KR102687220B1 - Composition for prevention or treatment of oral disease comprising d-tetrahydropalmatine - Google Patents

Abstract

The present invention relates to a composition for preventing or treating oral diseases containing D-tetrahydropalmatine, and more specifically, to a quasi-drug composition that has the effect of preventing or improving dental caries, periodontal disease, dry teeth, and bad breath. . The composition of the present invention has excellent antibacterial activity against bacteria that cause dental caries and periodontal disease, suppresses PGE2, a pain and inflammation marker, in a concentration-dependent manner, and has excellent effects in suppressing gingivitis formation, suppressing symptoms of sensitive teeth, and removing bad breath. It has high utility as a quasi-drug composition for preventing or improving one or more oral diseases selected from the group consisting of dental caries, periodontal disease, dry teeth, and bad breath. Additionally, the composition of the present invention can be used as a pharmaceutical composition and food composition.

Description

Composition for prevention or treatment of oral disease comprising d-tetrahydropalmatine}

The present invention relates to a composition for preventing or treating oral diseases containing D-tetrahydropalmatine, and more specifically, to a quasi-drug composition that has the effect of preventing or improving dental caries, periodontal disease, dry teeth, and bad breath. . Additionally, the present invention relates to a pharmaceutical composition containing D-tetrahydropalmatine, a food composition, and an oral composition containing D-tetrahydropalmatine.

Healthy teeth are such an important factor in determining the quality of life that they are called one of the five blessings. Among oral diseases, dental caries (cavities) and periodontal disease (periodontal disease) are diseases with a high incidence worldwide and are associated with various clinical symptoms such as pain, impaired chewing function, destruction of periodontal tissue, bad breath, and sensitive teeth. It is known to be the main factor causing tooth loss, and the causative factors of oral diseases are increasing due to changes in eating habits.

It is known that approximately 600 to 800 types of microorganisms exist in the human oral cavity, and these microorganisms are controlled by enzymes such as lysozyme secreted by saliva. However, an oral environment rich in nutrients and moisture is a good condition for the growth of microorganisms, and the tongue and dental plaque provide an excellent habitat for microorganisms. Some of these microorganisms are opportunistic pathogens and cause diseases such as dental caries, periodontal disease, and dentinal hypersensitivity, as well as bad breath.

There are antibacterial agents as a way to suppress the growth of oral pathogens that live in plaque and cause dental caries, periodontal disease, bad breath, and sensitive teeth. Various types of antibacterial agents, including antibiotics that have sterilizing and bacteriostatic effects on oral pathogens, are used to treat cavities, It has been developed as a treatment and suppressant for periodontal disease, dental pulp, and periapical infections.

However, antibiotics have the disadvantage of being difficult to use long-term and being used only as a treatment because they can cause systemic side effects on our body and the emergence of resistant bacteria in the oral cavity and bacterial superinfection. In addition, antibacterial agents used in mouthwashes include Sangquinarine, Listerine, Peroxide, and Chlorhexidine, but the effectiveness of Sangquinarine against bacteria in the oral cavity is unclear. Not only is the treatment effect for periodontal disease more unclear, but it is also more expensive. Listerine has alcohol as its main ingredient and has a slight bacteriostatic effect, but it only has a temporary effect in the oral cavity and may be harmful to tissues when used for a long period of time. There are disadvantages that may appear. In addition, pyroxide, which has recently been added for whitening effect, is toxic to bacteria, but at the same time, it is toxic to human tissue, so not only is there a safety problem, but bacteria resistant to pyroxide sometimes appear in bacteria. In addition, chlorhexidine is known to be the best among the agents known to date as a preventive and treatment agent for periodontal disease in addition to inhibiting plaque formation. However, it causes tissue irritation, discoloration and degeneration, and has side effects such as a particularly strong irritating taste and strong odor. In addition to the problems it presents, it has the disadvantage of not being able to be used for long periods of time for treatment or especially prevention purposes, such as it can cause bacterial hyperplasia and its use in pregnant women is limited due to its carcinogenic properties.

Meanwhile, d-tetrahydropalmatine is an alkaloid compound with a molecular formula of C ₂₁ H ₂₅ NO ₄ and a molecular weight of 355.4. It can be separated from Corydalis genus, such as Corydalis remotafisch, and is known to be soluble in solvents such as DMSO.

Against this background, the present inventors conducted research to derive natural materials that are effective in preventing and improving oral diseases such as dental caries, periodontal disease, toothache, sensitive teeth, and bad breath, without concerns about the above-mentioned side effects. . As a result, D-tetrahydropalmatine is a naturally derived composition that is safe for the body and can be safely used. It has an antibacterial effect on bacteria that cause dental caries and periodontal disease, a PGE2 inhibitory effect, an inhibitory effect on gingivitis formation, an anti-inflammatory effect, and a bad breath effect. By discovering that it exhibits a removal effect, quasi-drug compositions, pharmaceutical compositions, food compositions, and oral compositions using it were completed.

