KR102133753B1 - Oral composition containing silk protein, 4-hexylresorcinol and natural oil - Google Patents

Abstract

Since the oral composition according to the present invention exhibits excellent antibacterial effects against various oral microorganisms by including 4-hexylresorcinol and natural oil, it can be usefully used as an oral cleaning composition or an antibacterial composition for oral microorganisms, It can be used for the prevention and treatment of bad breath, dental caries and periodontal disease caused by the oral microorganisms.

Description

Oral composition containing silk protein, 4-hexylresorcinol and natural oil}

The present invention relates to an oral composition, and more specifically, by including silk protein, 4-hexyl resorcinol and natural oil in a specific ratio, it exhibits a strong antibacterial effect against oral microorganisms that cause oral disease, but is transparent, thereby eliminating bad breath. It relates to an oral composition that can be beneficially used.

There are approximately 600 to 800 or more various microorganisms in the oral cavity of humans, and it is known that most of the oral microorganisms that cause oral diseases are present in a plaque, a bacterial membrane formed between teeth and gums. The oral microorganisms produce toxins in the plaque, and the toxins they produce invade into the periodontal tissue, causing gingivitis, destruction of the alveolar bone, and the like, causing periodontal disease, and when the microorganisms produce acid, the cause of dental caries It also becomes.

An enamel is a milky, translucent, hard material that covers the surface of the head of the tooth and protects the dentin of the tooth. Dental caries is caused by microorganisms that form plaque fermenting sugar, starch, and the like to make various organic acids such as lactic acid, and the organic acid thus produced is dissolved in hydroxyapatite, the main component of teeth, to corrode enamel. Plaque is made by attaching oral microbes such as Streptococcus mutans, a type of streptococcus, on a thin, sticky membrane formed on a tooth by saliva to form a biofilm.

Periodontal disease is often referred to as pungchi, and is divided into gingivitis and periodontitis depending on the severity of the disease. The periodontal disease is a relatively light and fast-recovering periodontal disease that is limited to the gums, ie, soft tissues, and is called periodontitis when the inflammation has progressed to the periphery of the gums and gums. One of the main causes of periodontal disease is excessive plaque accumulation and thus an increase in bacterial activity. In the case of Gram-negative anaerobic bacteria, toxins and metabolites produced from the bacteria destroy oral tissue or stimulate the immune system, causing inflammation. In addition, when plaque and tartar accumulate, the gums fall from the teeth, from which gaps are formed between the gums and the teeth, forming the periodontal pockets. As the inflammation progresses, the gap between the gums and the teeth spreads further, and the alveolar bone and periodontal ligament are destroyed.

Bad breath occurs mainly in the process of decaying large amounts of oral microorganisms that reside inside the tongue, food debris, dead cells, and runny nose. Bad breath is a symptom of unpleasant odor in the mouth due to volatile sulfur compounds produced by oral microorganisms such as Peugeot bacterium nucleatum and Porphyromonas ginsivalis decomposing proteins containing sulfur. In addition, bad breath may occur due to dry mouth or an increase in pH in the oral cavity, white plaque, and gum disease.

These dental caries, periodontal disease, bad breath, etc. are related to the proliferation of oral microorganisms, and in order to prevent or treat them, germs in the oral cavity must be sterilized and fundamentally removed. In general, in the case of dental caries and periodontal disease, chlorhexidine hydrochloride and cetylpyridinium chloride have been used to remove plaque, but chlorhexidine hydrochloride causes discoloration of teeth, and cetylpyridinium chloride, a cation, is somewhat effective when reacted with an anionic substance. There is a downside. In addition to this, oral cleaning agents based on fluorine compounds are commercially available, but this has not been verified for the preventive effect of periodontal disease.

In addition, patients undergoing surgery at the Oral and Maxillofacial Surgery have difficulty in brushing teeth with a toothbrush because they have a wound in the oral cavity. However, as of yet, oral cleaning agents for these patients have not been developed.

On the other hand, sericin separated from the cocoon is well known in connection with bone formation (non-patent documents 1 and 2). Although it has been disclosed through the non-patent documents 1 and 2 that sericin can promote bone regeneration by increasing the expression of TNF-α related to bone formation, the case of applying sericin to the mouthwash is still unknown. to be.

Thus, for patients with intraoral wounds, it is a multifunctional oral hygiene composition that can not only have a strong antibacterial effect against oral microorganisms that cause wound area infections, but also promote bad breath removal and healing of wounds in the oral cavity. Research and development of the situation is necessary.

