U.S. patent application number 09/988860 was filed with the patent office on 2002-08-29 for rhinologically active substances.
Invention is credited to Loges, Hubert, Machinek, Arnold, Surburg, Horst.
Application Number | 20020120014 09/988860 |
Document ID | / |
Family ID | 7664566 |
Filed Date | 2002-08-29 |
United States Patent
Application |
20020120014 |
Kind Code |
A1 |
Surburg, Horst ; et
al. |
August 29, 2002 |
Rhinologically active substances
Abstract
Acyclic ethers can be used as rhinologically active substances.
In the regions of the mouth, the throat and the airways they
produce a refreshing and clearing feeling.
Inventors: |
Surburg, Horst; (Holzminden,
DE) ; Machinek, Arnold; (Holzminden, DE) ;
Loges, Hubert; (Hoexter, DE) |
Correspondence
Address: |
BAYER CORPORATION
PATENT DEPARTMENT
100 BAYER ROAD
PITTSBURGH
PA
15205
US
|
Family ID: |
7664566 |
Appl. No.: |
09/988860 |
Filed: |
November 21, 2001 |
Current U.S.
Class: |
514/715 |
Current CPC
Class: |
A61K 9/0056 20130101;
A23L 27/203 20160801; A61P 1/02 20180101; A61K 31/075 20130101;
A61P 11/12 20180101; A61P 11/16 20180101; A23G 4/06 20130101; A61P
11/02 20180101; A61Q 11/00 20130101 |
Class at
Publication: |
514/715 |
International
Class: |
A61K 031/075 |
Foreign Application Data
Date |
Code |
Application Number |
Nov 24, 2000 |
DE |
10058459.4 |
Claims
What is claimed is:
1. Rhinologically active substances of the formula 3wherein x is 0
or 1, R.sup.1 denotes an alkyl group having 1 to 4 carbon atoms,
R.sup.2 denotes a methyl or ethyl group and R.sup.3 denotes a
monocyclic carbon system having 5, 6, 7 or 8 carbon atoms that can
be unsubstituted or substituted with further alkyl groups having 1
to 4 carbon atoms or alkenyl groups having 2 to 4 carbon atoms.
2. Rhinologically active substances according to claim 1, wherein
R.sup.1 denotes a methyl or ethyl group, and R.sup.3 denotes a
monocyclic carbon system having 6 or 7 carbon atoms that can be
unsubstituted or substituted with further alkyl groups having 1 to
3 carbon atoms and/or alkenyl groups having 3 carbon atoms.
3. Rhinologically active substances according to claim 1, wherein
said rhinologically active substances are selected from the group
consisting of l-menthyl methyl ether, d-menthyl methyl ether,
dl-menthyl methyl ether, menthyl ethyl ether, menthyl propyl ether,
menthyl isobutyl ether, isopulegyl methyl ether,
2-isopropylcyclohexyl methyl ether, 2-isopropylcyclohexyl ethyl
ether, 3,3,5-trimethylcyclohexyl methyl ether,
1-(3,3-dimethylcyclohexyl)ethyl ethyl ether,
1-(3,3-dimethylcyclohexyl)ethyl propyl ether, and
1-(3,3-dimethylcyclohex- yl)ethyl methyl ether.
4. Preparations having a refreshing activity comprising
rhinologically active substances of the formula 4wherein x is 0 or
1, R.sup.1 denotes an alkyl group having 1 to 4 carbon atoms,
R.sup.2 denotes a methyl or ethyl group and R.sup.3 denotes a
monocyclic carbon system having 5, 6, 7 or 8 carbon atoms that can
be unsubstituted or substituted with further alkyl groups having 1
to 4 carbon atoms or alkenyl groups having 2 to 4 carbon atoms.
5. Preparations having a refreshing activity according to claim 4,
wherein R.sup.1 denotes a methyl or ethyl group, and R.sup.3
denotes a monocyclic carbon system having 6 or 7 carbon atoms that
can be unsubstituted or substituted with further alkyl groups
having 1 to 3 carbon atoms and/or alkenyl groups having 3 carbon
atoms.
