KR101759828B1 - Composition for the prevention or treatment of periodontal disease - Google Patents

Composition for the prevention or treatment of periodontal disease Download PDF

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KR101759828B1
KR101759828B1 KR1020160028866A KR20160028866A KR101759828B1 KR 101759828 B1 KR101759828 B1 KR 101759828B1 KR 1020160028866 A KR1020160028866 A KR 1020160028866A KR 20160028866 A KR20160028866 A KR 20160028866A KR 101759828 B1 KR101759828 B1 KR 101759828B1
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extract
periodontal disease
gardenia
treatment
alveolar bone
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양웅모
이혜지
김미혜
박정철
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경희대학교 산학협력단
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
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    • A61K36/23Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/232Angelica
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105Plant extracts, their artificial duplicates or their derivatives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/53Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/539Scutellaria (skullcap)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/74Rubiaceae (Madder family)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/74Rubiaceae (Madder family)
    • A61K36/744Gardenia
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00Food compositions, function of food ingredients or processes for food or foodstuffs
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00Function of food ingredients
    • A23V2200/30Foods, ingredients or supplements having a functional effect on health
    • A23V2200/312Foods, ingredients or supplements having a functional effect on health having an effect on dental health
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

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Abstract

The present invention provides a composition for preventing, ameliorating or treating periodontal disease, which comprises Angelica gigas, Gardenia and a golden compound extract as an active ingredient.
The composition comprising the complex extract according to the present invention as an active ingredient inhibits the production of osteoclasts, induces recovery of cementum and gingival tissue, and significantly reduces the adjustment distance due to periodontitis, thereby remarkably improving the prevention and treatment of periodontal disease Lt; / RTI >

Description

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

The present invention relates to a composition comprising, as an active ingredient, an extract of Angelica keiskei, a gardenia and a golden compound for preventing and treating periodontal disease, or a combination extract of Angelica keiskei, Gardenia sp.

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 bone formation and osteoclast-induced bone resorption in the alveolar bone, when the bone mass is reduced below a certain limit due to various factors, causes alveolar bone disorder such as osteoporosis.

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 pharmaceutical composition for the prevention and treatment of periodontal disease, which comprises Angelica keiskei, Gardenia and a golden compound extract as an active ingredient.

The present invention also provides an oral composition for the prevention and treatment of periodontal disease, comprising the extract of Angelica gigas, gardenia, and a golden compound as an active ingredient.

The present invention also provides a composition for external use for oral use comprising Angelica gigas, Gardenia and a golden compound extract as an active ingredient.

In addition, the present invention provides a health functional food for prevention and improvement of periodontal disease, which comprises the extract of Angelica gigas, gardenia and a golden compound as an active ingredient.

Also, it is intended to provide a pharmaceutical composition for prevention and treatment of periodontal disease, which comprises an extract of Angelica keiskei, a gardenia extract and a gold extract, and which is effective as an ingredient thereof.

Also, it is intended to provide an oral composition for prevention and treatment of periodontal disease, which comprises an extract of Angelica keiskei, a gardenia, and a golden extract and contains an extract of Angelica keiskei koidz.

Also, it is intended to provide a composition for external use for oral use, which comprises the Angelica keiskei, the gardenia,

In addition, the present invention provides a health functional food for prevention and improvement of periodontal disease, which comprises an extract of Angelica keiskei, a gardenia, and a golden extract and a extract of Angelica keiskei koidz.

The inventors of the present invention conducted research to develop a natural medicinal composition having a therapeutic and preventive effect for periodontal disease, and found that the extracts of Angelica gigas, Gardenia and Golden complex, especially Angelica gigas, Gardenia and Golden extract, The present inventors have found that the extract has a remarkable effect on the treatment and prevention of periodontal disease and completed the present invention.

The extract of the present invention is a preventive and therapeutic agent for periodontal disease, which has no side effects and is a safe natural agent for preventing periodontal disease using Angelica keiskei, ginger, gold, chrysanthemum and white paper. It is a complex extract of Angelica gigas, When used, have remarkable preventive and therapeutic effects as compared with individual single extracts.

In particular, when Angelicae gigantis, Gardenia, and Golden extract are added to the extracts of Chuncheon and Bleach, they have an advantage in that they have a synergistic effect on regeneration, recovery and anti-inflammatory effects of pubic bone tissue.

