KR20160014356A - Composition for the prevention or treatment of periodontal disease comprising extract of Siegesbeckiae herbs - Google Patents

Abstract

Provided in the present invention is a composition for preventing, treating or mitigating periodontal diseases, comprising an extract of Sigesbeckia glabrescens Makino as an active component. The composition comprising the extract of Sigesbeckia glabrescens Makino as an active component of the present invention induces diffraction of periodontal cells, increases mineralization of bones, regenerates alveolar bones, and promotes anti-inflammation and anti-bacterial effects, thereby being effective to treatment and prevention of periodontal diseases.

Description

TECHNICAL FIELD The present invention relates to a composition for preventing or treating periodontal disease,

The present invention relates to a composition comprising an excipient extract for preventing or treating periodontal disease as an active ingredient.

The teeth are the hardest hard tissue in the human body and are supported on the alveolar bone. The alveolar bone is firmly attached to the base bone of the jaw, and the 2-3 mm portion immediately adjacent to the root is called a periodontal bone, but the alveolar bone generally refers to both the hard tissue including the periodontal bone. Alveolar bone is gradually lowered with age, and tooth root is exposed. In addition, when the tooth is lost, the alveolar bone gradually disappears. These oral alveolar bone attaches and supports the teeth by a layer of undifferentiated mesenchymal cells called periodontal ligaments with an average thickness of about 0.2 mm and distributes the force to the alveolar bone so that the teeth can buffer during food chewing And the sense of teeth is transmitted to the alveolar bone through the periodontal ligament. In addition, periodontal ligaments are structured to adapt to pressure, continuing bone remodeling, without destroying the structure and function of the entire fiber, continuing to layers of undifferentiated mesenchymal cells. Undifferentiated mesenchymal cells in periodontal ligaments are moved to adjacent tissues, moving to the alveolar bone to perform alveolar bone remodeling and, on the other hand, move to the teeth to produce collagen fibers, which are constantly modified to hold the teeth more tightly. These teeth are allied with osteoblast-induced bone formation and osteoclast-induced bone resorption in the alveolar bone, and are maintained in balance through continuous remodeling.

Periodontal diseases include gingivitis and periodontitis, which affect teeth and gingiva supporting the teeth. Gingivitis is an early periodontal disease that causes inflammation of the soft tissues of the gingiva, and its symptoms are relatively light and the recovery is reversible. Periodontitis is a condition in which gingivitis is not treated and the inflammation progresses to the gums and around the pubic bone. When the chronic inflammatory reaction stimulated by the bacterial toxin develops, the periodontal pocket is formed between the gums and the teeth and the periodontal pocket is formed. Deepening of the depth of the periodontal ligament results in inflammation of the periodontal ligament and bone loss. In addition, osteoblast-induced osteoblast-induced osteoblast-induced osteoblast-like metabolism by osteoblast-like cells causes osteoblast-like disorders such as osteoporosis when bone mass exceeds bone formation due to various factors.

Treatment of periodontal disease has been based on the establishment of improved oral hygiene in patients, non-surgical or surgical calculus removal, root resorption, gingival curettage, and regeneration of periodontal tissue using neoadjuvant. However, these surgical treatment methods are difficult to treat, effective treatment is difficult, and the disease is limited to the treatment that is performed when the disease progresses rather than the prevention, and most cases are chronic when not treated. In addition, systemic antibiotics and local sustained release agents have been used as adjunctive therapies. However, excessive release of drugs to unnecessary sites has resulted in side effects, and a case in which periodontal disease bacteria showing resistance to recently used antibiotics have been isolated It is reported that it has a serious problem. In addition, periodontal disease is characterized by multiple factors such as loss of alveolar bone, inflammation, and periodontitis bacteria such as Jinji valis unlike general inflammation and arthritis. Therefore, periodontal disease is caused by antibacterial and anti-inflammatory, Although a complex treatment method is required, there is no developed drug or therapeutic method for such treatment.