6. Preparations having a refreshing activity according to claim 4,
comprising rhinologically active substances selected from the group
consisting of l-menthyl methyl ether, d-menthyl methyl ether,
dl-menthyl methyl ether, menthyl ethyl ether, menthyl propyl ether,
menthyl isobutyl ether, isopulegyl methyl ether,
2-isopropylcyclohexyl methyl ether, 2-isopropylcyclohexyl ethyl
ether, 3,3,5-trimethylcyclohexyl methyl ether,
1-(3,3-dimethylcyclohexyl)ethyl ethyl ether,
1-(3,3-dimethylcyclohexyl)ethyl propyl ether, and
1-(3,3-dimethylcyclohex- yl)ethyl methyl ether.
7. Preparations having a refreshing activity according to claim 4,
wherein said preparations comprise 0.0001 to 10% by weight of said
rhinologically active substances.
8. An oral care composition comprising preparations having a
refreshing activity comprising rhinologically active substances of
the formula 5wherein x is 0 or 1, R.sup.1 denotes an alkyl group
having 1 to 4 carbon atoms, R.sup.2 denotes a methyl or ethyl group
and R.sup.3 denotes a monocyclic carbon system having 5, 6, 7 or 8
carbon atoms that can be unsubstituted or substituted with further
alkyl groups having 1 to 4 carbon atoms or alkenyl groups having 2
to 4 carbon atoms.
9. An oral care composition according to claim 8, wherein said oral
care composition is a toothpaste.
10. An oral care composition according to claim 8, wherein said
oral care composition is a mouthwash.
11. An oral care composition according to claim 8, wherein said
oral care composition is a chewing-gum.
12. A food product comprising preparations having a refreshing
activity comprising rhinologically active substances of the formula
6wherein x is 0 or 1, R.sup.1 denotes an alkyl group having 1 to 4
carbon atoms, R.sup.2 denotes a methyl or ethyl group and R.sup.3
denotes a monocyclic carbon system having 5, 6, 7 or 8 carbon atoms
that can be unsubstituted or substituted with further alkyl groups
having 1 to 4 carbon atoms or alkenyl groups having 2 to 4 carbon
atoms.
13. Tobacco products comprising preparations having a refreshing
activity comprising rhinologically active substances of the formula
7wherein x is 0 or 1, R.sup.1 denotes an alkyl group having 1 to 4
carbon atoms, R.sup.2 denotes a methyl or ethyl group and R.sup.3
denotes a monocyclic carbon system having 5, 6, 7 or 8 carbon atoms
that can be unsubstituted or substituted with further alkyl groups
having 1 to 4 carbon atoms or alkenyl groups having 2 to 4 carbon
atoms.
14. Confectionary products comprising preparations having a
refreshing activity comprising rhinologically active substances of
the formula 8wherein x is 0 or 1, R.sup.1 denotes an alkyl group
having 1 to 4 carbon atoms, R.sup.2 denotes a methyl or ethyl group
and R.sup.3 denotes a monocyclic carbon system having 5, 6, 7 or 8
carbon atoms that can be unsubstituted or substituted with further
alkyl groups having 1 to 4 carbon atoms or alkenyl groups having 2
to 4 carbon atoms.
15. Pharmaceutical preparations having a refreshing activity
comprising rhinologically active substances of the formula 9wherein
x is 0 or 1, R.sup.1 denotes an alkyl group having 1 to 4 carbon
atoms, R.sup.2 denotes a methyl or ethyl group and R.sup.3 denotes
a monocyclic carbon system having 5, 6, 7 or 8 carbon atoms that
can be unsubstituted or substituted with further alkyl groups
having 1 to 4 carbon atoms or alkenyl groups having 2 to 4 carbon
atoms.
16. Novel acyclic ethers selected from the group consisting of
isopulegyl methyl ether, 1-(3,3-dimethylcyclohexyl)ethyl ethyl
ether, 1-(3,3-dimethylcyclohexyl)ethyl propyl ether and
1-(3,3-dimethylcyclohexy- l)ethyl methyl ether.
Description
FIELD OF THE INVENTION
[0001] The invention relates to rhinologically active substances
which give rise to a refreshing and clearing feeling in the area of
the mouth, the throat and the airways, and to preparations which
comprise these compounds.
BACKGROUND OF THE INVENTION
[0002] 1,8-Cineole (eucalyptol) is a substance which is used in
large amounts as a rhinologically active substance in
pharmaceutical preparations, oral care preparations, such as
toothpastes and mouthwashes, and confectionery products, such as
cough sweets and chewing-gum, especially because of its property of
producing a cooling-refreshing and thus clearing feeling in the
region of the mouth, the throat and the airways. In addition to
this effect, 1,8-cineole (eucalyptol), however, has a strong
typical flavor, which, because of its pronounced medicinal note, is
perceived as unpleasant by many consumers.
