WO2020060277A1 - Composition pour la prévention ou le traitement de maladies buccales ou de maladies osseuses - Google Patents

Composition pour la prévention ou le traitement de maladies buccales ou de maladies osseuses Download PDF

Info

Publication number
WO2020060277A1
WO2020060277A1 PCT/KR2019/012220 KR2019012220W WO2020060277A1 WO 2020060277 A1 WO2020060277 A1 WO 2020060277A1 KR 2019012220 W KR2019012220 W KR 2019012220W WO 2020060277 A1 WO2020060277 A1 WO 2020060277A1
Authority
WO
WIPO (PCT)
Prior art keywords
extract
disease
oral
forest
bone
Prior art date
Application number
PCT/KR2019/012220
Other languages
English (en)
Korean (ko)
Inventor
배지명
김성환
Original Assignee
원광대학교산학협력단
한국화학연구원
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from KR1020180114244A external-priority patent/KR102061981B1/ko
Priority claimed from KR1020180114243A external-priority patent/KR102167725B1/ko
Priority claimed from KR1020180114242A external-priority patent/KR102167724B1/ko
Application filed by 원광대학교산학협력단, 한국화학연구원 filed Critical 원광대학교산학협력단
Publication of WO2020060277A1 publication Critical patent/WO2020060277A1/fr

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, 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
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/11—Pteridophyta or Filicophyta (ferns)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/888—Araceae (Arum family), e.g. caladium, calla lily or skunk cabbage
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis

