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Weight Loss Patent Abstract
The present invention relates to compositions comprising compounds
that induce weight and fat loss and compounds that mask the bitter
and harsh taste of the composition. The invention further relates
to a food, beverage, dietary supplement, medical food, or pet food
comprising compounds that induce weight loss and compounds that
mask the bitter and harsh taste of the product. The invention is
further related to methods of reducing or controlling weight by
administering such compositions. Further provided are cosmetic sheets
for topical administration of compositions for inducing weight and
fat loss.
Weight Loss Patent Claims
We claim:
1. A composition comprising: (i) one or both of a compound of formula
(1) or formula (2) 4wherein R.sup.1 is H, OH, or OCH.sub.3, R.sup.2
is H, COR.sup.3, or a sugar group, and R.sup.3 is a C.sub.2-C.sub.20
alkyl group; and (ii) an effective taste-masking amount of one or
more extract selected from the group consisting of extracts of oolong
tea, puerh tea, roasted adlay tea, eucommia leaves, jasmine flower,
banzakuro (guava fruit), barley, mate tea (Paraguay tea), rooibos
tea, tinpi (matured peal of Citrus unshiu), juemingzi, sanzashi
(Crataegus), soybean germ, ginger, ginseng, kouki tea, and yucca.
2. The composition of claim 1, wherein said one or more extract
is selected from the group consisting of extracts of oolong tea,
puerh tea, roasted adlay tea, eucommia leaves, and jasmine flower.
3. The composition of claim 1, wherein the compound of formula
(1) or formula (2) is selected from the group consisting of raspberry
ketone, zingerone and BK-180.
4. The composition of claim 1, wherein the ratio by weight of component
(i) to component (ii) ranges from about 10:1 to about 1:20.
5. The composition of claim 1, in the form of a food, beverage,
dietary supplement, medical food, pet food, cosmetic, or topical
application patch.
6. A method of reducing or controlling weight and/or fat comprising
administering an effective amount of the composition according to
claim 1 to a mammal to reduce or control weight and/or fat.
7. A composition comprising: (i) one or both of a compound of formula
(1) or formula (2) 5wherein R.sup.1 is H, OH, or OCH.sub.3, R.sup.2
is H, COR.sup.3, or a sugar group, and R.sup.3 is a C.sub.2-C.sub.20
alkyl group; and (ii) an effective taste-masking amount of one or
more members selected from the group consisting of malthol, ethyl
maltol, furaneol, furaneol derivatives, vanillin, and ethyl vanillin.
8. The composition of claim 7, wherein the compound of formula
(1) or formula (2) is selected from the group consisting of raspberry
ketone, zingerone, or BK-180.
9. The composition of claim 7, wherein the ratio by weight of component
(i) to component (ii) ranges from about 10:1 to about 1:20.
10. The composition of claim 7, in the form of a food, beverage,
dietary supplement, medical food, pet food, cosmetic, or topical
application patch.
11. A method of reducing or controlling weight and/or fat comprising
administering an effective amount of a composition according to
claim 7 to a mammal to reduce or control weight and/or fat.
12. A clathrate comprising a compound represented by formula (1)
or formula (2) 6wherein R.sup.1 is H, OH, or OCH.sub.3, R.sup.2
is H, COR.sup.3, or a sugar group, and R.sup.3 is a C.sub.2-C.sub.20
alkyl group, included in a cyclodextrin.
13. The clathrate of claim 12, wherein said cyclodextrin is a .beta.-cyclodextrin.
14. The clathrate of claim 12, wherein said compound of formula
(1) or formula (2) is selected from the group consisting of raspberry
ketone, zingerone, and BK-180.
15. A composition comprising the clathrate of claim 12, in the
form of a food, beverage, dietary supplement, medical food, pet
food, cosmetic, bath salt, or topical application patch.
16. A method of reducing or controlling weight and/or fat comprising
administering an effective amount of the clathrate of claim 12 to
a mammal to reduce or control weight and/or fat.
Weight Loss Patent Description
[0001] This application claims the benefit of Japanese Patent Application
No. 2002-128770, filed Apr. 30, 2002, and Japanese Patent Application
No. 2002-156911, filed May 30, 2002, both of which are hereby incorporated
by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to compounds that induce weight
loss and fat loss and compositions and clathrates that mask the
bitter and harsh taste of such compounds. The invention further
relates to a food, beverage, dietary supplement, medical food, pet
food, cosmetic or bath salt comprising compounds that induce weight
loss and compositions and clathrates that mask the bitter and harsh
taste of,the product. The invention is further related to methods
of reducing or controlling weight or fat by administering such compositions
or clathrates.