[0003] There is, therefore, a requirement for substances which, in
a similar manner to 1,8-cineole (eucalyptol), produce a
cooling-refreshing and thus, clearing feeling as a rhinologically
active compound in the region of the mouth, the throat and the
airways, especially in the nasal cavity, and in the pharyngeal
cavity, but which do not have such a strong and unpleasant typical
taste.
[0004] The advantage of such rhinologically active substances is
that they are universally usable, that is to say can be used in
preparations having a multiplicity of aromas of the most varying
flavor notes.
[0005] Lower alkyl ethers of isobornane, here particularly of
methyl isobornyl ether (Food Chem. Toxicol. 30 (Suppl.), 53S
(1992), and of bomane, for example bornyl methyl ether and bornyl
ethyl ether, (U.S. Pat. No. 4,131,687) have already been known for
a relatively long time as fragrance and aroma substances having
fresh, herb-like, rosemary-like or eucalyptus-like sensory
properties. However, because of their strong typical flavor, they
cannot be used as replacement products for 1,8-cineole (eucalyptol)
in the sense described above.
SUMMARY OF THE INVENTION
[0006] New rhinologically active substances have been found, which
are of the formula 1
[0007] wherein
[0008] x is 0 or 1,
[0009] R.sup.1 denotes an alkyl group having 1 to 4 carbon
atoms,
[0010] R.sup.2 denotes a methyl or ethyl group and
[0011] R.sup.3 denotes a monocyclic carbon system having 5, 6, 7 or
8 carbon atoms that can be unsubstituted or substituted with
further alkyl groups having 1 to 4 carbon atoms or alkenyl groups
having 2 to 4 carbon atoms.
DETAILED DESCRIPTION OF THE INVENTION
[0012] The inventive new rhinologically active substances are
acyclic ethers.
[0013] The alkyl group having 1 to 4 carbon atoms can be methyl,
ethyl, propyl, isopropyl, butyl or isobutyl.
[0014] The alkenyl group having 2 to 4 carbon atoms can be vinyl,
2-propenyl, allyl or 2-buten-1-yl.
[0015] The radical R.sup.3 can be unsubstituted or can be
substituted, for example, with 1 to 3 methyl groups or with 1
isopropyl group or with 1 methyl group and 1 isopropyl group or
with 1 methyl group and 1, 2-propenyl group.
[0016] The inventive rhinologically active substances exhibit an
activity comparable to 1,8-cineole (eucalyptol) with respect to a
refreshing clearing feeling in the mouth, pharyngeal cavity and the
airways, without producing an unpleasant taste sensation.
[0017] These rhinologically active substances, in addition to their
activity of producing a refreshing clearing feeling in the mouth,
pharyngeal cavity and the airways, exhibit fresh, ethereal, minty,
cooling, sweet and fruity flavor notes and are therefore, also
outstandingly suitable as flavor compounds.
[0018] The fact that the inventive rhinologically active compounds
exhibit an activity comparable to 1,8-cineole (eucalyptol), with
respect to a refreshing clearing feeling in the mouth, pharyngeal
cavity and the airways, was surprising and not predictable to the
extent that the inventive ethers do not have a cyclic structure
like 1,8-cineole (eucalyptol), but have an acyclic structure.
[0019] Preferred rhinologically active compounds in the context of
the present invention are compounds of the formula 2
[0020] wherein
[0021] x can have the value 0 or 1,
[0022] R.sup.1 denotes a methyl or ethyl group,
[0023] R.sup.2 denotes a methyl or ethyl group and
[0024] R.sup.3 denotes a monocyclic carbon system having 6 or 7
carbon atoms that can be unsubstituted or substituted with further
alkyl groups having 1 to 3 carbon atoms and/or alkenyl groups
having 3 carbon atoms.
[0025] The present flavor compounds, render pleasantly tasting
flavor compounds, which have the activity of causing a refreshing
clearing feeling in the mouth, pharyngeal cavity and the airways.