Korean Patent Publication No. 10-2015-0050239

Zhuo Qu et al. Protective effect of tetrahydropalmatine against D-galactose induced memory impairment in rat, 2016, 114-125.

The purpose of the present invention is to provide a quasi-drug composition for preventing or improving oral diseases containing D-tetrahydropalmatine or a pharmaceutically acceptable salt thereof as an active ingredient.

Another object of the present invention is to provide a pharmaceutical composition for preventing or treating oral diseases containing D-tetrahydropalmatine or a pharmaceutically acceptable salt thereof as an active ingredient.

Another object of the present invention is to provide a food composition for preventing or improving oral diseases containing D-tetrahydropalmatine or a foodologically acceptable salt thereof as an active ingredient.

Another object of the present invention is to provide an oral composition containing D-tetrahydropalmatine or an acceptable salt thereof as an active ingredient.

In order to solve the above problems and achieve the object of the present invention, the present invention provides a quasi-drug composition for preventing or improving oral diseases containing D-tetrahydropalmatine or a pharmaceutically acceptable salt thereof as an active ingredient. .

In another aspect of the present invention, a pharmaceutical composition for preventing or treating oral diseases comprising D-tetrahydropalmatine or a pharmaceutically acceptable salt thereof as an active ingredient is provided.

In another aspect of the present invention, a food composition for preventing or improving oral diseases is provided, comprising D-tetrahydropalmatine or a foodologically acceptable salt thereof as an active ingredient.

In another aspect of the present invention, an oral composition containing D-tetrahydropalmatine or an acceptable salt thereof as an active ingredient is provided.

The present invention provides a quasi-drug composition containing D-tetrahydropalmatine or a pharmaceutically acceptable salt thereof as an active ingredient.

In the present invention, “d-tetrahydropalmatine (d-tetrahydropalmatine)” is a member of the genus Corydalis, such as Corydalis remotafisch, which is represented by the above formula (1), has a molecular formula of C ₂₁ H ₂₅ NO ₄ , and a molecular weight of 355.4. It is an organic compound separated into the alkaloid series that can be separated from ( Corydalis ).

The Corydalis remotafisch is the dried tuber of Corydalis remotafisch, a plant of the opium flower family, and other Corydalis remotafisch plants. It is spicy in taste and warm in nature, promotes qi and blood circulation, eliminates stagnant blood, soothes pain, and evenly regulates menstruation.

The present invention is not particularly limited to the method of obtaining D-tetrahydropalmatine, and it can be chemically synthesized by a method known in the art, or a commercially available material can be used.

D-tetrahydropalmatine of the present invention may exist in solvated as well as unsolvated forms. D-tetrahydropalmatine of the present invention may exist in crystalline or amorphous form, and all such physical forms are included within the scope of the present invention.

The present invention provides a quasi-drug composition for preventing or improving oral diseases containing D-tetrahydropalmatine or a pharmaceutically acceptable salt thereof as an active ingredient.

In addition, specifically, the present invention relates to a treatment group consisting of dental caries, periodontal disease (periodontitis or gingivitis), toothache, sensitive teeth, and bad breath containing D-tetrahydropalmatine or a pharmaceutically acceptable salt thereof as an active ingredient. A quasi-drug composition for preventing or improving one or more selected oral diseases can be provided.

In the present invention, “oral disease” refers to various diseases that occur in the oral region, and the oral region refers to the space in the mouth connected to the pharynx from the front lip to the back oral cavity. In the present invention, the oral disease is a concept that includes all diseases that occur in the oral cavity, regardless of the condition, and non-limiting examples of the oral disease include dental caries, periodontal disease (periodontitis or gingivitis), toothache, dry teeth, and bad breath. etc. can be mentioned.

In the present invention, “dental cavities” is an infectious disease caused by bacteria living on the surface of teeth, also called cavities, and shows symptoms of erosion and loss of hard tissue of teeth. Specifically, the milky-white, translucent, hard substance that covers the surface of the head of the tooth and protects the tooth dentin is called tooth enamel or enamel. It is damaged by acids produced when sugar, starch, etc. are broken down by oral pathogens living in the mouth. This means that the enamel of the teeth is damaged, resulting in cavities. The main cause of dental caries is dental plaque, which is a bacterial film formed on the surface of teeth. Saliva forms a thin, sticky film on the teeth, and Streptococcus sobrinus, a type of streptococcus, forms on it. Oral microorganisms such as ( Streptococcus sobrinus ) and Streptococcus mutans attach to form a biofilm, creating dental plaque, which is further thickened by Fusobacterium . Lose. Dental caries of the present invention includes all causative bacteria that cause dental caries regardless of their type, but specifically, Streptococcus mutans , Streptococcus sanguinis , and Streptococcus sobrinus. sobrinus ), Streptococcus ratti , Streptococcus criceti , Streptococcus anginosus , and lactic acid bacteria. More specifically, Streptococcus Could be mutans.