Definitions

  • the present invention relates to a composition for the prevention or treatment of oral diseases or bone diseases comprising at least one selected from the group consisting of taro extract, tail fern extract and forest buckwheat extract, specifically taro extract, tail It relates to a pharmaceutical composition, food composition, quasi-drug composition and dental composition for the prevention or treatment of oral diseases or bone diseases comprising at least one selected from the group consisting of fern extract and forest buckwheat extract.
  • RAW264.7 monocytes of mice are differentiated into multinucleated osteoclasts by a receptor activator of nuclear factor ⁇ B (RANK) ligand (RANKL).
  • RANK nuclear factor ⁇ B
  • This differentiation process promotes the activity of mitogen-activated protein kinase (MAPK) by binding RANKL from the outside of the cell to RANK, which is a TRAP associated with osteoclast differentiation due to the transcription factor NF- ⁇ B entering the nucleus. It is possible by increasing the expression of (tartrate-resistant acid phosphatase), MMP-9 (matrix metalloproteinase-9), c-Src tyrosine kinase, etc.
  • MMP-9 matrix metalloproteinase-9
  • c-Src tyrosine kinase etc.
  • the multinuclear osteoclasts formed by this process are able to replace mineralized bone. It serves to absorb.
  • RANKL binds to RANK, it promotes the activity of TRAF6 (tumor necrosis factor receptor-associated factor 6), thereby promoting the activity of transcription factors such as MARK, or NF- ⁇ B, AP-1, NFATc1 (LEE ZH, KIM) HH.Signal transduction by receptor activator of nuclear factor kappa B in osteoclasts.Biochem Biophys Res Commun. 2003 May 30, 305, 211-4). Therefore, blocking the signaling pathway activated by RANKL is recognized as one of the therapeutic approaches in the treatment of diseases associated with osteoclast differentiation.
  • Osteoblasts cause abnormal destruction and absorption of bone tissue due to imbalance with osteoblasts in the bone, and thereby, osteoporosis, which decreases bone mass and bone density, osteomalacia, where lime is lost from bone, normal Fibrous dysplasia where bone tissue is replaced by fibrous connective tissue and immature bone soju, periodontal disease in which alveolar bone is lost, and rheumatoid arthritis that causes joint destruction and deformation. It is known. As such, there is a close relationship between osteoclast differentiation and periodontal disease and bone disease.
  • LPS lipopolysaccharide
  • ciliary mediation Wilson, 1998; Kadono et al. 1999
  • the LPS is a well-known stimulator of the synthesis of inflammatory cytokines or eicosanoids as a pathogenic component present in the outer membrane of the bacterium. It stimulates osteoblasts to osteolytic factors, namely IL-1, IL-6, PGE2, oxidation It is known as a major structure that destroys periodontal tissue by secreting nitrogen.
  • antibiotics and antibacterial agents such as Sangquinarine, Listerine, Peroxide, and Chlorhexidine are widely used as therapeutic agents to treat oral diseases including periodontal disease.
  • antibiotics can induce the appearance of resistant bacteria in the oral cavity and superinfection along with systemic side effects on our body, there is a drawback that long-term use is difficult and can only be used as a therapeutic agent.
  • raw guinarine has an unclear effect on bacteria in the oral cavity and a more unclear treatment effect on periodontal disease, and also has a disadvantage in that it is expensive. It has a short-term effect, but also has the disadvantage that it may have a harmful effect on tissues when used for a long time.
  • chlorhexidine is known to be the best among the formulations known to date as a preventive and therapeutic agent for periodontal disease along with inhibition of plaque formation, but it causes irritation to tissues, coloring and degeneration of tissues, and has a particularly strong, irritating and odorous side effect.
  • bisphosphonate-based treatments are widely used to treat bone damage caused by osteoclasts such as osteoporosis.
  • patients taking bisphosphonate-based drugs have been increasing year by year with various side effects such as osteonecrosis, severe atrial fibrillation, disabling bone or joints, and musculoskeletal pain (Br J Cancer 98: 1736). -1740 (2008)). Therefore, there is a need to develop pharmaceuticals that compensate for the disadvantages of the existing bisphosphonate-based drugs, have low toxicity, and can effectively suppress osteoclast formation and differentiation.
  • One object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of oral disease or bone disease comprising at least one selected from the group consisting of taro extract, tail fern extract and forest buckwheat extract as an active ingredient. .
  • Another object of the present invention is to provide a food composition for preventing or improving oral disease or bone disease, including any one or more selected from the group consisting of taro extract, tail fern extract and forest buckwheat extract as an active ingredient. .
  • Another object of the present invention is to provide a quasi-drug composition for the prevention or improvement of oral disease or bone disease comprising at least one selected from the group consisting of taro extract, tail fern extract and forest buckwheat extract as an active ingredient will be.
  • Another object of the present invention is to provide a dental composition for the prevention or improvement of oral diseases comprising at least one selected from the group consisting of taro extract, tail fern extract and forest buckwheat extract as an active ingredient.
  • the present inventors have shown that they are less toxic from natural products, and have studied politely to find compounds that can inhibit the activity of oral disease-causing bacteria and inhibit osteoclast formation or differentiation.
  • Oral disease by remarkably inhibiting the activity of Porphyromonas gingivalis , which is an oral disease-causing bacterium, and at least one selected from the group consisting of extracts and forest buckwheat extracts, and significantly inhibits the formation or differentiation of osteoclasts
  • the present invention was completed.
  • composition comprising at least one selected from the group consisting of taro extract, tail fern extract and forest buckwheat extract of the present invention as an active ingredient is derived from a natural product and has low toxicity, but also causes oral disease-causing bacteria, Porphyromonas jinjibali S. ( Porphyromonas gingivalis ) by significantly inhibiting the activity and by significantly suppressing the formation or differentiation of osteoclasts can be useful for the prevention or treatment of oral disease or bone disease.
  • 1B is a graph showing cytotoxicity (cell viability) according to the treatment concentration of tail fern extract.
  • Figure 1c is a graph showing the cytotoxicity (cell viability) according to the treatment concentration of the forest buckwheat extract.
  • Figure 2a is a graph showing the effect of inhibiting the production of nitrogen oxides according to the treatment concentration of the taro extract.
  • the significance test was performed through the student t-test, and the significance # of the LPS-treated group compared to the control group was p ⁇ 0.001.
  • the significance of the taro extract-treated group compared to the LPS-treated group was p ⁇ 0.05, ** was p ⁇ 0.01, and *** was p ⁇ 0.001.
  • Figure 2b is a graph showing the effect of inhibiting the production of nitric oxide according to the treatment concentration of the tail fern extract.
  • the significance test was performed through the student t-test, and the significance # of the LPS-treated group compared to the control group was p ⁇ 0.001.
  • the significance of the tail fern extract-treated group compared to the LPS-treated group was p ⁇ 0.05, ** is p ⁇ 0.01, and *** is p ⁇ 0.001.
  • Figure 2c is a graph showing the effect of inhibiting the production of nitric oxide according to the treatment concentration of the forest buckwheat extract.
  • the significance test was performed through the student t-test, and the significance # of the LPS-treated group compared to the control group was p ⁇ 0.001.
