Composition for preventing or alleviating gum retraction comprising organically modified metal

Abstract

Provided is a composition for preventing or alleviating gum retraction, the composition comprising organic vanadium as an active ingredient, wherein the organic vanadium is a chelate compound of vanadium and an organic acid or amino acid.

Description

Composition for preventing or improving gum recession containing an organic metal

[0001] The present invention relates to a composition for the purpose of preventing or improving gum recession, comprising an organic rare earth metal.

[0002] Teeth are supported by the periodontal tissue surrounding them. The teeth themselves consist of hard tissues: enamel on the outer layer and dentin on the inner layer. The periodontal tissue is based on the alveolar bone, and includes the gums and periodontal ligament. Teeth can be lost due to diseases of the tooth itself, as well as periodontal disease. Furthermore, if the alveolar bone dissolves, it becomes difficult to support the teeth, making implant placement difficult.

[0003] The gums are the mucosal tissues that cover part of the teeth and the roots of the teeth. In a narrow sense, gums refers to the gingiva, but in a broader sense, it is used to mean the periodontal tissue, which is the surrounding tissue that supports the teeth below the gums, the alveolar bone that surrounds the tooth root, and the periodontal ligament that connects to the alveolar bone. Gingival fibers are composed of collagen, and are located in the gingival tissue adjacent to the teeth. They help the gingival tissue adhere well to the teeth and fix them, and provide strength to withstand the force applied to the gums during chewing.

[0004] Furthermore, two types of cells with specialized functions are involved in bone tissues such as teeth and alveolar bone: osteoblasts and osteoclasts. Osteoblasts synthesize and fill the bone matrix, while osteoclasts resorb bone. In normal adults, the balance between osteoblasts and osteoclasts is maintained. In other words, a balance is maintained between the amount of bone formation and bone resorption in normal adults.

[0005] However, due to poor eating habits and aging in modern society, the number of patients with weakened immunity or dental and periodontal diseases caused by nutritional and metabolic disorders is increasing.

[0006] In particular, when the balance between osteoblasts and osteoclasts is disrupted, excessive bone destruction by osteoclasts occurs, leading to diseases such as periodontal disease. These osteoclasts are specialized cells responsible for bone resorption during the bone metabolism process, and are formed through a differentiation program from precursor cells such as monocytes or macrophages. In addition, osteoclasts bind to bone through αvβ integrins and create an acidic environment, while secreting various collagenases and proteases to induce bone resorption. Therefore, inhibiting the action of these osteoclasts can be an effective method for treating periodontal disease.

[0007] An imbalance between osteoblast and osteoclast activity manifests as skeletal abnormalities, resulting in overall bone loss (osteoporosis) or gain (osteosclerosis). Various theories and arguments have been put forward regarding whether this bone metabolic imbalance is primarily due to a decline in osteoblast function or to increased bone resorption, i.e., enhanced osteoclast activity.

[0008] Among these periodontal diseases, gum recession occurs when the gum tissue (gingiva) is lost or recedes due to a decrease in collagen in the gingival fibers, exposing the tooth root. This loss of tooth-supporting tissue can lead to symptoms such as tooth mobility or tooth hypersensitivity to external stimuli. This gum recession can be caused by various factors, including gingivitis or periodontitis, aging, excessive brushing, nutritional deficiencies, and genetic predisposition. Since gum recession usually progresses gradually over a long period of time, products that can prevent or improve it in daily life are needed. However, most products on the market are limited to preventing or improving inflammation such as gingivitis or periodontitis. Furthermore, even if periodontitis is improved or treated, already receded gum tissue does not regenerate, and regenerative surgical treatment to regenerate gum tissue is only possible in extremely limited cases.

[0009] Therefore, there is a need to develop a product that can prevent gum recession caused by other causes than inflammation in the gum tissue and actually improve gum recession by promoting collagen production in the gum tissue.

[0010] The present invention is intended to solve the problems revealed in the above-mentioned prior art, and one of the objects of the present invention is to provide a composition for preventing or improving gum recession with excellent bone formation performance by activating cell division and promoting differentiation of osteoblasts.

