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WO1997035599A1 - Composition de prevention et de traitement d'affections periodontiques - Google Patents

Composition de prevention et de traitement d'affections periodontiques Download PDF

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Publication number
WO1997035599A1
WO1997035599A1 PCT/KR1997/000048 KR9700048W WO9735599A1 WO 1997035599 A1 WO1997035599 A1 WO 1997035599A1 KR 9700048 W KR9700048 W KR 9700048W WO 9735599 A1 WO9735599 A1 WO 9735599A1
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WO
WIPO (PCT)
Prior art keywords
extract
composition
zizyphi fructus
cortex
effect
Prior art date
Application number
PCT/KR1997/000048
Other languages
English (en)
Inventor
Chong-Pyoung Chung
Ki-Hwan Bae
Chong-Keun Chung
Original Assignee
Daewoong Pharmaceutical Co., Ltd.
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Filing date
Publication date
Application filed by Daewoong Pharmaceutical Co., Ltd. filed Critical Daewoong Pharmaceutical Co., Ltd.
Priority to AU21800/97A priority Critical patent/AU2180097A/en
Publication of WO1997035599A1 publication Critical patent/WO1997035599A1/fr

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Classifications

    • 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)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/57—Magnoliaceae (Magnolia family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • 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)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/534—Mentha (mint)
    • 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)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/57—Magnoliaceae (Magnolia family)
    • A61K36/575—Magnolia
    • 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)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/72—Rhamnaceae (Buckthorn family), e.g. buckthorn, chewstick or umbrella-tree
    • A61K36/725—Ziziphus, e.g. jujube
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/0216—Solid or semisolid forms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • 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

Definitions

  • the present invention relates to a composition for the prevention and treatment of periodontal diseases. More specifically, the present invention relates to a composition for the prevention and treatment of periodontal diseases comprising an extract of Zizyphi fructus and an extract of Magnoliae cortex.
  • a composition for the prevention and treatment of periodontal diseases comprising an extract of Zizyphi fructus and an extract of Magnoliae cortex.
  • the extracts of Zizyphi fructus and Magnoliae cortex are combined so that the ratio of the weight of the former to the weight of the latter ranges from 1:6 to 1:12, and more particularly from 1:8 to 1:10, their combination exhibits a synergistic effect in treating periodontal disease that is superior to the sum of their individual effects.
  • the combination is excellent for preventing and treating periodontal disease compared to agents disclosed in the prior art.
  • Periodontal diseases are generally classified as dental caries and periodontal diseases.
  • a periodontal disease is an infectious oral disease which most frequently occurs in adult man, and results in the loss of teeth due to gingival bleeding and swelling, formation of periodontal inflammation and disruption of alveolar bone, and the like.
  • plaque is mechanically accumulated in periodontal pocket and then serves as a habitat for microorganisms. These microorganisms gradually change from aerobic gram -positive bacteria to anaerobic gram- negative bacteria as they penetrate deep into the periodontal pocket. Fully grown anaerobic gram-negative bacteria produce toxins and other substances which directly disrupt the periodontal tissues and trigger the immunologic system.
  • the stimulated immunological system induces the disruption of alveolar bone and the inflammation of periodontal tissues through various mechanisms.
  • the causative microorganisms of periodontal disease are Porphyrom ⁇ nas gingi ⁇ alis, Prevotella intermedia, Actinobacillus actinomycetemcomitans, etc., which are all gram-negative anaerobic bacteria normally present in the oral cavity, in contrast to the causative organisms of dental caries.
  • periodontal diseases generally occur in adult man because periodontal tissues are weakened with age.
  • antibiotics for example, chlorhexidine, cetylpyridinium chloride
  • chemotherapeutic agents for example, chlorhexidine, cetylpyridinium chloride
  • antibiotics and chemotherapeutic agents have undesirable side effects such as ulceration of oral mucous membranes, induction of desquamative ginigivitis, colouring, etc.
