. However, only research on useful ingredients has been conducted, and development is needed for polymer sheets that directly contact the skin, and furthermore, the inconvenience of having to remove the sheet covering the skin remains.

Republic of Korea Patent Publication No. 10-1221472 U.S. Patent Publication No. 5,679,657

Carmela Saturnino et al., “Acetylated Hyaluronic Acid: Enhanced Bioavailability and Biological Studies”, BioMed Research International, Volume 2014, Article ID 921549.

The examples below were devised to solve the above problems, and the purpose of the present invention is to provide a biodegradable product that promotes skin regeneration or improves skin wounds by the polymer itself and exhibits melting properties without the need to separate it from the skin. To provide a film and a method for manufacturing the same.

In order to achieve the above-described object of the present invention, one embodiment of the present invention provides a film for promoting skin regeneration or improving skin wounds, which includes a biodegradable polymer.

Another embodiment of the present invention includes the steps of acetylating biodegradable hyaluronic acid in a solvent to obtain a biodegradable acetyl hyaluronic acid solution; and obtaining a film by casting and drying the biodegradable acetyl hyaluronic acid solution. It provides a method for producing the film for promoting skin regeneration or improving skin wounds, including a step.

According to the present invention, the polymer itself has the effect of promoting skin regeneration or improving skin wounds and at the same time exhibiting melting properties without the need to separate it from the skin.

Figure 1 is a photograph showing the equipment used in the production of acetyl hyaluronic acid according to an embodiment of the present invention.
Figure 2 is a photograph of an acetyl hyaluronic acid film according to an embodiment of the present invention.
Figure 3 is a ¹ H-NMR spectrum graph of an acetyl hyaluronic acid film according to an embodiment of the present invention.
Figure 4 is a photograph of clinical data on bedsores after application of an acetyl hyaluronic acid film according to an embodiment of the present invention.
Figure 5 is a diagram showing the structure of acetyl hyaluronic acid according to an embodiment of the present invention.

Hereinafter, embodiments will be described in detail with reference to the attached drawings. However, various changes can be made to the embodiments, so the scope of the patent application is not limited or limited by these embodiments. It should be understood that all changes, equivalents, or substitutes for the embodiments are included in the scope of rights.

Specific structural or functional descriptions of the embodiments are disclosed for illustrative purposes only and may be modified and implemented in various forms. Accordingly, the embodiments are not limited to the specific disclosed form, and the scope of the present specification includes changes, equivalents, or substitutes included in the technical spirit.

Terms such as first or second may be used to describe various components, but these terms should be interpreted only for the purpose of distinguishing one component from another component. For example, a first component may be named a second component, and similarly, the second component may also be named a first component.

When a component is referred to as being “connected” to another component, it should be understood that it may be directly connected or connected to the other component, but that other components may exist in between.

The terms used in the examples are for descriptive purposes only and should not be construed as limiting. Singular expressions include plural expressions unless the context clearly dictates otherwise. In this specification, terms such as “include” or “have” are intended to designate the presence of features, numbers, steps, operations, components, parts, or combinations thereof described in the specification, but are not intended to indicate the presence of one or more other features. It should be understood that this does not exclude in advance the possibility of the existence or addition of elements, numbers, steps, operations, components, parts, or combinations thereof.

Unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as generally understood by a person of ordinary skill in the technical field to which the embodiments belong. Terms defined in commonly used dictionaries should be interpreted as having a meaning consistent with the meaning in the context of the related technology, and should not be interpreted in an ideal or excessively formal sense unless explicitly defined in the present application. No.

The advantages and features of the present invention and methods for achieving them will become clear by referring to the embodiments described in detail below along with the accompanying drawings. However, the present invention is not limited to the embodiments disclosed below and will be implemented in various different forms. The present embodiments only serve to ensure that the disclosure of the present invention is complete and that common knowledge in the technical field to which the present invention pertains is not limited. It is provided to fully inform those who have the scope of the invention, and the present invention is only defined by the scope of the claims.