[0011] Another object of the present invention is to provide a composition for preventing or improving gum recession having an antibacterial effect.

[0012] According to one aspect, a composition for preventing or improving gum recession is provided, which comprises organic vanadium as an active ingredient, wherein the organic vanadium is a chelate compound of vanadium and an organic acid or amino acid.

[0013] In one embodiment, the composition for preventing or improving gum recession may contain 3 μM or more of the organic vanadium.

[0014] In one embodiment, the composition for preventing or improving gum recession further comprises at least 2,000 ppm of organic rare earth, wherein the organic rare earth may be a chelate compound of a rare earth metal and an organic acid or amino acid.

[0015] In one embodiment, the rare earth metal may be at least one selected from the group consisting of cerium (Ce), yttrium (Y), scandium (Sc), lanthanum (La), neodymium (Nd), dysprosium (Dy), europium (Eu), gadolinium (Gd), holmium (Ho), samarium (Sm), terbium (Tb), ytterbium (Yb), erbium (Er), and praseodymium (Pr).

[0016] In one embodiment, the organic acid may be at least one selected from phosphoric acid, fumaric acid, lactic acid, citric acid, malic acid, butyric acid, formic acid, acetic acid, gluconic acid, succinic acid, tartaric acid, glutamic acid, oxalic acid, and ascorbic acid.

[0017] In one embodiment, the amino acid may be at least one selected from the group consisting of Alanine, Arginine, Asparagine, Aspartic acid, Cysteine, Glutamine, Glutamic acid, Clycine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Proline, Serine, Threonine, Tryptophan, Tyrosine, and Valine.

[0018] In one embodiment, the composition for preventing or improving gum recession may further comprise a complex of collagen, hyaluronic acid, ascorbic acid, and natural xylitol.

[0019] In one embodiment, the complex may comprise 80 to 120 parts by volume of the hyaluronic acid, 120 to 180 parts by volume of the ascorbic acid, and 250 to 350 parts by volume of the natural xylitol, per 100 parts by volume of the collagen.

[0020] In one embodiment, the collagen may have a molecular weight of 300 Da or less.

[0021] The composition for preventing or improving gum recession of the present invention can promote differentiation of osteoblasts present in the gums, activate cell division, prevent gum recession, and improve symptoms of patients with gum recession.

[0022] In addition, when the composition for preventing or improving gum recession of the present invention is ingested, it has antibacterial properties and thus has the effect of preventing gum recession and infection.

[0023] It should be understood that the effects of one aspect of the present invention are not limited to the effects described above, but include all effects that can be inferred from the detailed description of the invention or the composition described in the claims of this specification.

[0024] Figure 1 is [ 3 [H]Thymidine analysis results.

[0025] Figure 2 shows the results of cell viability analysis.

[0026] Figure 3 shows the results of measuring alkaline phosphatase activity.

[0027] Figure 4 shows the results of Type Ⅰα 2 collagen mRNA analysis.

[0028] Figure 5 shows the results of an analysis of antibacterial performance according to the addition of organic rare earth elements.

[0029] The following describes one aspect of this specification. However, the contents of this specification may be implemented in various different forms and are therefore not limited to the embodiments described herein.

[0030] Throughout the specification, whenever a part is said to "include" a component, this does not mean that it excludes other components, but rather that it may include other components, unless otherwise stated.

[0031] When a range of numerical values ​​is stated herein, unless the specific range is otherwise specified, the values ​​have the precision of the significant figures provided according to the standard rules in chemistry for significant figures. For example, the number 10 includes the range of 5.0 to 14.9, and the number 10.0 includes the range of 9.50 to 10.49.

[0032] Hereinafter, a composition for preventing or improving gum recession, which is one aspect of the present invention, will be described in detail.

[0033] A composition for preventing or improving gum recession according to one aspect of the present invention comprises organic vanadium as an active ingredient, and is characterized in that the organic vanadium is a chelate compound of vanadium and an organic acid or amino acid.