The Streptococcus mutans is a type of streptococcus, a gram-positive bacterium, and is also called a caries bacteria. The Streptococcus mutans grows only on the surface of teeth, and deciduous teeth are not completed until around 30 months of age. Therefore, until this period, it is difficult for mutans bacteria to proliferate like after infancy. If a person is not infected with mutans bacteria from the adult's mouth during infancy and other oral bacteria take up residence in the mouth, it becomes difficult for new mutans bacteria to enter the already balanced oral ecosystem, significantly increasing the probability of developing cavities throughout the life after infancy. It becomes lower. If you have already been infected with the causative bacteria through the mouth of an adult, brushing your teeth frequently and keeping your mouth clean will help prevent cavities. However, once mutans bacteria have established themselves in the oral cavity, eradication of mutans bacteria is impossible.

In one embodiment of the present invention, after inoculating a disk containing D-tetrahydropalmatine into the medium on which Streptococcus mutans was smeared, the size of the growth-inhibiting ring was measured, and the results showed that In the case of the experimental group, the growth-restricted ring diameter was more than 10.0 mm, showing significantly excellent antibacterial activity against Streptococcus mutans, confirming that the composition containing D-tetrahydropalmatine can be used to prevent or improve dental caries ( Table 2).

In the present invention, “periodontal disease” is a disease in which inflammation occurs in the gingiva, periodontal ligament, and bone tissue supporting the teeth. It is also commonly referred to as gum disease, and depending on the degree of the disease, it can be classified into gingivitis and periodontitis. It is divided into It is a relatively mild and fast-recoverable form of periodontal disease. When it is limited to the gums, or soft tissue, it is called gingivitis. When this inflammation progresses to the area around the gums and gum bones, it is called periodontitis. There is a V-shaped gap between the gingiva (gum) and the tooth. When oral pathogens attack the area below the gum line in this groove (sulcus), they release lipopolysaccharide (LPS), a inflammatory irritant, and this causes Inflammation occurs, including swelling and bleeding of the gums, which damages the periodontal ligament and adjacent tissues. As periodontitis progresses, the periodontal ligament and even the alveolar bone are damaged, ultimately leading to tooth loss. Malnutrition such as protein and vitamins, hormonal disorders such as pregnancy or diabetes, smoking, and acquired immunodeficiency syndrome (AIDS) can worsen the disease. Additionally, other causes of periodontal disease include plaque and tartar. The periodontal disease of the present invention includes all causative bacteria that cause periodontal disease, regardless of the type, but specifically, Actinobacillus Actinomycetemcomitans actinomycetemcomitans ), Porphyromonas gingivalis , Tannerella forsythia , Treponema denticola ( Treponema ) denticola ) and Fusobacterium nucleatum ( Fusobacterium nucleatum ) may be one or more species selected from the group consisting of, and more specifically, it may be Porphyromonas gingivalis.

The Porphyromonas gingivalis is a type of Bacteroide flexible bacteria, a Gram-negative bacterium, and an anaerobic bacterium. The Porphyromonas gingivalis is found in the oral cavity where periodontal disease occurs, and is also found in the upper gastrointestinal tract, respiratory tract, and colon. In patients with chronic periodontal disease, collagen is decomposed by the collagenase enzyme of the bacteria, and the bacteria can invade gingival fibroblasts and survive even under high concentrations of antibiotics. Additionally, the bacteria can invade gingival epithelial cells and survive for a long time.

In one embodiment of the present invention, a disk containing D-tetrahydropalmatine was inoculated into a medium on which Porphyromonas gingivalis was smeared, and the size of growth-inhibiting rings was measured. As a result, the D-tetrahydropalmatine was In the case of the experimental group, the diameter of the growth-restricted ring was 10.0 mm or more, showing quite excellent antibacterial activity against Porphyromonas gingivalis, indicating that the composition containing D-tetrahydropalmatine can be used to prevent or improve periodontal disease. Confirmed (Table 2).

In addition, in one embodiment of the present invention, as a result of conducting a clinical experiment by selecting test subjects with gingival inflammation, it was found that the test group using the test group toothpaste containing D-tetrahydropalmatine had an excellent effect of suppressing gingival inflammation. Even after 6 months, normal bleeding was maintained and the effect of suppressing gingival inflammation continued, confirming that the composition containing D-tetrahydropalmatine can be used to prevent or improve periodontal diseases including gingivitis (Table 4 ).

In the present invention, “toothache” refers to pain in the tooth when eating sweet food, or very cold or hot food. Generally, it refers to pain in the tooth itself, as well as pain in the periodontal tissue that supports the tooth to the jawbone. This includes pain. It usually causes pain when chewing, gums swell, and foul-smelling discharge comes out. Toothache causes slightly different pain depending on the cause of the disease. Specifically, the pain caused by dental caries is painless in the beginning, but gradually progresses and pain appears when the nerve inside the tooth is deeply rotted, and in the case of an impacted tooth, inflammation of the tissues around the tooth causes pain. Pain is caused, and when a tooth is broken or cracked, when it touches cold food or bites hard, the tooth splits and irritates the nerve, causing pain. In the case of pulpitis, pain is felt when cold food touches it in the beginning, and in more advanced cases, pain is felt when hot food touches it. As the inflammation progresses and the pulp tissue dies, there is no response to cold or hot things, and the periapex (end of the tooth root) Pain occurs due to inflammation.