  • an enzyme preparation that decomposes plaque stroma, and a fluorine preparation that inhibits the adsorption of bacteria onto the surfaces of teeth have also been disclosed for preventing periodontal disease.
  • the present inventors have intensively studied various medicinal herbs in order to develop a therapeutic agent which overcomes the above mentioned disadvantages of the prior art agents for treatment of periodontal disease using medicinal herbs.
  • the present inventors have found that the extract of Magnoliae cortex shows a good anti -inflammatory effect and a potent antibacterial effect on the causative organisms of periodontal disease, without the harmful side effects exhibited by the prior art antibiotics (see, Korean Laid-open Patent
  • the extract of Magnoliae cortex displays good anti- inflammatory and antibacterial activities, it has the disadvantage of lowering the activity of periodontal tissue cells as its dosage increases. Meanwhile, the extracts of Zizyphi fructus and Ginkgo folium together exhibit a good tissue regenerating effect but also have a weak antibacterial effect. Therefore, they are disadvantageous in view of the fact that they exhibit the effect through only some ways among various mechanisms involved in the prevention and treatment of periodontal diseases.
  • the present invention relates to a composition
  • a composition comprising the extract of Zizyphi fructus and the extract of Magnoliae cortex as its effective components which, at certain weight ratios of its active components, is broadly effective for preventing and treating periodontal diseases (i.e. exhibits (1) a regenerative effect on weakened or disrupted periodontal tissues, (2) an inhibitory effect on the inflammatory response which disrupts the periodontal tissues, and (3) an antibacterial effect on causative organisms of periodontal diseases) and which is far more effective than each of the extracts of Zizyphi fructus and Magnoliae cortex alone.
  • the composition of the present invention has the additional advantage that it has no harmful side effects such as those exhibited by antibiotics of the prior art.
  • Figure 1 is a photograph ( 40) of the calvaria of a mouse of the fifth group, which was used as the negative control group according to Experiment 4, 2 weeks after the defect operation. This photograph shows that at both sides of the defected portion having diameter of 5mm in the calvaria some new bone has formed in line but that the whole defected portion has filled with fibrous connective tissues.
  • Figure 2 is a photograph ( X 40) of the calvaria of a mouse of the third group (unsaponified extract of Zea mays, O.lg/kg), which was used as the positive control group according to Experiment 4, 2 weeks after the defect operation.
  • This photograph shows that most of the defected portion having diameter of 5mm in the calvaria has filled with fibrous connective tissues and that new bone and bone-like tissues have formed around the existing defected bone tissue.
  • Figure 3 is a photograph ( X40) of the calvaria of a mouse of the fourth group (unsaponified extract of Zea mays, 0.5g/kg), which was used as the positive control group according to Experiment 4, 2 weeks after the defect operation. This photograph shows that most of the defected portion having diameter of 5mm in the calvaria has filled with fibrous connective tissues and that new bone and bone-like tissues have formed within the inner bone-defected space but that the total unification has not occurred.
  • Figure 4 is a photograph ( 40) of the calvaria of a mouse of the first group (present composition, O.lg/kg), which was used as the test group according to Experiment 4, 2 weeks after the defect operation. This photograph shows that the defected portion having diameter of 5mm in the calvaria has filled with connective tissues and new bone and bone -like tissues have actively formed at the existing defected bone tissue but not fill all the bone-defected space, and that the total unification has not occurred.
  • Figure 5 is a photograph ( 40) of the calvaria of a mouse of the second group (present composition, 0.5g/kg), which was used as the test group according to Experiment 4, 2 weeks after the defect operation. This photograph shows that the defected portion having diameter of 5mm in the calvaria has fully filled with newly formed bone and bone-like tissues, that some unification has occurred, and in the bone-like tissue active bone cells are found and new bone is greatly produced.