[0034] Vanadium does not exist in nature as a metal, but mostly exists in inorganic forms such as V2O5. Because inorganic vanadium exhibits toxicity, including kidney damage and nervous system problems, the United States sets a permissible level of approximately 0.009 mg / kg for drinking water. In Korea, the Clean Air Conservation Act and the Occupational Safety and Health Act also set permissible concentrations.

[0035] However, organic vanadium, which is made water-soluble by converting inorganic vanadium into organic vanadium, is known to promote metabolism in the human body, such as lowering blood sugar levels in diabetics or lowering cholesterol levels by inhibiting cholesterol synthesis.

[0036] The present inventors further discovered for the first time that organic vanadium is involved in the activation of bone formation activating factors and in promoting the absorption and metabolism of glucose, thereby playing an important role in the formation of cartilage, bones, teeth, and alveolar bone, and thus can be preferably used as an effective ingredient of a composition for preventing or improving gum recession, thereby completing the present invention.

[0037] The content of organic vanadium may be 3 μM or more, preferably 4 μM or more, and more preferably 5 μM or more. Since a higher content of organic vanadium is advantageous for tooth and alveolar bone formation, there is no particular limitation regarding the upper limit. However, considering that excessive content may result in excessive increase in cost and saturation of the effect, the upper limit may be limited to 200 μM, preferably 150 μM.

[0038] Organic vanadium can be manufactured by the following methods, but is not limited thereto.

[0039] First, prepare inorganic vanadium powder. Here, the inorganic vanadium may be at least one selected from the group consisting of vanadium pentoxide (V2O5), vanadium trioxide (V2O3), sodium metavanadate (NaVO3), ammonium metavanadate (NH4VO3), vanadium tetrachloride (VCl4), and vanadium oxychloride (VOCl3), but is not limited thereto.

[0040] At this time, it is desirable to use inorganic vanadium with a purity of 99.0 or higher and a mesh size of 325 or higher, and in this case, it may be advantageous in terms of reactivity, but is not limited thereto.

[0041] Next, after preparing amino acids and / or organic acids, they are mixed with distilled water to obtain an acid solution. The temperature of the acid solution is preferably 0.5 to 1.5 N (normal concentration), and more preferably 0.8 to 1.2 N (normal concentration). If the concentration of the acid solution is too low, the carboxyl group (RCOO) contained in the amino acid and / or organic acid may be removed. - ) may be insufficient to replace the oxygen ions of inorganic vanadium, and conversely, if the concentration of the acid solution is too high, there may be an excessive amount of amino acids or organic acids that do not participate in the reaction.

[0042] Here, the organic acid may be at least one selected from, for example, fumaric acid, lactic acid, citric acid, malic acid, butyric acid, formic acid, acetic acid, gluconic acid, succinic acid, tartaric acid, glutamic acid, oxalic acid, and ascorbic acid, but is not limited thereto.

[0043] Additionally, the amino acid may be at least one selected from the group consisting of, for example, Alanine, Arginine, Asparagine, Aspartic acid, Cysteine, Glutamine, Glutamic acid, Clycine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Proline, Serine, Threonine, Tryptophan, Tyrosine, and Valine, but is not limited thereto.

[0044] Next, the acid solution and the inorganic vanadium powder are mixed in a weight ratio of 2:1 to 4:1, and reacted for 12 hours or more (preferably 24 hours or more) while stirring at a speed of 1,000 rpm to 6,000 rpm.

[0045] By this reaction, chelation is performed as the carboxyl group of the amino acid and / or organic acid replaces the oxygen ion of the inorganic vanadium, and organic vanadium is formed.

[0046] Taking vanadium pentoxide among inorganic vanadium as an example, the reaction formula for producing an organic vanadium compound is as shown in Equation 1 below.

[0047] (Equation 1) V2O5+ 10RCOOH →V2((RCOO)2)5+ 10H +

[0048] The reaction temperature of the above acid and inorganic vanadium is preferably 25 to 60°C, more preferably 35 to 40°C. If the reaction temperature is too low, the reaction rate may become excessively slow, and conversely, if the reaction temperature is too high, amino acid denaturation may occur.