In one embodiment of the present invention, as a result of confirming the inhibitory effect of PGE2, known as a pain and inflammation marker, it was confirmed that the experimental group containing D-tetrahydropalmatine exhibited a concentration-dependent inhibitory effect on PGE2 (Figure 1) .

In the present invention, “syrin” refers to teeth with hypersensitive dentine, and “syrin” refers to dentine hyperesthesia. Sensitivity is a symptom in which the exposed dentin of teeth feels sensitive when it comes in contact with cold air or irritating food, and 60 to 98% of adults with periodontal disease show the symptom. Symptoms of sensitive teeth occur when teeth are dented in the gum area due to incorrect tooth brushing habits, excessive bite force, dissolution by acid, poor oral hygiene, after periodontal treatment, after receiving restorative treatment, or when teeth are dissolved due to acidification. It may appear. The fundamental cause of this symptom is that many of the tubules present in the dentin of the tooth are exposed to the outside. Due to this exposure, all stimulation is transmitted directly to the nerves within the pulp, making it more sensitive than usual to the same stimulation and causing pain. there is. Symptoms of sensitive teeth can range from mild symptoms to intense and persistent pain. Due to the nature of teeth, they do not regenerate, so taking painkillers or anti-inflammatory drugs is not a fundamental solution to the sensitive condition. Sensitivity may appear throughout the teeth, or may be limited to specific areas such as the upper or lower jaw, or the right or left side. The most affected area varies depending on the cause, but it is mainly the canines and premolars, and the most painful area in more than 90% of cases is the cervical region, which is the border between the gums and teeth.

In one embodiment of the present invention, as a result of conducting a clinical experiment by selecting test subjects with dentin hypersensitivity teeth, it was found that the test group using the test toothpaste containing D-tetrahydropalmatine had an excellent effect of suppressing the symptoms of sensitive teeth. , it was confirmed that the composition containing D-tetrahydropalmatine can be used to prevent or improve syrin (Table 6).

In the present invention, “bad breath” refers to odor originating from the oral cavity and adjacent organs, and 85 to 90% of bad breath originates from the oral cavity, especially from the back of the tongue. The main components of bad breath are volatile sulfur compounds, and 90% of the total amount of volatile sulfur compounds are hydrogen sulfide made from cysteine, and methyl mercaptan and dimethyl sulfide made from methionine. These ingredients are mainly produced by protein enzymes secreted by anaerobic bacteria, and the back of the tongue is their most important habitat. This area is not cleaned well by saliva and has many small depressions, making it a place where bacteria continue to live. The production of volatile sulfur compounds by anaerobic bacteria is the most important cause of bad breath, but it can also be caused by other oral diseases such as dental caries, periodontitis, and dry mouth. Many types of anaerobic bacteria are involved in causing bad breath, and a non-limiting example of the bacteria causing bad breath is Porphyromonas gingivalis , which secretes many types and large amounts of enzymes.

In one embodiment of the present invention, as a result of conducting a clinical experiment on test subjects without dental caries, the test group using the test group toothpaste containing D-tetrahydropalmatine had an excellent bad breath removal effect, and D- It was confirmed that the composition containing tetrahydropalmatine can be used to prevent or improve bad breath (Table 7).

The quasi-drug composition of the present invention may include a quasi-drug for oral use. The ingredients included in the quasi-drug composition of the present invention are active ingredients and may include ingredients commonly used in oral quasi-drug compositions in addition to the above-mentioned active ingredients, such as abrasives, wetting agents, binders, foaming agents, sweeteners, preservatives, medicinal ingredients, and flavors. It may include agents, pigments, solvents, brighteners, solubilizers, or pH adjusters.

The oral quasi-drug composition of the present invention can be manufactured in any formulation commonly manufactured in the art, for example, toothpaste, mouthwash, mouthwash, gum, candy, oral spray, oral ointment, and oral varnish. , oral rinse, gum massage cream, etc., but is not limited thereto.

As an example, when the oral quasi-drug composition of the present invention is in the form of toothpaste, it may contain a wetting agent, an abrasive, a binder, a foaming agent, a flavoring agent, a sweetening agent, a coloring agent, a preservative, a medicinal ingredient, a solvent, a pH adjuster, etc.

The humectant is used to make the powder among the toothpaste ingredients into a paste and to prevent the toothpaste from solidifying in the air. It is made of glycerin, sorbite solution, propylene glycol, polyethylene glycol, etc., alone or in combination of two or more, in an amount of 1 to 60 weight of the total weight of the composition. %, specifically 10 to 50 wt% can be used.