  • the significance of the forest buckwheat extract treatment group compared to the LPS treatment group is p ⁇ 0.05, ** is p ⁇ 0.01, and *** is p ⁇ 0.001.
  • Figure 3a is a graph showing the inhibitory effect of inflammatory cytokines, (a) IL-6 and (b) TNF- ⁇ production according to the treatment concentration of the taro extract.
  • the significance test was performed through the student t-test, and the significance # of the LPS-treated group compared to the control group was p ⁇ 0.001.
  • the significance of the taro extract-treated group compared to the LPS-treated group was p ⁇ 0.05, ** was p ⁇ 0.01, and *** was p ⁇ 0.001.
  • Figure 3c is a graph showing the inhibitory effect of inflammatory cytokines, (a) IL-6 and (b) TNF- ⁇ production according to the treatment concentration of the forest buckwheat extract.
  • the significance test was performed through the student t-test, and the significance # of the LPS-treated group compared to the control group was p ⁇ 0.001.
  • the significance of the forest buckwheat extract treatment group compared to the LPS treatment group is p ⁇ 0.05, ** is p ⁇ 0.01, and *** is p ⁇ 0.001.
  • Figure 4a is a graph showing the growth inhibitory effect of Porphyromonas gingivalis according to the treatment concentration of the taro extract.
  • the significance test was performed through the student t-test, and the significance * compared to the control group was p ⁇ 0.05, ** indicates p ⁇ 0.01, and *** indicates p ⁇ 0.001.
  • Figure 4b is a graph showing the growth inhibitory effect of Porphyromonas gingivalis according to the treatment concentration of the tail fern extract.
  • the significance test was performed through the student t-test, and the significance * compared to the control group was p ⁇ 0.05, ** indicates p ⁇ 0.01, and *** indicates p ⁇ 0.001.
  • Figure 4c is a graph showing the growth inhibitory effect of Porphyromonas gingivalis according to the treatment concentration of the forest buckwheat extract.
  • the significance test was performed through the student t-test, and the significance * compared to the control group was p ⁇ 0.05, ** indicates p ⁇ 0.01, and *** indicates p ⁇ 0.001.
  • Figure 5a is a graph showing the sustained effect of growth inhibition of Porphyromonas gingivalis according to the control group, fluoride varnish treatment group, fluoride varnish + taro treatment group.
  • the significance test was conducted through the student t-test, and the significance ### of the fluoride varnish treatment group compared to the control group was p ⁇ 0.001.
  • the significance *** of the fluoride varnish + taro treatment group compared to the fluoride varnish treatment group represents p ⁇ 0.001.
  • Figure 5c is a graph showing the sustained effect of growth inhibition of Porphyromonas gingivalis according to the control group, fluoride varnish treatment group, fluoride varnish + forest wheat treatment group.
  • the significance test was conducted through the student t-test, and the significance ### of the fluoride varnish treatment group compared to the control group was p ⁇ 0.001.
  • the significance *** of the fluoride varnish + forest cultivation treatment group compared to the fluoride varnish treatment group was p ⁇ 0.001.
  • Figure 6 is a photograph showing the TRAP staining results of (a) TRAP-positive cells, and (b) differentiated osteoclasts according to the treatment concentration of the taro extract.
  • the significance test was performed through the student t-test, and the significance * compared to the control group was p ⁇ 0.05, ** indicates p ⁇ 0.01, and *** indicates p ⁇ 0.001.
  • FIG. 7 is a photograph showing the results of TRAP staining of differentiated osteoclasts, and (a) a graph showing the number of TRAP positive cells according to the treatment concentration of the tail fern extract.
  • the significance test was performed through the student t-test, and the significance * compared to the control group was p ⁇ 0.05, ** indicates p ⁇ 0.01, and *** indicates p ⁇ 0.001.
  • FIG. 8 is a photograph showing the results of TRAP staining of differentiated osteoclasts, and (a) a graph showing the number of TRAP-positive cells according to the treatment concentration of the forest buckwheat extract.
  • the significance test was performed through the student t-test, and the significance * compared to the control group was p ⁇ 0.05, ** indicates p ⁇ 0.01, and *** indicates p ⁇ 0.001.
  • one aspect of the present invention is for the prevention or treatment of oral disease or bone disease comprising at least one selected from the group consisting of taro extract, tail fern extract and forest buckwheat extract as an active ingredient
  • a pharmaceutical composition comprising at least one selected from the group consisting of taro extract, tail fern extract and forest buckwheat extract as an active ingredient
  • the pharmaceutical composition for preventing or treating oral disease or bone disease of the present invention includes an extract of taro, tail fern or forest buckwheat; Or fractions thereof.
  • Taro is known to have various pharmacological properties such as fatty liver, diabetes complications, and depression treatment effects, but its prevention, treatment, or improvement effects on oral diseases or bone diseases have not been known.
  • tail fern Asplenium incisum
  • tail fern Asplenium incisum
  • the term "tail fern ( Asplenium incisum )" is a small fern plant with short rhizomes. Since the outpost has various effects such as detoxification, it uses raw juice for medicinal purposes. Antibacterial activity and bronchodilatory activity against skin disease causative bacteria have been reported.
  • the tail fern is known to have various pharmacological properties such as hepatitis, tinnitus, and chronic manganese poisoning treatment effects, but the effect of preventing, treating or improving its oral disease or bone disease is not yet known.
  • the term "forest buckwheat ( Brachypodium sylvaticum )" is a perennial plant belonging to the family Gramineae and forest stalk ( Brachypodium ), inhabiting the southern regions of Korea, especially the coastal islands.
  • Forest wheat is known to be used as feed for livestock, but its various pharmacological properties, or its prevention, treatment, or improvement effects on oral diseases or bone diseases have not been known.
  • the present inventors have conducted various studies on substances that show excellent prevention or treatment effects of oral diseases or bone diseases from natural resources existing in nature, as a result of taro extract, tail fern extract or forest buckwheat extract, Porphyromonas, which is an oral disease-causing bacteria. It was confirmed that it can be effectively used for the prevention or treatment of oral diseases or bone diseases by inhibiting the activity of Porphyromonas gingivalis and inhibiting the formation or differentiation of osteoclasts. Through this, it was found that taro extract, tail fern extract or forest buckwheat extract can be used as a pharmaceutical composition for preventing or treating oral disease or bone disease.
  • composition comprising any one or more selected from the group consisting of taro extract, tail fern extract and forest buckwheat extract having the effect of preventing or treating the oral disease or bone disease has not been known so far, and the inventors It has a very great significance in that it was first developed by.
  • taro, tail fern or forest wheat is not limited to its kind, and can be used cultivated, commercially available, or used without limitation in its source.
  • extract means that any one or more selected from the taro, tail fern or forest wheat is extracted, but is not limited thereto, an extract obtained by the extraction process, a dilution or concentrate of the extract .
  • the dried product obtained by drying the extract may be included in the extract itself and the extracts of all formulations that can be formed using the extract, such as a refined product or a mixture thereof.
  • it can be extracted from various organs of natural, hybrid, and varietal plants of the taro, tail fern or forest clover, for example, roots, rhizomes, ground parts, stems, leaves, and fruits.