Kim JW, Jo YY, Kweon HY, Kim DW, Kim SG. The effects of proteins released from silk mat layers on macrophages. Maxillofac Plast Reconstr Surg 2018;40:10. Jo YY, Kweon H, Kim DW, Baek K, Kim MK, Kim SG, Chae WS, Choi JY, Rotaru H. Bone regeneration is associated with the concentration of tumour necrosis factor-α induced by sericin released from a silk mat. Sci Rep. 2017;7:15589.

Thus, the present inventors have research to develop an oral composition having a strong antibacterial effect against oral microorganisms and an excellent bad breath removal effect for a long period of time, and when the composition includes 4-hexylresorcinol and natural oil in a specific blending ratio The present invention was completed by confirming that it exhibits excellent organoleptic properties through a transparent formulation while having a strong antibacterial effect and a bad breath removal effect against oral microorganisms causing oral diseases.

Accordingly, an object of the present invention is to provide a transparent oral composition while having an antibacterial and bad breath removal effect on oral microorganisms.

As a means for solving the above problems, the present invention provides an oral composition for removing bad breath of a transparent formulation comprising 4-hexylresorcinol and natural oil.

In the present invention, "halt breath" may mean a symptom of unpleasant odor in the mouth, but is not limited thereto, and representatively, in the mouth due to volatile sulfur compounds produced by microorganisms in the oral cavity decomposing proteins. An unpleasant smell may be caused.

In addition, the present invention provides a pharmaceutical composition for the prevention and treatment of dental caries or periodontal disease comprising 4-hexylresorcinol and natural oil.

In the present invention, "tooth caries" refers to a disease caused by corrosion of enamel by melting hydroxyapatite, which is a main component of teeth, from organic acids produced by oral microorganisms fermenting sugar, starch, and the like.

In the present invention, "periodontal disease" is a disease caused by oral microbes, including stomatitis, gingivitis, periodontitis, alveolar bone breakage, alveolar osteoporosis, alveolar softening, alveolar bone reduction, alveolar bone remodeling disorder, bad breath, caries, and the like.

Hereinafter, the configuration of the present invention will be described in detail.

The oral composition of the present invention includes 4-hexylresorcinol (4-HR) and natural oil.

In the present invention, the 4-hexylresorcinol and natural oil may be included to implement antibacterial activity against oral microorganisms.

In the present invention, the 4-hexyl resorcinol is based on 100 parts by weight of the total composition, 0.001 parts by weight to 1 part by weight, for example, 0.005 parts by weight to 0.8 parts by weight, 0.01 parts by weight to 0.5 parts by weight, 0.03 parts by weight Parts to 0.3 parts by weight, and 0.05 parts to 0.15 parts by weight. Compared to 100 parts by weight of the total composition, when the content of 4-hexylresorcinol is less than 0.001 part by weight, it is difficult to expect an antibacterial effect against oral microorganisms, and when it exceeds 1 part by weight, 4-hexylresorcinol has toxicity. It can adversely affect individuals with oral disease.

In the present invention, the natural oil may select one or more oils selected from the group consisting of lavender oil, eucalyptus oil, spamint oil, basil oil and menthol oil. The natural oil is based on 100 parts by weight of the total composition, 0.002 to 5 parts by weight, for example, 0.005 parts to 3 parts by weight, 0.01 parts by weight to 1 part by weight, 0.05 parts by weight to 0.5 parts by weight, 0.1 parts by weight to 0.3 parts by weight, but is not limited thereto. The content of natural oils can be adjusted according to the aroma and taste of each oil.

In addition, the 4-hexyl resorcinol and natural oil may be included in a weight ratio of 1:1.8 to 1:5, for example 1:2 to 1:3, 1:2.1 to 1:2.3. While maintaining the transparency of the oral composition in the weight ratio of 4-hexyl resorcinol and natural oil as described above, the sensory characteristics such as taste and aroma may be most excellent.

The oral composition according to the present invention may exhibit antibacterial effects against microorganisms that exist in the oral cavity and have a negative effect by including 4-hexylresorcinol and natural oil in the above-described content or weight ratio. In the present invention, the oral microorganisms include Streptococcus aureus , Streptococcus mutans , Porphyromonas gingivalis , Fusobacterium, Fusobacterium nucleatum , Prevotella intermedia , Actinobacillus actinomycetemcomitans , Actinomyces viscosus , Aggregatibacter actinomycetactomiters Aggregatibac actinomycetemcomitans ) and Tannerella forsythia . The oral microorganisms may be the causative agent of dental caries or periodontal disease.