  • Figure 6 is a photograph ( 40) of the calvaria of a mouse of the fifth group, which was used as the negative control group according to Experiment 4, 3 weeks after the defect operation. This photograph shows that the formation of new bone and bone-like tissues has initiated at both sides of defected portion having diameter of 5m_ ⁇ in the calvaria and has actively penetrated into the middle part, but the middle part of the bone-defected portion has still filled with fibrous connective tissues.
  • Figure 7 is a photograph ( 40) of the calvaria of a mouse of the third group (unsaponified extract of Zea mays, O.lg/kg), which was used as the positive control group according to Experiment 4, 3 weeks after the defect operation.
  • This photograph shows that the formation of new bone and bone-like tissues has begun at both sides of defected portion having diameter of 5mm in calvaria and has actively penetrated into the middle part, but the middle part has filled with fibrous connective tissues, and the type of newly formed bone and bone-like tissues is similar to that of Figure 6.
  • Figure 8 is a photograph ( 40) of the calvaria of a mouse of the fourth group (unsaponified extract of Zea mays, 0.5g/kg), which was used as the positive control group according to Experiment 4, 3 weeks after the defect operation.
  • This photograph shows that the formation of new bone and bone-like tissues has actively initiated at both sides of defected portion having diameter of 5m ⁇ in calvaria and attained up to near the middle part of bone-defected portion, but the middle part of the bone- defected portion has filled with some fibrous connective tissues, and the formation of new bone is greater than that in Figures 6 and 7.
  • Figure 9 is a photograph ( 40) of the calvaria of a mouse of the first group (present composition, O.lg/kg), which was used as the test group according to Experiment 4, 3 weeks after the defect operation. This photograph shows that the formation of new bone and bone-like tissues has actively progressed from both sides of the defected portion having diameter of 5mm in calvaria to fill all the bone-defected portion with bone-like tissue and the bone-like tissues are rapidly replaced with new bone.
  • Figure 10 is a photograph ( x 40) of the calvaria of a mouse of the second group (present composition, 0.5g/kg), which was used as the test group according to Experiment 4, 3 weeks after the defect operation. This photograph shows that the formation of new bone has actively progressed from both sides of the defected portion having diameter of 5mm in calvaria to fill all the bone-defected portion with new bone and the unification is perfectly occurred.
  • the extract of Magnoliae cortex is best obtained by extracting Magnoliae cortex with an alcohol, preferably with a lower alkanol such as ethanol. It is also preferable to use an extract of Magnoliae cortex containing at least 5.0% of magnolol and at least 1.0% of honokiol as its major ingredients.
  • the extract of Zizyphi fructus is best obtained by extracting Zizyphi fructus with an alcohol, preferably with a lower alkanol such as ethanol, in a water bath and then concentrating the extract under reduced pressure.
  • composition comprising the extracts of Zizyphi fructus and Magnoliae cortex as its active components according to the present invention exhibits a surprising synergistic effect for treating periodontal diseases when these extracts are present in specific proportions. Specifically, as demonstrated by the experiments detailed below, a synergistic effect is evident when the ratio of the weight of the extract of Zizyphi fructus to the weight of the extract of Magnoliae cortex ranges from 1:6 to 1:12, and preferably from 1:8 to 1:10.
  • composition of the present invention uses the extract of Zizyphi fructus and the extract of Magnoliae cortex in the mixing ratio ranging from 1:6 to 1:12, particularly preferably in the mixing ratio ranging from 1:8 to 1:10, on the basis of weight.
  • composition of the present invention comprising the extracts of Zizyphi fructus and Magnoliae cortex in the mixing ratios mentioned above
  • the composition would preferably be used in pharmaceutical preparations formulated by adding conventional pharmaceutically acceptable excipients to the composition.
  • the pharmaceutical preparations used for this purpose include tablets, ointments, solutions (gargles), sprays, etc.
  • the composition of the present invention may be included in the toothpaste or formulated as tablets for internal use, ointments for external use, or solutions by mixing the extracts with pharmaceutically acceptable carriers.