In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing and treating periodontal disease, which comprises Angelica gigas, Gardenia, and a golden compound extract as an active ingredient. The present invention provides a pharmaceutical composition for preventing and treating periodontal disease, which comprises an extract of Bombyx mori, a gardenia extract and a gold extract as an active ingredient.

The Angelica gigantis, the gardenia, and the golden compound extract of the present invention have a remarkable effect on the prevention and treatment of periodontal disease by inhibiting the osteoclast formation, inducing the recovery of cementum and gum tissue, and decreasing the adjusted distance of the teeth due to periodontitis. In addition, by containing more than 1000 mg of Bacillus thuringiensis in the gastric juice extract, prophylactic and therapeutic effects of periodontal disease become remarkable through gastric effect.

In the present invention, Angelica gigas is the root of Angelica gigas ( Angelica gigas ) belonging to the family Umbelliferae . Stems and leaf residues remain from the coarse and short main roots. The length of the main muscle is about 3 ~ 7cm, the diameter is 2 ~ 5cm and the length of the branch root is 15 ~ 20cm. Outer surface is light yellow to dark brown, and the main and branch roots have many vertical wrinkles and some have horizontal wrinkles. The folded surface is flat and the neck and skin are distinguished by the cambium. The skin around the throat and cambium is dark yellow while the rest is white. There is a peculiar smell, and the taste is sweet with a little writing.

In the present invention, Gardenia jasminoides belongs to the family Rubiaceae It is a ripe fruit of Japanese gardenia, and it is distributed in Japan, Taiwan and China. It grows up to 4m in height. Leaves are opposite to each other and are oval or obovate, with both ends pointed, flat edge, 3 ~ 15cm long. It is distributed in Japan, Taiwan and China. It is believed that it was imported from China 500 years ago in China. Fruit is effective as a medicine in oriental medicine because it has effects of fever, ejaculation, topography, and inflammation. It is used for symptoms such as inflammatory diseases, hepatitis, jaundice, and hematemesis.

In the present invention, gold (Scutellaria baicalensis Georgi ) is the same as the root of the sparrow grass belonging to the Lamiaceae (Labiatae). It is conical, twisted and bent with roots, 8 ~ 25cm long and 1 ~ 3cm in diameter. Outer surface is yellowish-brown to dark yellow, and lump-like fine roots are sparse. On the upper side there are relatively rough, twisted, curved vertical wrinkles or irregular net patterns. The vagina is hard, fragile and easy to cut. The cut surface is yellow and the center is reddish brown. The old age is decayed or empty in the center of the roots and dark brown to reddish brown. It is distributed in China and Korea.

In the present invention, the white paper ( Angelica dahurica ) is a generic name indicating the root portion of the copper band belonging to the Umbelliferae. The roots are pale yellowish brown, but they are hypertrophied, and when they fall down, they become ligneous and die. As a herbal medicine, it is good to have one or two years of life, but it is written that the pedicel has not come up. If you chew roots, there is a very strong taste.

In the present invention, Zanthoxylum piperitum is a fruit of a primavera belonging to Rubiaceae. It is a deciduous broad - leaved shrub belonging to. It is a perennial vine plant and has an orange fat root. The stems that hang many branches are clumpy and have small spines that are pointing downward on the hairs. Four leaves of each node are in the shape of a heart with a cross-shaped leaf. The leaves have long petiole and the edges are plain. On the back side of the leaf, 3 ~ 7 lines of parallel veins can be seen. There are small thorns like hooks on the leaf veins together with petiole. The flowers bloomed in the inside and outside of the diameter of 3.5mm are gathered together in the tips of the branches and the axilla of the leaves, and have five petals. After the flower has been cut, the two fruits are rounded together and they are darkened as they are ripe.

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, 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. By such concentration, the extract of Angelica gigas, Gardenia and Golden complex is extracted in liquid or powder form. The extract of Angelica gigas, Gardenia and Golden complex can 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 selected from the group consisting of water, C 1 to C 4 alcohols, and mixed solvents thereof. The extraction 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 extracting solvent is 2 to 15 times the weight of Angelica grisea, Gardenia and the golden dry weight. The ginseng, gardenia, and golden complex extract of the present invention have an amount of 0.1 wt% to 95 wt% based on the total weight of the ginseng, gardenia, and golden complex extract. The compound extract according to the present invention may be separately extracted and mixed, or the three kinds of drugs may be mixed and extracted.

