Title of Invention
ANTIMICROBIAL COMPOSITION
Technical Field
The present invention relates to a safer antimicrobial composition which
possesses excellent antimicrobial activity. Furthermore, the present invention also
relates to a product comprising said the antimicrobial composition.
Background
Traditionally, various antimicrobial agents, such as natural and synthetic
antimicrobial agents, are utilised in order to improve the preservation of food and
cosmetic products. Benzoates, sorbates and so on are commercialized as synthetic
antimicrobial agents. However, in the case where synthetic antimicrobial agents are
used in products, such as food and cosmetics, which are in direct contact with the
human body, it has been pointed out that further assurance of the safety of the
antimicrobial agent is needed. On the other hand, it has been pointed out that a
steady supply of natural antimicrobial agents cannot be ensured and cost a lot of
money to produce.
Thus, it is desirable to obtain an antimicrobial agent which is safe and
readily available, as well as easy to use with foods, cosmetics and so on when
compared to common antimicrobial agents. In addition, as noted in the following
document, work is being conducted with various antimicrobial agents to improve the
shelf life of foods, cosmetics and so on.
JP 2007-45754A describes Macaranga extract extracted with a solvent such
as an organic solvent as the natural antimicrobial agent.
JP 2011-06346A describes hydroxyundecanoic acid and a salt thereof
produced by chemical synthesis as the synthetic antimicrobial agent.
JP 2004-1 847OA describes the art of using fragrance ingredient etc of foods
as such mint oil which consists primarily of menthol as an antimicrobial agent.
WO 201 1/050871A describes an antimicrobial agent in which an active
ingredient is menthoxypropan diol produced by chemical synthesis.
Summary of Invention
Accordingly, an objective of the present invention is to provide an
antimicrobial composition that can be safely used with a broad range of foods and
beverages, cosmetics, drugs, and other similar products while showing growth
inhibition activity against a wide variety of microorganisms.
As a result of extensive studies aimed at solving the above problems, the
present inventors have found that specific groups of cooling agents among the many
compounds which are commonly known as cooling agents have remarkable
antimicrobial activity which a person skilled in the art cannot predict, and the
inventors have achieved the present invention. In addition, the compounds used as
antimicrobial agents in the present invention have been used as cooling agents for
long time, and thus the safety of the compounds in humans has been confirmed.
The present invention provides an antimicrobial composition comprising at
least one cooling agent selected from the group consisting of menthyl
3-hydroxybutanoate, 2-methyl-3-(menthoxy)propane-l ,2-diol, 2-(menthoxy)ethanol,
3-menthoxypropan-l-ol, 2-(2-menthoxyethoxy)ethanol, and menthyl glyoxylate.
Moreover, the present invention provides a flavor and/or fragrance
composition comprising the above antimicrobial composition.
Moreover, the present invention provides a food and beverage, a cosmetic, a
grocery good, a composition for oral or a drug comprising the above antimicrobial
composition or the above flavor and/or fragrance composition.
Moreover, the present invention provides a method for producing a flavor
and/or fragrance composition, a food and beverage, a cosmetic, a grocery good, a
composition for oral or a drug, comprising the step of blending the antimicrobial
composition with the food and beverage, the cosmetic, the grocery good, the
composition for oral or the drug.
In addition, the term "cooling agent" in the present claims as used herein
comprehends a dextrorotatory isomer and a levorotatory isomer, as well as a
stereoisomeric mixture thereof.
The present invention can provide an antimicrobial composition and a flavor
and/or fragrance composition which can have a broad range of safe applications with
foods, cosmetics and drugs, and show a growth inhibition activity against a wide
variety of microorganisms.
Furthermore, the present invention can provide a product, comprising said
antimicrobial composition or said flavor and/or fragrance composition, in which the
growth of microorganisms can be inhibited.
Description of Embodiments
Hereafter, each component used in the present antimicrobial composition
will be described in detail.
< Antimicrobial composition >
The antimicrobial composition of the present invention comprises at least
one cooling agent selected from the group consisting of menthyl 3-hydroxybutanoate,
2-methyl-3-(l-menthoxy)propane- 1,2-diol, 2-(menthoxy)ethanol,
3-menthoxypropan-l-ol, 2-(2-menthoxyethoxy)ethanol, and menthyl glyoxylate
(hereafter, the cooling agent in the present composition is sometime referred to as
"the present cooling agent").
The present cooling agent has an unexpected remarkable antimicrobial
activity. For example, when compared to a cooling agent other than the present
cooling agent (e.g. N-alkyl-p-menthane-3-carboxamide,
N-methyl-2-isopropyl-2,3-dimethylbutanamide, menthol,
3-menthoxypropane-l,2-diol and p-menthane-3,8-diol etc.), it can be understood that
the present cooling agent has a extraordinary antimicrobial activity.
Although the all present cooling agents can have growth inhibition activities
against both aerobic and anaerobic microorganisms (e.g. bacteria and fungi, etc.),
menthyl 3-hydroxybutanoate and 3-menthoxypropan-l-ol have specifically high
growth inhibition activities and potent growth inhibition activities against both
aerobic and anaerobic microorganisms. Examples of microorganisms include
Corynebacterium, Actinomyces and so on. Menthyl 3-hydroxybutanoate and
3-menthoxypropan-l-ol have 2 to 8 times as much growth inhibition activity as
3-menthoxypropane-l,2-diol (which is known as an antimicrobial agent), and can
have more than or equal to 8 times as much growth inhibition activity as
3-menthoxypropane-l,2-diol, depending on kinds of target microbe species.