In the embodiments of the present invention, unless otherwise defined, all terms used herein, including technical or scientific terms, are the same as those commonly understood by a person of ordinary skill in the technical field to which the present invention pertains. It has meaning. Terms defined in commonly used dictionaries should be interpreted as having a meaning consistent with the meaning in the context of the related technology, and unless clearly defined in the embodiments of the present invention, have an ideal or excessively formal meaning. It is not interpreted as

The shapes, sizes, proportions, angles, numbers, etc. disclosed in the drawings for explaining embodiments of the present invention are illustrative, and the present invention is not limited to the matters shown. Additionally, in describing the present invention, if it is determined that a detailed description of related known technologies may unnecessarily obscure the gist of the present invention, the detailed description will be omitted. When ‘includes’, ‘has’, ‘consists of’, etc. mentioned in this specification are used, other parts may be added unless ‘only’ is used. When a component is expressed in the singular, the plural is included unless specifically stated otherwise.

When interpreting a component, it is interpreted to include the margin of error even if there is no separate explicit description.

The size and thickness of each component shown in the drawings are shown for convenience of explanation, and the present invention is not necessarily limited to the size and thickness of the components shown.

Each of the features of the various embodiments of the present invention can be combined or combined with each other, partially or entirely, and as can be fully understood by those skilled in the art, various technical interconnections and operations are possible, and each embodiment may be implemented independently of each other. It may be possible to conduct them together due to a related relationship.

Hereinafter, the present invention will be described in detail with reference to examples and drawings. However, it is obvious that the present invention is not limited to the following examples and drawings.

Film for improving skin function

In one aspect, the present invention provides a film for promoting skin regeneration or improving skin wounds, which includes a biodegradable polymer.

In particular, the present inventors have developed a biodegradable polymer sheet that comes in direct contact with the skin, without concerns about microbial contamination, and has the function of promoting skin regeneration or improving skin wounds by the polymer itself, while also exhibiting melting properties without the need to separate it from the skin. The present invention was completed through knowledge of film.

The acetyl hyaluronic acid film according to the present invention has rapid disintegration properties. Rapid disintegration means that the film formulation breaks down into submicrometer particles or breaks down within an acceptable time (e.g., within 60 seconds, within 45 seconds, within 30 seconds, within 20 seconds, or within 20 seconds of being administered, i.e., placed in the mouth). It refers to the ability to completely dissolve (within 15 seconds). In one embodiment, the film is an orally dissolving film or an oral mucosal adhesive film. By attaching the film to the oral mucosa, etc., the effective substance can be absorbed into the oral mucosa. When transported through the oral mucosa, the difference in absorption is higher than when administered orally, and the absorption rate is much higher because digestive juices, first-pass liver, and liver metabolism can be avoided.

One embodiment of the present invention is a biodegradable film containing a natural polymer or a derivative thereof and having an effect of improving skin function, an ampoule having an effect of improving skin function, a biodegradable film having a skin regeneration function, or a biodegradable film considering the convenience of taking by dogs. Provides a film or a method of manufacturing the same. In one aspect, the present invention provides a biodegradable film containing a natural polymer or a derivative thereof and having an effect of improving skin function, an ampoule having an effect of improving skin function, a biodegradable film having a skin regeneration function, or a biodegradable film considering the convenience of taking by dogs. Provides a film or a method of manufacturing the same. In one embodiment, the present invention relates to an acetyl hyaluronic acid film that can be used as a treatment for bedsores and burns, skin care, and films for dogs, as a method of manufacturing a hyaluronic acid film with excellent transdermal absorption rate. In one embodiment, the film melts away when applied to the skin. In one embodiment, the acetyl hyaluronic acid film of the present invention is in a solid state with a dried surface rather than a liquid, so there is no concern about microbial contamination and can be applied to bedsores and burn treatments, skin care products, and edible films for dogs.

In one embodiment, the biodegradable polymer is biodegradable acetyl hyaluronic acid according to the following formula (1), and the degree of acetylation of the biodegradable acetyl hyaluronic acid is 50% to 80%.

[Formula 1]

.

According to the measurement and calculation of the degree of acetylation using the acetylation degree test method, the degree of acetylation of the biodegradable acetyl hyaluronic acid is 50% to 80%. More specifically, the degree of acetylation of the biodegradable acetyl hyaluronic acid is 50% to 80%. The acetylation degree of the biodegradable acetyl hyaluronic acid is 50% or more, 55% or more, 60% or more, 65% or more; It may be 80% or less, 75% or less, 70% or less, and 65% or less, but is not limited thereto. The present inventors completed the present invention by discovering that the biodegradable acetyl hyaluronic acid exhibits excellent biodegradation and dissolution properties when the degree of acetylation is within the above range.