In the present invention, the oral composition may further include 4-hexylresorcinol and natural oil, as well as sericin. The sericin is a protein surrounding the two strands of fibroin, and is known to increase the activity of lymphocytes involved in the immune response. In the following examples, by treating sericin on macrophages, the expression of wound healing-related genes according to the concentration of sericin was confirmed (FIGS. 6 and 7 ). As a result, as the concentration of sericin treated in macrophages increased, the expressions of PDGF-B and TIMP-1, genes that promote wound healing, increased, and, conversely, of the genes that inhibited wound healing, MMP-2 and MMP-3. It was confirmed that the expression decreased. Therefore, the present invention may further include sericin to promote healing of wounds such as inflammation in the oral cavity, and additionally include sericin in the composition, which is concomitantly effective in preventing and treating periodontal diseases related to inflammation. Can represent. The composition according to the present invention may contain 0.001 part by weight to 0.5 part by weight of sericin relative to 100 parts by weight of the total composition.

According to the following examples, oral compositions according to the present invention are Streptococcus mutans , Streptococcus aureus and Porphyromonas gingivalis ) has been shown to have an antibacterial effect against oral microorganisms, and it was confirmed that the bad breath removal effect lasted for a long time. Furthermore, the present invention also confirmed the optimal weight ratio of 4-hexylresorcinol and oil for indicating a clear formulation of the oral composition.

According to the present invention, the present invention can provide a product for oral hygiene comprising the oral composition. The oral composition for removing bad breath according to the present invention comprising 4-hexylresorcinol and natural oil is an oral composition that can be included in all products manufactured and marketed for oral health in general. no limits.

The oral composition according to the present invention may include components commonly used in oral compositions in addition to the 4-hexylresorcinol, natural oil and sericin. For example, the components may include abrasives, wetting agents, binders, foaming agents, sweeteners, preservatives, drug active ingredients, flavoring agents, pigments, solvents, brighteners, solubilizers or pH adjusting agents.

The oral composition of the present invention may be prepared in any formulation conventionally prepared in the art, and is not particularly limited. For example, the composition may have a formulation such as toothpaste, mouthwash or mouthwash, chewing gum, candy, mouthwash and mouthwash.

In one embodiment, when the composition for oral hygiene of the present invention is a formulation of a mouthwash or toothpaste, wetting agents, abrasives, binders, foaming agents, sweeteners, colorants, preservatives, active ingredients, solvents, pH adjusting agents and the like may be included.

In the case of toothpaste, the wetting agent is intended to prevent the powder from becoming a paste and to prevent the composition from solidifying in the air, glycerin, sorbitate, propylene glycol, polyethylene glycol, etc., alone or in combination of two or more, 1 to 60 weight of the total weight of the composition Part, more specifically, may be included in 10 to 50 parts by weight, but is not limited thereto.

The foaming agent diffuses the composition into the oral cavity to enhance the cleaning effect, and acts as a surfactant to clean oral contamination, and surfactants such as sodium lauryl sulfate, sodium lauryl sarcosinate, and sucrose fatty acid esters are mixed singly or two or more. The composition may be included in 0.5 to 10 parts by weight of the total weight, more specifically 0.5 to 5 parts by weight, but is not limited thereto.

The binder is to prevent separation between the powder and the liquid component in the composition, by mixing cellulose derivatives such as sodium carboxymethylcellulose, methylcellulose, hydroxypropylcellulose and sodium alginate, carrageenan, xanthan gum, etc. alone or in combination of two or more. The total weight of the composition may be included in 0.1 to 5 parts by weight, more specifically 0.3 to 2 parts by weight, but is not limited thereto.

The abrasive is to remove the deposits on the surface of the tooth without damaging the surface of the tooth, so that the original luster of the tooth is obtained, calcium carbonate (CaCO ₃ ), dicalcium phosphate (CaHPO ₄ , CaHPO ₄ · 2H ₂ O), anhydrous Silicic acid (SiO ₂ ·2H ₂ O), aluminum hydroxide (Al(OH) ₃ ), potassium pyrophosphate, magnesium carbonate, etc., alone or in combination of two or more, 1 to 60 parts by weight of the total weight of the composition, more specifically 10 to It may be included as 50 parts by weight, but is not limited thereto.

The sweetener is to remove the unpleasant taste caused by the raw material of the toothpaste and to improve the refreshing feeling. Saccharinic acid, aspartame, xylitol, licorice acid, etc., alone or in combination of two or more, 0.01 to 60 parts by weight of the total weight of the composition, more specifically 0.01 to 5 parts by weight, but is not limited thereto.