  • the taro extract, tail fern extract or forest buckwheat extract may be extracted with water, alcohol having 1 to 1 carbon atoms (C 1 ) to 4 carbon atoms (C 4 ), or a mixed solvent thereof, but is not limited thereto. Accordingly, since the extraction degree and loss degree of the active ingredient may be different, an appropriate organic solvent may be selected and used. Specifically, it can be extracted using water, an organic solvent, or a mixed solvent thereof. More specifically, ethanol may be used, but is not limited thereto.
  • the solvent extract may further include filtering the extract to remove floating solid particles.
  • the particles may be filtered using cotton, nylon, or the like, an ultrafiltration method, a freezing filtration method, or a centrifugation method may be used, but is not limited thereto.
  • freeze drying, vacuum drying, hot air drying, spray drying, vacuum drying, foam drying, high frequency drying, or infrared drying may be used.
  • a process of grinding the final dried extract may be further included.
  • fraction in the present invention means a result obtained by performing a fraction to separate a specific component or a specific component group from a mixture containing various various components.
  • the fractionation method for obtaining the fraction in the present invention is not particularly limited as long as it can exhibit the prevention or treatment effect of oral diseases or bone diseases, but may be performed according to methods commonly used in the art. For example, a solvent fractionation method performed by treating various solvents, an ultrafiltration fractionation method performed by passing through an ultrafiltration membrane having a constant molecular weight cut-off value, and various chromatography (separation according to size, charge, hydrophobicity or affinity) Chromatography), and combinations thereof.
  • the type of fractional solvent used to obtain the fraction is not particularly limited, and any solvent known in the art may be used.
  • the fractional solvent include polar solvents such as water, distilled water, and alcohol; And non-polar solvents such as hexane, ethyl acetate, chloroform and dichloromethane. These may be used alone or in combination of two or more.
  • an alcohol in the fractional solvent preferably, an alcohol having 1 to 2 carbon atoms (C 1 ) to 4 (C 4 ) carbon atoms can be used.
  • extract or fraction may be prepared and used in a dry powder form after extraction, but is not limited thereto.
  • oral disease refers to various diseases that occur in the oral area, and the oral area refers to a space in the mouth that is connected to the pharynx from the anterior lip to the posterior canal.
  • the oral disease is a concept that includes all irrespective of the pathology if the disease occurs in the oral cavity, and non-limiting examples of the oral disease include dental caries, periodontal disease (periodontitis or gingivitis), toothache, and bad breath. And the like.
  • gingivitis a form limited to soft tissues, is a relatively light and fast-recovering oral disease called gingivitis, and periodontitis is the case when such inflammation has progressed to the gingiva and alveolar bones.
  • the term "halt breath” is an odor originating from the oral cavity and adjacent organs, and 85 to 90% of the bad breath originates from the oral cavity, particularly from the back of the tongue.
  • the main components of bad breath are volatile sulfur compounds, with 90% of the total amount of volatile sulfur compounds being hydrogen sulfide made from cysteine, methyl mercaptan made from methionine, and dimethyl sulfide. These components are produced primarily by protein enzymes released by anaerobic bacteria, and the back of the tongue is the most important habitat. This part does not clean well by saliva, and has many small depressions, making it a place where bacteria can continue to live.
  • anaerobic bacteria The production of volatile sulfur compounds by anaerobic bacteria is the most important cause of bad breath, but it is also caused by oral diseases such as dental caries, periodontitis, and dry mouth. Many types of anaerobic bacteria are involved in the development of bad breath, and non-limiting examples of bad breath-causing bacteria include Porphyromonas gingivalis , which secretes many types and large amounts of enzymes.
  • taro extract, tail fern extract or forest buckwheat extract of the present invention As a result of administering the taro extract, tail fern extract or forest buckwheat extract of the present invention to Porphyromonas ginsalis, it was confirmed that it exhibits antimicrobial activity against Porphyromonas ginsalis in a concentration-dependent manner. (Fig. 4a, 4b, 4c), it was confirmed that the taro extract, tail fern extract or forest buckwheat extract of the present invention also exhibits an antibacterial lasting effect (Fig. 5a, 5b, 5c). Through this, it was confirmed that the taro extract, tail fern extract, or forest buckwheat extract is effective in preventing or treating oral diseases through antibacterial activity and antibacterial lasting activity against Porphyromonas gingivalis.
  • bone disease means to include all diseases induced by a decrease in bone loss or bone density, the balance of osteoblast and osteoclast production and differentiation is lost. Specifically, osteoporosis, osteomalacia, osteoopenia, bone atrophy, osteoarthritis, rheumatoid arthritis, periodontal disease, osteolysis, May include fibrous dysplasia, Paget's disease, osteogenesis imperfect, hypercalcemia, and more specifically osteoporosis due to osteoclast differentiation. However, it is not limited thereto.
  • osteoclast is a cell derived from a macrophage precursor (macrophage precursor), osteoclast progenitor cells are macrophage colony stimulating factor (M-CSF), NF- ⁇ B It refers to differentiation into osteoclasts by a receptor activating factor ligand (RANKL) and the like, to form multinucleated osteoclasts through fusion.
  • M-CSF macrophage colony stimulating factor
  • NF- ⁇ B NF- ⁇ B It refers to differentiation into osteoclasts by a receptor activating factor ligand (RANKL) and the like, to form multinucleated osteoclasts through fusion.
  • RNKL receptor activating factor ligand
  • Osteoclast cells bind to the bone through ⁇ v ⁇ 3 integrin, etc., create an acidic environment, and secrete various collagenase and protease to cause bone resorption. Osteoclasts do not proliferate as fully differentiated cells and cause apoptosis when the
  • tarrate-resistant acid phosphate an osteoclast differentiation marker
  • prevention refers to all actions to suppress or delay the development of bone disease by administration of the pharmaceutical composition according to the present invention, “treatment” suspects bone disease by administration of the pharmaceutical composition And all actions in which the symptoms of the affected individual are improved or beneficially changed.
  • the pharmaceutical composition of the present invention may further include a pharmaceutically acceptable carrier, excipient, or diluent, which carrier may include a non-naturally occurring carrier.
  • carriers, excipients, and diluents that may be included in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium Silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, polycaprolactone, polylactic acid (Poly Lactic Acid), poly-L-lactic acid, Mineral oil and the like.
  • the pharmaceutical composition is an oral dosage form such as pills, powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, and sterile injections according to conventional methods for preventing and treating oral diseases or bone diseases It can be used by formulating in the form of a solution, and in particular, when the pharmaceutical composition of the present invention is for the prevention or treatment of oral diseases, specifically, it may have a formulation of an oral spray, an oral ointment, or an oral varnish.
  • the carrier may include various types of amorphous carriers, microspheres, nanofibers, and rosin.
  • formulation it may be prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, etc., which are usually used.
  • diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, etc., which are usually used.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations include at least one excipient in the extract and its fractions, for example, starch, calcium carbonate, It can be prepared by mixing sucrose or lactose, gelatin, and the like. In addition, lubricants such as magnesium stearate and talc may be used in addition to simple excipients.
