KR102618266B1 - Biodegradable film for companion animal has improved convenience for internal use and method for preparing thereof - Google Patents

Abstract

The present invention relates to a biodegradable film considering the convenience of taking by pets and a manufacturing method thereof. According to the present invention, it has the effect of increasing the convenience of taking by pets by exhibiting a melting property without inconvenience in administration of oral medications. .

Description

Biodegradable film and manufacturing method thereof considering the convenience of pet use {BIODEGRADABLE FILM FOR COMPANION ANIMAL HAS IMPROVED CONVENIENCE FOR INTERNAL USE AND METHOD FOR PREPARING THEREOF}

The examples below relate to a biodegradable film and its manufacturing method considering the convenience of pet use.

Recently, as the number of one-person households and one-child households increases, the number of households adopting companion animals is increasing. Additionally, as perceptions of animals change, more and more people are now accepting companion animals as new family members rather than simply keeping them as animals. Companion animals live with people and provide psychological stability and intimacy. According to 2015 statistical data, the proportion of households keeping companion animals was 21.8%, or approximately 4.57 million households, and is increasing every year. The most widely kept companion animals are dogs (19.1%) and cats (5.2%), and the size of the companion animal-related market is continuously increasing, and the materials, types, and forms of products are becoming increasingly specialized and specialized. However, when a skin-related disease occurs in a pet, it is not easy to manage it, and it is even more difficult to administer oral medications for the pet.

Accordingly, Republic of Korea Patent Publication No. 10-2017-0103834 discloses a method comprising orally administering an enteric or non-enteric coated composition to the animal in need. However, as described above, it is not easy to administer oral medications to companion animals.

Republic of Korea Patent Publication No. 10-2017-0103834 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 produce a biodegradable film that exhibits a skin improvement function by the polymer itself and at the same time exhibits melting properties without the need for separate removal from the skin, and the production thereof. It provides a method.

In order to achieve the above-described object of the present invention, one embodiment of the present invention provides a film for improving skin function containing 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.

According to the present invention, it has the effect of increasing the convenience of administration to companion animals by exhibiting soluble properties without the inconvenience of administering oral medications.

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 unless explicitly defined in the present application, should not be interpreted in an ideal or excessively formal sense. 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 the 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.

Pet Oral Film

In one aspect, the present invention provides an oral film for companion animals comprising a biodegradable polymer.

In particular, the present inventors completed the present invention by discovering a biodegradable film that has the effect of increasing the convenience of administration to companion animals by showing melting properties without concerns about microbial contamination and inconvenience in the administration of oral medications.

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, or within 20 seconds of being administered, i.e., placed in the pet's mouth). , or within 15 seconds) refers to the ability to completely dissolve. 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 pets. A film or a method of manufacturing the same is provided. 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 pets. A film or a method of manufacturing the same is provided. 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 pets, 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 pets. .

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]

In one embodiment, the companion animal is a dog or a cat. The above companion dogs include Chihuahua, Pug, Dachshund, Spitz, English Bulldog, Siberian Husky, Alaskan Malamute, Radrador Retriever, Greyhound, Jindo Dog, Golden Retriever, Dalmatian, Saint Bernard, Maltese, Shih Tzu, Schnauzer, Yorkshire Terrier, Cocker Spaniel, It may be a breed selected from the group consisting of sheepdog, mini pin, poodle, and Pomeranian, but is not limited thereto. The above cats include British Shorthair, Persian, Maine Coon, Siamese Cat, Ragdoll, Sphynx, Abyssinian, Bengal, Birman, American Shorthair, Exotic Shorthair, Russian Blue, Scottish Fold, Burmese Cat, Devon Rex, Siberian Cat, and Mang. It may be a species selected from the group consisting of a British cat, Turkish Angora, American Bobtail, Cornish Rex, and Himalian, but is not limited thereto.

In one embodiment, the film is a health functional food film for improving joint health, a pharmaceutical film for preventing or treating arthritis, or a quasi-drug film for preventing or improving arthritis.

Joint health can be interpreted as meaning the absence of inflammation, damage, disease, etc. in joints and the cartilage that constitutes them, joint capsule, joint lining, connective tissue, ligaments, and synovial membrane, but is not limited to this. Therefore, in the present invention, improvement of joint health is achieved by reducing pain due to friction of joints, reducing joint inflammation, suppressing wear or destruction of joints or cartilage and improving its recovery, or increasing the expression of hyaluronic acid synthase. This may include, but is not limited to, improving joint lubrication due to stimulation. Additionally, in the present invention, improving joint health may include, without limitation, delaying the onset or progression of joint diseases including osteoarthritis, rheumatoid arthritis, etc., or improving symptoms resulting from the onset of the joint diseases.