Under such circumstances, it is necessary to develop a drug or a therapeutic agent capable of effectively treating periodontal disease.

KR 10-2013-0128953, 2013.11.27 KR 10-1354923, 2014.01.17

The present invention provides a composition for the prevention or treatment of periodontal disease, which comprises the extract as an active ingredient. The present invention also provides a composition for oral administration for the prevention and treatment of periodontal disease, which comprises the extract as an active ingredient. The present invention also provides a health functional food for preventing or ameliorating periodontal disease, which comprises as an active ingredient a wholesome extract.

The inventors of the present invention have found that, in the course of research to develop a natural medicinal composition having a therapeutic and preventive effect on periodontal disease, the present invention has a remarkable effect on the treatment and prevention of periodontal disease and completed the present invention.

The extract of the present invention has no side effects and is a preventive and therapeutic agent for periodontal disease using a safe natural agent,

In order to accomplish the above object, the present invention provides a pharmaceutical composition for preventing or treating periodontal disease, which comprises a whitening extract as an active ingredient.

The pharmaceutical composition for the prevention or treatment of periodontal disease containing the extract of Helianthus as an active ingredient according to the present invention is effective for prevention and treatment of periodontal disease through the enhancement of mineralization by the increase of alkaline phosphatase and the anti- I have.

In the present invention, the scarlet yarn is obtained from Siegesbeckia pubescens Makino , or Siegesbeckia glabrescenes Makino , which may be purchased or taken directly. The scorpion according to one embodiment of the present invention is the Siegesbeckia glabrescenes Makino . It is widely distributed in Korea, Japan, China, etc., and it is easy to secure raw materials at low cost. As the appearance characteristic of the scion, the stem of the ground part is squared, branch is divided, length is 30cm to 60cm, diameter is 0.3cm to 1cm. Outer surface is yellowish brown with many white hairs. The folded side is white and green, the inside is wide white and empty. Leaves are opposite and shrunk, but when they look straight they are egg-shaped or have a triangular egg-shaped tip and sharp ends. The upper surface is light green with 3 rows of veins clearly and hairs on the underside veins closely.

In the present invention, periodontal disease includes gingivitis, periodontal inflammation, alveolar bone breakage, or alveolar bone osteodystrophy, and is preferably periodontitis. In addition, the alveolar bone formation disorder includes alveolar bone osteoporosis, alveolar bone osteomalacia, or alveolar bone osteopenia.

In the present invention, prevention or treatment of periodontal disease may be due to mineralization enhancement, antibacterial activity, and anti-inflammatory effect in the alveolar bone.

In the present invention, the extraction method such as hot water extraction, immersion extraction, reflux cooling extraction and ultrasonic extraction can be used. The number of times of extraction is preferably 1 to 5 times, more preferably 3 times, but is not limited thereto. It is preferable to use a vacuum decompression concentrator or a vacuum rotary evaporator for the decompression concentration, but the present invention is not limited thereto. The extract is extracted in liquid or powder form by such concentration. The excipient extract may be obtained by extracting with an extraction solvent selected from the group consisting of water, an alcohol having 1 to 4 carbon atoms, and an aqueous solution of an alcohol having 1 to 4 carbon atoms. Preferably, the extraction solvent may be an aqueous ethanol solution, more preferably a 40 to 90% aqueous ethanol solution. The extraction with the aqueous ethanol solution can be carried out at room temperature for 1 to 7 days, preferably for 3 days. It may also be carried out under shading and / or warming (e.g., warming) conditions, if desired. The amount of the extraction solvent is 2 to 15 times the dry weight of the recycled solvent. The excipient extract of the present invention has an amount of 0.1 wt% to 95 wt% with respect to the total weight of the excipient extract.