  • Liquid preparations for oral administration include suspensions, intravenous solutions, emulsions, syrups, etc.
  • various excipients such as wetting agents, sweeteners, fragrances, and preservatives, can be included. have.
  • Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories, and the like.
  • Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate.
  • the content of any one or more or fractions thereof selected from the group consisting of taro extract, tail fern extract and forest buckwheat extract contained in the pharmaceutical composition of the present invention is not particularly limited, but is 0.01 based on the total weight of the final composition It may be included in an amount of 100 to 100% by weight, 0.01 to 50% by weight, and more specifically 0.01 to 20% by weight.
  • the present invention provides a method for preventing or treating oral disease or bone disease, comprising administering the pharmaceutical composition to an individual.
  • the method of the present invention comprising the step of administering it to an individual may be usefully used for the prevention or treatment of oral disease or bone disease. have.
  • the term "individual” refers to all animals including humans who may or may have oral disease or bone disease, for example, monkeys, dogs, cats, rabbits, mormots, rats, mice, cows, sheep, pigs , Goat, bird, fish, etc., and specific examples may include mammals including humans, but are not limited thereto.
  • a pharmaceutical composition containing any one or more selected from the group consisting of taro extract, tail fern extract and forest buckwheat extract as an active ingredient may be administered in a pharmaceutically effective amount.
  • the term "pharmaceutically effective amount” means an amount sufficient to treat or prevent a disease at a reasonable benefit / risk ratio applicable to medical treatment or prevention, and the effective dose level is the severity of the disease, the activity of the drug , The patient's age, weight, health, sex, patient's sensitivity to the drug, the time of administration of the composition of the present invention used, the route of administration and the rate of excretion, the duration of treatment, the drug used in combination or coincidental with the composition of the present invention used. Factors and other factors well known in the medical field can be determined.
  • the pharmaceutical composition of the present invention may be administered alone or in combination with a known pterygium therapeutic agent. Considering all of the above factors, it is important to administer an amount that can achieve the maximum effect in a minimal amount without side effects.
  • the dosage of the pharmaceutical composition can be determined by a person skilled in the art in consideration of the purpose of use, the degree of poisoning of the disease, the age, weight, sex, history of the patient, or the type of substance used as an active ingredient.
  • the pharmaceutical composition of the present invention may be administered at 1 mg / kg to 200 mg / kg per adult, specifically 1 mg / kg to 100 mg / kg, more specifically 20 to 40 mg / kg, ,
  • the frequency of administration of the composition of the present invention is not particularly limited, but may be administered once a day or divided into doses several times. The above dosage does not limit the scope of the present invention in any way.
  • a food composition for preventing or improving oral disease or bone disease including any one or more selected from the group consisting of taro extract, tail fern extract and forest buckwheat extract as an active ingredient.
  • the food composition for preventing or improving oral disease or bone disease of the present invention may include any one or more or fractions thereof selected from the group consisting of taro extract, tail fern extract and forest buckwheat extract.
  • the term, "improvement” is an oral disease that is prevented or treated by using a composition comprising at least one or a fraction thereof selected from the group consisting of taro extract, tail fern extract and forest buckwheat extract as an active ingredient, or Refers to all actions that improve or benefit the suspected bone disease and the symptoms of the affected individual.
  • the term "food” in the present invention meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages , Vitamin complexes, health functional foods, and the like, all of the foods in the usual sense, and as long as it can contain the taro extract or fractions thereof of the present invention, it is not limited. It may also include forms such as pills, powders, granules, needles, tablets, capsules or liquids.
  • health functional food refers to food manufactured and processed using ingredients or ingredients having useful functionality for the human body according to Act No. 6727 on the Health Functional Food, and 'functional' is the structure of the human body And it means to obtain a useful effect in health applications such as adjusting nutrients for function or physiological action.
  • health foods mean foods that have an active health maintenance or enhancement effect compared to general foods
  • health supplements mean foods for the purpose of supplementing health, and in some cases, terms of health functional foods, health foods, and health supplements Can be used interchangeably.
  • the health functional food of the present invention can be manufactured by a method commonly used in the art. It can be manufactured in various types of formulations, and unlike general medicines, it has the advantage of not having side effects that can occur when taking medicines for a long time using food as a raw material, and can be excellent in portability.
  • the food composition When preparing the food composition, it may be prepared by adding raw materials and ingredients that are conventionally added in the art, and the type is not particularly limited. For example, as a conventional food, various herbal extracts, food additives, food supplements, or natural carbohydrates may be included as additional ingredients, but are not limited thereto.
  • a quasi-drug composition for preventing or improving oral disease or bone disease comprising at least one selected from the group consisting of taro extract, tail fern extract and forest buckwheat extract as an active ingredient is provided.
  • the quasi-drug composition for preventing or improving oral disease or bone disease of the present invention may include any one or more or fractions thereof selected from the group consisting of taro extract, tail fern extract and forest buckwheat extract.
  • the term "quasi-drug” is a fiber, rubber product or the like used for the purpose of treating, alleviating, treating or preventing a disease of a person or animal, has a weak effect on the human body or does not act directly on the human body, Or a non-mechanical and similar product, one of the agents used for sterilization, pesticide, and similar purposes for the prevention of infection type, and diagnoses human or animal diseases.
  • a non-mechanical and similar product one of the agents used for sterilization, pesticide, and similar purposes for the prevention of infection type, and diagnoses human or animal diseases.
  • the quasi-drug may include an external preparation for skin or a personal hygiene product.
  • the external preparation for skin is not particularly limited thereto, and specifically, it may be prepared and used in the form of an ointment, lotion, spray, patch, cream, powder, suspension, gel or gel.
  • soap, cosmetics, wipes, tissue shampoo, skin cream, face cream, toothpaste, lipstick, perfume, makeup, foundation, ball touch, mascara, eye shadow, sunscreen lotion, hair care products, It may be an air freshener gel or a cleaning gel.
  • another example of the quasi-drug composition of the present invention is a disinfecting cleaner, shower foam, oral brushing solution, oral spray, wipes, detergent soap, hand wash, humidifier filler, mask, ointment or filter filler.