The foaming agent increases the cleaning effect by diffusing the toothpaste in the oral cavity and acts as a surfactant to clean oral contamination. It is made up of surfactants such as sodium lauryl sulfate, sodium lauryl sarcosate, sodium alkyl sulfosuccinate, and sucrose fatty acid ester. Alternatively, two or more types may be mixed and used in an amount of 0.5 to 10% by weight, specifically 0.5 to 5% by weight, of the total weight of the composition.

The binder prevents separation between the powder and liquid components in the toothpaste and is made by combining cellulose derivatives such as sodium carboxymethylcellulose, methylcellulose, and hydroxypropylcellulose with sodium alginate, carrageenan, and xanthan gum, either alone or in combination of two or more types. It can be used in an amount of 0.1 to 5% by weight, specifically 0.3 to 2% by weight, of the total weight of the composition.

The abrasive removes attachments from the tooth surface without damaging the tooth surface and gives the tooth its original shine. It contains calcium carbonate (CaCO ₃ ), dicalcium phosphate (CaHPO ₄ , CaHPO ₄ 2H ₂ O), and silicic acid anhydride (SiO ₂ 2H ₂ O), aluminum hydroxide (Al(OH) ₃ ), potassium pyrophosphate, magnesium carbonate, etc., alone or in a mixture of two or more, in an amount of 1 to 60% by weight, specifically 10 to 50% by weight, of the total weight of the composition. You can use it.

The flavoring agent is intended to enhance the feeling of use by giving a refreshing feeling and smell to the toothpaste. Peppermint oil, spearmint oil, menthol, etc. are used alone or in a mixture of two or more types, and are used in an amount of 1 to 60% by weight of the total weight of the composition, specifically 0.01 to 0.01% by weight. 5% by weight can be used.

The sweetener is intended to remove the unpleasant taste caused by toothpaste raw materials and improve the refreshing feeling, and is composed of saccharinic acid, aspartame, xylitol, licorice acid, etc. alone or in a mixture of two or more types, 1 to 60% by weight of the total weight of the composition, specifically. 0.01 to 5% by weight can be used.

The medicinal ingredients are used to prevent dental caries, prevent periodontal disease, prevent toothache, prevent sensitive teeth, and remove bad breath, and include fluoride, zinc chloride, chlorhexidine, aminocaproic acid, tranexamic acid, cetylpyridium chloride, pyridoxine chloride, Triclosan, tocopherol acetate, sodium monofluorophosphate, etc. can be used alone or in combination of two or more. In the present invention, D-tetrahydropalmatine can be used as an additional medicinal ingredient.

The oral quasi-drug composition of the present invention can be used alone or in combination, or can be used in combination with other oral quasi-drug compositions other than the present invention.

In another aspect of the present invention, a pharmaceutical composition comprising D-tetrahydropalmatine or a pharmaceutically acceptable salt thereof as an active ingredient is provided. In addition, specifically, the present invention provides a pharmaceutical for preventing or treating one or more oral diseases selected from the group consisting of dental caries, periodontal disease (periodontitis or gingivitis), sensitive teeth, and bad breath, containing D-tetrahydropalmatine as an active ingredient. A composition can be provided. D-tetrahydropalmatine, oral disease, dental caries, periodontal disease, dry teeth, and bad breath are as described above.

The pharmaceutical composition of the present invention is administered in the form of tablets, pills, powders, granules, capsules, suspensions, oral solutions, emulsions, syrups, aerosols, sterilized injectable solutions, etc. according to conventional methods for preventing and treating oral diseases. Formulation is possible.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations are prepared by mixing at least one excipient, such as starch, calcium carbonate, sucrose, lactose, gelatin, etc. It can be. Additionally, in addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid preparations for oral administration include suspensions, oral solutions, emulsions, syrups, etc. In addition to the commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives are included. can be used

Preparations for parenteral administration may include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, suppositories, etc. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate.

Additionally, the pharmaceutical composition of the present invention may further include a carrier, excipient, or diluent. Carriers, excipients or diluents include lactose, textrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, hydroxyl. Propyl methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, silicon dioxide, etc. can be used. there is.

The specific dosage of the pharmaceutical composition according to the present invention depends on factors such as formulation method, patient's condition and weight, patient's gender, age, degree of disease, drug form, administration route and period, excretion rate, reaction sensitivity, etc. It can be selected in various ways by those skilled in the art, and the dosage and frequency of administration do not limit the scope of the present invention in any way.

The pharmaceutical composition of the present invention can be administered to mammals such as rats, mice, livestock, and humans through various routes. All modes of administration are contemplated and may be administered, for example, by oral, intravenous, intramuscular or subcutaneous injection.