  • composition of the present invention may be included in conventional gargle preparations for washing the mouth, or it may be mixed with a propellant to prepare a spray packaged in a pressurized container and then sprayed onto the attacked periodontal portion, or it may be included in toothpaste which is used over a long period of time to obtain the preventive and therapeutic effect on periodontal diseases.
  • the effective dosage of the present composition can be varied depending on the purpose of use, the severity of periodontal disease to be treated, the preparation employed, etc., but is generally from 50mg to 5g, particularly from lOOmg to 3g, per day for an adult man, as the combination of the extracts of Zizyphi fructus and Magnoliae cortex.
  • the content of the combination of the extracts of Zizyphi fructus and Magnoliae cortex in the total composition may be varied depending on the purpose of its use. However, when the content of the active ingredients is too low, the pharmaceutical effect of the composition rapidly decreases, whereas when their content is too high, the quality of the product may be reduced due to the colouring effects of the extracts of Zizyphi fructus and Magnoliae cortex.
  • a tablet contains from 50mg to 250mg of the combination of the present invention and the ointment, solution (gargle), toothpaste and spray contain the combination of the present invention in the concentration of 0.2 to 5.0 wt%.
  • the composition of the present invention can further contain additional medicinal herbs used to prevent and treat periodontal diseases, for example, extract of Ginkgo folium, Myrrha, extract of Mori radicis cortex, Sanguinaria extract, extract of Zea mays, etc.
  • Magnoliae cortex 500g was sliced off and then extracted twice with 2.5 i of 70% ethanol for 3 hours, each time while refluxing in a water bath. The extracts were combined and then filtered. The filtrate was concentrated to obtain 60g of the extract of Magnoliae cortex.
  • composition comprising the combination of the extracts of Zizyphi fructus and Magnoliae cortex can be prepared in tablet, ointment, toothpaste, solution (gargles) or spray form using conventional methods in the pharmaceutical field.
  • the mixing ratio by weight of the extracts of Zizyphi fructus and Magnoliae cortex ranges from 1:6 to 1:12, particularly, and preferably from 1:8 to 1:10, in view of the following experimental results.
  • the specific examples of the present composition are as follows.
  • Composition 1 Film coated tablet (in each 600mg tablet)
  • the tablet was prepared from the above mentioned components using conventional method for preparing tablets.
  • Composition 2 Ointment (in wt%)
  • the ointment was prepared from the above mentioned components using the conventional method for preparing ointments.
  • Composition 3 Toothpaste (in wt%)
  • Composition 4 Solution (in wt%)
  • the solution was prepared by mixing and dissolving the above mentioned components and then adjusting the pH value to 5.0 using conventional method for preparing solutions.
  • Composition 5 Sprav (in wt%)
  • the spray was prepared by mixing the above mentioned components and then packaging the mixture into a pressurized container using conventional method for preparing sprays.
  • gingival fibroblasts were obtained by collecting the gingiva of first premolar from the patients attending Seoul National University Hospital for teeth correction. Just before collecting the gingiva, dental calculus and plaque were removed using curette and the mouth was washed several times with 0.1% cyclohexidine digluconate solution. Then, the gingiva was locally anesthesized and then the normal gingival tissues were taken by incising the inner slanting surface between teeth.
  • the collected tissue specimen was incubated in the a -MEM medium (Gibco, Inc., Grand Island, N.Y., U.S.A.) supplemented with 100U/m£ of penicillin, 100 -g/n of streptomycin and 10% FBS and then subjected to subculture 5 times while replacing the medium with the same volume of fresh medium at the intervals of three days. During incubation, humidity of 95% and temperature of 37 TJ were maintained and 95% air and 5% CO2 were continuously supplied. The subcultured gingival fibroblast was treated with 0.25% trypsin-EDTA (ethylenediaminetetraacetate) solution and centrifuged at 1200rpm to obtain the cell suspension in the medium.