Arthritis is a disease that causes inflammation and pain in joints, and can be mainly divided into osteoarthritis (degenerative arthritis) and rheumatoid arthritis. First, osteoarthritis is when the cartilage layer developed within the joint to relieve the shock and friction that occurs when bones collide directly is damaged, causing pain as the bones rub directly against each other, making movement of the joint difficult. refers to a disease. This type of osteoarthritis can mainly occur in a single joint, such as the knee, hip joint, hand, foot, or spine, but can also occur in joints in multiple areas simultaneously. Osteoarthritis is mainly caused by aging without any specific organic cause, and when it progresses chronically, it is accompanied by movement disorders such as gait disorders due to deformation of the joint structure. Looking at the mechanism, as osteoarthritis progresses, the production of pro-inflammatory cytokines such as TNF-α and IL-1 increases, and the secretion of MMPs such as collagenase and stromelysin increases, thereby damaging articular cartilage. destruction occurs.

Arthritis is a disease that collectively refers to inflammatory changes within the joint due to any cause such as bacteria or trauma. Specifically, it includes osteoarthritis, rheumatoid arthritis, spondyloarthropathy, ankylosing spondylitis, psoriatic arthritis, gout, bacterial arthritis, juvenile rheumatoid arthritis, Lupus, scleroderma, multiple sclerosis, fibromyalgia, polymyositis, dermatomyositis, Behcet's disease, Reiter's syndrome, Lyme arthritis, adhesive capsulitis, frozen shoulder, tendon synovitis, elbowcap pocketitis, DeQuervain's tenosynovitis, polymyalgia rheumatica, adult This includes Still's disease, and more specifically, osteoarthritis and rheumatoid arthritis, but is not limited thereto.

In one embodiment, the film comprises one or more extracts selected from the group consisting of brachyury extract, lignified extract, ginger extract, tetrahydrocurcumin, dermal extract, and boswellia extract. The extract may inhibit the production of PGE2 (Prostaglandin E2). PGE2 (Prostaglandin E2) is one of a series of biologically active substances with a prostanic acid skeleton, and is known to mediate reactions such as vasodilation, edema, fever, and pain. In addition, PGE2 is secreted by the action of COX-2 and induces the production of MMPs (Matrix metalloproteinase) in inflammatory diseases such as periodontitis and arthritis, and plays an important role in aggravating inflammation or tissue destruction mechanism.

In one embodiment, the film is a film for improving skin function.

The skin function improvement is one selected from the group consisting of skin trouble care, skin soothing, skin elasticity enhancement, and skin wrinkle improvement.

The skin trouble refers to a skin disease that can be caused by inflammation caused by excessive production of nitric oxide in macrophages. The skin trouble includes any type of skin disease related to inflammation, and non-limiting examples of skin diseases related to inflammation include atopic dermatitis, psoriasis, erythematous disease triggered by radiation, chemicals, burns, etc. Acid burns, bullous dermatoses, lichenoid diseases, itching due to allergies, seborrheic eczema, acne rosacea, pemphigus vulgaris, erythema multiforme exudative, erythema nodosum, balanitis, vulvitis, inflammatory hair loss such as alopecia areata, skin T- Cellular lymphoma, etc. specifically includes, but is not limited to, skin rash, acne, pimples, rosacea (red nose), etc. The skin trouble care refers to suppressing or inhibiting the formation of skin troubles or alleviating troubles that have already been created.

The skin soothing means providing coolness to the skin, enhancing skin temperature, providing a refreshing feeling to the skin, or providing a cool feeling to the skin.

The skin elasticity is caused by elastic fibers composed of elastin present in the dermal layer. These elastic fibers have a very low elastic modulus like rubber, so they are easily deformed even by a small force, and when the force is removed, It returns to its original shape easily. In addition, elastic fibers have microfibrils embedded in an amorphous matrix called elastin, and elastin is a very unique fiber found only in elastic fibers called desmosine and isodesmosine, which are derived from lysine. It is a protein composed of one amino acid. These desmosins and isodesmosins form cross-links within long peptide chains, and this structure gives elastin rubber-like properties. The improvement of skin elasticity means that elastic fibers made of elastin exist together with collagen fibers called collagen, and skin elasticity is maintained in a state where elastin and collagen are sufficiently present.

The skin wrinkles refer to fine lines that occur as the skin ages, and can be caused by genes, a decrease in collagen and elastin present in the dermis of the skin, and external environments. The improvement of skin wrinkles means suppressing or inhibiting the formation of wrinkles on the skin, or alleviating wrinkles that have already been formed.

In one embodiment, the film further includes one or more skin function improving substances selected from the group consisting of AZULENE, Niacinamide, Madecassoside, and Adenosine (Adenine Riboside).