In another aspect of the present invention, the present invention provides a food composition containing the D-tetrahydropalmatine or a foodologically acceptable salt thereof as an active ingredient. In addition, specifically, the present invention provides a food for preventing or improving one or more oral diseases selected from the group consisting of dental caries, periodontal disease (periodontitis or gingivitis), sensitive teeth, and bad breath, containing D-tetrahydropalmatine as an active ingredient. A composition may be provided. D-tetrahydropalmatine, oral disease, dental caries, periodontal disease, dry teeth, and bad breath are as described above. The food composition may be used in the form of a health functional food, but is not limited thereto.

The D-tetrahydropalmatine or a foodologically acceptable salt thereof contained in the food composition of the present invention may be contained in the form of animals or plants containing D-tetrahydropalmatine, extracts thereof, fractions thereof, or processed products thereof. Additionally, the composition may include food additives that are foodologically acceptable in addition to the active ingredients.

In the present invention, “food supplement” refers to a component that can be added to food as an auxiliary ingredient, and can be appropriately selected and used by a person skilled in the art as it is added to manufacture each type of health functional food. Examples of food supplements include various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic and natural flavors, colorants and fillers, pectic acid and its salts, alginic acid and its salts, organic acids, and protective colloidal thickeners. , pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc., but the types of food supplements of the present invention are not limited to the above examples.

The food composition of the present invention may include health functional foods. In the present invention, “health functional food” refers to food manufactured and processed in the form of tablets, capsules, powders, granules, liquids, and pills using raw materials or ingredients with functional properties useful to the human body. Here, “functionality” means controlling nutrients for the structure and function of the human body or obtaining useful effects for health purposes, such as physiological effects. The health functional food of the present invention can be manufactured by a method commonly used in the art, and can be manufactured by adding raw materials and components commonly added in the art. Additionally, the formulation of the health functional food can also be manufactured without limitation as long as it is a formulation recognized as a health functional food. The food composition of the present invention can be manufactured in various types of formulations, and unlike general drugs, it is made from food as a raw material and has the advantage of not having side effects that may occur when taking the drug for a long period of time. It is also excellent in portability and can be used as a pharmaceutical composition according to the present invention. Health functional foods can be consumed as supplements to prevent or improve oral diseases.

There is no limit to the form that the health functional food of the present invention can take, and it can include all foods in the conventional sense, and can be used interchangeably with terms known in the art, such as functional food. In addition, the health functional food of the present invention can be manufactured by mixing known additives with other appropriate auxiliary ingredients that can be included in the food according to the selection of a person skilled in the art. Examples of foods that can be added include meat, sausages, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, and There are vitamin complexes, etc., and it can be manufactured by adding it to juices, teas, jellies, juices, etc. prepared using D-tetrahydropalmatine according to the present invention as a main ingredient. It also includes foods used as feed for animals.

The quasi-drug composition containing D-tetrahydropalmatine or a pharmaceutically acceptable salt thereof of the present invention as an active ingredient is excellent in preventing or improving oral diseases. Specifically, the composition of the present invention has excellent antibacterial activity against bacteria that cause dental caries and periodontal disease, suppresses PGE2, a pain and inflammation marker, in a concentration-dependent manner, has an effect of suppressing gingivitis formation, an effect of suppressing symptoms of cold teeth, and an effect of removing bad breath. It is excellent and has high utility as a quasi-drug composition for preventing or improving one or more oral diseases selected from the group consisting of dental caries, periodontal disease, sensitive teeth, and bad breath. Additionally, the composition containing D-tetrahydropalmatine of the present invention can be used as a pharmaceutical composition and a food composition.

The following drawings attached to this specification illustrate preferred embodiments of the present invention, and serve to further understand the technical idea of the present invention along with the contents of the above-described invention. Therefore, the present invention is limited to the matters described in such drawings. It should not be interpreted in a limited way.
Figure 1 shows the results of confirming the PGE2 inhibitory effect by treating macrophages with LPS (control group), an inflammatory stimulus, and LPS and D-tetrahydropalmatine (experimental group), respectively.

Hereinafter, the configuration and effects of the present invention will be described in more detail through examples and experimental examples. These examples and experimental examples are only for illustrating the present invention and the scope of the present invention is not limited by these examples and experimental examples.

Experiment example One : dental caries and antibacterial effect against periodontitis-causing bacteria

An antibacterial activity experiment was performed to confirm the preventive or therapeutic effect of D-tetrahydropalmatine on dental caries and periodontitis. To confirm the effect of inhibiting the growth of oral pathogens, the antibacterial activity was tested using the paper disk test using Streptococcus mutans, a major cause of dental caries, and Porphyromonas gingivalis , a common cause of periodontal disease. was carried out.

