US20100069477A1 - Methioninase inhibitor and composition and food or drink containing the same - Google Patents

Methioninase inhibitor and composition and food or drink containing the same Download PDF

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US20100069477A1
US20100069477A1 US12/309,645 US30964507A US2010069477A1 US 20100069477 A1 US20100069477 A1 US 20100069477A1 US 30964507 A US30964507 A US 30964507A US 2010069477 A1 US2010069477 A1 US 2010069477A1
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myrsinoic
extract
myrsinoic acid
ethanol
methioninase
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Satomi Itoh
Atsushi Narise
Takanori Tsugane
Susumu Shimura
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Lotte Co Ltd
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Lotte Co Ltd
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Assigned to LOTTE CO., LTD. reassignment LOTTE CO., LTD. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: ITOH, SATOMI, NARISE, ATSUSHI, SHIMURA, SUSUMU, TSUGANE, TAKANORI
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    • 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
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • 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)
    • 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
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A61K8/368—Carboxylic acids; Salts or anhydrides thereof with carboxyl groups directly bound to carbon atoms of aromatic rings
    • 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
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • 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
    • A61K8/9728—Fungi, e.g. yeasts
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74—Biological properties of particular ingredients
    • A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
    • A61K2800/782—Enzyme inhibitors; Enzyme antagonists