[0049] The reaction acidity of the above acid and inorganic vanadium may be pH 0.9 to 4.5, preferably 1.2 to 1.8. If the reaction acidity is too low, the degree of dissociation of the carboxyl group may be low, resulting in an excessively small number of carboxyl groups participating in the reaction. Conversely, if the reaction acidity is too high, the degree of dissociation of the carboxyl group may be high, but the concentration of hydrogen ions may become excessively high.

[0050] Next, the upper layer is taken from the reaction solution of the acid solution and the inorganic vanadium powder to obtain organic vanadium.

[0051] The composition for preventing or improving gum recession of the present invention may further comprise organic rare earth elements. The greatest risk factor in dental treatment (particularly implants) is bacterial infection. The use of rare earth elements with antifungal or antibiotic properties can be of great help in inhibiting the growth of pathogenic fungi. Rare earth elements typically exist in nature in inorganic form, and these inorganic rare earth elements have low bioabsorption rates. Therefore, in the present invention, inorganic rare earth elements with low bioabsorption rates are replaced with organic elements.

[0052] Organic rare earths are chelate compounds of rare earth metals and organic acids or amino acids. The organic acids and amino acids are the same as those used in the production of organic vanadium, and organic rare earths can be produced by the same method as organic vanadium, so a detailed description thereof is omitted.

[0053] The rare earth metal may be at least one selected from the group consisting of, but is not limited to, cerium (Ce), yttrium (Y), scandium (Sc), lanthanum (La), neodymium (Nd), dysprosium (Dy), europium (Eu), gadolinium (Gd), holmium (Ho), samarium (Sm), terbium (Tb), ytterbium (Yb), erbium (Er), and praseodymium (Pr).

[0054] The content of organic rare earth elements may be 2,000 ppm by weight or more, preferably 2,500 ppm by weight or more, and more preferably 3,000 ppm by weight or more. The higher the content of organic rare earth elements, the more advantageous it is for the growth inhibition activity of pathogenic fungi, so there is no particular limitation on the upper limit. However, considering that if the content is excessive, the cost may increase excessively and the effect may be saturated, the upper limit may be limited to 20,000 ppm by weight, preferably 15,000 ppm by weight.

[0055] The composition for preventing or improving gum recession of the present invention may further comprise a complex of collagen, hyaluronic acid, and ascorbic acid. Collagen is a major component of bone and alveolar bone. When combined with hyaluronic acid and ascorbic acid, collagen can increase its absorption rate in the body, thereby maximizing the effect of preventing or improving gum recession. In this case, small, low-molecular-weight collagen may be used, taking into account absorption and recovery rates. For example, collagen having a molecular weight of 300 Da or less may be used, but is not limited thereto.

[0056] The above complex may contain 80 to 120 parts by volume of the hyaluronic acid and 120 to 180 parts by volume of the ascorbic acid for 100 parts by volume of the collagen, in which case the effect of preventing or improving gum recession may be maximized.

[0057] Meanwhile, in the present invention, the content of the complex is not particularly limited, but for example, the complex may be included in an amount of 1 to 5 parts by volume, preferably 2 to 4 parts by volume, per 100 parts by volume of the composition for preventing or improving gum recession.

[0058] The composition for preventing or improving gum recession of the present invention is not limited to its formulation, and may be, for example, a solid, semi-solid, or liquid formulation.

[0059] The composition for preventing or improving gum recession of the present invention may further include abrasives, humectants, foaming agents, binders, sweeteners, pH regulators, preservatives, flavoring agents, whitening agents, pigments, solvents, etc., which are commonly used depending on the intended use, and may also be formulated according to a method commonly used in the art in the form of an orally disintegrating film, jelly stick, toothpaste, liquid, ointment, paste, spray, chewing gum, etc.