After increasing the activity of each of the oral pathogens under the optimal culture conditions shown in Table 1 below, the turbidity of the culture medium was increased by culturing the bacteria in the optimal medium for about 4 to 6 hours using Macfarland turbidity No. It was adjusted to 0.5 ( ^1.5 Afterwards, the D-tetrahydropalmatine was inoculated onto the sterilized paper disc at a concentration of 10 mg/disc and allowed to absorb and dry for 1 hour. Then, after culturing each oral pathogen at the optimal temperature for 24 to 48 hours, the size (diameter mm) of the growth-inhibiting rings was measured, and the results are shown in Table 2 below.

strain optimal conditions Gram stain
(Gram staining) Strain name temperature badge characteristics Gram (+) Streptococcus mutans 37 BHI facultative anaerobic Gram (-) Porphyromonas gingivalis 37 TSA Hemin Menadione Badge anaerobic

Result of measuring antibacterial activity of D-tetrahydropalmatine against oral pathogens Growth retardation ring diameter (mm) Streptococcus mutans Porphyromonas gingivalis Untreated - (Growth is not inhibited) - (Growth is not inhibited) D-tetrahydropalmatine treatment 10.6 10.1

As shown in Table 2, when compared to the untreated group that was not treated with D-tetrahydropalmatine, the group treated with D-tetrahydropalmatine had a growth inhibition ring diameter for the two types of oral pathogens. Above 10.0 mm, it showed quite excellent antibacterial activity against Streptococcus mutans and Porphyromonas gingivalis. Therefore, it was found that D-tetrahydropalmatine can be used to prevent or treat dental caries or periodontal disease.

Experiment example 2: Gingivitis formation inhibition effect

In order to confirm the effectiveness of D-tetrahydropalmatine in preventing or treating gingivitis, a clinical experiment was conducted by selecting a test subject group.

First, sodium carboxymethyl cellulose, sodium lauryl sulfate, glycerin, colloidal silicon dioxide, silica, sodium cocoyl isethionate, dodicine, and sweeteners, fragrances, and colorants, which are commonly used in the manufacture of toothpaste, are used. A control toothpaste was prepared, and an experimental group toothpaste was prepared by containing 0.01% by weight of D-tetrahydropalmatine in the control toothpaste.

In order to select experimental subjects, a detailed oral examination was conducted on 30 patients by gender at 10-year intervals from 30 to 50 years old, targeting gingival inflammation patients with even dentition and no missing teeth. Then, a group of 120 experimental subjects was selected. After selection, 60 people were divided into groups and a clinical experiment on the effectiveness of treating gingival inflammation was performed as follows.

Specifically, the experimental group was divided into a control group and an experimental group, and the control group was taught to use the prepared control toothpaste 3 times a day 2 hours after eating and before going to sleep, and the experimental group was taught to use the prepared experimental group toothpaste 3 times a day at the same time. trained to do so. Afterwards, dental cleaning was performed to score the initial gingivitis index, the control group used the control toothpaste prepared above, and the experimental group used the experimental group toothpaste prepared above, and oral examinations were performed after 1 week, 1 month, 3 months, and 6 months. Gingivitis index was tested. The method of measuring the gingivitis index is to insert a periodontal probe into the gingival sulcus and probe around each tooth without applying force. After 30 seconds, the bleeding condition is measured and measured according to the standards shown in Table 3 below. The scores were recorded accordingly, and the results are shown in Table 4.

Gingivitis index criteria score detail 0 points No bleeding state 1 point normal bleeding condition 2 points Linear hemorrhage condition 3 points Triangular bleeding condition in the interproximal area 4 points Gingival bleeding condition

Gingival inflammation inhibition effect hour control group experimental group 0 weeks 1.04 1.04 1 week 1.59 1.05 1 month 2.62 1.05 3 months 2.75 1.05 6 months 2.84 1.06

As shown in Table 4, compared to the control group, the experimental group using toothpaste containing D-tetrahydropalmatine maintained normal bleeding even after 6 months, and the effect of suppressing gingival inflammation continued. Therefore, it was found that D-tetrahydropalmatine can be used to prevent or treat gingivitis.

Experiment example 3: Pain and inflammation marker PGE2 inhibitory effect

In order to confirm the effectiveness of D-tetrahydropalmatine in preventing or treating toothache, the inhibitory effect of PGE2, known as a pain and inflammation marker, was confirmed.

First, macrophages were inoculated at ^a concentration _of 1.5 Then, LPS 1㎍/ml and D-tetrahydropalmatine, which are inflammation-inducing stimuli, were treated at different concentrations and cultured for 24 hours. Then, a PGE2 ELISA assay kit (Thermo SCIENTIFIC) was purchased and D-tetrahydropalmatine was incubated using the supernatant. PGE2 inhibitory ability was analyzed according to Martin concentration (Figure 1).

As shown in Figure 1, compared to the group treated only with LPS, D-tetrahydropalmatine at a concentration of 2ppm inhibits PGE2 by about 50%, and D-tetrahydropalmatine at a concentration of 20ppm inhibits PGE2 by about 80%. It was found to be effective.

Experiment example 4 : Sirin inhibitory effect

In order to confirm the effectiveness of D-tetrahydropalmatine in preventing or treating sensitive teeth, a clinical experiment was conducted by selecting test subjects. The control and experimental group toothpastes used in the clinical experiment were prepared in the same manner as the toothpaste in Experimental Example 2. Each was manufactured.