In one embodiment, the acetyl hyaluronic acid (AcHA) has a structure in which a hydrophilic -OH group is replaced with an acetyl group having amphipathic properties, and as a result, it has a better moisturizing effect than existing hyaluronic acid. The acetyl hyaluronic acid can be synthesized through the acetylation reaction of hyaluronic acid. The key in this reaction is acetylation of all -OH groups present in the hyaluronic acid molecule (a total of 4 -OH groups exist per hyaluronic acid monomer). It is important to obtain a uniform product by site-selectively acetylating certain -OH groups (1 to 4). The acetylation reaction performed at this time can be performed according to Scheme 1 below.

[Scheme 1]

The skin regeneration is a process of tissue recovery from damage and is a complex biological process that includes chemotaxis, cell differentiation and replication, matrix protein synthesis, angiogenesis, and wound reconstruction. Meanwhile, the damage may be caused by ultraviolet rays, external contaminants, wounds, trauma, burns, stress, etc., but is not limited thereto. The promotion of skin regeneration is a phenomenon in which when part of the skin tissue is shed or defected due to disease or trauma, the skin cells surviving around the exfoliated tissue divide and proliferate and move to the defect area, thereby ensuring rapid skin cell regeneration. It refers to a composition that can promote

The wound means that the normal continuity of the skin structure is disrupted due to physical damage to the skin, specifically contusion or bruise, laceration, avulsion, penetrating wound, Non-healing traumatic wounds, destruction of tissue by irradiation, abrasion, bone gangrene, gun shot wound, cut, burn, frostbite, skin ulcer, dry skin, keratosis, cracking, bursting, dermatitis, Pain due to dermatophytosis, surgical wounds, vascular disease wounds, corneal wounds, bedsores, flat sores, conditions related to diabetes and poor circulation, chronic ulcers, suture sites after plastic surgery, spinal injury wounds, gynecological wounds, chemical It comprehensively refers to damage to parts of an object, such as wounds and acne. The wound healing refers to a complex process in which the skin or body tissue spontaneously recovers its discontinuity after treatment. Therefore, ultimately, wound healing means promoting, improving, progressing, accelerating or progressing one or more steps or processes involved in the skin wound healing process.

In one embodiment, the film includes cell growth factor (EGF, Epidermal growth factor), platelet-derived growth factor-AA (PDGF-AA, Platelet-derived growth factor-AA), and insulin-like growth factor-1 (IGF-1, It further includes one or more skin regeneration promoting or skin wound improving substances selected from the group consisting of insulin-like growth factor 1).

The growth factor refers to a polypeptide that promotes division, growth, and differentiation of various cells, including epidermal growth factor (EGF), platelet-derived growth factor-AA (PDGF-AA), and insulin-like growth factor-1 (IGF-1). ), transforming growth factor-β (TGF-β), or fibroblast growth factor (FGF).

The epithelial cell growth factor is a growth factor that is secreted not only from the skin but also from mucous membranes such as the oral cavity and stomach to promote the growth, differentiation and division of epithelial cells. When damage is done to epithelial tissue, it quickly recovers and protects against external infectious agents or gastric juice. It is known to prevent tissue damage from internal factors. The platelet-derived growth factor-AA is a growth factor that has a significant effect on mesenchymal stem cell division during development. It is known to promote the growth, division, and migration of mesenchymal-derived cells not only during development but also in adults, and especially in the skin, to promote the division of fibroblasts. The insulin-like growth factor-1 is basically a growth factor that acts similar to insulin in the body, and examples include skeletal muscle cells, bone cells, cartilage cells, liver cells, kidney cells, nerve cells, skin cells, and hematopoietic cells. It is known to promote the growth of all types of cells in the body. Additionally, since this growth factor plays an important role in growth, deficiency of this growth factor in infancy may lead to growth failure, and it is known to play a role in controlling energy assimilation after growth is completed.

The transforming growth factor-β is a growth factor that plays a role in maintaining cellular homeostasis by regulating cell division and differentiation. It also induces apoptosis in many cells and acts as a factor that inhibits division in epithelial cells and cancer cells. It is known to have a whitening effect by inhibiting tyrosinase in the skin.