[0060] In addition, the composition for preventing or improving gum recession of the present invention may be a pharmaceutical composition, and in this case, it may further include pharmaceutical adjuvants such as preservatives, stabilizers, wetting agents or emulsifying agents, salts for osmotic pressure control, and / or buffers, and other therapeutically useful substances. The pharmaceutical composition may be formulated into various oral or parenteral dosage forms according to conventional methods. As an example, the oral dosage forms include tablets, pills, hard and soft capsules, liquids, suspensions, emulsifiers, syrups, powders, granules, granules, pellets, etc., and these dosage forms may include, in addition to the active ingredient, a surfactant, a diluent (e.g., lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, and glycine), a lubricant (e.g., silica, talc, stearic acid and its magnesium or calcium salts, and polyethylene glycol). The tablet may also contain a binder such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, and polyvinylpyrrolidine, and optionally pharmaceutical additives such as disintegrants such as starch, agar, alginic acid or its sodium salt, absorbents, coloring agents, flavoring agents, and sweetening agents. As an example, the parenteral administration agent may be in the form of, but is not limited to, injections, drops, ointments, lotions, gels, creams, sprays, suspensions, emulsions, patches, and the like. For example, the pharmaceutical composition may be administered topically, transdermally, intravenously, intramuscularly, subcutaneously, and the like.

[0061] Hereinafter, the embodiments of this specification will be described in more detail. However, the experimental results below represent only representative experimental results among the above embodiments, and the scope and content of this specification cannot be interpreted as being reduced or limited by the embodiments, etc. The effects of each of the various implementation examples of this specification that are not explicitly presented below will be specifically described in the relevant sections.

[0062] Example

[0063] <Manufacturing Example>

[0064] Vanadium pentoxide was purified to a high purity (6N:99.9999%) as inorganic vanadium, and reacted with a 1N acetic acid solution at pH 1.5 and 36℃. At this time, the weight ratio of the acetic acid solution and vanadium pentoxide was mixed in a reaction tank at 3:1, and the reaction was performed at 3,000 rpm for 24 hours, and the upper layer was collected to obtain organic vanadium.

[0065] <Experimental Example>

[0066] Experimental Example 1: [ 3 H]thymidine analysis

[0067] To verify the effect of improving cell proliferation by using organic vanadium, osteoblast cells (MC3T3-E1 cells) were seeded in 12-well culture plates at 1 × 10 5　 Cells were seeded at a density of 10 cells / mL and cultured in a cell culture medium (Dulbecco's modified Eagle's medium, Gibco-BRL, USA) containing 10% fetal bovine serum (FBS, Gibco-BRL, USA) at 37°C for 24 hours in a cell incubator (MCO-18M, Sanyo, Japan) under 5% carbon dioxide conditions. Afterwards, the cells were cultured in a control group containing nothing in a serum-free medium (Gibco, BRL, USA) and the same serum-free medium containing organic vanadium at concentrations of 5 μM, 10 μM, 30 μM, 60 μM, and 120 μM, and the same serum-free medium containing vanadium pentoxide (inorganic vanadium) at concentrations of 5 μM, 10 μM, 30 μM, 60 μM, and 120 μM, respectively, and then cultured for 24 hours. After culturing, the cells were stimulated with 50 ng / mL PDGF-BB and 2 μCi / mL of [ 3H]thymidine was treated. After 4 hours, the medium was aspirated to terminate the labeling reaction, and the culture medium was washed with phosphate-buffered saline (PBS) containing 10% trichloroacetic acid and ethanol / ether (1:1, volume ratio). Acid-insoluble [ 3 H]Thymidine was extracted with 300 μL of 0.5 M sodium hydroxide (NaOH) solution per well, and this solution was mixed with 3 mL of scintillation cocktail (Ultimagold, Packard Bioscience, USA), and quantified using a liquid scintillation counter (Scintillation model LS3801, Beckman, Germany). The experiment was repeated three times, and the standard deviation of the values ​​was recorded, and the results are shown in Figure 1.