BACKGROUND OF THE INVENTION
[0003] In developed countries, obesity has increased in recent
years due to overall lifestyle changes including increased caloric
intake and insufficient exercise. In turn, being overweight or obese
is directly or indirectly associated with a vast number of diseases
including high blood pressure, diabetes, heart disease, and gallstones.
People who are overweight often experience more health problems
and shortened life expectancies. Therefore, there continues to be
a search for new and effective means to facilitate weight and fat
loss or to control weight and fat.
[0004] Herbal and natural products that contain gymunema extract,
garcinia extract, or carnitine are known to prevent fat accumulation
through the inhibition of fat absorption, enhancement of fat decomposition,
and the enhancement of fat consumption by the body. The active ingredients
in these extracts, however, have a characteristic bitter and harsh
taste and peculiar aroma. For example, hydroxy citric acid (HCA),
an active component in garcinia, is known to inhibit the citric
acid ATP lipase that metabolizes sugar to fat. HCA, however, has
a characteristic bitter and harsh taste, and the addition of an
amount of HCA effective to cause weight or fat loss spoils food
flavor.
[0005] Hydroxyphenylbutan-2-ones or hydroxyphenylbutan-2-ols of
formulas (1) and (2), represented by the formula 1
[0006] where
[0007] R.sup.1=H, --OH, or --OCH.sub.3
[0008] R.sup.2=H, C--OR.sup.3, or sugar group and
[0009] R.sup.3=C.sub.2-C.sub.20 alkyl,
[0010] have been found to enhance fat decomposition (JP 2000-169325
and JP 2001-226263). The compounds raspberry ketone (4-(4-hydroxyphenyl)-butan-2-
-one) and zingerone (4-(3-methoxy-4-hydroxyphenyl)-butan-2-one)
and BK-180 (4-(3,4-dihydroxyphenyl)butan-2-one) and its derivatives,
for example, have the ability to promote the decomposition of fats
accumulated in fatty tissue and are effective for inhibiting obesity
and for improving pyknic constitutions (Japanese Patent Laid-Open
No. 2000-169325).
[0011] Compounds of formulas (1) and (2) are less pungent and bitter,
compared to other natural weight loss ingredients, such as capsaicin.
However, compounds of formulas (1) and (2), e.g., raspberry ketone
and zingerone, have a taste and peculiar aroma that are unpleasant
when these compounds are present in high amounts. Despite these
complications, hydroxyphenylbutan-2-ones or hydroxyphenylbutan-2-ols
of formulas (1) and (2) are used satisfactorily as minor substituents
and relatively low amounts in compositions to impart fragrance or
flavor. Large amounts of these compounds are necessary, however,
to achieve weight loss. Accordingly, they are generally unsatisfactory
for use in compositions (e.g., food, tablets, drink, pet food, cosmetics
or bath salts) designed to effect loss of weight or fat, due to
the unpleasant aroma and taste associated with the large amounts
of the compounds.
[0012] In order to mask the unpleasant taste of these active ingredients,
components such as sweeteners or particular flavors can be added
to compositions. These additives, however, do not always effectively
mask active ingredients that have a strong bitter taste. Nor are
they typically effective in masking unpleasant aromas. There is,
therefore, a need for improved methods of masking unpleasant taste
and/or aromas of active ingredients of formulas (1) and (2).
[0013] It has now been found that the unpleasant taste and aroma
of compounds of formula (1) and formula (2) may be masked with specific
flavorants, through encapsulation methods, or by including compounds
of formula (1) or (2) in a clathrate. The ability to mask the unpleasant
taste and/or aroma of compounds of formulas (1) and (2) permits
application or ingestion of higher amounts of these compounds by
a mammal, directly or in a composition, leading to increased efficacy
of the compounds in fat reduction and weight loss.