In addition, it can be extracted in the same manner as above with the addition of Angelica gigas, Gardenia, and gold to white paper and perennial. The above five kinds of medicines can be extracted by separately extracting each medicament and mixing them, or by mixing the above five medicines.

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 additives according to the present invention are preferably included in an amount of 0.1 to 90 parts by weight based on 100 parts by weight of the combined extract, but are 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 simple diluents commonly used . 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 prevention and improvement of periodontal disease comprising Angelica gigas, Gardenia, and a golden compound extract as an active ingredient. The present invention provides an oral composition for prevention and improvement of periodontal disease, which comprises as an active ingredient, white ginseng and mulberry extract added to Angelica gigas, Gardenia and Golden extract.

In the present specification, the "oral composition" is a composition which is orally administered with inhibition of differentiation of osteoclasts, reduction of cementum and gum tissue recovery distance, and the like. 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 a wetting agent, a foaming agent, a preservative, a sweetening agent, an aging agent, a water-soluble polymer, a fragrance, and other components in addition to the above extract as an active ingredient. 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 combined 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.

Further, the present invention provides a composition for oral use for external use containing oral ginseng, gardenia and a golden compound extract as an active ingredient. Preferably, the composition for external use for oral use is provided by adding white ginseng and ginseng extract to Angelica gigas, Gardenia, and Golden extract and containing it as an active ingredient.

Specifically, the oral composition for oral use may be used for periodontal disease, and the periodontal disease is as described above.

The external preparation for oral use is not particularly limited but may be preferably prepared in the form of an ointment, a lotion, a spray, a patch, a cream, a powder, a suspension, a gel or a gel. Preferably a film, a dentifrice, a mouthwash solution, an ointment, a spray, a dressing solution, an application agent, a dental floss or a periodontal tissue. In the case of using the external preparation for oral use of the present invention, it is further possible to use a solubilizer, a thickening agent and a gelling agent, a softening agent, an antioxidant, a suspending agent, a stabilizer, a foaming agent, a fragrance, Such as any of the other ingredients commonly used in oral topical agents such as emulsifiers, emulsifiers, fillers, sequestering and chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, And may contain commonly used adjuvants.

In addition, the present invention provides a health functional food for preventing and improving periodontal disease, which comprises Angelica gigas, Gardenia and a golden compound extract as an active ingredient. The present invention provides a health functional food for prevention and improvement of periodontal disease, which comprises as an active ingredient, white ginseng and mulberry extract added to Angelica gigantosa, Gardenia and Golden extract.

The present invention can be used as it is or in combination 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 compound extract 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 complex extract of the present invention may further contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, , A carbonating agent used in carbonated drinks, and the like. In addition, the complex extract of the present invention may contain flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components may be used independently or in combination.

The composition comprising the complex extract according to the present invention as an active ingredient inhibits the production of osteoclasts, induces recovery of cementum and gingival tissue, and significantly reduces the adjustment distance due to periodontitis, thereby remarkably improving the prevention and treatment of periodontal disease Lt; / RTI >

FIG. 1 shows the result of measuring the degree of alveolar bone loss and confirming the restoration effect of tooth damage by treating Angelica gigas, Gardenia, and a golden compound extract.
FIG. 2 shows the results of RT-PCR analysis of changes in the expression of pro-collagen and MMP-9 according to the treatment of Angelica gigas, Gardenia, and a golden compound extract.
FIG. 3 shows the results of RT-PCR measurement of changes in expression of inflammation-related factors by treating Angelica gigas, Gardenia, and a golden compound extract.
FIG. 4 shows the result of western blot analysis of changes in osteoblast proliferation and osteoclast differentiation-related factors treated with Angelica gigas, Gardenia, and a golden compound extract.
FIG. 5 shows the results of in vivo restoration of tooth damage and measurement of alveolar bone loss by treating the combined extracts of Angelicae gigantis, Chinese ginseng, Chinese ginseng, white ginseng and Chinese ginseng.
FIG. 6 shows the results of examining the cementum recovery effect and the gum tissue regeneration effect by treating the extract of Angelica gigas Nakai, Gardenia japonica, Golden, White and Chrysanthemum.