The active ingredient is for the prevention of dental caries, periodontal disease and gingivitis, or removal of bad breath. Fluoride, zinc chloride, chlorhexidine, aminocaproic acid, tranexamic acid, cetylpyridinium chloride, pyridoxine chloride, triclosan, acetic acid Tocopherol, sodium monofluorophosphate, and the like may be included alone or in combination of two or more, but are not limited thereto.

The oral composition of the present invention may be used alone or in combination with a known oral composition.

In addition, the present invention provides a pharmaceutical composition for the prevention and treatment of dental caries or periodontal disease comprising 4-hexylresorcinol and natural oil.

The periodontal disease is a disease caused by oral microorganisms, and includes stomatitis, gingivitis, periodontitis, alveolar bone damage, alveolar osteoporosis, alveolar softening, alveolar bone reduction, alveolar bone remodeling disorder, bad breath, tooth decay.

In the pharmaceutical composition of the present invention, all contents related to the 4-hexyl resorcinol, natural oil, and sericin may be applied as described above in the oral composition.

The pharmaceutical composition for preventing and treating dental caries or periodontal disease of the present invention may further include a known active ingredient having a therapeutic effect on dental caries or periodontal disease together with 4-hexylresorcinol and natural oil.

In the present invention, the term "pharmaceutically acceptable carrier" refers to a carrier or diluent that does not significantly stimulate the organism and does not inhibit the biological activity and properties of the administered ingredient. The pharmaceutically acceptable carrier in the present invention can be used by mixing one or more components of saline, sterile water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol and these components, If necessary, other conventional additives such as antioxidants, buffers, and bacteriostatic agents can be added to formulate in the form of injections suitable for injection into tissues or organs. In addition, it may be formulated as an isotonic sterile solution, or, in some cases, a dry preparation (especially a freeze-dried preparation) that can be an injectable solution by adding sterile water or physiological saline. In addition, a target organ-specific antibody or other ligand can be used in combination with the carrier so that it can specifically act on the target organ.

In addition, preferably, the composition of the present invention may further include a filler, an excipient, a disintegrant, a binder, and a lubricant. Compositions of the invention can also be formulated using methods known in the art to provide rapid, sustained or delayed release of the active ingredient after administration to a mammal.

In the present invention, the term "administration" refers to introducing the composition of the present invention to a patient in any suitable way, and the route of administration of the composition of the present invention is administered through various routes, oral or parenteral, as long as it can reach the target tissue. Can be administered. Intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, oral administration, topical administration, intranasal administration, intrapulmonary administration, rectal administration, but are not limited thereto.

As used herein, "effective amount" refers to the amount necessary to delay or entirely stop the onset or progression of the particular disease to be treated. In the present invention, the composition may be administered in a pharmaceutically effective amount. It is obvious to a person skilled in the art that a suitable total daily dosage can be determined by the treating physician within the proper medical judgment.

For the purposes of the present invention, a specific therapeutically effective amount for a particular patient is a specific composition, including the type and extent of the reaction desired to be achieved, and, if appropriate, whether other agents are used, the patient's age, weight, general health status, gender And various factors, including diet, time of administration, route of administration and secretion rate of the composition, duration of treatment, drugs used with or concurrently with the specific composition, and similar factors well known in the pharmaceutical field.

Carriers, excipients and diluents that may be included in the formulation include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose , Microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. When formulating the composition, it is usually prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations include at least one excipient in the composition, such as starch, calcium carbonate, sucrose, lactose, gelatin, etc. It is prepared by mixing. In addition, lubricants such as magnesium stearate and talc are used in addition to simple excipients. Liquid preparations for oral use include suspensions, liquid solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used as diluents, various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, can be included. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As a base for suppositories, witepsol, macrogol, tween61, cacao butter, laurin butter, and glycerogelatin may be used. In the present invention, "administration" means providing the composition of the present invention to a subject in any suitable way. The preferred dosage of the pharmaceutical composition of the present invention depends on the patient's condition and body weight, the degree of disease, the drug form, the route and duration of administration, but can be appropriately selected by those skilled in the art. However, for the desired effect, the pharmaceutical composition of the present invention may be administered in an amount of 1 to 10000 mg/kg per day. The composition may be administered once a day, or may be divided into several times. The pharmaceutical composition of the present invention can be administered to a subject by various routes. All modes of administration can be envisaged, preferably oral administration. The composition of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modifiers for the prevention or treatment of dental caries or periodontal disease.