The inventive rhinologically active compounds are selected from the
group of l-menthyl methyl ether, d-menthyl methyl ether, dl-menthyl
methyl ether, menthyl ethyl ether, menthyl propyl ether, menthyl
isobutyl ether, isopulegyl methyl ether, 2-isopropylcyclohexyl
methyl ether, 2-isopropylcyclohexyl ethyl ether,
3,3,5-trimethylcyclohexyl methyl ether,
1-(3,3-dimethylcyclohexyl)-ethyl ethyl ether,
1-(3,3-dimethylcyclohexyl)e- thyl propyl ether, and
1-(3,3-dimethylcyclohexyl)ethyl methyl ether.
[0026] The activity of causing a refreshing clearing feeling in the
mouth, pharyngeal cavity and the airways, in the case of the
inventive rhinologically active compounds, applies to all isomeric
forms, that is to say to diastereomers and enantiomers.
[0027] The following acyclic ethers for the inventive
rhinologically active compounds are novel:
[0028] Isopulegyl methyl ether, 1-(3,3-dimethylcyclohexyl)ethyl
ethyl ether, 1-(3,3-dimethylcyclohexyl)ethyl propyl ether and
1-(3,3-dimethyl-cyclohexyl)ethyl methyl ether.
[0029] Preparation of the acyclic ethers for the inventive
rhinologically active compounds is known per se. It can be
performed, for example, by etherification of the corresponding
alcohols with alkylating agents, such as alkyl halides, alkyl
tosylates, alkyl mesylates or alkyl halides in the presence of an
equivalent amount of a basic compound. Particularly advantageous
here is etherification by the phase-transfer process, which is
described, for example, in Angew. Chem. 85, 868-869 (1973), and is
carried out as follows: the alcohol to be etherified is vigorously
stirred in a nonpolar solvent in the presence of a phase-transfer
catalyst, for example tetrabutylammonium iodide, with a 2.5-fold
excess of 50% strength sodium hydroxide solution and 1.2-fold
excess of an alkylating agent is added. After a customary cleanup,
the corresponding ether is obtained, which is separated off from
unreacted alcohol by distillation or liquid chromatography.
[0030] To achieve fresh ethereal, minty, cooling, sweet and fruity
flavor notes in combination with a refreshing clearing feeling in
the mouth, pharyngeal cavity and the airways, the inventive
rhinologically active compounds can be combined with one another in
pure form, or, in a preferred form, can be combined with aroma
substances or flavor substances.
[0031] Suitable aroma substances are both complex natural raw
materials, such as extracts and essential oils produced from
plants, and fractions and homogeneous substances produced
therefrom, and also homogeneous synthetically or biotechnologically
produced aroma substances.
[0032] Examples of natural raw materials are, for example:
peppermint oils, spearmint oils, Mentha arvensis oils, aniseed
oils, clove oils, citrus oils, cinnamon bark oils, winter green
oils, cassia oils, davana oils, spruce needle oils, eucalyptus
oils, fennel oils, galbanum oils, ginger oils, camomile oils, cumin
oils, rose oils, geranium oils, sage oils, yarrow oils, star anise
oils, thyme oils, juniper berry oils, rosemary oils, angelica root
oils, and fractions of these oils.
[0033] Examples of homogeneous aroma substances are, for example:
anethole, menthol, menthone, isomenthone, menthyl acetate,
menthofuran, mint lactone, eucalyptol, limonene, eugenol, pinene,
sabinene hydrate, 3-octanol, carvone, gamma-octalactone,
gamma-nonalactone, germacrene-D, viridiflorol,
1,3E,5Z-undecatriene, isopulegol, piperitone, 2-butanone, ethyl
formate, 3-octyl acetate, isoamyl isovalerate, hexanol, hexanal,
cis-3-hexenol, linalool, alpha-terpineol, cis and trans carvyl
acetate, p-cymol, damascenon, damascone, rose oxide, dimethyl
sulfide, fenchol, acetaldehyde diethyl acetal, cis-4-heptenal,
isobutyraldehyde, isovaleraldehyde, cis-jasmone, anisaldehyde,
methyl salicylate, myrtenyl acetate, 2-phenylethyl alcohol,
2-phenylethyl isobutyrate, 2-phenylethyl isovalerate,
cinnamaldehyde, geraniol, nerol. In the case of chiral compounds,
the aroma substances can be present as racemate or an individual
enantiomer or as enantiomer-enriched mixture.