[0068] Referring to Figure 1, in the case of the experimental example using the organic vanadium compound of the manufacturing example, compared to the control group, [ 3 H] DNA incorporation rate was confirmed. In particular, when the concentration is 30 μM or higher, the DNA incorporation rate is 3 times higher in the experimental example using the organic vanadium compound than in the experimental example adding the inorganic vanadium solution even when the vanadium concentration is the same. Therefore, it was confirmed that when the organic vanadium of the present invention is included, the cell division rate of the osteogenic cells present in the teeth is greatly improved, thereby suppressing the gum recession phenomenon.

[0069] Experimental Example 2: Cell Viability Analysis

[0070] A Cell Viability Assay was performed to determine whether organic vanadium was cytotoxic.

[0071] Osteoblast cells (MC3T3-E1 cells) were seeded at 5x10 in each well of a 24-well plate using DMEM (Dubelccos Modified Eagle Medium, Gibco) containing 10% FBS and 100 UL S / P, an animal cell culture medium. 5 Cells were placed and cultured in a 37℃ 5% CO2 incubator for 24 hours. After that, a control group was set up in the same way as Experimental Example 1 without adding a separate substance, and solutions with organic vanadium concentrations of 5 μM, 10 μM, 30 μM, 60 μM, and 120 μM, respectively, were added using the manufacturing example, and solutions with vanadium pentoxide (inorganic vanadium) concentrations of 5 μM, 10 μM, 30 μM, 60 μM, and 120 μM, respectively, were added, and then both the control group and the experimental group were additionally cultured for 48 hours. After 12 hours, 24 hours, and 48 hours, the EZ-cytox solution was added to each well, reacted for 1 hour, and measured at 450 nm with a plate reader. The experiment was repeated three times to obtain a relative viability value, and the standard deviation of the values ​​was recorded, and the results are shown in Figures 2a to 2c.

[0072] Referring to Fig. 2, it was confirmed that when the organic vanadium compound of the manufacturing example was used, a high level of cell viability was exhibited for up to 48 hours. In particular, when inorganic vanadium was used, it was confirmed that higher cytotoxicity was exhibited compared to the organic vanadium of the present invention at a concentration of 10 μM or higher. Therefore, it was confirmed that only when organic vanadium is used can the gum recession improvement effect of the present invention be maintained while being absorbed into the body with low toxicity.

[0073] Experimental Example 3: Alkaline phosphatase activity analysis

[0074] Alkaline phosphatase activity was measured to determine the degree of osteoblast differentiation and bone formation performance at the protein level according to the use of organic vanadium and its complexes.

[0075] For this purpose, osteoblast cells (MC3T3-E1 cells) were seeded and 3 x 10 5 Cells were cultured in a 48-well plate at a density of 10 cells / well. Subsequently, a control group was set up in which no separate substance was added, similar to Experimental Example 1, and solutions with organic vanadium concentrations of 5 μM, 10 μM, 30 μM, 60 μM, and 120 μM, respectively, were added using the manufacturing example, and solutions with vanadium pentoxide (inorganic vanadium) concentrations of 5 μM, 10 μM, 30 μM, 60 μM, and 120 μM, respectively, were added, and then both the control group and the experimental group were additionally cultured for 24 hours. After treatment for 24 hours, the cells were washed twice using cold PBS, and 100 μL of cold RIPA buffer was added to each well. Whole cell lysates were centrifuged at 14,000 rpm for 20 min at 4°C, and 20 μL of the supernatant was added to 100 μL of CSPD substrate and incubated at room temperature for 30 min. Luminescence intensity was assessed by a luminometer (Glomax, Promega, USA). Total cell lysates were measured to normalize protein concentration (KA / mg protein) using a protein assay kit. The experiments were repeated three times, and the standard deviation of the values ​​was recorded. The results are shown in Figure 3a.

[0076] In addition, a control group was set up in which no separate substance was added in the above setting, and an experimental group 1 was set up in which a solution having a concentration of 30 μM organic vanadium was added using the manufacturing example, and an experimental group 2 was set up in which a solution having a concentration of 30 μM organic vanadium and containing 1% by volume, 1% by volume, and 1.5% by volume of collagen, hyaluronic acid, and ascorbic acid, respectively, was added. These were measured in the same manner as above, and the results are shown in Fig. 3b.