Furthermore, when compared 2-methyl-3-(menthoxy)propane-l,2-diol with
3-menthoxypropane-l,2-diol (which is known as an antimicrobial agent), the former
has about 2 times as much growth inhibition activity as the latter, depending on kinds
of target microbe species.
Therefore, it is further preferable that the present invention comprises at
least one cooling agent selected from the group consisting of menthyl
3-hydroxybutanoate, 2-methyl-3-(l-menthoxy)propane-l,2-diol, and
3-menthoxypropan-1-ol.
Furthermore, it is preferable that menthyl 3-hydroxybutanoate is used as the
antimicrobial agent against Porphyromonas such as Porphyromonas gingivalis
(Periodontal pathogen), Staphylococcus such as Staphylococcus aureus (skin flora)
and Corynebacterium such as Corynebacterium xerosis (armpit odor-causing
bacteria), and it is preferable that 2-methyl-3-(l-menthoxy)propane-l,2-diol is used
as the antimicrobial agent against Staphylococcus such as Staphylococcus aureus
(skin flora).
Furthermore, 2-(menthoxy)ethanol and 2-(2-menthoxyethoxy)ethanol have
the growth inhibition activity against anaerobic microorganisms specially, further
specifically 2-(menthoxy)ethanol and 2-(2-menthoxyethoxy)ethanol have more than
2 times as much growth inhibition activity against Propionibacterium acnes
(JCM6473) and (ATCC6919) as well as Fusobacterium nucleatum as
3-menthoxypropane-l,2-diol (which is known as an antimicrobial agent).
Futhermore, menthyl glyoxylate has 2 to 16 times or more than 16 times as
much growth inhibition activity as 3-menthoxypropane-l,2-diol (which is known as
an antimicrobial agent), depending on kinds of target microbe species.
The above cooling agents are readily commercially available, and can be
synthesized by common methods.
Furthermore, it is preferable that the present antimicrobial composition
further comprises at least one component selected from the group consisting of
menthol, isopulegol, menthone, camphor, pulegol, cineol, mint oil,
N-alkyl-p-menthane-3-carboxamide, p-menthane-3,8-diol, 4-1-menthoxybutane-1-ol,
l-(2-hydroxy-4-methyl-cyclohexyl)-ethanone, menthyl lactate, menthol glycerol
ketal, N-methyl-2-isopropyl-2,3-dimethylbutanamide, menthyl succinate, menthyl
glutarate, peppermint oil, eucalyptus oil, spearmint oil, vanillyl ethyl ether, vanillyl
propyl ether, vanillin propylene glycol acetal, ethyl vanillin propylene glycol acetal,
capsaicin, gingerol, vanillyl butyl ether,
4-(1-menthoxy-methyl)-2-phenyl- 1,3-dioxolane,
4-(1-menthoxy-methyl)-2-(3 ' ,4' -dihydroxy-phenyl)- 1,3-dioxolane, 4-(1-menthoxy
methyl)-2-(2 '-hydroxy-3 '-methoxy-phenyl)- 1,3-dioxolane,
4-(l-menthoxy-methyl)-2-(4'-methoxyphenyl)-l,3-dioxolane,
4-(1-menthoxy-methyl)-2-(3 ' ,4' -methylenedioxy-phenyl)- 1,3-dioxolane,
4-(1-methoxy-methyl)-2-(3 '-methoxy-4' -hydroxyphenyl)- 1,3-dioxolane, red pepper
oil, red pepper oleoresin, vanillylamide nonylate, jambu oleoresin, Japanese pepper
extract, sanshool-I, sanshool-II, sanshoamide, black pepper extract, chavicine,
piperine and spilanthol (hereafter, the component comprised in this group is
sometime referred to as "combined component"). It is expected that in the present
antimicrobial composition, the combined component will further enhance the
antimicrobial activity of the present antimicrobial composition, as well as that the
combined component will be able to provide and control pleasant cooling and
heating sensations.