[0034] Examples of other flavor substances which can be
advantageously combined with the inventive rhinologically active
substances are, for example, substances having a physiologically
cooling action, that is to say substances which cause an impression
of cold in the mucous membranes. Such substances having a cooling
action are, for example, l-menthol, 1-isopulegol, menthone glycerol
acetal, menthyl lactate, substituted menthane-3-carboxamides (for
example N-ethylmenthane-3-carboxamide),
2-isopropyl-N,2,3-trimethylbutanamide, substituted
cyclohexanecarboxamides, 3-menthoxy-1,2-propanediol,
2-hydroxyethylmenthyl carbonate, 2-hydroxypropylmenthyl carbonate,
N-acetylglycine menthyl ester, menthylhydroxycarboxylic esters (for
example menthyl 3-hydroxybutyrate), menthyl monosuccinate,
2-mercaptocyclodecanone, and menthyl 2-pyrrolidin-5-one
carboxylate.
[0035] The inventive rhinologically active substances can be
present in the aroma or flavor substance compositions at a content
of 0.1 to 100% by weight. Preference is given to a content of 0.1
to 70% by weight; more preference is given to a content of 0.5 to
40% by weight.
[0036] The aroma or flavor substance compositions comprising the
inventive rhinologically active substances can be used in pure
form, as solutions, or else in specially prepared form, and
incorporated into ready-to-use products.
[0037] Suitable solvents are, for example, ethyl alcohol,
1,2-propylene glycol, triacetin, benzyl alcohol and fatty oils, for
example coconut oil or sunflower seed oil.
[0038] The aroma or flavor substance compositions comprising the
inventive rhinologically active substances can also comprise
additives and aids, for example preservatives, pigments,
antioxidants, anticaking agents, thickeners, etc.
[0039] In particular prepared forms, the aroma or flavor substance
compositions comprising the inventive rhinologically active
substances can be bound to a carrier, spray-dried or else
encapsulated.
[0040] In the bound form, the aroma or flavor substance
compositions can be bound on or in a carrier, for example sodium
chloride, sugar, starches or sugar melts.
[0041] The spray-dried form is produced from the liquid
compositions by producing an emulsion with addition of defined
amounts of a carrier, preferably biopolymers such as starch,
modified starches, maltodextrin and gum arabic. This emulsion is
dried in spray-dryers by very fine distribution with uniform
temperature application. A powder results having the desired
loading of liquid composition.
[0042] The encapsulated form is also produced from the liquid
compositions by adding a carrier. Various technologies exist by
which capsules can be produced. The most familiar are extrusion,
spray-granulation and coacervation. The particle sizes customarily
extend from 10 .mu.m to 5 mm. The most familiar capsule materials
are various starches, maltodextrin and gelatin. In these capsules,
the liquid or solid aroma or flavor substance compositions are
enclosed and can be released by various mechanisms such as use of
heat, pH shift or chewing pressure.
[0043] The inventive rhinologically active substances are suitable
for producing preparations of the most varied flavors, particularly
for use in aroma compositions having a cooling-refreshing mint-like
flavor. The mint compositions are essentially characterized by a
content of peppermint oils, Mentha arvensis oils, spearmint oils,
eucalyptus oils, 1,8-cineole (eucalyptol), menthol and substances
having a physiologically cooling activity.
[0044] The contents of the individual composition constituents of
the mint compositions can vary here generally between 0.1 and
99.9%
[0045] Mint compositions which are preferably used are those having
1 to 90% by weight of menthol, 1 to 60% by weight of menthone, 1 to
90% by weight of peppermint or Mentha arvensis oils, 1 to 90% by
weight of spearmint oils, 1 to 90% by weight of eucalyptol or
eucalyptol-containing eucalyptus oils, 0.5 to 70% by weight of the
inventive rhinologically active substances, for example menthyl
methyl ether, isopulegyl methyl ether or the like and 0.5 to 70% by
weight of substances having a physiologically cooling action.
[0046] Mint compositions which are preferably used are those having
20 to 60% by weight of menthol, 5 to 30% of menthone, 5 to 60% by
weight of peppermint or Mentha arvensis oils, 5 to 60% by weight of
spearmint oils, 2 to 50% by weight of eucalyptol or
eucalyptol-containing eucalyptus oils, 0.5 to 40% by weight of the
inventive rhinologically active substances, for example menthyl
methyl ether, isopulegyl methyl ether or the like and 1 to 30% by
weight of substances having a physiological cooling action.