The fibroblast growth factor promotes the growth and division of epithelial cells and has a better angiogenic effect than vascular endothelial growth factor (VEGF). In addition, this growth factor is known to be involved as an important growth factor in the wound healing process by creating new blood vessels at the wound site and proliferating fibroblasts to create granulation tissue.

The skin regeneration promoter including epithelial cell growth factor, platelet-derived growth factor-AA, and insulin-like growth factor-1 according to one aspect of the present invention includes each growth factor at 1 to 5: 1 to 5: 1 to 5, specifically. It can be included in a weight ratio of 1~3: 1~3: 1~3, more specifically 1~2: 1~2: 1~2. The skin regeneration promoter comprising epithelial cell growth factor, platelet-derived growth factor-AA, insulin-like growth factor-1, transforming growth factor-β, and fibroblast growth factor according to another aspect of the present invention includes each growth factor as 1 ~5 : 1~5 : 1~5 : 1~5 : 1~5, specifically 1~3 : 1~3 : 1~3 : 1~3 : 1~3, more specifically 1~2 : 1~ It can be included in a weight ratio of 2: 1~2: 1~2: 1~2.

In one embodiment, the content of the skin regeneration promoting or skin wound improving material is 10 to 70% by weight based on the total weight of the film. More specifically, the content of the skin regeneration promoting or skin wound improving material is 10% by weight or more, 20% by weight or more, 30% by weight or more, or 40% by weight or more based on the total weight of the film; It may be 70% by weight or less, 60% by weight or less, 50% by weight or less, and 40% by weight or less, but is not limited thereto.

In one embodiment, the thickness of the film is between 4 μm and 20 μm. More specifically, the thickness of the film is 4 μm or more, 5 μm or more, 6 μm or more, 7 μm or more, 8 μm or more, 9 μm or more, 10 μm or more, 11 μm or more, 12 μm or more; It may be 20 μm or less, 19 μm or less, 18 μm or less, 17 μm or less, 16 μm or less, 15 μm or less, 14 μm or less, 13 μm or less, and 12 μm or less, but is not limited thereto.

In one embodiment, the present invention also provides a treatment for bedsores and burns comprising the acetyl hyaluronic acid film. In one embodiment, the present invention provides for cosmetic, cosmetic applications.

In one embodiment, the material for promoting skin regeneration or improving skin wounds can form a cosmetic composition, and the formulation of the cosmetic composition is not particularly limited and can be appropriately selected depending on the purpose. For example, skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nutritional lotion, massage cream, nutritional cream, moisture cream, hand cream, foundation, essence, nutritional essence, pack, soap, cleansing. It may be manufactured in one or more formulations selected from the group consisting of foam, cleansing lotion, cleansing cream, body lotion, and body cleanser, but is not limited thereto.

Depending on the formulation of the cosmetic composition according to the present invention, commonly used carrier components may be additionally included, and functional additives and components included in general cosmetic compositions may be additionally included. The functional additive may include ingredients selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, polymer peptides, polymer polysaccharides, sphingolipids, and seaweed extract. In addition to the above-mentioned functional additives, the cosmetic composition according to the present invention may also contain components included in general cosmetic compositions, if necessary. Other ingredients included include oils and fats, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, disinfectants, antioxidants, plant extracts, pH adjusters, alcohol, pigments, fragrances, and blood circulation agents. Examples include accelerators, cooling agents, antiperspirants, and purified water.

As an embodiment, the composition may be a food composition, and the formulation of the food composition is not particularly limited, but includes, for example, tablets, granules, pills, powders, liquids such as drinks, caramels, gels, bars, and tea bags. It can be formulated as such. In addition to the active ingredients, the food composition of each formulation can be appropriately selected and mixed by a person skilled in the art according to the formulation or purpose of use with ingredients commonly used in the field, and can have a synergistic effect when applied simultaneously with other raw materials. can happen Additionally, the food may be a health functional food. The composition can be administered in various ways, such as simple ingestion, drinking, injection, spray administration, or squeeze administration. Food compositions according to one aspect of the present invention include, for example, various food products such as chewing gum, caramel products, candies, ice cream, and confectionery, beverage products such as soft drinks, mineral water, and alcoholic beverages, and health products containing vitamins and minerals, etc. It may be a functional food product. In addition to the above, the food composition according to one aspect of the present invention contains various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic and natural flavors, colorants and enhancers (cheese, chocolate, etc.), pectic acid, and the like. It may include salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc. In addition, food compositions according to one aspect of the present invention may include pulp for the production of natural fruit juice, fruit juice beverages, and vegetable beverages. These ingredients can be used independently or in combination.