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 > Manufacture of Angelica gigas, Gardenia and Golden complex extract

(Origin: China, Origin: Domestic Origin: Domestic Origin: Domestic Origin: Omni Herb) and Chinja (Origin: China) Origin: Domestic, purchased from: Omni Herb) The extracts were prepared by dissolving 100 mg of the lyophilized product of the test substance in 1 mL of distilled water.

Based on these individual extracts, the extracts of Angelica gigas, Gardenia and Golden complexes were prepared at 100 mg / mL, and the extracts of Angelica gigas, Gardenia, Golden, White and Chrysanthemum were also prepared at 100 mg / mL.

< Example  1> According to the treatment of Angelica gigas, Gardenia and Golden complex extract in periodontal disease model Periodontal disease  Confirm recovery effect

Sprague Dawley rats were bred at a temperature of 22-24 ° C and a relative humidity of 55-60% to evaluate the effects of Angelica gigas, Grasshopper and Golden Composite Extracts on alveolar bone resorption. Feeds of experimental animals were fed with solid feed (Raon Bio, Korea), and feed and water were constantly consumed.

The experimental animals were divided into three groups: 1) normal group (NL) that did not cause periodontitis; 2) an experimental group (L) that caused periodontitis and no drug administration; 3) periodontal disease; 3 mg / mL of Angelica gigas (LF3), and 4) combined treatment group (LF300) in which 300 mg / mL of Angelica keiskei, Chinese gardenia, and a golden compound extract (preparation example) were administered.

The periodontal ligament was knotted so that the dental floss was inserted between the first and second molars, and then treated with 100 μL of the experimental material in both molars that were tied together daily for 2 weeks.

After removal of the surrounding tissues of the mandible after the sacrifice of the experimental animals, the recovery effect of periodontal disease according to the treatment of Angelica gigas, Gardenia, and the golden compound extract was examined through methylene blue staining and the degree of alveolar bone loss was measured and shown in FIG.

As can be seen in FIG. 1, significant gingival damage was noted in the experimental group (L) in which periodontitis was induced compared to the normal control group (NL). However, it was confirmed that these injuries were greatly reduced in alveolar bone damage according to the treatment of Angelica gigas, Gardenia and Golden composite extract (LF3, LF300). In addition, it was confirmed that the degree of alveolar bone loss was greatly decreased according to the treatment of Angelica gigas, Gardenia and Golden complex extract (LF3, LF300).

From the above results, it was confirmed that the extract of Angelica gigas, Gardenia, and the golden compound was effective for the prevention and treatment of periodontal disease.

< Example  2> According to the treatment of Angelica gigas, Gardenia and Golden complex extract in periodontal disease model Collagenase  Confirm inhibitory activity

In periodontal disease, periodontal tissue composed of collagen is degraded by collagenase, a collagenase, and collagen. Inhibition of collagenase is important in the regeneration and recovery of periodontal tissue composed of collagen.

Thus, by using the animal model of periodontal disease of Example 1, collagenase inhibitory activity by the treatment of Angelica gigas Nakai, gardenia and golden compound extract was confirmed by RT-PCR.

The extracted gum tissue was pulverized with a homogenizer using the Trizol method and 1 μg of RNA was synthesized by RT-PCR (reverse transcriptase-polymerase chain reaction). The nucleotide sequence of the PCR primer for each gene is as follows.

Figure 112016023297611-pat00001

Experimental results of the RT-PCR are shown in FIG. 2, and their relative numerical values are shown in FIGS. 2 (a) and 2 (b).

As shown in FIG. 2, the expression of pro-collagen was increased by the treatment of Angelica gigantosa, Gardenia, and a golden compound extract, indicating regeneration of gum tissue. However, expression of MMP-9, a collagenase degrading collagen, It was confirmed that it inhibited the denaturation of &lt; RTI ID = 0.0 &gt;

From the above results, the prevention and treatment of periodontal disease was confirmed by the treatment of Angelica gigas, Gardenia and Golden complex extract.

< Example  3> Inhibition of Inflammatory Factor Inhibition by Treatment of Angelica gigas, Gardenia and Golden Complex Extracts in Periodontal Animal Model

Using the animal model of periodontal disease of Example 1, the inflammation-related factors (IL-1β, IL-6 and IL-8) following the treatment of Angelica gigas Nakai,

Figure 112016023297611-pat00002

Experimental results of the RT-PCR are shown in FIG. 3, and their relative numerical values are shown in FIGS. 3 (a) to 3 (c).