Furthermore, it is also possible to provide the desired antimicrobial activity
synergistically by using the present cooling agent in combination with the following
compound which is used widely as a typical antimicrobial agent: paraben, benzoic
acids (e.g. benzoic acid, sodium benzoate etc.), salicylic acids, 1,2-alkane diol, ester
or ether of hydroxycarboxylic acid, benzalkonium chloride, benzethonium chloride,
lysozyme chloride, halocarban, trichlorocarbanilide, chlorhexidine hydrochloride,
isopropyl methyl phenol, aluminum phenol sulfonate, triclosan, chlorhexidine
gluconate, a solution of sodium hydrogen sulfite, sodium sulfite (crystal),
(anhydrous) sodium sulfite, Udo extract, Styrax japonica extract, Artemisia capillaris
extract, enzyme-degradable hatomugi (Adlay) extract, Sodium hyposulfite, Milt
protein extract, sorbic acid, potassium sorbate, thujaplicin (extract), sodium
dehydroacetate, sulfur dioxide, isobutyl paraoxybenzoate, isopropyl paraoxybenzoate,
ethyl paraoxybenzoate, butyl paraoxybenzoate, propyl paraoxybenzoate, potassium
pyrosulfite, sodium pyrosulfitesodium, propionic acid, calcium propionate, sodium
propionate, pectin degradation products, Magnolia obovata extract, e-polylysine,
forsythia extract, allspice oil, origanum oil, orange oil, cassia oil, cumin oil, clove oil,
coriander oil, perilla oil, citronella oil, cinnamon oil, calamus oil, sage oil, geranium
oil, thyme oil, dill oil, tree moss oil, Thujopsis dolabrata oil, pimento oil, fennel oil,
bay oil, vetiver oil, penny royal oil, Peru balsam oil, eucalyptus oil, lavender oil,
lemongrass oil, lemon oil, rosemary oil, rose oil, laurel oil, Thujopsis dolabrata oil,
anise oil, wintergreen oil, estoragon oil, onion oil, cardamom oil, caraway oil, cade
oil, star anise oil, cedarwood oil, celery oil, tarragon oil, Formosan cypress oil,
nutmeg oil, birch oil, black pepper oil, basil oil, white pepper, marjoram oil, mace oil,
cananga oil, jasmine oil, spearmint oil, peppermint oil, patchouli oil, bois de rose oil,
green tea extract, oolong tea extract, tea catechins, ginger oil, cereli seed oil, lovage
oil, valerian oil, hop oil, ambrette seed oil, dill seed oil, pennyroyal oil, tansy oil,
winelees oil, ephedra herb extract, Zanthoxylum piperitum oil, ophiopogon tuber
extract.
«Evaluation of the antimicrobial activity»
In the present invention, the growth inhibition activity, which is an indicator
of the antimicrobial activity, is evaluated by determining the Minimum Inhibitory
Concentration (MIC) with an agar or liquid medium. In addition, although it cannot
be determined if the microbicidal or bacteriostatic activity contributes to the growth
inhibition activity, in the Determining the Minimum Inhibitory Concentration in the
present specification, since antimicrobial activity can include microbicidal and
bacteriostatic activities, the above evaluation does not matter.

The present flavor and/or fragrance composition composes the above
mentioned antimicrobial composition. Although the content of the present cooling
agent in the flavor and/or fragrance composition can be arbitrarily regulated
depending on the dosage level of the flavor and/or fragrance composition, the content
is generally 0.01 to 50 % by weight, preferably 0.01 to 20 % by weight, further
preferably 0.05 to 10 % by weight, based on the total mass of the flavor and/or
fragrance composition. When the content is more than 50 % by weight, there are
few economic advantages, while when the content is less than 0.01 % by weight, the
effect caused by the present flavor and/or fragrance composition may be not
sufficiently displayed.
The present flavor and/or fragrance composition can further comprise any
components to the extent not to spoil the antimicrobial activity, which, include (but
not limited to) natural essential oils, synthetic essential oils, citrus oils, animal
perfume.
The synthetic aromachemicals used in the present flavor and/or fragrance
composition are not particularly limited as long as they have been commonly used in
flavors and fragrances industry, and examples of the which include at least one
selected the group consisting of esters, alcohols, aldehydes, ketones, phenols, ethers,
lactones, hydrocarbons, nitrogen-containing compounds, sulfur-containing
compounds and acids described in "Synthetic flavoring ingredient chemicals and
product knowledge" (Genichi Indo, Chemical Daily Co.,Ltd.) etc.
Examples of the esters include, propyl formate, butyl formate, amyl formate,
octyl formate, linalyl formate, citronellyl formate, geranyl formate, neryl formate,
terpinyl formate, ethyl acetate, isopropyl acetate, isoamyl acetate, hexyl acetate,
cis-3-hexenyl acetate, trans-2-hexenyl acetate, octyl acetate, nonyl acetate, decyl
acetate, dodecyl acetate, dimethyl undecadienyl acetate, styrallyl acetate, ocimenyl
acetate, myrcenyl acetate, dihydro myrcenyl acetate, linalyl acetate, citronellyl
acetate, geranyl acetate, neryl acetate, tetrahydro-mugol acetate, lavandulyl acetate,
nerolidol acetate, dihydrocuminyl acetate, terpinyl acetate, citril acetate, nopyl
acetate, dihydroterpinyl acetate, 2,4-dimethyl-3-cyclohexenyl methyl acetate,
myraldyl acetate, veticol acetate, decenyl propionate, linalyl propionate, geranyl
propionate, neryl propionate, terpinyl propionate, tricyclodecenyl propionate,
styrallyl propionate, anisil propionate, octyl butyrate, neryl butyrate, cinnamyl
butyrate, isopropyl isobutyrate, octyl isobutyrate, linalyl isobutyrate, neryl
isobutyrate, linalyl isovalerate, terpinyl isovalerate, phenylethyl isovalerate,
2-methylpentyl 2-methylvalerate, methyl 3-hydroxyhexanoate, ethyl
3-hydroxyhexanoate, methyl octanoate, octyl octanoate, linalyl octanoate, methyl
nonanoate, methyl undecylenate, linalyl benzoate, methyl cinnamate, isoprenyl
angelicate, methyl gelanate, triethyl citrate, ethyl acetoacetate, ethyl
2-hexylacetoacetate, ethyl benzyl-acetoacetate, ally 2-ethylbutyrate, ethyl
3-hyoxybutyrate, ethyl nonanoate, ethyl decanoate, ethyl 2,4-decadienoate, propyl
2,4-decadienoate, methyl anthranylate, ethyl N-methyl-anthranylate, and the like.