[0077] Referring to Fig. 3a, when inorganic vanadium was used, no significant difference was observed compared to the control group, but when organic vanadium was used, alkaline phosphatase activity was observed at a concentration of 10 μM or higher, which was more than twice that of the control group. Therefore, it was confirmed that when the organic vanadium of the present invention is used, differentiation of osteoblasts progresses and bone formation performance can be improved.

[0078] Referring to Figure 3b, it can be seen that when only organic vanadium was used, alkaline phosphatase activity was about twice that of the control group, and when both organic vanadium and the complex were included, alkaline phosphatase activity was more than four times that of the control group. Therefore, it was confirmed that when the organic vanadium and the complex of the present invention are used together, differentiation of osteoblasts progresses rapidly, and bone formation performance can be greatly improved.

[0079] Experimental Example 4: Type Ⅰα 2 collagen mRNA analysis

[0080] To investigate the osteogenic potential at the mRNA level according to the use of organic vanadium and its complexes, Type Ⅰα 2 collagen mRNA levels were measured.

[0081] First, osteoblast cells (MC3T3-E1 cells) were seeded at 3 x 10 5Cells were cultured in a 48-well plate at a density of 10 cells / well. Subsequently, a control group was set up in which no separate substance was added, similar to Experimental Example 1, and solutions with organic vanadium concentrations of 5 μM, 10 μM, 15 μM, and 20 μM, respectively, were added using the manufacturing example, and solutions with vanadium pentoxide (inorganic vanadium) concentrations of 5 μM, 10 μM, 15 μM, and 20 μM, respectively, were added, and then each control group and experimental group were additionally cultured for 24 hours. Afterwards, the amount of Type Ⅰα 2 collagen mRNA, which is a marker for the expression of Type Ⅰα 2 collagen, was measured using qRT-PCR (quantitative real-time PCR). Specifically, cells were harvested and treated with TRIzol Reagent to extract total RNA. The extracted total RNA concentration (% of control) was quantified using Nanodrop, and the experiment was repeated three times. The standard deviation of the values ​​was recorded. The relative value of the control group was set to 100%, and the values ​​of the experimental group were expressed as a ratio to the control group. The results are shown in Fig. 4a.

[0082] In addition, a control group was set up in which no separate substance was added in the above setting, and an experimental group 3 was set up using the manufacturing example to which a solution with an organic vanadium concentration of 20 μM was added, and an experimental group 4 was set up to which a solution with an organic vanadium concentration of 20 μM and containing collagen, hyaluronic acid, and ascorbic acid at 1 vol%, 1 vol%, and 1.5 vol%, respectively, was added. This was measured using the same method as above, the experiment was repeated three times, and the standard deviation of the values ​​was recorded. Then, the relative value of the control group was set to 1, and the values ​​of the experimental group were expressed as a ratio to the control group, and the results are shown in Fig. 4b.

[0083] Referring to Fig. 4a, when inorganic vanadium was used, no significant difference was observed compared to the control group, but when organic vanadium was used, the Type Ⅰα 2 collagen mRNA (col1a2 mRNA) level was 1.5 times higher than the control group at a concentration of 15 μM or higher. Therefore, it was confirmed that when the organic vanadium of the present invention is used, the amount of collagen expression increases at the mRNA level, thereby improving bone formation performance.

[0084] Referring to Fig. 4b, it can be seen that when only organic vanadium was used, the col1a2 mRNA level was about twice that of the control group, and when both organic vanadium and the complex were included, the col1a2 mRNA level was more than three times that of the control group. Therefore, it was confirmed that when the organic vanadium and the complex of the present invention are used together, the bone formation performance can be significantly improved as the col1a2 mRNA expression of osteoblasts increases.