  • the extract or fraction can be added as it is or used with other quasi-drugs or quasi-drug components, and can be suitably used according to a conventional method, and the active ingredient mixture amount is used It can be determined accordingly.
  • a dental composition for preventing or improving oral diseases comprising at least one selected from the group consisting of taro extract, tail fern extract and forest buckwheat extract as an active ingredient is provided.
  • the dental composition for preventing or improving oral disease of the present invention may include any one or more or a fraction thereof selected from the group consisting of taro extract, tail fern extract and forest buckwheat extract.
  • the term "dental use” may mean a use for preventing or treating diseases and damages in the teeth and its supporting tissues and oral cavity.
  • the dental composition can be applied to dental products such as antibacterial fluorine varnish by adding it to fluorine varnish, oral brushing solution, dental crust relieving agent, antibacterial dental adhesive, dental filling material, dental restorative material, dental It can be applied to and used in dental materials such as root canal fillers, dental root canal sealers, sonar fissure sealants, dental coatings, and dental cement.
  • dental products such as antibacterial fluorine varnish by adding it to fluorine varnish, oral brushing solution, dental crust relieving agent, antibacterial dental adhesive, dental filling material, dental restorative material, dental It can be applied to and used in dental materials such as root canal fillers, dental root canal sealers, sonar fissure sealants, dental coatings, and dental cement.
  • the dental composition can be used for all articles used for oral health.
  • the article include dental products such as dental floss, toothbrush, interdental toothbrush, electric toothbrush, tongue cleaner, mouthwash, toothbrush sterilizer, dental devices such as braces, implants, or all dental tools and instruments used in dental care. However, it is not limited thereto.
  • the article is immersed in the dental composition, the dental composition is applied or sprayed on the surface of the article, the surface of the article is washed several times with the dental composition, or the dental composition seeps
  • Any towel or the like can be used for the article by a method such as wiping the surface of the article, and the method is not particularly limited as long as the article and the dental composition can be contacted for a predetermined time.
  • the time for performing the method is not limited as long as the dental composition can react sufficiently with the surface of the article, and those skilled in the art can appropriately select it.
  • RAW264.7 cells 4 ⁇ 10 3 RAW264.7 cells were plated on GM's 96-well plate. After incubation for 24 hours, in the presence of lipopolysaccharide (LPS, 1 ⁇ g / mL) in cells, the taro extract, tail fern extract and forest buckwheat extract prepared in Example 1 for 1 day were each concentration (0, 3, 10). And 30 ⁇ g / mL). Cell viability (%) was measured three times using Cell Counting Kit-8 (CCK-8, Dojindo, Rockville, ML, USA) according to the manufacturer's manual. Absorbance was measured with a microplate reader (VERSA max TM , Molecular Devices, Sunnyvale, CA) and converted to cell number using a standard curve.
  • LPS lipopolysaccharide
  • Example 2-2 Nitric oxide production inhibitory activity
  • the cells were streaked with 1 ⁇ 10 6 cells in a 60 mm dish, and each of the taro extract, tail fern extract and forest buckwheat extract prepared in Example 1 for 2 hours in concentration (0, 3, 10 and 30 ⁇ g / mL) Treatment. Then, LPS (1 ⁇ g / mL) was added. After incubation for 24 hours, nitrogen oxide (NO) levels were analyzed using a grease reaction. Cell culture medium (100 ⁇ L) was mixed with grease reagent and incubated for 10 minutes at room temperature. Absorbance was measured with a microplate reader at 540 nm. As a blank in all experiments, fresh culture medium was used. Nitrite (NO 2 ) was measured by a standard curve using sodium nitrite (NaNO 2 ).
  • a bacterium Porphyromonas gingivalis P. gingivalis , ATCC33277 .
  • BHI broth containing hemin and menadione was used as a medium to activate Porphyromonas gingivalis bacteria, and after incubation for 72 hours in a 37 ° C CO 2 incubator, each well of a 96-well plate ( into the well) 90 ⁇ L each, 10 ⁇ L each of the taro extract, tail fern extract and the forest buckwheat extract prepared in Example 1 were added.
  • Evaluation of the antimicrobial sustained activity of the taro extract, tail fern extract or forest buckwheat extract against Porphyromonas gingivalis was performed as follows.
  • the film (OHP film) in the form of a disk with a diameter of 5 mm was put in sterile packaging and sterilized with EO gas, and then a sample was prepared as shown in Table 1, and evenly applied to the entire surface of the film with the same thickness, evenly filling the entire surface.
  • three films were made per sample, placed in a petri dish with a diameter of 35 mm, and dried in a clean bench for 30 minutes while UV was turned on.
  • Sample 2 Fluorine varnish KR610 Sample 3 Taro 50 mg / ml (50 ⁇ L) + Fluorine varnish KR610 (50 ⁇ L)
  • Sample 4 Tail fern 50 mg / ml (50 ⁇ L) + Fluorine varnish KR610 (50 ⁇ L)
  • Sample 5 Forest wheat 50 mg / ml (50 ⁇ L) + Fluorine varnish KR610 (50 ⁇ L)
  • the film stored at 80 rpm in a 37 ° C. shaking bath for 3 days was placed on an agar medium. At this time, the surface of the film coated with the sample was allowed to be bonded to the agar medium downward. Subsequently, after incubation in a CO 2 incubator at 37 ° C. for 72 hours, the diameter of the Porphyromonas gingivalis inhibitor band formed around the OHP film was measured in a right angle direction to determine the average as an inhibition zone (mm).
  • the fluoride varnish treatment group showed a significant antibacterial effect compared to the control group, and the fluoride varnish + taro treatment group, the fluoride varnish + tail fern treatment group, and the fluoride varnish + forest remodeling. It was confirmed that all the treatment groups exhibited a significant antibacterial lasting effect compared to the fluoride varnish treatment group.
  • the taro extract, tail fern extract or forest buckthorn extract of the present invention exhibits excellent antibacterial and antibacterial lasting effects against strains causing oral diseases, so the composition comprising any one or more of the extracts may be used for oral diseases. It was found that it can be effectively used for treatment.
  • the bovine varnish treatment group showed an increase of about 60%, and the treatment group of the combination of the fluoride varnish and each extract increased about 150% compared to the control group, and about 50% compared to the control group. It was confirmed to increase.
  • a 5 week old male ICR mouse was purchased and the femur and tibia were taken and washed with ⁇ -MEM containing antibiotics (100 units / mL penicillin and 100 ⁇ g / mL streptomycin) to bone marrow cells ).
  • the bone marrow cells were cultured for 1 day in ⁇ -MEM containing 10% fetal bovine serum (FBS) and macrophage colony-stimulating factor (M-CSF) 10 ng / mL.
  • FBS fetal bovine serum
  • M-CSF macrophage colony-stimulating factor
  • Non-adherent bone marrow cells were dispensed into Petri dishes and cultured for 3 days in the presence of M-CSF (30 ng / mL).
  • TRAP tartrate-resistant acid phosphatase
  • 100 ⁇ l of TRAP buffer solution 100 mM sodium citrate pH 5.0, 50 mM sodium tartrate, 3 mM p-nitrophenyl phosphate
  • 37 After reacting at ° C for 5 minutes, the reaction was terminated by adding 100 ⁇ l of 0.1 N NaOH. Thereafter, the absorbance at 405 nm was measured to measure TRAP activity.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Botany (AREA)
  • Mycology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • General Chemical & Material Sciences (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Biotechnology (AREA)
  • Rheumatology (AREA)
  • Microbiology (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medical Informatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Food Science & Technology (AREA)
  • Nutrition Science (AREA)
  • Polymers & Plastics (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Cosmetics (AREA)