Method for manufacturing a film for promoting skin regeneration or improving skin wounds

In another aspect, the present invention includes the steps of acetylating biodegradable hyaluronic acid in a solvent to obtain a biodegradable acetyl hyaluronic acid solution; and casting and drying the biodegradable acetyl hyaluronic acid solution to obtain a film; It provides a method for manufacturing the film for promoting skin regeneration or improving skin wounds, including.

In one embodiment, prior to the step of obtaining the film by casting, cell growth factor (EGF, Epidermal growth factor), platelet-derived growth factor-AA (PDGF-AA, Platelet-derived growth factor-AA), and insulin-like growth factor. Obtaining a mixture by mixing a solution containing at least one skin regeneration promoting or skin wound improving material selected from the group consisting of -1 (IGF-1, Insulin-like growth factor 1) and the biodegradable acetyl hyaluronic acid solution. Includes more.

In one embodiment, the acetylation is performed after mixing biodegradable hyaluronic acid with a molecular weight of 1×10 ³ to 5×10 ⁵ Da and biodegradable hyaluronic acid with a molecular weight of 1×10 ⁶ to 4×10 ⁶ Da. .

In one embodiment, in the biodegradable acetyl hyaluronic acid solution, biodegradable hyaluronic acid having a molecular weight of 1×10 ³ to 5×10 ⁵ Da and biodegradable hyaluronic acid having a molecular weight of 1×10 ⁶ to 4×10 ⁶ Da. The content is 0.02% to 3.5% by weight, respectively.

In one embodiment, the drying temperature is 20°C to 300°C. More specifically, the drying temperature is 20°C or higher, 30°C or higher, 40°C or higher, 50°C or higher, 60°C or higher, 70°C or higher, 80°C or higher, 90°C or higher, 100°C or higher, 110°C or higher, and 120°C. or higher, 130°C or higher, 140°C or higher, 150°C or higher, 160°C or higher; It may be 300℃ or lower, 290℃ or lower, 280℃ or lower, 270℃ or lower, 260℃ or lower, 250℃ or lower, 240℃ or lower, 230℃ or lower, 220℃ or lower, 210℃ or lower, and 200℃ or lower, but is limited thereto. no.

In one embodiment, the solvent is a 5 to 50% by volume aqueous ethanol solution. More specifically, the solvent is present in an amount of 5 volume% or more, 6 volume% or more, 7 volume% or more, 8 volume% or more, 9 volume% or more, 10 volume% or more; It may be an aqueous ethanol solution of 50 vol% or less, 40 vol% or less, 30 vol% or less, 20 vol% or less, and 10 vol% or less of ethanol, but is not limited thereto.

In one embodiment, the casting speed is between 5 and 80 mm/s. More specifically, the casting speed is 5 mm/s or more, 6 mm/s or more, 7 mm/s or more, 8 mm/s or more, 9 mm/s or more, 10 mm/s or more; It may be 80 mm/s or less, 70 mm/s or less, 60 mm/s or less, 50 mm/s or less, 40 mm/s or less, 30 mm/s or less, 20 mm/s or less, and 10 mm/s or less, It is not limited to this.

In another aspect, the present invention relates to a method of producing a film of acetyl hyaluronic acid with excellent transdermal absorption rate, and can be used as a treatment for bedsores and burns.

In the present invention, the present invention was completed after confirming that an acetyl hyaluronic acid film with excellent transdermal absorption rate could be produced when acetyl hyaluronic acid was dissolved in an ethanol aqueous solution, casted, and dried under specific molecular weight and conditions.

In one embodiment, the method for producing an acetyl hyaluronic acid film according to the present invention includes preparing a solution by dissolving acetyl hyaluronic acid in powder form into a solution, applying the hyaluronic acid solution to an automatic applicator, and drying at a temperature of 20°C. The film is manufactured by drying under conditions ranging from 300°C.

{Example}

Hereinafter, the present disclosure will be described in detail through examples. However, the following examples are merely examples to aid the overall understanding of the present disclosure, and the content of the present disclosure is not limited to the following examples.