[0047] Substances having a physiological cooling action can be the
above-described, in which case they are used individually or as
mixtures. If mixtures are used, these are generally mixtures, for
example, of menthone glycerol acetal, menthyl lactate, substituted
menthyl-3-carboxamides (for example N-ethylmenthyl-3-carboxamide),
2-hydroxyethylmenthyl carbonate and 2'-hydroxypropylmenthyl
carbonate.
[0048] Generally, mixtures are used which have 1 to 99% by weight
of menthone glycerol acetal, 1 to 99% by weight of menthyl lactate,
1 to 99% by weight of N-ethylmenthyl-3-carboxamide, 1 to 99% by
weight of 2-hydroxyethylmenthyl carbonate and 1 to 99% by weight of
hydroxypropylmenthyl carbonate.
[0049] Preference is given to mixtures having 1 to 70% by weight of
menthone glycerol acetal, 1 to 70% by weight of menthyl lactate, 1
to 70% by weight of N-ethylmenthyl-3-carboxamide, 1 to 70% by
weight of 2-hydroxyethylmenthyl carbonate and 1 to 70% by weight of
2-hydroxypropylmenthyl carbonate.
[0050] By adding other aroma substances, for example of the sweet,
sweet-aromatic, fresh, fruity types, or if appropriate, of other
flavors also, these mint compositions can be modified in flavor,
with the content by weight of the added aroma substances generally
being 0.001 to 50% by weight, based on the weight fraction of minty
compounds and cooling compounds. Preference is given to an addition
of 0.01 to 30% by weight, preferably an addition of 0.1 to 10% by
weight, based on the weight fraction of the minty and cooling
substances.
[0051] By using the inventive rhinologically active substances in
such compositions, the content of the eucalyptus oils and of
1,8-cineole (eucalyptol) and thus the strong medicinal flavor note
can be reduced, without reducing the refreshing clearing feeling in
the mouth, pharyngeal cavity and the airways. The perception of
freshness which is produced by the inventive rhinologically active
substances in the airways, in the mouth and in the pharyngeal
cavity is of longer duration than that caused by 1,8-cineole
(eucalyptol).
[0052] It is noteworthy, here, that the flavor intensity and
roundness of flavor of the mint compositions are increased by using
the inventive rhinologically active substances, and the cooling
action of the substances having a physiological cooling action is
intensified.
[0053] The preparations comprising the inventive rhinologically
active substances can advantageously be used, especially in oral
care compositions, such as toothpastes and mouthwashes,
chewing-gum, foods, such as confectionery and sweets for sucking,
luxury consumption merchandise, such as tobacco, pharmaceutical
preparations, nasal sprays.
[0054] The content of the preparations comprising the inventive
rhinologically active substances is, in ready-to-use mouthwashes
0.01 to 1% by weight, preferably 0.1 to 0.3% by weight. In
mouthwash concentrates, the content of the compositions comprising
the inventive rhinologically active substances is between 0.01 and
20% by weight, preferably 0.1 to 10% by weight, and more preferably
3 to 5% by weight. In toothpastes and chewing-gum, the compositions
comprising the inventive rhinologically active substances are used
at a concentration between 0.1 and 5% by weight, preferably 0.5 to
2% by weight, and more preferably between 0.8 and 1.5% by weight.
In sweets for sucking, the content of the compositions comprising
the inventive rhinologically active substances is between 0.01 and
2% by weight, preferably 0.05 to 1 % by weight; and more preferably
between 0.1 and 0.5%.
[0055] Toothpastes that are flavored with the compositions
comprising the inventive rhinologically active substances generally
consist of an abrasive system (abrasives or polishes), for example
silicic acids, calcium carbonates, calcium phosphates, aluminum
oxides and/or hydroxyl apatites; surface-active substances, for
example sodium lauryl sulphate, sodium lauryl sarcosinate and/or
cocamidopropylbetaine; humectants, for example glycerol and/or
sorbitol; thickeners, for example carboxymethyl cellulose,
polyethylene glycols, carrageenans and/or Laponites.RTM.,
sweeteners, for example saccharin; stabilizers; and active
compounds, for example sodium fluoride, sodium monofluorophosphate,
tin difluoride, quaternary ammonium fluorides, zinc citrate, zinc
sulphate, tin pyrophosphate, tin dichloride, mixtures of various
pyrophosphates, triclosan, cetylpyridinium chloride, aluminum
lactate, potassium citrate, potassium nitrate, potassium chloride,
strontium chloride, hydrogen peroxide and/or sodium
bicarbonate.