Definitions

  • the present invention relates to an inhibitor of methioninase engaged in production of methyl mercaptan that is a causative substance of a bad smell, as well as a composition and a food or drink containing the same.
  • the main components of a bad smell from an oral cavity are volatile sulfur compounds, and especially methyl mercaptan is known to have a high correlation with the intensity of bad breath.
  • Methyl mercaptan is generated from food debris, intraoral desquamated epithelial cells and salivary proteins metabolized or decomposed by oral bacteria.
  • Volatile sulfur compounds such as methyl mercaptan are known to have adverse effects, such as inhibition of intraoral synthesis of proteins, inhibition of collagen synthesis, inhibition of growth and division of endothelial cells, and increase of permeability of intraoral mucosa. Consequently inhibition of methyl mercaptan is an important task not only for suppression of the bad breath, but also for prevention of a periodontal disease or maintenance of the human body's internal environment.
  • Methyl mercaptan is generated from L-methionine, that is an intraoral protein decomposition product, utilized as a substrate, by an oral bacterial enzyme of methioninase (L-methionine- ⁇ -lyase).
  • L-methionine- ⁇ -lyase an oral bacterial enzyme of methioninase
  • Fusobacterium nucleatum and Porphyromonas gingivalis have high methioninase activity, and by inhibiting their methioninase activity the generation of methyl mercaptan, a causative substance of bad smell, as well as hydrogen sulfide, ammonia and ⁇ -ketobutyrate can be inhibited.
  • Methyl mercaptan is generated also by enteric bacteria, and known as a causative substance of odors of kitchen garbage and feces. Consequently, by inhibiting methioninase, the odors of garbage and feces are expected to be eliminated.
  • the use of a disinfectant might have an adverse effect by disturbing a balance of an intraoral bacterial flora, and the odor eliminating by chemical conversion or masking does not inhibit generation of the odor itself and the effect does not last long.
  • the methioninase inhibitor of the present invention is safe, inhibits the generation of methyl mercaptan itself and therefore shows high sustainability.
  • Methioninase inhibitors originated from natural materials, such as a tomato extract and a ginger extract (e.g. Patent Documents 1 and 2), or an extract of Iceland moss, an extract of alkanet, an extract of green tea and the like (e.g. Patent Document 3) have been reported, and their inhibition of the methyl mercaptan production by oral bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum , has been disclosed. Inhibitory activity on the methyl mercaptan production by oral bacteria of a plant belonging to the family Asteraceae , genera Chrysanthemum, Cynara , and Tagetes (e.g.
  • Patent Document 4 the family Rutaceae , genus Zanthoxylum (e.g. Patent Document 5) and a plant essential oil component (e.g. Non-Patent Document 1); and furthermore inhibitory activity on the methyl mercaptan production by oral bacteria of a certain perfume component (e.g. Patent Documents 6 and 7), and ⁇ -ketobutyrate and a salt thereof (e.g. Patent Document 8) have been reported. However, none of them are satisfactory in terms of sustainability of the activity and the like.
  • myrsinoic acid A, myrsinoic acid B, myrsinoic acid C, myrsinoic acid E and myrsinoic acid F have been identified from Myrsine seguinii or Rapanaea neriifolia , a plant belonging to the family Myrsinaceae , genus Myrsine , which are substances inhibiting cutaneous inflammation (e.g. Non-Patent Documents 2, 3 and 4).
  • myrsinoic acid A is known to inhibit cutaneous inflammation by inhibiting a DNA polymerase, but its odor eliminating activity has not been disclosed.
  • Methyl esters of myrsinoic acids A, B and C have been identified from Rapanea unbellata , a plant of the same genus, but the bioactivities have not been disclosed (e.g. Non-Patent Documents 5 and 6).
  • Patent Document 1 Japanese Patent Application Laid-Open No. 2002-3353
  • Patent Document 2 Japanese Patent Application Laid-Open No. 2003-160459
  • Patent Document 3 Japanese Patent Application Laid-Open No. 2005-162697
  • Patent Document 4 Japanese Patent Application Laid-Open No. 2002-114660
  • Patent Document 5 Japanese Patent Application Laid-Open No. 2003-26527
  • Patent Document 6 Japanese Patent Application Laid-Open No. 2001-348308
  • Patent Document 7 Japanese Patent Application Laid-Open No. 2002-3369
  • Patent Document 8 Japanese Patent Application Laid-Open No. H07-138139
  • Non-Patent Document 1 Tsuneda, F., Journal of Odor Research and Engineering, 2000, Vol. 31 (2), p. 91-96
  • Non-Patent Document 2 Biosci. Biotechnol. Biochem., 63(9), 1650-1653, 1999
  • Non-Patent Document 3 Biosci. Biotechnol. Biochem., 66(3), 655-659, 2002
  • Non-Patent Document 4 Biosci. Biotechnol. Biochem., 67(9), 2038-2041, 2003
  • Non-Patent Document 5 Biochimicaet Biophysica Acta, 2000 Jun. 1; 1475 (1): 1-4
  • Non-Patent Document 6 Phytochemistry, 1991; 30 (6): 2019-2023
  • An object of the present invention is to provide a methioninase inhibitor, as well as a composition and a food or drink containing the same, which includes a plant extract that has no adverse effect on human bodies and is highly safe, or myrsinoic acids originated from the plant extract, as an active ingredient, and inhibits methioninase originated from bacteria to suppress the production of an odor substance of methyl mercaptan.
  • the present inventors have directed attention to natural extracts, such as galenicals or herbs, that have been used since ancient times to establish time-tested safety, and carried out inhibition tests using a cell lysate and a live cell suspension originated from Fusobacterium nucleatum that is a causative bacterium of bad breath having high methioninase activity, and discovered that an extract obtained from a plant of family Myrsinaceae , genus Myrsine has an inhibitory activity against methioninase and that the active ingredient thereof is myrsinoic acids, thereby completing the present invention.
  • natural extracts such as galenicals or herbs