Advantages and features of the present invention, and methods for achieving them will be clarified with reference to experimental examples and manufacturing examples described in detail below. However, the present invention is not limited to the experimental examples and manufacturing examples disclosed below, but will be implemented in various different forms, only to make the disclosure of the present invention complete, and to have ordinary knowledge in the technical field to which the present invention pertains. It is provided to completely inform the person of the scope of the invention.

Since the oral composition according to the present invention exhibits excellent antibacterial effects against various oral microorganisms by including 4-hexylresorcinol and natural oil, it can be usefully used as an oral cleaning composition or an antibacterial composition for oral microorganisms, It can be used for the prevention and treatment of bad breath, dental caries and periodontal disease caused by the oral microorganisms.

1 is a graph confirming the cell viability according to the treatment of the mouthwash composition of the present invention.
Figure 2 is a picture of observing the transparency of the mouthwash composition of the present invention.
High 3 shows the change in the results of bad breath measurement before and after the use of the mouthwash composition of the present invention (left: before cleaning of the mouthwash composition, right: after cleaning of the mouthwash composition).
Figure 4 shows the results of halitosis measurement over time after the use of the mouthwash composition of the present invention.
Figure 5 shows the results of the measurement of bad breath after 1 hour of use of the mouthwash composition of the present invention (left: the treatment group of Example 1, right: the treatment group of Comparative Example 1).
FIG. 6 shows the bad breath measurement value of Comparative Example 1 (commercial mouthwash) as a relative value based on the results of the bad breath measurement after 1 hour of use of the mouthwash of the present invention (assuming 1).
7 is a result of confirming the gene expression level after 2 hours after treatment with sericin in macrophages.
8 is a result of confirming the gene expression level after 8 hours after treatment with sericin in macrophages.

Hereinafter, the present invention will be described in detail by examples. However, the following examples are only to illustrate the present invention, the content of the present invention is not limited to the following examples.

Example 1. Preparation of oral composition

Oral compositions were prepared with the composition of Table 1 below. First, 4-hexylresorcinol was first dissolved in three types of oils (eucalyptus oil, basil oil, and menthol oil). Since sericin is water-soluble, it was separately dissolved in water. After mixing the dissolved 4-hexylresorcinol and sericin with each other, purified water was added to prepare a turbid solution mixed with oil droplets. The resulting turbidity solution was placed on a heating plate (30°C to 50°C), and polysorbate 20 was added dropwise by 0.1 ml and uniformly mixed using a magnetic stirrer. When the amount of the accumulated polysorbate 20 reached 1 ml, the dropping of the polysorbate 20 was stopped. At this time, the solution becomes transparent.

Ingredient (content: Parts by weight ) Example One Purified water 98.66 4-hexylresorcinol 0.1 Sericin 0.02 Eucalyptus oil 0.1 Basil oil 0.1 Menthol oil 0.02 Polysorbate 20 One total 100

Experimental Example 1. Confirm cytotoxicity

Toxicity of the oral composition prepared in Example 1 and commercially available mouthwashes were confirmed. First, the washed macrophage cell line RAW264.7 cells (10 ⁴ cells/180 μl) were placed in a 96-well plate and cultured overnight. After incubation, the supernatant (medium) was removed and replaced with fresh DMEM medium. At this time, 10 µl of the test drug was added together with the new medium and cultured overnight. The test drug was 0.05% of the medium of the oral composition of Example 1 prepared previously ( Example 2 ) and 0.1% ( Example 3 ) was added, and commercially available oral cleansers (Listerin) were added so that they were 0.05% (Comparative Example 1) and 0.1% (Comparative Example 2) of the medium, respectively. Did. After incubation, the supernatant (medium) was removed and 10 μl of MTT (5 mg/mL in PBS) and 90 μl of DEME medium were added. Again the supernatant (medium) was removed and 100 μl (or 200 μl) of DMSO was added. The OD value at a wavelength of 540 nm was measured using a spectrophotometer. The results are shown in Table 2 and Figure 1 below.

Control 0.05% 0.10% Example 2 Comparative example One Example 3 Comparative example 2 0.343 0.313 0.245 0.313 0.164 0.332 0.338 0.285 0.338 0.205 0.349 0.379 0.234 0.379 0.149 0.339 0.325 0.303 0.325 0.144 medium 0.341 0.339 0.267 0.339 0.166 Cell viability ( % ) 100.0 99.4 78.3 99.4 48.6 Standard error 0.35678 1.435488 1.631142 1.435488 1.383534

As a result, it can be seen from FIG. 1 that cytotoxicity is lower than that of a commercially available product.