  • trypsin-EDTA ethylenediaminetetraacetate
  • This suspension was distributed into 96-well plate using standard hemocytometer in an amount of 1 x 10 5 cells per well and then incubated at 37 °C, 5% CO2 for one day. After one day, each well was washed with HBSS (Hank's Balanced Salt Solution) and then the medium was replaced with fresh medium.
  • HBSS Hort's Balanced Salt Solution
  • PDGF-BB platelet derived growth factor
  • Genzyme Co., Cambridge, M.A., U.S.A.
  • DMSO dimethylsulf oxide
  • T abbreviates the cell activity with test substance and C abbreviates the cell activity in the negative control group.
  • EMC Extract of Magnoliae cortex
  • T abbreviates the cell activity with test substance and C abbreviates the cell activity in the negative control group.
  • the extract of Zizyphi fructus and the extract of Magnoliae cortex are each used alone, the extract of Zizyphi fructus enhances the activity of gingival fibroblasts while the extract of Magnoliae cortex inhibits the activity of gingival fibroblasts.
  • composition of extracts of Zizyphi fructus and Magnoliae cortex shows a synergistic effect at certain mixing ratios in comparison to the use of each extract alone and is evidently a good agent for treatment of periodontal disease.
  • the anti -inflammatory effect of the composition containing the extracts of Zizyphi fructus and Magnoliae cortex according to the present invention was determined by measuring the effect of inhibiting PGE 2 production of gingival fibroblast in vitro.
  • the gingival fibroblast subcultured 5 to 7 times was distributed in 24- well plate in the concentration of 10 5 cells in l ⁇ u2 of a -MEM medium (Gibco, In. Grand Island, N.Y., U.S.A.) containing 1% antibiotics and 10% FBS per each well, and then lng/m£ of rHUIL-1 /5 (Genzyme, Co., Cambridge, M.A., U.S.A.) was added to each well to induce the production of PGE 2 .
  • a -MEM medium Gibco, In. Grand Island, N.Y., U.S.A.
  • EMC Extract of Magnoliae cortex
  • Porphyromonas gingivalis W50 (PG) and Pre ⁇ otella intermedia ATCC 25611 (PI) were inoculated onto trypticase soy agar blood medium containing 5 g of hemin and 0.5/.g of menadione and then incubated in the manner of pure culture in an anerobic incubator containing 10% CO 2 , 10% H2 and 80% N2 at 37 " C.
  • Actinobacillus actinomycetemcomitans Y4 (AA) was inoculated onto trypticase soy agar blood medium and then aerobically incubated in the manner of pure culture in a bacterial incubator containing 10% CO2.
  • Each bacterial strain was purely incubated for 4 to 7 days, then inoculated onto trypticase soy broth and incubated for 48 to 72 hours in either an anerobic or an aerobic incubator as mentioned above until the bacterial count reaches 10 7 cells/nv2.
  • the incubated bacterial strains were inoculated onto the blood agar medium combined with the test substances in the concentration as described in the following table using a multi-inoculator.
  • the medium was incubated in an anerobic incubator containing 10% CO2, 10% H2 and 80% N2 at 37 "C for 3 to 5 days and the growth of bactrial strains was then visually identified to determine the minimum inhibitory concentration (MIC) of the test substance on the growth of each strain.
  • the measured MICs are described in the following Table 7.
  • EZF Extract of Zizyphi fructus
  • EMC Extract of Magnoliae cortex
  • EGF Extract of Ginkgo folium
  • the composition of the extracts of Zizyphi fructus and Magnoliae cortex which was identified as showing a synergistic effect in the experiments for gingival fibroblast activity in Experiment 1 and for showing an anti- inflammatory effect in Experiment 2, also exhibits a superior antibacterial effect at a mixing ratio of the two extracts ranging from 1:6 to 1:12 on the basis of weight, in comparison to the single use of each extract.