Examples of the alcohols include, 3-heptanol, 1-nonanol, 1-undecanol,
2-undecanol, 1-dodecanol, prenol, 10-undecen-l-ol, dihydrolinalool,
tetrahydromugol, myrcenol, dihydromyrcenol, tetrahydromyrcenol, ocimenol,
terpineol, hotnenol, 3-thujanol, benzylalcohol, b-phenylethyl alcohol, a-phenylethyl
alcohol, 3-methyl-l-pentanol, 1-heptanol, 2-heptanol, 3-octanol, 1-nonanol,
2-nonanol, 2,6-dimethyl-heptanol, 1-decanol, trans-2-hexenol, cis-4-hexenol,
methyltrimethylcyclopentenylbutenol, citronellol, dihydro-myrcenol, rhodinol,
geraniol, nerol, linalool, tetrahydrolinalool, dimethyloctanol, hydroxycitronellol,
isopulegol, menthol, terpineol, dihydro-terpineol, carveol, dihydro-carveol, perilla
alcohol, 4-thujanol, myrtenol, a-fenchyl alcohol, farnesol, nerolidol, cedrenol,
anisealcohol, hydratropic alcohol, 3-phenyl-propyl alcohol, cinnamic alcohol,
amylcinnamic alcohol, and the like.
Examples of the aldehydes include, acetaldehyde, n-hexanal, n-heptanal,
n-octanal, n-nonanal, 2-methyloctanal, 3,5,5-trimethylhexanal, decanal, undecanal,
2-methyldecanal, dodecanal, tridecanal, tetradecanal, trans-2-hexenal,
trans-4-decenal, cis-4-decenal, trans-2-decenal, 10-undecenal, trans-2-undecenal,
trans-2-dodecenal, 3-dodecenal, trans-2-tridecenal, 2,4-hexadienal, 2,4-decadienal,
2,4-dodecadienal, 5,9-dimethyl-4,8-decadienal, citral, dimethyloctanal, a-methylene
citronellal, citronellyl oxyacetaldehyde, myrtenal, neral, a- or b-sinensal, myrac
aldehyde, phenyl acetoaldehyde, octanal dimethyl acetal, nonanal dimethyl acetal,
decanal dimethyl acetal, decanal diethyl acetal, 2-methyl undecanal dimethyl acetal,
citral dimethyl acetal, citral diethyl acetal, citral propylene glycol acetal,
n-valeraldehyde, iso-valeraldehyde, 2-methyl butanal, 2-pentenal, trans-2-heptenal,
trans-2-nonenal, 2,6-dimethyl-5-heptenal, 2,4-undecadienal, tnmethyl decadienal,
citronellal, hydroxyl citronellal, safranal, vernaldehyde, benzaldehyde,
p-isopropyl-phenyl acetoaldehyde, p-methyl-hydro-tropaldehyde, phenyl
propionaldehyde, 2-methyl-3-(4-methyl phenyl)-propanal, cycramen aldehyde,
cinnamic aldehdye, salicylaldehyde, anisaldehyde, p-methyl-phenoxyacetaldehyde,
acetaldehyde diethyl acetal, citronellyl methyl acetal, acetaldehyde
2-phenyl-2,4-pentandiol acetal, 2-hexenal diethyl acetal, cis-3-hexenal diethyl acetal,
heptanal diethyl acetal, 2-hexyl-5-methyl-l,3-dioxolane,
citronellal-cyclo-mono-glycol acetal, hydroxyl-citronellal dimethyl acetal, phenyl
acetaldehyde dimethyl acetal, and the like.
Examples of the ketones include, 2-pentanone, 3-hexanone, 2-heptanone,
3-heptanone, 4-heptanone, 2-octanone, 3-octanone, 2-nonanone, 2-undecanone,
methyl heptenone, dimethyl octenone, geranyl acetone, farnesyl acetone,
2,3,5-trimethyl-4-cyclohexenyl-l-methyl ketone, nerone, nootkatone,
dihydronootkatone, acetophenone, 4,7-dihydro-2-isopentyl-2 -methyl-1,3-dioxepin,
2-pentanone, 3-hexanone, 2-heptanone, 2,3-hexanedione, 3-nonanone, ethyl isoamyl
ketone, diacetyl, amyl-cyclopentenone, 2-cyclopentyl cyclopentanone, hexyl
cyclopentanone, heptyl cyclopentanone, cis-jasmone, dihydro-jasmone, trimethyl
pentyl cyclopentanone,
2-(2-(4-methyl)-3-cyclohexanone- 1-yl)-propyl-cyclopentanone, damascone,
a-dynascone, trimethyl cyclohexenyl butenone, jonan (ionone), methylionone,
allylionone, pricatone, cashmeran, L-carvone, menthone, camphor, p-methyl
acetophenone, p-methoxy-acetophenone, benzylidene acetone, raspberry ketone,
methyl naphtyl ketone, benzophenone, furfural acetone, homofuronol, maltol, ethyl
maltol, acetoacetic acid ethyl ethyleneglycol ketal, and the like.
Examples of the phenols include, thymol, carvacrol, b-naphthol isobutyl
ether, anethole, b-naphthol methyl ether, b-naphthol ethyl ether, creosol, veratrole,
hydroquinone dimethyl ether, 2,6-dimethoxyl phenol, 4-ethyl guaiacol, eugenol,
isoeugenol, ethyl isoeugenol, tert-butyl hydroquinone dimethyl ether, and the like.