The test subjects were 40 volunteers who had dentine hypersensitivity teeth and agreed to participate in this experiment, and the total number of teeth subject to the test was 80. Additionally, among the test subjects, there were 20 men and 20 women, and their ages ranged from 20 to 50 years old. The test subjects were kept unaware of the contents of the toothpaste, and the total experiment period was 2 weeks.

The experiment was conducted by measuring the subject's response after applying a temperature stimulus. Before conducting the experiment, the hypersensitive area of the dentin hypersensitivity tooth of each test subject was checked in advance, and cold water at about 5°C was dropped with a dropper on the sensitive area of the tooth, and the control group was evaluated according to the standards shown in Table 5 below. The control group toothpaste and the experimental group were made to use the test group toothpaste 3 times a day for 2 weeks, and after 2 weeks, cold water at about 5°C was again added using a dropper to score the test group toothpaste. For statistical processing, the stimulus scores before and 2 weeks after the experiment were tested using a paired Student-t test, and the response scores to the temperature stimulus after 2 weeks are shown in Table 6 below.

Subject's rating criteria after stimulation score detail 0 points There is no discomfort. 1 point Slightly uncomfortable or cold. 2 points very cold 3 points sick.

Degree of suppression of irritability hour control group experimental group 0 weeks 2.15±0.17 2.13±0.15 2 weeks 2.15±0.13 1.82±0.13 p>0.05 *p<0.05

※ p>0.05: 95% confidence, no statistically significant difference. *p<0.05: 95% confidence, statistically significant difference.

As shown in Table 6, compared to the control group, the experimental group using toothpaste containing D-tetrahydropalmatine had suppressed tooth sensitivity after 2 weeks. Therefore, it was found that D-tetrahydropalmatine can be used to prevent or treat syrinx.

Experiment example 5: Bad breath removal effect

In order to confirm the effectiveness of D-tetrahydropalmatine in preventing or treating bad breath, a clinical experiment was conducted by selecting test subjects, and the control and experimental group toothpastes used in the clinical experiment were prepared in the same manner as the toothpaste in Experimental Example 2. Manufactured.

Fifty men and women without dental caries were selected as test subjects, and a cross-over test was conducted on the control group toothpaste and the experimental group toothpaste. Commercially available garlic powder was dispersed in water and left for 24 hours, then diluted to obtain a Halimeter measurement value of 700 ppb or more, and the diluted solution was used as a bad breath inducer. The test subjects gargled with 15 ml of garlic powder dilution for 30 seconds, and after 1 minute, measured the degree of bad breath with a halimeter. The control group used the control toothpaste and the experimental group brushed their teeth for 30 seconds to 1 minute using the test group toothpaste. . The degree of bad breath was measured with a halimeter 1 minute, 5 minutes, and 30 minutes after brushing teeth to determine whether bad breath suppression was sustainable. The results are shown in Table 7 below.

Bad breath removal effect hour control group experimental group 1 min 56.6% 96.7% 5 minutes 50.0% 85.0% 30 minutes 45.9% 79.9%

As shown in Table 7, compared to the control group, the experimental group using toothpaste containing D-tetrahydropalmatine had more than 96% of bad breath removed after brushing their teeth, and the bad breath removal rate was about 80% even 30 minutes after brushing their teeth. The bad breath removal effect was significantly superior to that of the control group. It was found that D-tetrahydropalmatine can be used to prevent or treat bad breath.

Claims (13)

A quasi-drug composition for preventing or improving oral diseases containing d-tetrahydropalmatine or a pharmaceutically acceptable salt thereof as an active ingredient,
A quasi-drug composition in which the oral disease is dental caries, periodontal disease, dry teeth, or bad breath.
delete The quasi-drug composition of claim 1, wherein the dental caries is caused by Streptococcus mutans.
delete The quasi-drug composition of claim 1, wherein the periodontal disease is periodontitis or gingivitis.
The quasi-drug composition of claim 1, wherein the periodontal disease is caused by Porphyromonas gingivalis .
delete delete The quasi-drug composition according to claim 1, wherein the quasi-drug is for oral use.
The method of claim 9, wherein the formulation of the quasi-drug composition is one or more formulations selected from the group consisting of toothpaste, mouthwash, mouthwash, gum, candy, oral spray, oral ointment, oral varnish, oral rinse, and gum massage cream. A quasi-drug composition.
A pharmaceutical composition for preventing or treating oral diseases containing d-tetrahydropalmatine or a pharmaceutically acceptable salt thereof as an active ingredient,
A pharmaceutical composition wherein the oral disease is dental caries, periodontal disease, dry teeth, or bad breath.
A food composition for preventing or improving oral diseases containing d-tetrahydropalmatine or a foodologically acceptable salt thereof as an active ingredient,
A food composition wherein the oral disease is dental caries, periodontal disease, dry teeth, or bad breath.


delete