  • This observation resulted from the fact that although the extract of Zizyphi fructus itself has substantially no antibacterial effect, its combination with the extract of Magnoliae cortex increases the antibacterial effect of the extract of Magnoliae cortex.
  • composition of extracts of Ginkgo folium and Magnoliae cortex shows an evident synergistic antibacterial effect in comparison to the single use of each extract.
  • composition of the present invention the combination of the extract of Zizyphi fructus and the extract of Magnoliae cortex in the mixing ratio ranging from 1:10 on the basis of weight was administered daily in an amount of O.lg (first group) or 0.5g (second group) per kg of mouse body weight, and as the positive control group the unsaponified extract of Zea may was also administered daily in an amount of O.lg (third group) or 0.5g (fourth group) per kg of mouse body weight.
  • Mouse not receiving any test substance was used as the negative control group (fifth group).
  • the daily dosage of each test substance was divided into two, each of which was dissolved in lm*2 of distilled water and then administered directly to mouse stomach via oral zonde needle in the morning and in the afternoon, respectively.
  • Mouse weighing 200-250g was anesthesized with 30mg/kg of pentobarbital sodium (Hanlim Pharm. Co., Seoul, Korea) by intraperitoneal injection. Then, hair of mouse head was cut and then the portion to be operated was disinfected with 0.5% chlorhexidine. For the rest and convenience during operation, mouse head was fixed with cephalostat, and then cut out along the centerline from the front part of frontal bone to the rear part of occipital bone. The skin and mucous membrane were pulled outside to expose the calvaria. One side of temporal bone was perforated in a diameter of 5mm using trephine bur (3i, Florida, U.S.A.) without any defect to meninges and then sutured.
  • trephine bur 3i, Florida, U.S.A.
  • test substances were administered in the manner as mentioned above and, after 2 or 3 weeks mouse was sacrificed to remove the calvaria which was fixed in 10% formalin, introduced into 5% trichloroacetic acid for 5 days to remove the gray matter, and then subjected to dehydration and paraffin embedding.
  • the embedded specimen was sliced into sections having thickness of 6 ⁇ m and dyed with Masson-trichrome. Then the tissues were observed using an optical microscope, Olymphus BH-2 (Olymphus Optical Co., Ltd., Osaka, Japan). The results as observed are shown in Figures 1 to 10.
  • the composition of the present invention comprising the extract of Zizyphi fructus and the extract of Magnoliae cortex in the mixing ratio ranging from 1:6 to 1:12 on the basis of weight can overcome the one-sided effects obtained from the single use of each extract to provide various therapeutic effects on periodontal diseases.
  • the effect of the present composition shows synergistically and is far better than that obtained from the single use of each extract.
  • compositions 1 to 5 above each preparation was stored under the conditions described below and then the contents of magnolol in the extract of Magnohae cortex contained in the preparation was analysed with HPLC using UV detector at 254nm. The result is described in the following Table 8.
  • Test substances The test samples prepared in Compositions 1 to 5 were filled in a glass bottle or a compressed container, which was then plugged and put in a cardboard box.
  • composition 1 Frm-coated tablet
  • Composition 5 (Spray) : content

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Abstract

La présente invention, qui concerne une composition de prévention et de traitement d'affection périodontique, concerne plus particulièrement une composition de prévention et de traitement d'affection périodontique comprenant un extrait de jujube (Zizyphi fructus) et un extrait d'écorce de magnolia (Magnoliae cortex). Lorsque l'extrait de jujube et l'extrait d'écorce de magnolia sont combinés selon une proportion pondérale allant de 1 pour 6 à 1 pour 12, et de préférence de 1 pour 8 à 1 pour 10, ils font preuve ensemble d'un effet de synergie par rapport à l'utilisation de l'un d'eux pris isolément. En outre, il semblent convenir particulièrement mieux au traitement des affections périodontiques que les agents énoncés selon les états antérieurs de la technique pour la prévention et le traitement d'affections périodontiques.