<Reference Example 1> Production of film according to prior art

According to Non-Patent Document 1 and Patent Document 2, it was disclosed that all four -OH groups present in the hyaluronic acid molecule were acetylated, and an experiment was performed to confirm this. As a result of repeating the experiment as described in the two documents mentioned above, the results claimed in the literature could not be reproduced. In the reaction under the basic catalyst of Non-Patent Document 1, it was confirmed that acetylation occurred only on an average of 1 to 2 -OH groups per hyaluronic acid monomer instead of 4, and in the reaction under acidic catalyst conditions in Patent Document 2, the decomposition of the hyaluronic acid starting material was confirmed. The production of acetyl hyaluronic acid could not be confirmed.

<Preparation Example 1> Synthesis of acetyl hyaluronic acid

Add 0.02% by weight of biodegradable hyaluronic acid with a molecular weight of 1×10 ³ to 5×10 ⁵ Da and 3.5% by weight of biodegradable hyaluronic acid with a molecular weight of 1×10 ⁶ to 4×10 ⁶ Da to a 10% by volume ethanol aqueous solution. Then, the solution was stirred and dissolved for 1 to 12 hours using a homodisper to prepare a biodegradable acetyl hyaluronic acid solution. The acetylation reaction performed at this time is performed according to Scheme 1 below.

[Scheme 1]

Figure 1 is a photograph showing the equipment used in the production of acetyl hyaluronic acid according to an embodiment of the present invention.

<Preparation Example 2> Preparation of film according to Example 1

The biodegradable acetyl hyaluronic acid solution prepared in Preparation Example 1 was applied to an automatic applicator, and then a film was cast at a constant speed of 10 mm/s. The cast film was dried in a circulation dryer at 160°C for 1 to 48 hours. Subsequently, a film measuring 5 cm × 5 cm was manufactured using a small cutting machine.

<Preparation Example 3> Preparation of film according to Example 2

The film was manufactured in the same manner as in Preparation Example 2, except that the cast film was dried in a vacuum dryer at 100°C for 1 hour to 48 hours.

<Preparation Example 4> Preparation of film according to Example 3

Epidermal growth factor (EGF), Platelet-derived growth factor-AA (PDGF-AA), and Insulin-like growth factor 1 (IGF-1) ( A film was prepared in the same manner as in Preparation Example 2, except that it was mixed to obtain 40% by weight of a skin regeneration promoting or skin wound improving material (weight ratio 1:1:1).

<Reference Example 2> Preparation of film according to comparative example

A film according to Comparative Example 1 was prepared using a hyaluronic acid solution without acetylation. A film according to Comparative Example 2 was manufactured using the hyaluronic acid solution of Patent Document 2. A film according to Comparative Example 3 was prepared using the hyaluronic acid solution of Non-Patent Document 1. In addition, a film according to Comparative Example 4 was prepared using a hyaluronic acid solution in which acetylation occurred only on an average of 3 -OH groups.

<Experimental Example 1> Measurement of film thickness

The thickness of the acetyl hyaluronic acid film prepared in Preparation Example 2 was measured using a thickness meter, and the results are shown in Table 1.

division Example 1 Thickness (μm) 12

<Experimental Example 2> Measurement of shape of film

The shape of the acetyl hyaluronic acid film prepared in Preparation Example 2 was measured, and the results are shown in Figure 2. Figure 2 is a photograph of an acetyl hyaluronic acid film according to an embodiment of the present invention. From Figure 2, it can be seen that a film with a uniform surface was manufactured.

<Experimental Example 3> Measurement of structure of film

¹ H-NMR spectrum was measured at 600 MHz for the acetyl hyaluronic acid film prepared in Preparation Example 2, and the results are shown in FIG. 3. Figure 3 is a ¹ H-NMR spectrum graph of an acetyl hyaluronic acid film according to an embodiment of the present invention. Through this experiment, the key to the acetylation reaction of hyaluronic acid was to confirm that acetylation occurred on all -OH groups (a total of 4 -OH groups per hyaluronic acid monomer) present in the starting material, hyaluronic acid. The structure was able to be established.