SUMMARY OF THE INVENTION
[0014] The invention is directed to compositions comprising (i)
one or more compound represented by the formulas (1) and/or (2)
2
[0015] wherein R.sup.1=H, --OH, or --OCH.sub.3, R.sup.2=H, C--OR.sup.3,
or sugar group and R.sup.3=C.sub.2-C.sub.20 alkyl, and (ii) one
or more compound that masks or lessens an unpleasant taste or aroma
of a compound of formula (1) or formula (2).
[0016] Accordingly, in one aspect, the invention is drawn to a
composition comprising: (i) one or both of a compound of formula
(1) and a compound of formula (2) and (ii) an effective taste masking
amount of one or more member selected from the group consisting
of extracts of oolong tea, puerh tea, roasted adlay tea, eucommia
leaves, jasmine flower, banzakuro (guava fruit), barley, mate tea
(Paraguay tea), rooibos tea, tinpi (matured peal of Citrus unshiu),
juemingzi, sanzashi (Crataegus), soybean germ, ginger, ginseng,
kouki tea, and yucca. Preferably, the member is selected from the
group consisting of extracts from oolong tea, puerh tea, roasted
adlay tea, eucommia leaves, and jasmine flower.
[0017] In another aspect, the invention is drawn to a composition
comprising: (i) one or both of a compound of formula (1) and a compound
of formula (2) and (ii) an effective taste-masking amount of one
or more members selected from the group consisting of malthol, ethyl
maltol, furaneol, furaneol derivatives, vanillin, and ethyl vanillin.
[0018] In another aspect, the invention is drawn to a clathrate
comprising a compound of formula (1) or a compound of formula (2).
In a preferred embodiment, the clathrate comprises a compound of
formula (1) or formula (2) included in a cyclodextrin.
[0019] In further aspects, the foregoing compositions or clathrates
are suitable for administration to a mammal, and most preferably
to a human, dog, or cat.
[0020] In further aspects, the invention is also directed to methods
of using the foregoing compositions or clathrates to effect weight
loss and/or fat reduction in a mammal, and preferably a human, dog
or cat.
[0021] In preferred embodiments, any of the foregoing compositions
or clathrates are added to, mixed with, or formulated as, a food,
beverage, dietary supplement, medical food, pet food, cosmetic,
topical application sheet, or bath salt.
[0022] In certain embodiments, the invention is drawn to a method
of reducing or controlling weight, e.g., increasing weight loss,
or reducing or controlling fat by administering a clathrate including
compound of formula (1) or (2) or a composition comprising one or
both of a compound of formula (1) and a compound of formula (2)
in a formulation that masks an unpleasant taste or odor of the compound.
In preferred embodiments, the administered composition is a composition
as set forth above. Most preferably, the clathrate or composition
is administered in or as a food, beverage, dietary supplement, medical
food, pet food, cosmetic, or bath salt comprising a clathrate or
composition as set forth above. The clathrate or composition is
preferably administered to a mammal. Most preferably, the clathrate
or composition is administered to a human, dog, or cat.
BRIEF DESCRIPTION OF THE DRAWINGS
[0023] FIG. 1 is a differential scanning calorimetry pattern of
raspberry ketone heated at 10.degree. C./min.
[0024] FIG. 2 is a differential scanning calorimetry pattern of
.beta.-CD heated at 10.degree. C./min.
[0025] FIG. 3 is a differential scanning calorimetry pattern of
a mixture of .beta.-CD and raspberry ketone (9:1 by weight) heated
at 10.degree. C./min.
[0026] FIG. 4 is a differential scanning calorimetry pattern of
the clathrate of Example 7 heated at 10.degree. C./min.
[0027] FIG. 5 is a .sup.1H-NMR spectral pattern of raspberry ketone.
[0028] FIG. 6 is a .sup.1H-NMR spectral pattern of the clathrate
of Example 7.
DETAILED DESCRIPTION OF THE INVENTION
[0029] Compounds of formulas (1) and (2) have the property of reducing
or controlling weight and/or reducing or controlling fat when administered
to a mammal. Compounds of formulas (1) and (2) have certain undesirable
properties, however, that, in the past, have limited their use in
compositions and products that are effective in controlling and
reducing weight and fat. These undesirable properties include low
solubility in water and unpleasant taste and aroma, when compounds
of formula (1) or (2) are present in large amounts. As described
herein, the present inventors now provide new and improved compounds
and compositions that overcome undesirable taste and aroma characteristics
of compounds of formulas (1) and (2).