Examples of the ethers include, decyl vinyl ether, a-terpinyl methyl ether,
iso-proxen, 2,2-dimethyl-5-( 1-methyl-1-propenyl)-tetrahydro-furan, rosefuran,
1,4-cineol, nerol oxide, 2,2,6-trimethyl-6-vinyl tetrahydro-pyran, methyl hexyl ether,
ocimene epoxide, limonene oxide, rhubofix, caryophyllene oxide, linalool oxide,
5-isopropenyl-2-methyl-2-vinyl tetrahydro-furan, nerol oxide, rose oxide, and the
like.
Examples of the lactones include, g-undecalactone, d-dodecalactone,
g -hexylactone, g -nonalactone, g -decalactone, g -dodecalactone, jasmine lactone,
methyl g -decalactone, 7-decenolactone, jasmolactone, propylidene phthalide,
d-hexylactone, d-2-decenolactone, e -dodecalactone, dihydrocoumarin, coumarin,
and the like.
Examples of the hydrocarbons include, ocimene, limonene, a-phellandrene,
terpinene, 3-caren, bisabolene, valencene, alloocimene, myrcene, farnesene,
a-pynene, b-pynene, camphene, terpinolene, p-cymene, cedrene, b-caryophyllene,
cadinene, and the like.
Examples of the compounds containing nitrogen or sulfur include, methyl
anthranilate, ethyl anthranilate, methyl N-methyl-anthranilate, methyl
N-2'-methyl-pentylidyne-anthranilate, ligantral, dodecane nitrile, 2-tridecene nitrile,
geranyl nitrile, citronellyl nitrile, 3,7-dimethyl-2,6-nonadieno nitrile, indole,
5-methyl-3-heptanone oxime, limonene thiol, l-P-menthen-8-thiol, butyl anthranilate,
cis-3-hexenyl anthranilate, phenyl ethyl anthranilate, cinnamyl anthranilate, dimethyl
sulfide, 8-mercaptomenthone, and the like.
Examples of the acids include, acetic acid, propionic acid, butyric acid,
valeric acid, hexanoic acid, octanoic acid, decanoic acid, dodecanoic acid,
2-decenoic acid, geranoic acid, 2-methyl-butyric acid, 2-ethyl-butyric acid,
phenyl-acetic acid, cinnamic acid, iso-butyric acid, iso-valeric acid, 3-methyl valeric
acid, 2-hexenoic acid, 2-methyl-2-pentenoic acid, 2-methyl-heptanoic acid, myristic
acid, stearic acid, lactic acid, pyruvic acid, cyclohexane-carbonic acid, and the like.
Examples of the natural fragrances include, sweet orange, bitter orange,
neroli, mandarin, petit grain, bergamot, tangerine, onshuu mandarin orange, daidai
(Citrus aurantium), hassaku (Citrus hassaku) , iyokan (Citrus Iyo), lemon, lime,
grape fruit, yuzu (Citrus junos), sudachi (Citrus sudachi), cabosu (Citrus
sphaerocarpa), sweety and the like.
In addition, the following can also be used other than the above natural
fragrances as aroma and flavoring substance or improving agent of the aroma and
flavoring; citronella, elemi, olibanum, marjoram, angelica root, star anise, basil, hay,
calamos, caraway, cardamom, pepper, cascarilla, ginger, sage, clary sage, clove,
coriander, eucalyptus, fennel, pimento, juniper, fenugreek, laurel, mace, sugi (cedar),
senkyu, almond, apple mint, anise, artemisia, alfalfa, apricot, ambrette, rush,
strawberry, fig, ylang-ylang, winter green, ume apricot, elder, enju (Japanese-pagota
tree), oak moss, allspice, orris, currant, cassie, chamomile, galanga, Chinese quince,
gambir, guava, gooseberry, camphor tree, gardenia, cubeb, cumin, cranberry, cola,
japanese pepper, sandarac, sandal wood, red sandal wood, perilla, civet, jasmine,
ginger, ginseng, cinnamon, starfruit, styrax, spearmint, geranium, thyme, davana,
tansy, tangerine, champac, tuberose, camellia, dittany, tolu balsam, tonka, nut, jujube,
nutmeg, nanten, ti-tree, carrot, violet, pineapple, hibiscus, honey, mint, passion fruit,
vanilla, rose, hyssop, hinoki, fusel oil, buchu, peppermint, pepino, verbena, bois de
rose, popaw, boldo, boronia, pine, mango, bees wax, mimosa, milfoil, musk, maple,
melissa, melon, peach, yara-yara, lavender, liqueur, litsea, linden, rue, water apple,
rosemary, lovage, and the like.
These contents of these components for blending perfume are not specially
limited, and can be selected according to the purpose and use (application) arbitrary.