Abstract

La présente invention concerne : une composition pharmaceutique, une composition alimentaire, une composition de quasi-médicament et une composition dentaire, qui sont destinées à prévenir ou à traiter des maladies buccales ou des maladies osseuses et qui contiennent, en tant que principe actif, l'un quelconque ou plusieurs des extraits choisis dans le groupe constitué par un extrait de taro, un extrait d'Asplenium incisum et un extrait de Brachypodium sylvaticum. En particulier, l'extrait de taro, l'extrait d'Asplenium incisum et l'extrait de Brachypodium sylvaticum de la présente invention inhibent de manière significative l'activité des bactéries Porphyromonas gingivalis à l'origine de maladies buccales, et inhibent de manière significative la formation ou la différenciation d'ostéoclastes, tout en présentant une faible toxicité car ils sont issus de produits naturels, et peuvent ainsi être utiles pour prévenir ou traiter des maladies buccales ou des maladies osseuses.
PCT/KR2019/012220 2018-09-21 2019-09-20 Composition pour la prévention ou le traitement de maladies buccales ou de maladies osseuses WO2020060277A1 (fr)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
KR1020180114244A KR102061981B1 (ko) 2018-09-21 2018-09-21 숲개밀 추출물을 유효성분으로 포함하는 구강질환 또는 골질환의 예방 또는 치료용 조성물
KR1020180114243A KR102167725B1 (ko) 2018-09-21 2018-09-21 꼬리고사리 추출물을 유효성분으로 포함하는 구강질환 또는 골질환의 예방 또는 치료용 조성물
KR10-2018-0114242 2018-09-21
KR1020180114242A KR102167724B1 (ko) 2018-09-21 2018-09-21 토란 추출물을 유효성분으로 포함하는 구강질환 또는 골질환의 예방 또는 치료용 조성물
KR10-2018-0114243 2018-09-21
KR10-2018-0114244 2018-09-21

Publications (1)

Publication Number Publication Date
WO2020060277A1 true WO2020060277A1 (fr) 2020-03-26

Family

ID=69887604

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2019/012220 WO2020060277A1 (fr) 2018-09-21 2019-09-20 Composition pour la prévention ou le traitement de maladies buccales ou de maladies osseuses

Country Status (1)

Country Link
WO (1) WO2020060277A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022031151A1 (fr) * 2020-08-07 2022-02-10 고려대학교 산학협력단 Composition antivirale comprenant un extrait de fougère aigle orientale ou une fraction de celle-ci