As shown in FIG. 3, the expression of IL-1β, IL-6 and IL-8, which are inflammation-related factors, was reduced in a concentration-dependent manner according to the treatment of Angelica gigas Nakai,

From the above results, the prevention and treatment of periodontal disease was confirmed by the treatment of Angelica gigas, Gardenia and Golden complex extract.

< Example  4> According to treatment of Angelica gigas, Gardenia and Golden complex extract Osteoblast  Confirming inhibition of proliferation and osteoclast differentiation factor expression

Using Saos-2 cells, Osterix and Runx2 (Runt-related transcription factor 2) and RANKL (osteoclast differentiation factor associated with osteoblast proliferation promoting factor) -B ligand) and OPG (osteoprotegerin) were confirmed by Western blotting.

As shown in FIG. 4, it was confirmed that RANKL was inhibited in a concentration-dependent manner and the expression of OPG, Runx2 and Osterix was increased in a concentration-dependent manner by treatment with Angelica gigantosa, Gardenia and a golden compound extract.

From the above results, it was confirmed that the extracts of Angelica gigas, Gardenia, and Gold complex showed excellent effects on promoting the proliferation of osteoblasts and inhibiting the differentiation and production of osteoclasts, thus showing remarkable effects in the prevention and treatment of periodontal disease.

< Example  5> In the periodontal disease animal model, Angelica, Gardenia, Thousand  Depending on complex extract treatment Periodontal disease  Confirm recovery effect

Therapeutic effect was confirmed in the same manner as in Example 1, in order to evaluate the effect of the combined extract of Angelicae, Gardenia, Gold, White and Chrysanthemum on alveolar bone absorption. Experimental animals were divided into two groups: (1) normal group (NL), (2) periodontitis, (L), (3) periodontitis, (P100), which was administered with 100 mg / mL of combined extracts of Angelica gigas Nakai, Gijyuu, Gardenia, Gold, White and Chrysanthemum.

As can be seen in FIG. 5, significant gingival damage was noted in the experimental group (L) in which periodontitis was induced compared to the normal control group (NL). However, it was confirmed that these damages were greatly reduced according to the treatment with the extracts of Angelica gigas, Gypsum, Golden, White and Chrysanthemum complex (P1, P100). In addition, it was confirmed that the degree of alveolar bone loss was greatly decreased according to LF3, LF300 treatment of Angelica gigas, Gardenia, Golden, White and Chrysanthemum complex extracts.

< Example  6> In the periodontal disease animal model, Angelica, Gardenia, Thousand  Depending on complex extract treatment cement  And gum tissue recovery effect

(1) According to complex extract treatment cement  Confirm change

H & E staining of the first molar was performed to assess the effect of topical application of the combined extract on the cementum of periodontal disease induced animals.

The results are shown in Fig. 6 (a). The arrow indicates the cementum, and R indicates the root of the first molar.

In the animal model prepared in Example 1, denatured cementum was observed in the experimental group (L) in which periodontitis was induced by binding the dental floss compared to the normal group (NL) which did not cause periodontitis. On the other hand, it was confirmed that cementum treated with Angelica gigas, Gardenia, Golden, White and Chrysanthemum complex extract (P1 or P100) was recovered in all groups.

(2) In combination extract treatment Gum following  Identify changes in tissues (gingival tissues)

Histochemical staining of the first molar was confirmed by H & E staining to assess whether topical application of the combined extract affects the gingival tissues of periodontally induced animals.

The results are shown in Fig. 6 (b). Arrows indicate gum tissue.

In the experimental group (L), in which periodontitis was induced by binding the floss, gingival tissues were found to be resorbed compared to the normal group (NL) which did not induce periodontitis.

On the other hand, it was confirmed that the gingival tissues were recovered by treatment with the extracts of Angelica gigas Nakai, Gjiji, Golden, White and Chrysanthemum in the gingival tissues which were caused by periodontitis.

In other words, it was confirmed that the combined extract of Angelica gigas Nakai, Gijia, Golden, White and Chrysanthemum recovered denatured tooth shape by improving cementum recovery and gingival tissue recovery, and was effective in the prevention and treatment of periodontal diseases.