  • the present invention provides a methioninase inhibitor, a composition and a food or drink characterized by containing an extract obtained from a plant belonging to the family Myrsinaceae , genus Myrsine , preferably Myrsine seguinii belonging to the family Myrsinaceae , genus Myrsine , as an active ingredient; a methioninase inhibitor, a composition and a food or drink characterized by containing one or more selected from the group consisting of myrsinoic acid A, myrsinoic acid B, myrsinoic acid C, myrsinoic acid E and myrsinoic acid F as an active ingredient; and the methioninase inhibitor, the composition and the food or drink characterized in that the myrsinoic acid A, myrsinoic acid B, myrsinoic acid C, myrsinoic acid E and myrsinoic acid F are obtained from a plant
  • the methioninase inhibitor of the present invention has activity to suppress the production of methyl mercaptan, ammonia and ⁇ -ketobutyrate. Consequently, by ingesting orally a food or drink containing the same, or using the same in an oral composition, such as a mouth freshener or a tooth paste, reduction of bad breath, reduction of feces odor and improvement of mouth's and body's internal environment are possible. Additionally the same can be used as an odor inhibitor for the living environment, as for kitchen garbage.
  • myrsinoic acid A, myrsinoic acid B, myrsinoic acid C, myrsinoic acid E and myrsinoic acid F (the respective chemical formulas (I) to (V) being shown below) to be used in the present invention can be obtained by synthesis, but are preferably obtained from an extract of the whole, or a leaf, flower, twig, root or fruit part of a plant belonging to the family Myrsinaceae , genus Myrsine .
  • Examples of the plant belonging to the family Myrsinaceae include genus Myrsine containing the myrsinoic acids, taimin - tachibana that is a shrub native in middle to southern Japan and a tropical zone.
  • Taimin - tachibana also referred to as hichinoki or sogeki has scientific names Myrsine seguinii and Rapanaea neriifolia . Since the fruit of Myrsine seguinii has been traditionally eaten, there is no concern about its safety. As especially preferable parts for extraction, leaf and fruit may be named, because their production masses are large and the extraction rates can be high.
  • Myrsinoic acids have very high inhibitory activity, and among them myrsinoic acid B can be exemplified as an especially preferable type due to its strong methioninase inhibitory activity and a high content in the extract.
  • the plant is generally first crushed by an appropriate means. Then extraction is conducted according to a conventional extraction method using a mixed solvent of one or more of water, lower alcohols, such as methanol, ethanol, n-propanol, and n-butanol, organic solvents, such as ether, chloroform, ethyl acetate, acetone, glycerin and propylene glycol.
  • organic solvents such as ether, chloroform, ethyl acetate, acetone, glycerin and propylene glycol.
  • the present invention is directed to a medicament, an oral composition and a food or drink, as an extraction solvent a combination of water and
  • the thus obtained extract may be filtered, concentrated under a reduced pressure or freeze-dried before use.
  • the extract may be separated and purified to obtain myrsinoic acids by a publicly known means for separation and purification, such as adsorption chromatography, partition chromatography, high performance liquid chromatography and thin-layer chromatography. More specifically, the extract is subjected to a liquid-liquid extraction, to silica gel column chromatography with an ethyl acetate/hexane mixed solvent, and further to octadecyl silylated column chromatography with a methanol/water (85%) mixed solvent containing additionally 0.1% acetic acid to obtain high purity myrsinoic acids by elution, fraction, concentration and drying.
  • a publicly known means for separation and purification such as adsorption chromatography, partition chromatography, high performance liquid chromatography and thin-layer chromatography. More specifically, the extract is subjected to a liquid-liquid extraction, to silica
  • the methioninase inhibitor of the present invention can be prepared by using as an active ingredient the myrsinoic acids and an extract of a plant belonging to the family Myrsinaceae , genus Myrsine , for example an extract of Myrsine seguinii , prepared as above.
  • the ingredient may be dissolved or dispersed in an appropriate liquid vehicle, or mixed with an appropriate powder carrier or adsorbed thereon, and according to need mixed additionally with an emulsifier, a stabilizer or a dispersant to be formulated to a tablet, a powder, an emulsion, a water-dispersible powder, etc.
  • the content of the dry extract with respect to the total formulation is preferably 0.001 to 50% by weight, and more preferably 0.01 to 25% by weight.
  • the methioninase inhibitor of the present invention is superior in fragrance, taste and safety, it can be mixed and consumed routinely in an oral composition, such as a tooth paste, a mouthwash and a deodorant spray, confections, such as a chewing gum, a candy, a tablet candy, a gummy jelly, a chocolate and a biscuit, frozen desserts, such as an ice cream, a sherbet and a water ice, foods or drinks, such as beverages, soup and jam.
  • the content of the dry extract in the food or drink, or composition is about 0.001% by weight or more, and preferably about 0.01% by weight or more. In case of the food or drink, it is favorable to add the same to the content of about 0.001 to 5% by weight, and preferably about 0.01 to 1% by weight considering the taste.
  • This test was conducted to prepare a myrsinoic acid, an extract of Myrsine seguinii and comparative various plant extracts.
  • Myrsine seguinii and for comparison a whole grass dry powder of Iceland moss, an alkanet root, a guava leaf, and green tea were used.
  • a 1% aqueous solution of the extract of a leaf of Myrsine seguinii by 100% ethanol was solvent-fractionated three times with the same volume of hexane, and the solvent was removed by distillation to obtain the hexane fractions (yield about 20%).