Experimental Example 2. Confirmation of antibacterial activity against oral microorganisms

There are many microorganisms in the oral cavity, and certain microorganisms harm oral health such as dental caries, periodontal disease or bad breath. Thus, the antibacterial activity against oral microorganisms of the composition for oral hygiene of Example 1 prepared above was confirmed. The microorganisms used in this experiment were Streptococcus mutans , Porphyromonas gingivalis , and Streptococcus aureus . The antimicrobial effect was visualized by a paper disc method.

Specifically, an ATCC Medium 260 medium containing Tryptic soy agar (TSA) or Tryptic soy broth (TSB) (MB-T1053, manufacturer, manufacturer) and sheep blood defibrinated (MB-S1876, manufacturer, manufacturer) was used. After 0.1 ml of oral microorganisms were applied to the medium, 10 µl of the oral hygiene composition of the present invention was added dropwise and dried. Thereafter, the cells were incubated for 2 days at a temperature of 37° C. in an anaerobic chamber. Thereafter, the size of the inhibitory zone was measured to confirm the antibacterial effect of the composition, and the results are shown in Table 3 below.

microbe Inhibitory Size (mm) Example One Streptococcus Mutans 1.15 ± 0.74 Streptococcus Aureus 1.50 ± 1.33 Propyromonas Jinji Ballis 1.23 ± 0.95

As shown in Table 3, for Example 1, Streptococcus aureus , Streptococcus mutans , and Porphyromonas gingivalis ), it was confirmed that they all show antibacterial effects. Therefore, it can be seen that the oral composition of the present invention has an oral microbial growth inhibitory effect.

Experimental Example 3. Check transparency

To prepare an oral composition with the composition of Table 4, it was confirmed the transparency of the composition.

Ingredient (content: Parts by weight ) Example One Example 4 Comparative example 3 Comparative example 4 Purified water 98.66 98.56 98.76 98.71 4-hexylresorcinol 0.1 0.1 0.1 0.1 Sericin 0.02 0.02 0.02 0.02 Eucalyptus oil 0.1 0.15 0.05 0.075 Basil oil 0.1 0.15 0.05 0.075 Menthol oil 0.02 0.02 0.02 0.02 Polysorbate 20 One One One One total 100 100 100 100

As a result, sensory properties and transparency as shown in Table 5 and FIG. 2 were shown.

Sensory evaluation Example 1 Transparency Example 4 Transparency Comparative Example 3 Increased turbidity, powder form Comparative Example 4 Not transparent

Experimental Example 4. Bad breath removal effect

This experiment is for confirming the effect of removing bad breath according to the composition of the present invention, and 5 people without oral and systemic diseases that can affect the experiment were recruited. After the subjects had to stop oral environment management for 8 hours, the degree of bad breath was measured using a Halimeter. At this time, the degree of bad breath was confirmed to be the gas-induced level of bad breath-causing gas, and volatile sulfur compounds, particularly methyl mercaptan (CH ₃ SH) and hydrogen sulfide (H ₂ S), were selected as bad breath-causing gases. Hydrogen (H ₂ ) was selected.

1) Bad breath removal effect according to cleaning time

Subsequently, the test subjects were ingested with eggs as a bad breath-inducing food, and then washed with the oral composition of Example 1 for 30 seconds. Before and after oral cleaning, the degree of gas induction caused by bad breath was confirmed, and the results are shown in FIGS. 3 and 6.

Bad breath gas CH ₃ SH (ppm) H ₂ S ( ppb ) H ₂ ( ppb ) Experimenter 1 Before cleaning 0 11 One After cleaning 5 3 One Experimenter 2 Before cleaning 0 10 23 After cleaning 7 0 5 Experimenter 3 Before cleaning 18 16 4 After cleaning One 0 14 Experimenter 4 Before cleaning 0 33 16 After cleaning 2 0 33

As shown in Figure 3 and Table 6, when using the composition of the present invention, it was confirmed that it is possible to remove bad breath from the reduction of bad breath cause gas. Particularly, the effect of reducing the H ₂ S gas among the bad breath causing gases was observed excellently.

2) Deodorization ability and duration check

In the same manner as in 1), after subjecting the test subjects to eat eggs as a bad breath-inducing food, a certain amount of the oral composition of Example 1 was used. Afterwards, bad breath was measured every 20 minutes to evaluate sustainability. The results are shown in Fig. 4 and Table 7.