The pharmaceutical composition of the present invention may further include a pharmaceutically acceptable additive. Examples of the pharmaceutically acceptable additives include starch, gelatinized starch, microcrystalline cellulose, lactose, povidone, colloidal silicon dioxide, calcium hydrogen phosphate, Wherein the starch is selected from the group consisting of lactose, mannitol, sugar, arabic gum, pregelatinized starch, cornstarch, powdered cellulose, hydroxypropyl cellulose, opaques, sodium starch glycolate, carnauba wax, synthetic aluminum silicate, stearic acid, magnesium stearate, Calcium, white sugar, dextrose, sorbitol and talc may be used.

The pharmaceutically acceptable excipient according to the present invention is preferably contained in an amount of 0.1 to 90 parts by weight based on 100 parts by weight of the excipient extract, but is not limited thereto.

That is, the pharmaceutical composition of the present invention can be administered in various formulations of oral and parenteral administration in actual clinical administration. In the case of formulation, a diluent such as a filler, an extender, a binder, a wetting agent, a disintegrant, May be formulated using excipients. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose, , Lactose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate talc may also be used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions and syrups, and various excipients such as wetting agents, sweetening agents, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are commonly used simple diluents . Formulations for parenteral administration may include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, and freeze-drying agents. Propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used as the non-aqueous solvent and suspension agent.

The pharmaceutical composition of the present invention may be orally administered or parenterally administered according to the desired method, and may be administered orally or parenterally in the case of parenteral administration by external or intraperitoneal injection, rectal injection, subcutaneous injection, intravenous injection, intramuscular injection, It is desirable to select the method. The dosage varies depending on the patient's body weight, age, sex, health condition, diet, administration time, administration method, excretion rate, and disease severity.

The dosage of the pharmaceutical composition of the present invention varies depending on the patient's body weight, age, sex, health condition, diet, administration time, administration method, excretion rate and severity of disease, Kg, preferably 0.01 to 100 mg / kg, and can be administered 1 to 6 times a day.

The present invention provides an oral composition for the prevention and improvement of periodontal disease, which comprises an excipient extract as an active ingredient.

As used herein, "oral composition" is a composition which is put into oral form with mineralization enhancement, antibacterial and anti-inflammatory effects in alveolar bone. In the oral composition of the present invention, the formulations may be formulated into, for example, films, toothpastes, mouthwashes, ointments, sprayings, dressing solutions, coatings, dental floss or periodontal pouches.

The oral composition of the present invention may contain an excipient extract as an active ingredient and may further contain a wetting agent, a foaming agent, a preservative, a sweetening agent, a thickening agent, a water-soluble polymer, a perfume and other components. The additive according to the present invention is preferably contained in an amount of 0.1 to 90 parts by weight based on 100 parts by weight of the excipient extract, but is not limited thereto.

The wetting agent may be at least one selected from the group consisting of polyhydric alcohols such as glycerin, sorbitol solution, amorphous sorbitol solution, polyethylene glycol and propylene glycol as a component for suppressing the evaporation of water in the oral composition.

The foaming agent has an effect of emulsifying or solubilizing a water-soluble component and an oil-soluble component in the composition, and has a cleaning effect in the oral cavity. Examples of the foaming agent include sodium lauryl sulfate, sodium N-lauroylsartocate, N- Anionic surfactants such as sucrose fatty acid esters, polyoxyethylene hydrogenated castor oil, sorbitan fatty acid esters, polyoxyethylene polyoxypropylene copolymers, and the like may be mixed and used.

The preservative is a component for prolonging the preservation period, and methyl paraoxybenzoate, benzoic acid, sodium benzoate and the like can be used.

The sweetener and / or fragrance may be saccharin sodium, aspartame, stevioside, licorice acid, and the like. Examples of the sweetener include peppermint, spearmint oil, Menthol, carbo- nons, anethole, and augenol.

The thickening agent is a component which prevents phase separation depending on time by combining the water-insoluble inorganic powder component and the liquid component in the composition and gives a viscosity to the composition. Examples of the component include carboxymethyl cellulose (CMC), carrageenan, sodium alginate, Rubber, xanthan gum, other gums and the like may be mixed and used.