[0056] Chewing-gum that is flavored with the compositions
comprising the inventive rhinologically active substances generally
consists of a chewing-gum base, that is to say a chewing mass which
becomes plastic on chewing; sugars of various types; sugar
substitutes; sweeteners; sugar alcohols; humectants; thickeners;
emulsifiers; and stabilizers.
[0057] When finished products that comprise the compositions having
the inventive rhinologically active substances are used, it is
found that the inventive rhinologically active substances or the
compositions comprising the inventive rhinologically active
substances are particularly suitable for freshening the breath and
neutralizing or reducing bad breath.
[0058] The use of the inventive rhinologically active substances or
the compositions comprising the rhinologically active substances in
oral care products, for example mouthwashes and toothpastes, and
chewing-gum, leads to unpleasant, especially bitter, taste
impressions being masked or neutralized, as are caused, for
example, by substances such as triclosan, zinc citrate, zinc
sulphate, polyphosphates and pyrophosphates, bicarbonates,
strontium salts and potassium salts, tin pyrophosphate, tin
chloride, aluminum lactate, hydrogen peroxide, fluorides, vitamins,
cetylpyridinium chloride, and emulsifiers, for example,
particularly sodium lauryl sulphate, sodium lauryl sarcosinate and
cocamidopropylbetaine, and sweeteners, for example aspartame,
saccharin, acesulfame-K, sorbitol; xylitol, cyclamates (for example
sodium cyclamate), sucralose, alitame, neotame, thaumatin,
neohesperidin DC, maltitol, lactitol or chewing-gum bases.
[0059] A further positive property of the inventive rhinologically
active substances which must be emphasized is their stability in
toothpastes based on chalk or bicarbonate which, because of their
alkaline pH, are difficult to flavor.
[0060] The inventive rhinologically active substances and the
compositions comprising the inventive rhinologically active
substances are also suitable, however, for use in pharmaceutical
preparations, for example, nasal drops and nasal sprays or
embrocations. The compositions comprising the inventive
rhinologically active substances are suitable, in particular, for
masking the bitter taste of medicaments.
EXAMPLES
[0061] The examples below are intended to illustrate the use of the
inventive rhinologically active substances. However, the use of the
inventive rhinologically active substances is not restricted to the
examples cited.
Example 1
[0062] Preparation of the Alkyl Ethers
[0063] General Instructions:
[0064] 1 mol of the alcohol to be etherified is dissolved in 400 ml
of toluene and stirred vigorously after addition of 2.6 mol. of 50%
strength sodium hydroxide solution and 2 g of tetrabutylammonium
iodide. At a bottom temperature of a maximum of 45.degree. C., 1.2
mol of alkylating agent is added in the course of 1 h. The mixture
is then stirred for a further 3 h at this temperature. If dialkyl
sulphates were used as an alkylating agent, ammonia is added to
destroy them and the mixture is stirred for a further 30 min at
room temperature. After addition of water, the phases are
separated. The solvent is taken off from the organic phase and the
residue is fractionated by distillation. The pure ethers are
obtained by redistillation via a split-tube column.