  • the hexane fractions were subjected to silica gel column chromatography using a mixed solvent of ethyl acetate/hexane (10 to 20%) to separate about 20% of non-polar components to obtain a fraction containing myrsinoic acids (yield about 40%).
  • This fraction was subjected to octadecyl silylated column chromatography using 0.1% acetic acid added methanol/water (85%) for elution and separation to obtain 400 mg of myrsinoic acid B and 100 mg of myrsinoic acid C.
  • the hexane fractions were subjected to silica gel column chromatography and octadecyl silylated column chromatography for fractionation to obtain 60 mg of myrsinoic acid A, 3 mg of myrsinoic acid E and 1.5 mg of myrsinoic acid F.
  • Myrsinoic acid E was obtained by hydrolysis of a methyl ester prepared from 2-iodophenol by geranylation and carbonylation according to the method of Proceedings of Symposium on the Chemistry of Terpenes, Essential Oils, and Aromatics, Vol. 46, 396-398 (2002).
  • an alkanet root, a guava leaf and green tea were extracted respectively by 50% ethanol, and the extract liquids were concentrated or freeze-dried to prepare the extracts.
  • This test was conducted to examine the methioninase inhibitory activity of myrsinoic acids and the Myrsine seguinii extract.
  • the Myrsine seguinii extract and myrsinoic acids as well as for comparison extracts of the whole grass dry powder of Iceland moss, the alkanet root, the guava leaf, and the green tea prepared in Test Example 1 were used.
  • Methyl mercaptan, ammonia and ⁇ -ketobutyrate are produced from methionine by a reaction according to the methioninase.
  • the production amount of ⁇ -ketobutyrate that is a considerably stable compound among the reaction products was used as an index of the enzyme reaction.
  • Fusobacterium nucleatum JCM 8532 was cultured for 2 days under an anaerobic condition and disrupted by sonication to obtain the enzyme (final concentration: 300 ⁇ g-protein/mL), which was then mixed with methionine (final concentration: 30 mM), pyridoxal phosphate (final concentration: 50 ⁇ M), and the sample (final concentration: 200 ⁇ g/mL) in a phosphate buffer solution (50 mM, pH 7.6). After incubation at 37° C.
  • the absorbance was corrected using a blank sample (a reaction liquid of the aforedescribed reaction except that methionine is excluded), which value was deducted for compensation.
  • the amount of ⁇ -ketobutyrate was determined using a calibration curve prepared in advance, and an inhibition rate was calculated according to the following formula:
  • Inhibition rate(%) (( C ⁇ S )/ C ) ⁇ 100
  • C is the amount of ⁇ -ketobutyrate in the control
  • S is the amount of ⁇ -ketobutyrate when the sample is added.
  • the measurement results of the methioninase inhibitory activity are shown in Table 2.
  • the extract of the whole grass dry powder of Iceland moss, the extract of the alkanet root, the extract of the guava leaf, and the extract of the green tea see e.g. Japanese Patent Application Laid-Open No. 2003-26527
  • whose inhibitory activities against methioninase originated from oral bacterium Fusobacterium nucleatum
  • the respective inhibition rates were 29% for the extract of the whole grass dry powder of Iceland moss, 28% for the extract of the alkanet root, 22% for the extract of the guava leaf, and 26% for the extract of the green tea.
  • the extracts of a leaf, a twig and a fruit of Myrsine seguinii of the present invention exhibited respectively high inhibitory activities against methioninase.
  • the test results showed that the extracts of a leaf, a twig and a fruit of Myrsine seguinii of the present invention have strong inhibitory activities against methioninase.
  • myrsinoic acids A, B, C, E, and F inhibited methioninase by 50% at a concentration of 5 ⁇ g/mL or less. Consequently an isolated myrsinoic acid has strong inhibitory activity, indicating that the same is the active ingredient contained in the Myrsine seguinii extract.
  • This test was conducted to examine the inhibitory activity against methioninase of living bacteria by myrsinoic acids and the Myrsine seguinii extract.
  • the Myrsine seguinii extract as well as for comparison extracts of the whole grass dry powder of Iceland moss, the alkanet root, the guava leaf, and the green tea prepared in Test Example 1 were used.
  • Fusobacterium nucleatum JCM8532 cultured for about 16 hours under an anaerobic condition was centrifuged and suspended in a physiological saline buffer solution (40 mM phosphate buffer/50 mM sodium chloride, pH 7.7) to obtain a living bacterial suspension (10% of a reaction system), which was then reacted with methionine (final concentration: 1 mM) and the sample (final concentration: 1 to 200 ⁇ g/mL) in a physiological saline buffer solution at 37° C. for 90 min. Then 0.5 mL of the head-space gas was analyzed by gas chromatography.
  • a physiological saline buffer solution 40 mM phosphate buffer/50 mM sodium chloride, pH 7.7
  • the results are shown in Table 4.
  • the green tea extract was evaluated as a comparative sample, which inhibition rate was 66%.
  • the extracts of a Myrsine seguinii leaf of the present invention exhibited a high inhibitory activity against methioninase at a lower concentration.
  • compositions such as a tooth paste, a mouthwash, a deodorant spray, a breath spray, a tablet and a powder; and confections, such as a chewing gum, a candy, a tablet candy, a gummy jelly, a chocolate and a biscuit, frozen desserts, such as an ice cream, a sherbet and a water ice, foods or drinks, such as beverage, soup and jam were produced.
  • the mixture was filled in an aerosol container together with a propellant gas (nitrogen gas) to prepare a deodorant spray.
  • a propellant gas nitrogen gas
  • Powder sugar (39.8% by weight)
  • the mixture was filled in an aerosol container together with a propellant gas (nitrogen gas) to prepare a deodorant spray.
  • a propellant gas nitrogen gas
  • the components were finely milled, mixed and formed into tablets by a direct tableting method.
  • the total weight of each tablet is 100 mg and the active ingredient therein is 10 mg.
  • the components were finely milled and mixed to form powder.
  • One hundred (100) mg of the powder was filled in a hard capsule to produce a capsule formulation.