[0030] As described herein, the invention provides compositions
that include amounts of compounds of formula (1) and/or (2) sufficient
to effect weight and fat loss, in which the unpleasant taste and
aroma associated with compounds of formula (1) and/or (2) has been
masked. Also provided are new and improved compounds in which compounds
of formula (1) and/or (2) have been included in a clathrate. The
clathrates increase the solubility of compounds of formula (1) and
(2) and mask their unpleasant taste and aroma. The new and improved
compositions and clathrates are useful for administrating to a mammal
(e.g., a human, dog or cat) to effect weight or fat loss.
[0031] In particular, in regard to certain aspects of the invention,
the present inventors have found that, when hydroxyphenylbutan-2-ones
or hydroxyphenylbutan-2-ols having an effect of fat decomposition
and weight reduction are included in cyclodextrin ("CD"),
the solubility of the compounds in water, food, beverage, dietary
supplement, medical food, pet food, cosmetic, or others is increased.
The unpleasant taste and aroma characteristics of the compounds
are also reduced, without detracting from the effectiveness of the
compounds for fat decomposition, body reduction, and weight loss.
[0032] Hence, in certain embodiments, the invention improves the
solubility in water of hydroxyphenylbutan-2-ones and hydroxyphenylbutan-2-ols
of formula (1) or (2) and improves the taste and aroma properties
of the compounds. Specifically, the invention also provides a composition
of that compound, which is highly soluble in water, food, beverage,
dietary supplement, medical food, pet food, cosmetic, or the like
and has the advantages of pleasant taste and aroma, and stability,
and which is effective for promoting fat decomposition, body reduction,
and weight reduction.
[0033] Compounds of Formulas (1) and (2)
[0034] Compounds of formulas (1) and (2) have the following structures:
3
[0035] wherein
[0036] R.sup.1=H, --OH, or --OCH.sub.3,
[0037] R.sup.2=H, --COR.sup.3, or sugar group, and
[0038] R.sup.3=C.sub.2-C.sub.20 alkyl,
[0039] Examples of sugar groups that may be R.sup.2 include, but
are not limited to, monosaccharides such as glucose, galactose,
mannose, rhamnose, xylose, ribose, arabinose, glucosamine, and galactosamine,
and disaccharides such as lactose, maltose, cellobiose, isomaltose,
and epilactose.
[0040] Specific examples of compounds of formula (1) include compounds
contained in the fruit raspberry. For example, in raspberry ketone,
R.sup.1 and R.sup.2 are H and in zingerone (4-(3-methoxy-4-hydroxyphenyl)-
-butane-2-one), R.sup.1 is OCH.sub.3, R.sup.2 is H. Raspberry ketone
and zingerone both have a characteristic bitter and harsh taste
and an unpleasant aroma, when present in large amounts.
[0041] Other examples of compounds of formula (1) include, without
limitation, 4-(3,4-dihydroxyphenyl)-butane-2-one (formula (1) in
which R.sup.1 is OH and R.sup.2 is H) and glycosides, including
raspberry ketone glucoside (formula (1) in which R.sup.1 is H and
R.sup.2 is glucose) and raspberry ketone galactoside (formula (1)
in which R.sup.1 is H and R.sup.2 is galactose).
[0042] Examples of compounds of formula (2) include, without limitation,
4-(4-hydroxyphenyl)-butane-2-ol (formula (2) in which R.sup.1 and
R.sup.2 are H), 4-(3,4,-dihydroxyphenyl)butane-2-ol (formula (2)
in which R.sup.1 is OH and R.sup.2 is H), 4-(3-methoxy-4-hydroxyphenyl)-butane-2-ol
(formula (2) in which R.sup.1 is OCH.sub.3 and R.sup.2 is H), and
glycosides, for example glucoside and galactoside, thereof.
[0043] Hydroxyphenylbutan-2-ones for use in the invention include,
for example and without limitation, 4-(4-hydroxyphenyl)butan-2-one,
4-(4-hydroxy-3-methoxyphenyl)butan-2-one, and 4-(3,4-dihydroxyphenyl)buta-
n-2-one. Hydroxyphenylbutan-2-ols for use in the invention include,
for example and without limitation, 4-(4-hydroxyphenyl)butan-2-ol,
4-(4-hydroxy-3-methoxyphenyl)butan-2-ol, and 4-(3,4-dihydroxyphenyl)butan-
-2-ol.