Further, the present flavor and/or fragrance composition can be further
blended with other materials depending on purposes and applications. Particular
examples include citrus flavor such as orange, lemon, lime, grape fruit, yuzu (Citrus
junos) and sudachi (Citrus sudachi); berry flavor such as strawberry, raspberry, blue
berry; tropical fruit flavor such as mango, papaya, guava, passion fruit, litchi; fruit
flavor such as apple, grape, pineapple, banana, peach, melon, apricot, ume (Prunus
mume), and cherry; tea and coffee flavor such as green tea, oolong tea, black tea, and
coffee; meat flavor such as beef, pork, and chicken; herb and spice flavor such as
asafetida, ajowan, anise, angelica, fennel, allspice, cinnamon, cassia, chamomile,
mustard, cardamom, caraway, cumin, clove, pepper, coriander, sassafras, savory,
japanese pepper, perilla, juniperberry, ginger, star anise, horseradish, sage, thyme,
tarragon, dill, capsicum, jujube, nutmeg, basil, parsley, marjoram, rosemary, laurel,
and wasabi (Wasabia japonica); vegetable flavor such as onion, garlic, green onion,
cabbage, carrot, celery, shiitake (Lentinula edodes (Berk.) Pegler), matsutake
(Tricholoma matsutake), tomato, burdock, and honewort; mint flavor such as
peppermint, spearmint, and Japanese mint; vanilla flavor; nut flavor such as almond,
cashew nut, peanut, hazel nut, walnut, chestnut, macadamia nut, pecan nut, pistachio,
Brazil nut, and coconut; liqueur flavor such as wine, whisky, brandy, rum, gin and
liqueur; grain flavor such as corn, potato, sweet potato, cooked rice, and bread; sugar
flavor such as honey, maple syrup, sugar, brown sugar and molasses.
The synthetic aromachemicals are readily commercially available, and
easily synthesized if necessary. Also, the natural materials are readily commercially
available, and easily obtained with common methods like extraction/purification.
Dosage level of the present composition can be adjusted depending upon the
application for the designated products.
Furthermore, the formulation (eg., liquid, solid, poweder, gel, mist, aerosol
and so on) can be selected based on the character of designated products.

The present food and beverage, cosmetic, grocery good, composition for
oral or drug (hereafter, these are sometime referred to as "product(s)" collectively)
comprises the above antimicrobial composition or the above flavor and/or fragrance
composition. Although the content of the present cooling agent in the products can
be arbitrarily regulated depending on the dosage level of these products, the content
is generally 0.0001 to 30 % by weight, preferably 0.001 to 20 % by weight, further
preferably 0.005 to 10 % by weight, based on the total mass of the products. When
the content is more than 30 % by weight, there are few economic advantages, while
when the content is less than 0.0001 % by weight, the effect caused by the present
product may be not sufficiently displayed.
Moreover, the sum of the contents of cooling agent, combined component,
and common antimicrobial agent can be generally set to for example 0.01 to 50 % by
weight according to the total mass of the product.
Examples of the present food and beverage include, drinks such as fruit
juice drinks, fruit wines, milk drinks, carbonated drink, soft drink and drink
preparations; ices such as ice creams, sherbets and ice candies; desserts such as jelly
and pudding; Western style cakes such as cake, cookie, chocolate and chewing gum,
Japanese style confections such as bean-jam bun, sweet beans jelly and Uiro; jams;
candies; breads; tea drinks or luxury drinks such as green tea, Oolong tea, black tea,
persimmon leaf tea, chamomile tea, low striped bamboo tea, mulberry tea, dokudami
tea, Pu-erh tea, mate tea, Rooibos tea, Gymnema tea, Guava tea, coffee and cocoa;
soups such as Japanese style soup, Western style soup and Chinese soup; flavoring
and seasoning; various instant drinks or convenience foods; various snack foods and
the like.
Examples of the present cosmetic include, fragrance products (perfume, eau
de perfume, eau de toilette, eau de cologne and the like), basic cosmetics (cleansing
cream, banishing cream, cleansing cream, cold cream, massage cream, milky lotion,
skin lotion, beauty lotion, pack, makeup remover and the like), finishing cosmetics
(foundation, face powder, solid face powder, talcum powder, rouge, lip barm, cheek
rouge, eye liner, mascara, eye shadow, eyebrow pencil, eye pack, nail enamel,
enamel remover and the like), hair cosmetics (pomade, brilliantine, set lotion, hair
stick, hair solid, hair oil, hair treatment, hair cream, hair tonic, hair liquid, hair spray,
bandrine, revitalizing hair tonic, hair dye and the like), suntan cosmetics (suntan
products, sunscreen product and the like), medicated cosmetics (antiperspirant, after
shaving lotion or gel, permanent wave agent, medicated soap, medicated shampoo,
medicated skin cosmetics and the like).
Additionally, Examples of the present grocery good include deodorant and
air freshener (solid type, gel type, such as the liquid type), tissue paper, toilet paper
and the like.
Additionally, Examples of the present composition for oral include oral
goods (dentifrice, oral cavity cleaner, mouth wash, troche, chewing gums and the
like) and the like.
Additionally, Example of the present drug include skin external preparations
such as poultices and ointment, internal medicines and the like.
Examples
Hereafter, the present invention will be described in more detail with
reference to the following Examples, which do not limit the present invention.
Regarding substance names used in the following Examples and
Comparative examples, "Coolact®" is the registered trademark of TAKASAGO
INTERNATIONAL CORPORATION, and "WS" is the registered trademark of
Millennium specialty chemicals. This "Coolact®" is also referred to as "CA" herein.
The IUPAC names of these substances correspond to the designations as the
following Table 1.
In addition, the above menthol was purchased from TAKASAGO
INTERNATIONALCORPORATION.
Hereafter, the substance names is expressed using the designations.