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20150094958A (ko) * 2014-02-12 2015-08-20 재단법인 진안홍삼연구소 아카세틴을 유효성분으로 함유하는 치아우식증 및 치주질환을 예방, 개선 또는 치료하는 조성물

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20150094958A (ko) * 2014-02-12 2015-08-20 재단법인 진안홍삼연구소 아카세틴을 유효성분으로 함유하는 치아우식증 및 치주질환을 예방, 개선 또는 치료하는 조성물

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
"Non-official translation: Internet blog. Folk Remedy for Gum", 20 June 2018 (2018-06-20), Retrieved from the Internet <URL:https://blog.naver.com/angel42195/221302712929> *
"Non-official translation: Internet blog. Taro Stem Fried Rice Preventing Osteoporosis", 22 November 2012 (2012-11-22), Retrieved from the Internet <URL:https://blog.naver.com/yy2she/100172269466> *
"Non-official translation: MOODEUNGILBO. Unsaturated Fatty Acid Activating Brain Cell", 28 September 2016 (2016-09-28), Retrieved from the Internet <URL:http://mdilbo.com/article.php?aid=1474988400596106311> *
PAWAR, H. A.: "An overview of traditionally used herb, colocasia esculenta, as a phytomedicine", MEDICINAL & AROMATIC PLANTS, 30 August 2018 (2018-08-30), XP055694831 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022031151A1 (fr) * 2020-08-07 2022-02-10 고려대학교 산학협력단 Composition antivirale comprenant un extrait de fougère aigle orientale ou une fraction de celle-ci

Similar Documents

Publication Publication Date Title
WO2016117933A1 (fr) Composition orale contenant un extrait de feuilles de camellia, et son procédé de préparation
WO2018012848A1 (fr) Composition pharmaceutique permettant de stimuler la croissance des tissus parodontaux et prévenir ou traiter la parodontite, comprenant un mélange d&#39;extrait de cortex de magnoliae officinalis et d&#39;extrait de magnoliae flos en tant que constituant actif
WO2020060277A1 (fr) Composition pour la prévention ou le traitement de maladies buccales ou de maladies osseuses
WO2015030293A1 (fr) Composition contenant un extrait composite de raisin et de schisandra chinensis pour la prévention ou le traitement de maladies associées au syndrome métabolique
WO2019230996A1 (fr) Composition permettant la prévention ou le traitement de maladies de la bouche
KR102260037B1 (ko) 참꽃마리 추출물을 유효성분으로 포함하는 골질환의 예방 또는 치료용 조성물
WO2020138834A1 (fr) Composition pour la prévention ou le traitement de maladies de la peau comprenant de la spirée couronne de mariée
US7875598B2 (en) Compositions useful for the treatment of microbial infections
WO2019139403A1 (fr) Composition contenant de la séricine, un extrait de torilis japonica et un extrait de viscum album pour la régénération de la peau, l&#39;apaisement de la peau ou la cicatrisation des plaies
KR102167724B1 (ko) 토란 추출물을 유효성분으로 포함하는 구강질환 또는 골질환의 예방 또는 치료용 조성물
KR102167725B1 (ko) 꼬리고사리 추출물을 유효성분으로 포함하는 구강질환 또는 골질환의 예방 또는 치료용 조성물
KR102061981B1 (ko) 숲개밀 추출물을 유효성분으로 포함하는 구강질환 또는 골질환의 예방 또는 치료용 조성물
WO2021235807A1 (fr) Composition de soin de santé buccale comprenant comme principe actif un matériau d&#39;origine naturelle composite dérivé de palmier nipa contenant un phyto-sel, son procédé de préparation, et produit de soin de santé buccale fabriqué à l&#39;aide de la composition
KR102334997B1 (ko) 보풀 속 식물 추출물을 유효성분으로 포함하는 구강질환 또는 골질환의 예방 또는 치료용 조성물
KR20220085035A (ko) 노각나무 추출물을 포함한 구강 건강 개선용 조성물 및 이를 포함하는 제품
KR102284261B1 (ko) 섬초롱꽃 추출물을 유효성분으로 포함하는 골질환의 예방 또는 치료용 조성물
KR102380075B1 (ko) 노각나무 추출물을 포함하는 구강 질환 예방 또는 치료용 조성물
KR101634210B1 (ko) 캠페롤을 유효성분으로 함유하는 충치와 치주질환 예방 또는 치료용 조성물
KR102343906B1 (ko) 세리신을 포함하는 구강용 조성물
WO2017204412A1 (fr) Produit absorbant jetable comprenant une composition désodorisante présentant une activité anti-bactérienne et anti-inflammatoire
WO2024063550A1 (fr) Composition pour la prévention, l&#39;amélioration ou le traitement de maladies provoquées par une matière particulaire contenant un extrait de pépins de citri tangerinae et son utilisation
WO2022014931A1 (fr) Composition de film à désintégration orale pour animaux, ayant pour effet de réduire l&#39;halitose, le tartre dentaire, la stomatite et la parodontite
WO2022220502A1 (fr) Composition antibactérienne contenant un extrait d&#39;elaeocarpus sylvestris ou un filtrat de celui-ci comme principe actif
WO2020138833A1 (fr) Composition comprenant un extrait de corylus heterophylla pour la prévention ou le traitement d&#39;une maladie de la peau
KR101834758B1 (ko) 봉독을 유효성분으로 포함하는 치주염의 예방 또는 치료용 조성물

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 19862681

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 19862681

Country of ref document: EP

Kind code of ref document: A1