From Figure 3, it can be seen that the degree of acetylation of the acetyl hyaluronic acid film according to an embodiment of the present invention was formed in a desirable range. Acetyl hyaluronic acid contains a total of 5 acetyl groups, including the NHAc group (Ac=acetyl, i.e. NH-C(=O)CH ₃ group) present in hyaluronic acid, the starting material, and 4 acetyl groups newly created in the reaction. There are (3 x 5) hydrogen atoms. On the other hand, there are a total of 12 other hydrogen atoms, namely methine H. Since the acetyl hyaluronic acid synthesized in this study is a collection of polymers with different molecular weights, the H signals do not appear as a single signal peak in the ¹ H-NMR spectrum analysis, but the H of the acetyl group usually appears around the chemical shift, δ = 2. On the other hand, methine H appears at a chemical shift, δ = 3.5~5. In fact, in the ¹ H-NMR spectrum of acetyl hyaluronic acid synthesized in the present invention, a chemical shift, an integral value of 15.04 around δ = 2 was obtained, with respect to a chemical shift of 12.00, an integral value of δ = 3.5 to 5, so It can be confirmed that acetylation occurred on all four -OH groups.

<Experimental Example 4> Evaluation of the pressure ulcer removal ability of the film

For patients with bedsores, the film prepared in Preparation Example 4 was applied to the affected area. During the two-week test period, the acetyl hyaluronic acid film was replaced twice a day in the morning and evening, and after two weeks, the film's ability to remove pressure ulcers was confirmed. The results are shown in Figure 4. Figure 4 is a photograph of clinical data on bedsores after application of an acetyl hyaluronic acid film according to an embodiment of the present invention. From Figure 4, it can be seen that the acetyl hyaluronic acid film according to an embodiment of the present invention has excellent pressure ulcer removal ability.

<Experimental Example 5> Evaluation of the efficacy of film to promote skin regeneration or improve skin wounds

Using the manufactured film, the skin wound improvement efficacy was evaluated using a tensile strength method that well reflects the quality and quantity of regeneration of the wound area in the incision wound using 5-week-old male rats. After removing the hair from the rat's back, an incision was made with a scalpel and the incision was sutured. After attaching the film to the skin, remove it after 40 minutes. Apply the remaining cream evenly and lightly tap to absorb. It was to be used once a day in the evening. After 6 days, the rats used in the experiment were slaughtered and the skin of the wound area was removed. After extraction, three samples of skin with a width of 1 cm perpendicular to the iron cage line were made for each individual, and the bursting tension was measured using a rheometer. The measured tensile strength (g/cm) was used as an indicator of the strength of the regenerated collagen fibers. The tensile strength of the control group to which only ethanol was applied was set as 100% and expressed as relative strength. The results are shown in Table 2.

division (%) Example 1 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Tensile strength increase rate 140 105 102 102 110

Although the present invention has been described in connection with the above-mentioned preferred embodiments, various modifications and variations can be made without departing from the spirit and scope of the invention. Accordingly, the appended claims will include such modifications and variations as long as they fall within the spirit of the present invention.

Claims (3)

Contains biodegradable polymers as active ingredients,
The biodegradable polymer is biodegradable acetyl hyaluronic acid according to the following formula 1,
The biodegradable acetyl hyaluronic acid is an acetylated mixture of biodegradable hyaluronic acid with a molecular weight of 1Х10 ³ to 5Х10 ⁵ Da and biodegradable hyaluronic acid with a molecular weight of 1Х10 ⁶ to 4Х10 ⁶ Da,
The acetylation is where the -OH group of biodegradable hyaluronic acid according to the following formula (2) is replaced with an acetyl group,
A film for promoting skin regeneration or improving skin wounds, wherein the biodegradable acetyl hyaluronic acid has an acetylation degree of 50% to 80%:
[Formula 1]
,
[Formula 2]
. According to paragraph 1,
Epidermal growth factor (EGF), platelet-derived growth factor-AA (PDGF-AA), and insulin-like growth factor 1 (IGF-1). A film further comprising at least one skin regeneration promoting or skin wound improving material selected from the group consisting of. Obtaining a biodegradable acetyl hyaluronic acid solution by acetylating biodegradable hyaluronic acid in a solvent; and
Obtaining a film by casting and drying the biodegradable acetyl hyaluronic acid solution;
A method for producing a film for promoting skin regeneration or improving skin wounds according to claim 1 or 2, comprising a.