Bad breath gas CH ₃ SH (ppm) H ₂ S ( ppb ) H ₂ ( ppb ) Experimenter 1 Before cleaning 0 6 6 Immediately after cleaning 3 4 14 20 minutes after washing 5 8 15 After 40 minutes of washing 2 22 7 Experimenter 2 Before cleaning 8 30 7 Immediately after cleaning 9 6 20 20 minutes after washing 6 5 4 After 40 minutes of washing 6 17 8 Experimenter 3 Before cleaning One 15 6 Immediately after cleaning 0 4 32 20 minutes after washing 0 7 22 After 40 minutes of washing One 64 12 Experimenter 4 Before cleaning 8 2 11 Immediately after cleaning 4 17 8 20 minutes after washing 12 17 0 After 40 minutes of washing 5 30 4 Experimenter 5 Before cleaning One 81 18 Immediately after cleaning One 95 6 20 minutes after washing 0 65 9 After 40 minutes of washing One 145 16

As a result, as shown in FIG. 4, it can be seen that the concentration of H ₂ S, a typical bad breath cause gas, is restored to the state before washing after about 40 minutes, as observed in the example of five persons. Therefore, it can be seen that the cleaning effect of Example 1 lasts about 40 minutes.

3) Comparison of bad breath removal effect with commercial products

In the same manner as in 1), after ingesting the bad breath-inducing food eggs to the test subjects, oral cleaning was performed using the composition of Example 1 and a commercially available mouthwash (Listerine-Comparative Example 1). The results of the bad breath measurement after one hour after washing are shown in Fig. 5 and Table 8. At this time, in FIG. 5, the left data of each graph is the processing group of Example 1, and the right data is the processing group of Comparative Example 1.

Bad breath gas CH ₃ SH (ppm) H ₂ S ( ppb ) H ₂ ( ppb ) Experimenter 1 Example One 3 4 14 Comparative example One 0 20 5 Experimenter 2 Example One 9 6 20 Comparative example One 6 17 8 Experimenter 3 Example One 0 4 32 Comparative example One 0 50 67 Experimenter 4 Example One 4 17 9 Comparative example One 18 79 12 Experimenter 5 Example One One 95 6 Comparative example One 8 114 15

As a result (FIG. 5), it was found that the concentration of H ₂ S, a typical bad breath cause gas, is restored to the state before washing in the case of the existing product Listerin, after about 20 minutes after using the mouthwash, as observed in the example of 5 persons. Can. However, in the case of Example 1, it can be seen that it was kept low compared to the case where Listerin was used in the same person.

4) Comparison of the degree of discharge of compounds that cause bad breath with commercial products

After feeding one egg to five test subjects, the mouth was rinsed for 30 seconds with the oral composition of Example 1 and a commercially available product, Listerin (Comparative Example 1), and after 20 minutes, H ₂ S, H ₂ in the oral cavity. The emission amount of CH ₃ SH gas was measured. At this time, assuming that the gas emission of the experimental group is 1, the gas emission after using the mouthwash (Listerin) of Comparative Example 1 in the same participant is calculated and compared to the relative value of the experimental group emission, and shown in FIG.

H ₂ S H ₂ CH ₃ SH Example One One One One Comparative example One 5.24±4.34 2.83±3.37 1.37±0.97

As a result, the emission amount of H ₂ S in the treatment group of Comparative Example 1 was 5.24 ± 4.34 times higher than that of Example 1, 2.83 ± 3.37 times higher for H ₂ , and 1.37 ± 0.97 times higher for CH ₃ SH. In particular, the emission of H ₂ S was statistically significant as a result of analyzing by two-sided verification with paired samples t-test (P=0.036). Through the above results, it was confirmed that the oral composition of the present invention has an excellent effect of suppressing the emission of bad breath bad gases, and particularly effectively suppresses the emission of H ₂ S.