The water-soluble polymer may be selected from the group consisting of hydroxypropyl cellulose-Klucel (TM), hydroxypropyl methylcellulose, hydroxyethyl cellulose, ethyl cellulose, carboxymethylcellulose, dextran Dextran, gaur-gum, polyvinyl pyrrolidone (PVP), pectins, starches, gelatin, casein, sodium alginate, polyethlyene glycol, , Polyvinyl glycol, and the like may be used in combination.

As other additives, stabilizers such as sodium citrate for pH control, fluorinating agents having a cavity inhibiting function, astringent agents such as zinc chloride, and food colors such as blue No. 1 can be used.

The present invention also provides a health functional food for preventing or ameliorating periodontal disease, which contains an ori extract as an active ingredient.

The excipient extract of the present invention can be added as it is or can be used together with other food or food ingredients, and can be suitably used according to conventional methods.

There is no particular limitation on the kind of the food. Examples of the foods to which the extract of the present invention can be added include dairy products including meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen and other noodles, gums and ice cream, various soups, drinks, tea, , An alcoholic beverage and a vitamin complex, and includes all the health foods in a conventional sense.

In addition to the above, the excipient extract of the present invention may further contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acids and salts thereof, alginic acid and its salts, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, , A carbonating agent used in carbonated drinks, and the like. In addition, the extract according to the present invention may contain flesh for the production of natural fruit juice, fruit juice drink and vegetable drink. These components may be used independently or in combination.

The composition comprising the excipient extract of the present invention as an active ingredient induces differentiation of periodontal cells, promotes mineralization of bone, regenerates alveolar bone, promotes anti-inflammatory and antibacterial effects, .

FIG. 1 shows the result of measuring the activity (ALP) of alkaline phosphatase, which is an osteoblast differentiation marking factor, by treating the extract with the extract.
Fig. 2 shows the result of measuring the mineralization activity by treating the extract with the excipient.

Advantages and features of the present invention and methods of achieving them will become apparent with reference to the embodiments described in detail below. The present invention may, however, be embodied in many different forms and should not be construed as being limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. Is provided to fully convey the scope of the invention to those skilled in the art, and the invention is only defined by the scope of the claims.

< Manufacturing example > Recruitment  Preparation of extract

After removing the impurities by washing with water flowing through the scion (Origin: Made in China, Purchaser: Chinese herbal medicine market (http://www.hanyakjae.net/)), 6 L of 70% ethanol aqueous solution was added to 600 g of scalding, And extracted with stirring. The above procedure proceeded to 3-batch. The obtained extract was collected and concentrated under reduced pressure at 40 DEG C or lower to obtain 41 g (yield: 6.8%) of an extract-type extract.

< Example  1> Recruitment  Alkaline phosphatase activity by extract treatment Alkaline  포스화제 activity ) Confirm

The effect of alkaline phosphatase activity induction on the treatment with oryzae extract was confirmed, and the effect of preventing or treating periodontal disease was examined by the effect of promoting osteoblast differentiation and mineralization.

Human periodontal ligament cells (Periodontal ligament progenitor cells (PDLC) ) with 10% FBS (fetal bovine serum; FBS), 100 IU / ml penicillin and 100 ug / ml streptomycin into the DMEM medium is added 5% CO ₂ , And cultured in a cell incubator under the condition of 37 캜. The cultured cells were treated at a concentration of 1 × 10 ⁵ cells / ml in a 24-well plate and cultured in a cell incubator for 24 hours.

To investigate the alkaline phosphatase activity of periodontal ligament cells, the extracts were supplemented with 0.1, 1, 10, and 100 μg / ml of the extract extracts and then cultured for 72 hours. To measure alkaline phosphatase activity, the medium was removed from the plate, washed three times with PBS, and 50 μl of 0.15% Triton X-100 was added thereto, followed by lysis in a 37 ° C incubator for 30 minutes. After centrifugation at 3,000 rpm for 5 minutes, 40 μl of supernatant, 40 μl of 0.1 N glycine, and 20 μl of 100 mM p-nitrophenylphosphate (p-NPP) were added and reacted for 30 minutes at 37 ° C. After the reaction, 50 μl of 0.1 N NaOH was added to stop the reaction, and the absorbance at 405 nm was measured to calculate the amount of p-NPP converted to p-nitrophenol (p-NP) by ALP enzyme. The results are shown in Fig. (In Fig. 1, * indicates p-value < 0.05, ** indicates p-value < 0.01, *** indicates p-value < 0.001)