[Example 1] Measurement of growth inhibition activity against aerobic
bacteria
In the test for the growth inhibition activity, the following strains were used
as skin-related bacteria:
Staphylococcus epidermidis: Staphylococcus epidermidis (JCM2414T and
ATCC12228)
• Staphylococcus aureus: Staphylococcus aureus (NBRC12732 and
JCM2151)
• Skin indigenous bacteria which introduce a superficial infection:
Corynebacterium minutissimum (NBRC15361T)
•Armpit odor-causing bacteria: Corynebacterium xerosis (JCM1324)
Furthermore, the following bacteria were also used as other general aerobic
bacteria:
Escherichia coli: Escherichia coli (NBRC3972)
•Pseudomonas aeruginosa: Pseudomonas aeruginosa (NBRC13275)
Bacteria in intestines: Proteus vulgaris (NBRC3167)
• Pneumobacillus: Klebsiellapneumoniae (NBRC13277)
• Bacillus subtilis: Bacillus subtilis (NBRC3134)
The test strains were cultured in the liquid medium which the Bioresource
center recommends, and then the test strains were subcultured to a Mueller Hinton
Broth (Difco) at 30 degrees C. The grown bacteria were diluted to 106 CFU/ml
with saline to adjust the bacteria fluids for inoculation.
Furthermore, in order to examine the growth inhibition activities against the
bacteria by the above cooling agents, the concentration of the cooling agents:
(3S)-CA20, (3R)-CA20, CAl, CA5, CAl 5, CA55 or CA MGH was diluted with
ethanol to the required level of concentration for the determining the Minimum
Inhibitory Concentration to produce the sample liquids.
Next, IOOmI of each sample liquid was added to lOmL of a Mueller Hinton
Agar (Difco) agar medium solution in a soluble state, and each agar medium solution
was poured into a petri dish and solidified to prepare test plates having several
concentrations of the sample liquids (several concentrations of the above cooling
agents). Subsequently, 5mI of the above bacteria fluids for inoculation were
stamped on the test plates, and then the test plates were cultured at 37 degrees C
overnight.
In this way, the growth inhibition activities by (3S)-CA20, (3R)-CA20, CA1,
CA5, CA15, CA55, CA MGH were examined. The minimum concentration of the
cooling agent in which the growth of bacteria could not be confirmed was considered
as the MIC (Minimum Inhibitory Concentration).
[Comparative Example 1]
In a manner similar to Example 1, the effects of WS-3, WS-23, 1-menthol,
CA10, and CA38 were examined. The minimum concentration of the cooling agent
in which the grown strain could not be confirmed was considered as the MIC
(Minimum Inhibitory Concentration).
The MICs of Example 1 and Comparative Example 1 are denoted in Table 2
(Unit: ppm).
Table 2
In view of the result in Table 2, it was understood that (3S)-CA20,
(3R)-CA20, CAl, CA5, CAl 5, CA55, and CA MGH (the present Example) had low
MIC values against many strains compared with WS-3, WS-23, 1-menthol, CAIO and
CA38 (the Comparative Example). Thus, it was understood that the present cooling
agent can provide antimicrobial activities against skin-related bacteria such as
Staphylococcus aureus, and armpit odor-causing bacteria, and other aerobic bacteria.
[Example 2] Measurement of growth inhibition activity against anaerobic
bacteria
In the test for growth inhibition activity, the following strains were used:
•Acne bacteria: Propionibacterium acnes (JCM6473) and (ATCC6919)
• Abscess bacteria: Bacteroides fragilis (GAI5560)
• Cavity-causing bacteria: Streptococcus mutans (JCM5175), Actinomyces
naeslundii (JCM8350) and Actinomyces viscosus (JCM8352)
· Periodontal pathogen: Fusobacterium nucleatum (JCM6328),
Porphyromonas gingivalis (JCM8525), Prevotella nigrescens (JCM6322)
The test strains were cultured in a GAM medium (Nissui Pharmaceutical
Co., LTD), a Schaedler Broth (BBL) or a Trypticase Soy Broth (BBL) liquid medium,
and then the grown bacteria were diluted in saline to prepare turbidity 0.5 McFarland
of the bacteria fluids for inoculation. The the bacteria were cultured at 37 degrees
C for 3 days under an anaerobic condition by using AnaeroPack® from MGC.
Furthermore, in order to examine the growth inhibition activities against the
bacteria by the above cooling agent, the concentration of the cooling agents:
(3S)-CA20, (3R)-CA20, CAl, CA5, CA15, CA55 or CA MGH was diluted with
ethanol to the required level of concentrations for the determining the Minimum
Inhibitory Concentration to produce the sample liquids.
Next, IOOm of each sample liquid was added to lOmL of a Trypticase Soy
Broth agar medium solution in a soluble state, and each agar medium solution was
poured into a petri dish and solidified, to prepare the test plates. Subsequently, 5 mI
of above the bacteria fluids for inoculation were stamped on the test plates, and then
the test plates were cultured at 37 degrees C for 3 days.
In this way, in a manner similar to Example 1, the growth inhibition
activities by (3S)-CA20, (3R)-CA20, CAl, CA5, CAl 5, CA55, CA MGH were
examined. The minimum concentration of the cooling agent in which the growth of
bacteria could not be confirmed was considered as the MIC (Minimum Inhibitory
Concentration). The concentrations in this time are denoted in Table 3 (Unit: ppm).