Experimental Example 5. Check the wound healing effect of sericin

To confirm the wound healing effect of sericin, sericin was dissolved in cell culture and treated in a macrophage cell line. Specifically, sericin was treated with RAW264.7 cells (KCLB No. 40071) at a concentration of 3 to 10 μg/mL. In this case, the culture medium used for the cell line was α-MEM (HyClone, Logan, Utah, USA) and DEME (PAA Laboratories, Linz, Austria) medium culture medium of 1% penicillin/streptomycin (100X) and 10%. Autologous plasma was added and used. Cells were incubated at 37° C., 5% CO ₂ , 99% relative humidity until 80% colony was reached. After adding a predetermined concentration of sericin to the cell line, mRNA was extracted from the cells 2 and 8 hours later, and genetic changes were observed through cDNA microarray. At this time, the observed genes are PDGF-B, MMP-2, MMP-3 and TIMP-1. In wound healing, the relative expression of these genes is important. As the expression level of PDGF-B and TIMP-1 among the genes increases, the amount of expression of MMP-2 and MMP-3 decreases, the wound heals, and the ratio of TIMP-1/MMP-2 and TMP-1/ for chronic wounds It is known from the literature of (Patel S, et al., Biomarkers for wound healing and their evaluation.J Wound Care. 2016, Jan;25(1):46-55.) that the proportion of MMP-3 decreases. have.

Looking at the degree of gene expression when 2 hours elapse after treatment with sericin in macrophages, PDGF-B as the concentration of sericin increases in the range of 3 to 10 μg/mL, as shown in FIG. And it can be seen that the expression of TIMP-1 increases.

As shown in FIG. 8, when 8 hours elapse after treatment with sericin, it can be confirmed that the expression of PDGF-B and TIMP-1 increases in a range of 3 to 10 μg/mL of sericin.

On the other hand, when a wound is formed, the ratio of expression of TMIP-1 and MMP is important whether the wound is cured or leads to chronic inflammation. The ratio of TMIP-1 and MMP (MMP-2 and MMP-3 according to cell treatment of sericin is shown in Table 10 below.

Sericin concentration ( μg /ml) 3 4 8 10 TIMP -One/
MMP -2 After 2 hours 0.576143 0.795988 4.636659 5.238221 After 8 hours 0.837613 0.933772 6.589044 11.24224 TIMP -One/
MMP -3 After 2 hours 4.408949 3.444101 7.749219 10.05584 After 8 hours 0.92837 0.696215 2.014098 1.900229

As shown in Table 10 above, as the concentration of sericin treated in cells increased, the ratio of TIMP-1 and MMP increased, which was the same in both MMP-2 and MMP-3. Therefore, it can be seen from the above results that the sericin component can be used as a component that promotes wound healing at the wound site.

Claims (13)

Based on 100 parts by weight of the total composition,
4-hexylresorcinol 0.001 part by weight to 1 part by weight; And
Contains 0.002 parts by weight to 5 parts by weight of natural oil consisting of eucalyptus oil, basil oil and menthol oil,
The 4-hexyl resorcinol and natural oil is a oral composition for removing bad breath contained in a weight ratio of 1:1.8 to 1:5. According to claim 1,
The oral composition has antibacterial activity against one or more oral microorganisms selected from the group consisting of Streptococcus aureus, Streptococcus mutans, and Porphyromonas gingivalis. , Oral composition. delete According to claim 1,
The composition is an oral composition further comprising sericin. According to claim 4,
The sericin is an oral composition contained in 0.001 parts by weight to 0.5 parts by weight relative to 100 parts by weight of the total composition. According to claim 1,
The composition is an oral composition that is any one formulation selected from the group consisting of toothpaste, mouthwash, mouthwash and mouth spray. According to claim 1,
The composition is an oral composition that is a transparent formulation. Based on 100 parts by weight of the total composition,
4-hexylresorcinol 0.001 part by weight to 1 part by weight; And
Contains 0.002 parts by weight to 5 parts by weight of natural oil consisting of eucalyptus oil, basil oil and menthol oil,
The 4-hexyl resorcinol and natural oil is a pharmaceutical composition for the prevention and treatment of dental caries or periodontal disease contained in a weight ratio of 1:1.8 to 1:5. The method of claim 8,
The oral composition has antibacterial activity against at least one oral harmful bacteria selected from the group consisting of Streptococcus aureus, Streptococcus mutans and Porphyromonas gingivalis , Dental caries or periodontal disease prevention and treatment pharmaceutical composition. delete The method of claim 8,
The oral composition further comprises sericin, a pharmaceutical composition for the prevention and treatment of dental caries or periodontal disease. The method of claim 11,
The sericin is 0.001 parts by weight to 0.5 parts by weight compared to 100 parts by weight of the total composition, a pharmaceutical composition for the prevention and treatment of dental caries or periodontal disease. The method of claim 8,
The periodontal disease is stomatitis, gingivitis, periodontitis, alveolar bone breakage, alveolar osteoporosis, alveolar softening, alveolar bone reduction, alveolar bone remodeling disorder, a disease selected from the group consisting of bad breath and tooth decay, pharmaceutical composition for prevention and treatment of dental caries or periodontal disease .

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