As shown in Fig. 1, it was confirmed that the activity of alkaline phosphatase, which is an index of periodontal ligament cell differentiation, increases in a concentration-dependent manner. In other words, it was confirmed that the extract from the extract was effective in the prevention and treatment of periodontal disease by inducing an increase in activity of alkaline phosphatase.

< Example  2> Mineralization activity  Confirm

The periodontal ligament cells produce calcium and release it outside the cell. In the culture medium for periodontal ligament cells, mineralization occurs in which calcium accumulates around the cells. In this regard, it was evaluated whether or not the excipient extract of the present invention increased the mineralization of periodontal ligament cells.

Human periodontal ligament cells (Periodontal ligament progenitor cells (PDLC) ) with 10% FBS (fetal bovine serum; FBS), 100 IU / ml penicillin and 100 ug / ml streptomycin into the DMEM medium is added 5% CO ₂ , And cultured in a cell incubator maintained at 37 ° C. The cultured cells were subcultured in a 24-well plate at 1 × 10 ⁵ cells / ml and cultured in the cell incubator for 24 hours.

The periodontal ligament cells were activated by adding ascorbic acid and beta-glycerophosphate, known to activate periodontal ligament cells, to the medium at concentrations of 50 μg / ml and 10 mM, respectively. The activated cells were divided into two groups. No substance was added to the first group (control group), and the second group was further divided into three groups, with 1 μg / ml for the 2-1 group and 5 μg for the 2-2 group / ml, and in the group 2-3, 10 μg / ml of the extract extract was added to the culture medium. The medium was replaced with a medium containing the above extract at intervals of 3 days and cultured for 24 days.

After each cell was fixed with 10% neutral formaldehyde solution, it was treated with Alizarin red-S staining solution for 5 minutes and washed to determine whether or not a red calcified nodule was formed on the naked eye. Respectively. After confirming nodule formation, 10 mM sodium phosphate (10% cetylpyridinium chloride, pH 7.0) was added at 1 ml / well and absorbance was measured at 550 nm with an ELISA reader. The results are shown in Fig. (In Fig. 2, *** indicates p-value < 0.001).

As shown in FIG. 2, the mineralization during the treatment with the excreted extract was 110%, 167%, and 137% increased at 1, 5, and 10 μg / ml, respectively, as compared with the control. In other words, it was confirmed that the extract of Joy was effective in the prevention and treatment of periodontal disease by promoting mineralization.

Claims (7)

A pharmaceutical composition for the prevention or treatment of periodontal disease, which comprises an extract of Ornamentalus as an active ingredient. The method according to claim 1, wherein the scissors are Siegesbeckia pubescens Makino or Siegesbeckia glabrescenes Makino . The pharmaceutical composition according to claim 1, wherein the periodontal disease is selected from the group consisting of gingivitis, periodontal inflammation, alveolar bone breakage, and alveolar bone osteodystrophy. The pharmaceutical composition according to claim 1, wherein the prevention and treatment of periodontal disease is prevention and treatment by any one or more selected from the group consisting of mineralization enhancement, antibacterial activity, or anti-inflammatory effect in alveolar bone. The pharmaceutical composition according to claim 1, wherein the extract is extracted with at least one solvent selected from water, an alcohol having 1 to 4 carbon atoms, and an aqueous solution of an alcohol having 1 to 4 carbon atoms. A composition for oral administration for prevention and improvement of periodontal disease containing an extract of Ornamentalus as an active ingredient. A health functional food for prevention and improvement of periodontal disease which contains an extract as an active ingredient.

Images