PCT/KR1997/000048 1996-03-26 1997-03-26 Composition de prevention et de traitement d'affections periodontiques WO1997035599A1 (fr)

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AU21800/97A AU2180097A (en) 1996-03-26 1997-03-26 Composition for prevention and treatment of periodontal diseases

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KR1019960008393A KR0176015B1 (ko) 1996-03-26 1996-03-26 치주질환 예방 및 치료제 조성물
KR1996/8393 1996-03-26

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Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH11279039A (ja) * 1998-03-31 1999-10-12 Saiseido Yakuhin Kk 口腔用組成物
WO2001082922A1 (fr) * 2000-04-27 2001-11-08 The Procter & Gamble Company Compositions orales contenant des extraits vegetaux de polyphenol
WO2001085116A3 (fr) * 2000-05-10 2002-05-23 Colgate Palmolive Co Composition buccale synergique agissant contre la plaque dentaire et la gingivite
WO2004000235A3 (fr) * 2002-06-25 2004-09-30 Wrigley W M Jun Co Produit de rafraichissement de l'haleine et de nettoyage de la cavite orale contenant un extrait d'ecorce de magnolia
WO2006069209A1 (fr) * 2004-12-22 2006-06-29 Colgate-Palmolive Company Composition de soins buccaux anti-bacterienne et anti-inflammatoire
WO2006071653A1 (fr) 2004-12-29 2006-07-06 Colgate-Palmolive Company Procede destine a reduire l'inflammation des tissus buccaux au moyen d'extrait de magnolia
WO2007011504A1 (fr) * 2005-07-14 2007-01-25 Wm. Wrigley Jr. Company Produit de rafraichissement de l'haleine et de nettoyage buccal qui comprend un extrait d'ecorce de magnolia et un tensioactif
WO2007064519A1 (fr) * 2005-12-02 2007-06-07 Gic Innovations Company Excipients pour soins buccaux avec un extrait d’écorce de magnolia
WO2007126651A3 (fr) * 2006-03-29 2008-03-13 Wrigley W M Jun Co Produits de rafraîchissement de l'haleine et de purification de la cavité orale contenant des combinaisons synergiques d'extraits d'écorce de magnolia et d'huiles essentielles
US7347985B2 (en) 2002-06-25 2008-03-25 Wm. Wrigley Jr. Company Breath freshening and oral cleansing product with magnolia bark extract
EP1957169A1 (fr) * 2005-12-02 2008-08-20 GIC Innovations Company Compositions a macher avec de l'extrait d'ecorce de magnolia a liberation rapide
US7470442B2 (en) 2005-12-02 2008-12-30 Gic Innovations Company Confectionary compositions with magnolia bark extract
JP2009114101A (ja) * 2007-11-05 2009-05-28 Kazuo Nagai 歯周病の予防又は治療用の医薬組成物、口腔衛生剤、並びに食品組成物
WO2011106493A2 (fr) 2010-02-24 2011-09-01 Colgate-Palmolive Company Compositions de soin buccal
WO2011106492A1 (fr) 2010-02-24 2011-09-01 Colgate-Palmolive Company Compositions de soins buccaux
US9101555B1 (en) 2007-04-19 2015-08-11 Mary Kay Inc. Magnolia extract containing compositions
CN103893071B (zh) * 2004-12-22 2016-11-30 高露洁-棕榄公司 抗菌和抗炎的口腔护理组合物

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KR100361880B1 (ko) * 2000-06-22 2002-11-23 동국제약 주식회사 옥수수불검화 정량 추출물 및 후박 추출물을 함유하는치주질환 예방 및 치료제 조성물
KR101704589B1 (ko) * 2016-07-12 2017-02-08 주식회사 뉴트라팜텍 후박 추출물 및 신이 추출물의 혼합물을 유효성분으로 함유하는 치주조직 성장 촉진용 및 치주염 예방 또는 치료용 약학적 조성물
KR102621090B1 (ko) 2023-08-20 2024-01-23 주식회사 구강닥터 소취와 충치예방이 가능한 마시는 가글액 조성물 및 그의 제조방법

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WO2001082922A1 (fr) * 2000-04-27 2001-11-08 The Procter & Gamble Company Compositions orales contenant des extraits vegetaux de polyphenol