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WO2011014257A1 (en) * 2009-07-31 2011-02-03 The General Hospital Corporation Approaches to treat cancer using hb-egf inhibitors such as myrsinoic acid a
WO2013019955A1 (en) * 2011-08-02 2013-02-07 The Procter & Gamble Company Process for surfactant taste and/or odor improvement
US9072671B2 (en) 2012-08-02 2015-07-07 The Procter & Gamble Company Process for oral care material taste and/or odor improvement
US9078826B2 (en) 2011-08-02 2015-07-14 The Procter & Gamble Company Water-soluble surfactant compositions having improved taste
US10390555B2 (en) * 2013-04-25 2019-08-27 Japan Tobacco Inc. Manufacturing method of composition element of item including flavor component, and composition element of item, including flavor component
US10413844B2 (en) 2011-08-02 2019-09-17 The Procter & Gamble Company Liquid-liquid extraction composition useful in processing water-soluble surfactants

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JP6266891B2 (ja) 2013-03-29 2018-01-24 株式会社ロッテ 口腔内洗浄用組成物
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Cited By (10)

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Publication number Priority date Publication date Assignee Title
WO2011014257A1 (en) * 2009-07-31 2011-02-03 The General Hospital Corporation Approaches to treat cancer using hb-egf inhibitors such as myrsinoic acid a
US20110060047A1 (en) * 2009-07-31 2011-03-10 The General Hospital Corporation D/B/A Massachusetts General Hospital Approaches to treat cancer using hb-egf inhibitors
WO2013019955A1 (en) * 2011-08-02 2013-02-07 The Procter & Gamble Company Process for surfactant taste and/or odor improvement
US8697036B2 (en) 2011-08-02 2014-04-15 The Procter & Gamble Company Process for surfactant taste and/or odor improvement
US9078826B2 (en) 2011-08-02 2015-07-14 The Procter & Gamble Company Water-soluble surfactant compositions having improved taste
AU2012289995B2 (en) * 2011-08-02 2015-08-27 The Procter & Gamble Company Process for surfactant taste and/or odor improvement
US10413844B2 (en) 2011-08-02 2019-09-17 The Procter & Gamble Company Liquid-liquid extraction composition useful in processing water-soluble surfactants
US10653601B2 (en) 2011-08-02 2020-05-19 The Procter & Gamble Company Water soluble surfactant composition having improved taste
US9072671B2 (en) 2012-08-02 2015-07-07 The Procter & Gamble Company Process for oral care material taste and/or odor improvement
US10390555B2 (en) * 2013-04-25 2019-08-27 Japan Tobacco Inc. Manufacturing method of composition element of item including flavor component, and composition element of item, including flavor component

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WO2008013062A1 (en) 2008-01-31
KR101441149B1 (ko) 2014-09-17
US20140308218A1 (en) 2014-10-16
KR20090035605A (ko) 2009-04-09
JP2008031062A (ja) 2008-02-14
US9144539B2 (en) 2015-09-29
JP5089100B2 (ja) 2012-12-05
CN101495127A (zh) 2009-07-29
HK1135022A1 (en) 2010-05-28

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