[0085] Experimental Example 5: Analysis of Antibacterial Performance of Organic Rare Earths

[0086] In order to analyze the antibacterial performance of the organic rare earth used in the present invention, high-purity cerium oxide among rare earths was used and reacted with a 1N acetic acid solution at pH 1.5 and 36°C. At this time, the weight ratio of the acetic acid solution and cerium oxide was mixed in a reaction tank at 3:1, and the reaction was performed at 3,000 rpm for 24 hours, and the upper layer was collected to obtain an organic cerium compound.

[0087] The concentration of the manufactured organic cerium compound was adjusted so that the cerium concentration of each solution was (E): 500 ppm by weight, (F): 1000 ppm by weight, (G): 3000 ppm by weight, (H): 5000 ppm by weight, and 0.1 mL of each aqueous solution was dropped onto a medium inoculated with Escherichia coli (E. coli). After 24 hours, the condition of the medium was checked and recorded in the photograph of Fig. 5.

[0088] Referring to Fig. 5, it can be seen that E. coli grows normally when the organic rare earth concentration is 500 ppm and 1,000 ppm, but when the organic rare earth concentration is 2,000 ppm or higher, it can be seen that E. coli does not grow in the area where the aqueous solution is applied. Therefore, it can be confirmed that the antibacterial effect of the organic rare earth used in the present invention can be secured at a concentration of 2,000 ppm or higher.

[0089] The description of this specification above is for illustrative purposes only, and those skilled in the art will readily appreciate that aspects of this specification can be readily modified into other specific forms without altering the technical concepts or essential features described herein. Therefore, the embodiments described above should be understood as illustrative in all respects and not restrictive. For example, each component described as a single entity may be implemented in a distributed manner, and similarly, components described as distributed may be implemented in a combined manner.

[0090] The scope of this specification is indicated by the claims set forth below, and all changes or modifications derived from the meaning and scope of the claims and their equivalent concepts should be interpreted as being included within the scope of this specification.

Claims

1. Contains organic vanadium as an active ingredient, The above organic vanadium is a chelate compound of vanadium and an organic acid or amino acid. A composition for preventing or improving gum recession.

2. In paragraph 1, A composition for preventing or improving gum recession, comprising 3 μM or more of the organic vanadium.

3. In paragraph 1, Contains more than 2,000 ppm by weight of organic rare earth elements, A composition for preventing or improving gum recession, wherein the organic rare earth is a chelate compound of a rare earth metal and an organic acid or amino acid.

4. In paragraph 3, A composition for preventing or improving gum recession, wherein the rare earth metal is at least one selected from the group consisting of cerium (Ce), yttrium (Y), scandium (Sc), lanthanum (La), neodymium (Nd), dysprosium (Dy), europium (Eu), gadolinium (Gd), holmium (Ho), samarium (Sm), terbium (Tb), ytterbium (Yb), erbium (Er), and praseodymium (Pr).

5. In paragraph 1 or paragraph 3, A composition for preventing or improving gum recession, wherein the organic acid is at least one selected from phosphoric acid, fumaric acid, lactic acid, citric acid, malic acid, butyric acid, formic acid, acetic acid, gluconic acid, succinic acid, tartaric acid, glutamic acid, oxalic acid, and ascorbic acid.

6. In paragraph 1 or paragraph 3, A composition for preventing or improving gum recession, wherein the amino acid is at least one selected from the group consisting of Alanine, Arginine, Asparagine, Aspartic acid, Cysteine, Glutamine, Glutamic acid, Clycine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Proline, Serine, Threonine, Tryptophan, Tyrosine, and Valine.

7. In paragraph 1, A composition for preventing or improving gum recession, further comprising a complex of collagen, hyaluronic acid, ascorbic acid and natural xylitol.

8. In paragraph 7, A composition for preventing or improving gum recession, wherein the complex comprises 80 to 120 parts by volume of the hyaluronic acid, 120 to 180 parts by volume of the ascorbic acid, and 250 to 350 parts by volume of the natural xylitol, relative to 100 parts by volume of the collagen.

9. In paragraph 7, The above collagen is a composition for preventing or improving gum recession, having a molecular weight of 300 Da or less.

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