<110> University-Industry Cooperation Group of Kyung Hee University <120> Composition for the prevention or treatment of periodontal          disease <130> P16-001-KHU <160> 12 <170> KoPatentin 3.0 <210> 1 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> GAPDH Forward Primer <400> 1 ggcatggact gtggtcatga 20 <210> 2 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> GAPDH Reverse Primer <400> 2 ttcaccacca tggagaaggc 20 <210> 3 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> MMP-9 Forward Primer <400> 3 gggacgcaga catcgtcatc 20 <210> 4 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> MMP-9 Reverse Primer <400> 4 tcgtcatcgt cgaaatgggc 20 <210> 5 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Pro-collagenase Forward Primer <400> 5 tctactggcg aaacctgtat ccg 23 <210> 6 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Pro-collagenase Reverse Primer <400> 6 caaggaaggg caggcgtgat 20 <210> 7 <211> 23 <212> DNA <213> Artificial Sequence <220> IL-1beta Forward Primer <400> 7 ctctagagca ccatgctaca gac 23 <210> 8 <211> 21 <212> DNA <213> Artificial Sequence <220> IL-1beta Reverse Primer <400> 8 tggaatccag gggaaacact g 21 <210> 9 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> IL-6 Forward Primer <400> 9 cggagaggag acttcacaga gga 23 <210> 10 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> IL-6 Reverse Primer <400> 10 ggagagcatt ggaaattggg g 21 <210> 11 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> IL-8 Forward Primer <400> 11 tgtgggaggc tgtgtttgta 20 <210> 12 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> IL-8 Reverse Primer <400> 12 acgagaccag gagaaacagg 20

Claims (10)

(Gingivitis), periodontal inflammation, alveolar bone breakage, or alveolar bone osteodystrophy, which contains an extract of Angelica keiskei koidz A pharmaceutical composition for the prevention or treatment of periodontal disease. delete delete 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. (Gingivitis), periodontal inflammation, alveolar bone breakage, or alveolar bone osteodystrophy, which contains an extract of Angelica keiskei koidz An oral composition for preventing or ameliorating periodontal disease. delete (Gingivitis), periodontal inflammation, alveolar bone breakage, or alveolar bone osteodystrophy, which contains an extract of Angelica keiskei koidz A composition for external use for oral use for preventing or ameliorating periodontal disease. delete (Gingivitis), periodontal inflammation, alveolar bone breakage, or alveolar bone osteodystrophy, which contains an extract of Angelica keiskei koidz Health functional food for prevention or improvement of periodontal disease. delete
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KR20190027440A (en) * 2017-09-07 2019-03-15 태이생명과학 주식회사 Composition for Preventing or Treating Periodontal Disease Comprising Scutellaria Extract treated by Enzyme Isolated from Aspergillus niger as Active Ingredient
KR20190142510A (en) * 2018-06-18 2019-12-27 태이생명과학 주식회사 Composition for Preventing or Treating Periodontal Disease Comprising Scutellaria Extract treated by Aspergillus niger as Active Ingredient
KR20240041381A (en) 2022-09-21 2024-04-01 부산대학교 산학협력단 Composition for the prevention or treatment of periodontal disease

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Publication number Priority date Publication date Assignee Title
KR20190027440A (en) * 2017-09-07 2019-03-15 태이생명과학 주식회사 Composition for Preventing or Treating Periodontal Disease Comprising Scutellaria Extract treated by Enzyme Isolated from Aspergillus niger as Active Ingredient
KR102022006B1 (en) * 2017-09-07 2019-09-18 태이생명과학 주식회사 Composition for Preventing or Treating Periodontal Disease Comprising Scutellaria Extract treated by Enzyme Isolated from Aspergillus niger as Active Ingredient
KR20190142510A (en) * 2018-06-18 2019-12-27 태이생명과학 주식회사 Composition for Preventing or Treating Periodontal Disease Comprising Scutellaria Extract treated by Aspergillus niger as Active Ingredient
KR102166701B1 (en) * 2018-06-18 2020-10-16 스노우화이트팩토리(주) Composition for Preventing or Treating Periodontal Disease Comprising Scutellaria Extract treated by Aspergillus niger as Active Ingredient
KR20240041381A (en) 2022-09-21 2024-04-01 부산대학교 산학협력단 Composition for the prevention or treatment of periodontal disease

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