[0065] In this manner the following ethers were prepared:
1TABLE 1 Compound: Mass spectrum: Menthyl methyl ether m/z = 170
155 138 123 95 85 81 67 55 45 41 % 1 2 45 19 36 100 49 18 27 15 28
Menthyl ethyl ether m/z = 184 138 123 113 99 95 81 71 55 41 % 2 36
12 8 100 20 26 28 18 20 Menthyl propyl ether m/z 198 138 123 113 95
81 71 55 41 % 2 46 16 100 26 33 63 22 29 Menthyl isobutyl ether m/z
212 138 127 123 95 83 81 71 57 55 41 % 2 43 76 21 34 38 53 100 43
28 34 2-Isopropylcyclohexyl methyl ether m/z 156 141 124 113 109 99
95 81 71 67 55 41 % 5 12 100 16 58 21 23 60 90 36 25 56
2-Isopropylcyclohexyl ethyl ether m/z 170 155 127 124 109 99 95 85
81 67 57 41 % 8 16 24 100 55 18 20 96 50 26 75 38
1-(3,3-Dimethylcyclohexyl)ethyl ethyl ether m/z 184 123 81 73 69 55
45 41 28 % 2 16 8 100 7 10 59 14 10 1-(3,3-Dimethylcyclohexyl)ethyl
propyl ether m/z 198 183 123 87 81 69 55 45 41 % 1 2 16 93 9 14 13
100 23 1-(3,3-Dimethylcyclohexyl)ethyl methyl ether m/z 170 155 123
110 95 81 69 59 55 41 % 1 3 13 5 6 9 7 100 10 12
3,3,5-Trimethylcyclohexyl methyl ether m/z 156 141 124 109 99 85 67
58 55 41 % 4 3 29 61 87 100 23 18 28 30 Isopulegyl methyl ether m/z
168 153 136 121 111 98 93 85 81 67 55 41 % 18 13 9 41 30 34 28 100
24 21 23 25
Example 2
[0066] Production of a toothpaste flavoring of the eucalyptus
menthol type, using menthyl methyl ether:
2 The following were mixed: 0.5 parts by weight camphor 3 parts by
weight anethole 6 parts by weight peppermint oil of the Mentha
arvensis type 2 parts by weight menthyl lactate 2 parts by weight
2-hydroxyethylmenthyl carbonate 2 parts by weight
2-hydroxypropylmenthyl carbonate 20 parts by weight 1,8-cineole
(eucalyptol) 64.5 parts by weight I-menthol
[0067] In a second mixture batch, the 1,8-cineole (eucalyptol)
content was replaced by l-menthyl methyl ether. Both flavorings are
incorporated at a concentration of 1.3% by weight into a standard
toothpaste mix based on silicic acid. Both types of toothpaste were
tested under conditions of practice by an expert panel trained in
sensory testing. The result showed that the flavoring containing
l-menthyl methyl ether and without 1,8-cineole (eucalyptol)
markedly decreased the strongly medicinal taste, without the taste
impression of freshness in the airways, mouth and pharyngeal cavity
being reduced. Overall, the second flavoring led to a more clear
longer-lasting taste impression with more roundness and volume.
[0068] Comparable effects are obtained if isopulegyl methyl ether,
3,3,5-trimethylcyclohexyl methyl ether or
1-(3,3-dimethylcyclohexyl) ethyl methyl ether were used instead of
l-menthyl methyl ether.
Example 3
[0069] Production of toothpaste flavoring of the wintergreen type
using menthyl methyl ether:
3 The following were mixed: 10 parts by weight anethol 5 parts by
weight peppermint oil of the Mentha arvensis type 5 parts by weight
peppermint oil of the Mentha piperita type 25 parts by weight
methyl salicylate 40 parts by weight I-menthol 15 parts by weight
I-menthyl methyl ether
[0070] The flavoring was incorporated at a concentration of 1.3% by
weight into a standard toothpaste mix based on silicic acid. The
toothpaste was tested under conditions of practice by an expert
panel trained in sensory testing. The results showed that the
flavoring gave a taste impression of high intensity and
long-lasting duration, a pronounced markedly refreshing, clearing
feeling being perceived in the airways, in the mouth and in the
pharyngeal cavity.
Example 4
[0071] Production of a chewing-gum flavoring using l-menthyl methyl
ether:
4 The following were mixed: 40 parts by weight peppermint oil of
the Mentha arvensis type 20 parts by weight I-menthone 20 parts by
weight I-menthol 20 parts by weight I-menthyl methyl ether
[0072] The flavoring was incorporated at a concentration of 1.5% by
weight into a sugar-free standard chewing-gum base. The chewing gum
was tested for a sensory quality by a trained expert panel. It was
found that addition of l-menthyl methyl ether gave a markedly
refreshing clearing feeling in the airways, in the mouth and in the
pharyngeal cavity, and the taste roundness and intensity of the
peppermint flavoring was markedly increased.
[0073] Although the invention has been described in detail in the
foregoing for the purpose of illustration, it is to be understood
that such detail is solely for that purpose and that variations can
be made therein by those skilled in the art without departing from
the spirit and scope of the invention except as it may be limited
by the claims.
* * * * *