AU2001261309B2 (en) * 2000-05-10 2008-07-03 Colgate-Palmolive Company Synergistic antiplaque/antigingivitis oral composition
WO2001085116A3 (fr) * 2000-05-10 2002-05-23 Colgate Palmolive Co Composition buccale synergique agissant contre la plaque dentaire et la gingivite
US6500409B1 (en) 2000-05-10 2002-12-31 Colgate Palmolive Company Synergistic antiplaque/antigingivitis oral composition
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US8163304B2 (en) 2002-06-25 2012-04-24 Wm. Wrigley Jr. Company Breath freshening and oral cleansing product with magnolia bark extract in combination with surface active agents
EP3025703A1 (fr) * 2002-06-25 2016-06-01 Wm. Wrigley Jr. Company Produit de rafraichissement de l'haleine et de nettoyage de la cavite orale contenant un extrait d'ecorce de magnolia
US7632525B2 (en) 2002-06-25 2009-12-15 Wm. Wrigley Jr. Company Breath freshening and oral cleansing product with magnolia bark extract in combination with surface active agents
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US7595065B2 (en) 2002-06-25 2009-09-29 Wm. Wrigley Jr. Company Breath freshening and oral cleansing products with synergistic combinations of magnolia bark extract and essential oils
WO2004000235A3 (fr) * 2002-06-25 2004-09-30 Wrigley W M Jun Co Produit de rafraichissement de l'haleine et de nettoyage de la cavite orale contenant un extrait d'ecorce de magnolia
US8900644B2 (en) 2004-12-22 2014-12-02 Colgate-Palmolive Company Oral care compositions containing compounds from magnolia and hops extracts
WO2006069209A1 (fr) * 2004-12-22 2006-06-29 Colgate-Palmolive Company Composition de soins buccaux anti-bacterienne et anti-inflammatoire
CN103893071B (zh) * 2004-12-22 2016-11-30 高露洁-棕榄公司 抗菌和抗炎的口腔护理组合物
RU2406522C2 (ru) * 2004-12-29 2010-12-20 Колгейт-Палмолив Компани Способ уменьшения воспаления ткани ротовой полости с использованием экстракта магнолии
AU2005322191B2 (en) * 2004-12-29 2009-08-20 Colgate-Palmolive Company Method of reducing oral tissue inflammation using magnolia extract
WO2006071653A1 (fr) 2004-12-29 2006-07-06 Colgate-Palmolive Company Procede destine a reduire l'inflammation des tissus buccaux au moyen d'extrait de magnolia
WO2007011504A1 (fr) * 2005-07-14 2007-01-25 Wm. Wrigley Jr. Company Produit de rafraichissement de l'haleine et de nettoyage buccal qui comprend un extrait d'ecorce de magnolia et un tensioactif
AU2006270385B2 (en) * 2005-07-14 2010-02-18 Wm. Wrigley Jr. Company Breath freshening and oral cleansing product comprising a Magnolia Bark Extract and surfactant
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WO2007126651A3 (fr) * 2006-03-29 2008-03-13 Wrigley W M Jun Co Produits de rafraîchissement de l'haleine et de purification de la cavité orale contenant des combinaisons synergiques d'extraits d'écorce de magnolia et d'huiles essentielles
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JP2013520518A (ja) * 2010-02-24 2013-06-06 コルゲート・パーモリブ・カンパニー 口腔ケア組成物
JP2013520517A (ja) * 2010-02-24 2013-06-06 コルゲート・パーモリブ・カンパニー 口腔ケア組成物
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AU2180097A (en) 1997-10-17
KR0176015B1 (ko) 1999-03-20

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