The azulene serves to increase the effects of niacinamide and madecassoside and prevent and/or improve skin troubles. In addition, the niacinamide is used to inhibit the movement of melanin pigment to achieve the effect of increasing skin whitening, alleviating skin inflammation, and strengthening the skin barrier. Madecassoside is used to promote skin collagen synthesis, increase skin elasticity, reorganize the extracellular matrix of the dermis layer, and have a skin soothing effect, and adenosine is used to improve skin wrinkles, improve skin elasticity, and enhance cell proliferation in the skin dermis layer. It is to be used. When using all four improvers: azulene, niacinamide, madecassoside, and adenosine, 1 to 5 parts by weight of azulene, 1 to 5 parts by weight of madecassoside, and 0.5 parts by weight of adenosine are used for 100 parts by weight of niacinamide. It is recommended to use ~ 4 parts by weight, preferably 1.5 ~ 4.0 parts by weight of azulene, 1.5 ~ 4.0 parts by weight of madecassoside, and 1.0 ~ 3.0 parts by weight of adenosine, based on 100 parts by weight of niacinamide.

In one embodiment, the content of the skin function improving material is 10 to 70% by weight based on the total weight of the film. More specifically, the content of the skin function improvement 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 film is a film for promoting skin regeneration or improving skin wounds.

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 skin function improvement material 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.

Manufacturing method of companion animal oral film

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 improving skin function, including.

In one embodiment, prior to the step of obtaining the film by casting, improving skin function at least one selected from the group consisting of AZULENE, Niacinamide, Madecassoside, and Adenine Riboside. It further includes mixing a solution containing a substance and the biodegradable acetyl hyaluronic acid solution to obtain a mixture.

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

Excluding skin function improvement substances consisting of AZULENE, Niacinamide, Madecassoside and Adenosine (3:100:3:2) mixed to 40% by weight. Then, a film was manufactured in the same manner as in Preparation Example 2.

<Preparation Example 5> Preparation of film according to Example 4

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 the skin regeneration promoting or skin wound improving material (weight ratio 1:1:1) was mixed to 40% by weight.

<Preparation Example 6> Preparation of film according to Example 5

Manufactured except that the substance consisting of Pogonyeong extract, lignified extract, ginger extract, tetrahydrocurcumin, dermal extract and Boswellia extract (weight ratio 1:1:1:1:1:1) was mixed to 40% by weight. The film was prepared in the same manner as in Example 12.

<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 2> 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 3> 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 the figure, 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 4> Companion animal preference evaluation

The prepared acetyl hyaluronic acid film was orally administered to 30 dogs visiting a dog cafe. Meanwhile, compared with commercially available pills for improving skin wounds (Comparative Example 5), the number of dogs spitting up again was measured. The results are shown in Table 2.

division Example 3 Example 4 Example 5 Comparative Example 5 Number of spits 8 7 8 32

From Table 2 above, it can be seen that pet dogs take the acetyl hyaluronic acid film prepared according to an embodiment of the present invention without resistance.

<Experimental Example 5> Evaluation of the efficacy of film to inhibit PGE2 production

The film's efficacy in inhibiting PGE2 production was evaluated. Murine macrophage cell line RAW 264.7 cells were purchased from Korean Cell Line Bank (KCLB), and cultured in DMEM (Dulbecco's Modified Eagle's Medium) low medium supplemented with 10% FBS (Fetal Bovine Serum) and 1% antibiotics under 5% CO. Subculture was performed once every 2 to 3 days in an incubator at 37°C in the presence of ₂ . Afterwards, the PGE2 content in the RAW 264.7 cell culture was measured using an enzyme-linked immunosorbent assay (ELISA) kit. RAW 264.7 cells were distributed in 24-well plates at a concentration of 2×10 ⁵ cells/ml using DMEM low glucose medium, and each sample was mixed with 1 μg/mL of lipopolysaccharide (LPS), a bacterial inflammatory substance. Inflammation was induced and cultured for 24 hours. Accordingly, the film prepared in the production example was covered and treated. After 24 hours, the cell culture supernatant was taken and the amount of PGE2 produced was measured using ELISA. After confirming the effectiveness of each concentration of each raw material, IC50 (The half maximal inhibitory concentration) was presented. The results are shown in Table 3.

division Example 5 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 IC50 (ppm) 0.5 20 17 12 14

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 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,
The acetylation is where the -OH group of biodegradable hyaluronic acid according to the following formula (2) is replaced with an acetyl group,
Oral film for companion animals, wherein the degree of acetylation of the biodegradable acetyl hyaluronic acid is 50% to 80%:
[Formula 1]
,
[Formula 2]
. 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 an oral film for companion animals according to claim 1, comprising a. delete