[Comparative Example 2]
In a manner similar to Example 2, the effects of WS-3, WS-23, 1-menthol,
CA10, and CA38 were examined. The minimum concentration of the cooling agent
in which the growth of bacteria could not be confirmed was considered as the MIC
(Minimum Inhibitory Concentration). The concentrations in this time are denoted
in Table 3 (Unit: ppm).
Table 3
JCM6473 ATCC6919 GAI5560 JCM5175 JCM8350 JCM8352 JCM6328 JCM8525 JCM6322
sample
Example 2
(3S)-CA 20 200 200 100 200 100 100 50> 100
(3R)-CA 20 200 400 100 200 200 100 100 200
CA 1 400 400 100 800 800 50> 800 200 200
CA 5 400 400 200 800 800 200 400 200
CA 15 200 400 100 400 400 200 400 100
CA 55 800 800 100 800 800 800 800 100
CA MGH 200 100 50 100 200 200 100 50
Comparative Example 2
WS-3 >1600 > 1600 > 1600 > 1600 > 1600 >1600 200 > 1600
WS-23 >1600 >1600 > 1600 > 1600 >1600 >1600 > 1600 > 1600
l-menthol 1600 1600 1600 >1600 1600 1600 1600 1600
CA 10 800 800 100 800 800 50 > 800 200
CA 38 > 600 > 600 1600 >1600 >1600 >1600 >1600 1600
In view of the result in Table 3, it was understood that (3S)-CA20,
(3R)-CA20, CAl, CA5, CAl 5, CA55, and CA MGH (the present Example) had low
MIC values against many strains compared with WS-3, WS-23, l-menthol and CA38
(the Comparative Example). The former (the present Example) also had low MIC
values compared with CA 10. Thus, it was understood that the present cooling
agent can provide the antimicrobial activity against anaerobic bacteria such as acne
bacteria, abscess bacteria, cavity-causing bacteria, and Periodontal pathogen.
Although the present invention has been described and illustrated in detail, it
is clearly understood that the same is by way of illustration and example only and is
not to be taken by way of limitation, the spirit and scope of the present invention
being limited only by the terms of the appended claims.

CLAIMS
1. An antimicrobial composition comprising at least one cooling agent
selected from the group consisting of menthyl 3-hydroxybutanoate,
2-methyl-3-(menthoxy)propane-l,2-diol, 2-(menthoxy)ethanol,
3-menthoxypropan-l-ol, 2-(2-menthoxyethoxy)ethanol, and menthyl glyoxylate.
2. The antimicrobial composition according to claim 1, comprising at least
one cooling agent selected from the group consisting of menthyl 3-hydroxybutanoate,
2-methyl-3-(menthoxy)propane-l,2-diol and 3-menthoxypropan-l-ol.
3. The antimicrobial composition according to claim 1 or 2, further
comprising at least one component selected from the group consisting of menthol,
isopulegol, menthone, camphor, pulegol, cineol, mint oil,
N-alkyl-p-menthane-3-carboxamide, p-menthane-3,8-diol, 4-1-menthoxybutane-l-ol,
l-(2-hydroxy-4-methyl-cyclohexyl)-ethanone, menthyl lactate, menthol glycerol
ketal, N-methyl-2-isopropyl-2,3-dimethylbutanamide, menthyl succinate, menthyl
glutarate, peppermint oil, eucalyptus oil, spearmint oil, vanillyl ethyl ether, vanillyl
propyl ether, vanillin propylene glycol acetal, ethyl vanillin propylene glycol acetal,
capsaicin, gingerol, vanillyl butyl ether,
4-(l-menthoxy-methyl)-2-phenyl-l,3-dioxolane,
4-(1-menthoxy-methyl)-2-(3 ' ,4' -dihydroxy-phenyl)-1,3-dioxolane, 4-(1-menthoxy
methyl)-2-(2' -hydroxy-3 '-methoxy-phenyl)-1,3-dioxolane,
4-(1-menthoxy-methyl)-2-(4'-methoxyphenyl)-1,3-dioxolane,
4-(1-menthoxy-methyl)-2-(3 ' ,4'-methylenedioxy-phenyl)- 1,3-dioxolane,
4-(l-methoxy-methyl)-2-(3'-methoxy-4'-hydroxyphenyl)-l,3-dioxolane, red pepper
oil, red pepper oleoresin, vanillylamide nonylate, jambu oleoresin, Japanese pepper
extract, sanshool-I, sanshool-II, sanshoamide, black pepper extract, chavicine,
piperine and spilanthol.
4. A flavor and/or fragrance composition comprising the antimicrobial
composition according to any one of claims 1 to 3.
5. The flavor and/or fragrance composition according to claim 4, wherein
the cooling agent content is 0.01 to 50 % by weight.
6. A food and beverage, a cosmetic, a grocery good, a composition for oral
or a drug comprising the antimicrobial composition according to any one of claims 1
to 3, or the flavor and/or fragrance composition according to claim 4 or 5.
7. The food and beverage, the cosmetic, the grocery good, the composition
for oral or the drug according to claim 6, wherein the cooling agent content is 0.0001
to 30 % by weight.
8. A method for producing a flavor and/or fragrance composition, a food
and beverage, a cosmetic, a grocery good, a composition for oral or a drug,
comprising the step of blending the antimicrobial composition according to any one
of claims 1 to 3 with the food and beverage, the cosmetic, the grocery good, the
composition for oral or the drug.