[0044] Compounds of formulas (1) and (2) may be obtained by extraction
from natural materials. For instance, raspberry ketone glucoside
is extracted from appropriate fruits (e.g., raspberry fruit) by
solvent and is used as a concentrated form (Phytochemistry, 29,
12, 3853-3858, 1990).
[0045] Compounds of formulas (1) and (2) may also be synthesized
using methods well known in the art, such as described in Japanese
laid open applications P2000-169325 and P2001-22623, and PCT application
PCT/JP02/05090, published as WO 02/096399. Additional methods for
synthesis of compounds of formulas (1) and (2) may be found in European
patent application EP 0 516 082.
[0046] Preferred compounds of the invention are raspberry ketone,
zingerone and BK-180 which have high stability and are easily and
conveniently obtained.
[0047] Compounds of formula (1) and compounds of formula (2) may
be included in the compositions of the present invention singly
or combined. The preferred total amounts of the compounds of formulas
(1) and/or (2) are in the range of about 0.001 to about 30.0 weight
% of the total composition, which is an optimal range for sufficient
activity for body weight loss and modulation of unpleasant taste
and aroma characteristics. More preferably, the total amount of
the compounds of formulas (1) and/or (2) are in the range of about
0.03 to about 20.0 weight % of the total composition, and, most
preferably, the total amount of the compounds of formulas (1) and/or
(2) are in the range of about 0.1 to about 15.0 weight % of the
total composition. A particular preferred total amount of the compounds
of formulas (1) and/or (2) is in the range of about 1.0 to about
10 weight % of the total composition.
[0048] As used herein, the term "effective amount" refers
to an amount of a compound or an amount of a composition sufficient
to have a measurable effect on a defined state or condition. In
certain preferred embodiments, an "effective amount" of
compounds of formula (1) and/or (2) is administered to a mammal
to cause weight loss, fat loss, slimming, or any combination of
these effects. In such embodiments, an "effective amount"
may administered in single or multiple doses. In certain embodiments,
compositions (e.g., extracts) are provided that mask one or more
unpleasant characteristics of a compound of formula (1) and/or (2).
Accordingly, an "effective taste-masking amount" of a
composition is an amount sufficient to reduce an unpleasant characteristic
of a compound of formula (1) or (2). In certain preferred embodiments,
compositions are provided in an "effective taste-masking amount"
to mask a bitter taste and/or unpleasant odor of a compound of formula
(1) and/or (2). An "effective taste-masking amount" of
a composition can be determined by a panel of trained flavorists,
as set forth below.
[0049] Compounds of formula (1) and (2) have been proposed as skin
care materials having an inhibitory activity of melanin formation
(JP 2000-239143) and were found to have activity for enhancement
of fat decomposition and inhibition of obesity through topical treatment
(JP 2000-169325). Compounds of formulas (1) and (2) are presumed
to promote weight loss via fat decomposition. Fat decomposition
is enhanced by the increased contact and activity of hormone sensitive
lipase on intracellular fat. Intracellular fat is covered by a layer
of phospholipid, predominantly phosphatidyl choline, that inhibits
contact by the lipase. Hormones that promote lipocatabolism, e.g.,
norepinephrine, enhance fat decomposition by countering the lipase-inhibiting
action of phosphatidyl choline, thereby increasing affinity of the
lipase for intracellular fat. (Okuda, et al., J. Lipid Res., 35:36-44,
1994 and Okuda, et al., J. Lipid Res., 35:1267-1273, 1994). Compounds
of formulas (1) and (2) are presumed to enhance the affinity of
hormone sensitive lipase to intracellular fat in the same fashion
as fat decomposition hormones.
[0050] Compounds containing ester groups, wherein R.sup.2 is --COR.sup.3
and R.sup.3 is C.sub.2-C.sub.20 alkyl, are hydrolyzed upon acid
treatment to the active hydroxyl form of the ingredient. Such derivatives
may be administered orally and are consequently hydrolyzed in the
acid stomach environment to the active form.
[0051] Extracts and other Taste Masking Ingredients
[0052] In one aspect, the invention is drawn to a composition comprising
one or both of a compound of formula (1) and a compound of formula
(2) and one or more extracts to mask unpleasant taste and/or aroma
characteristics of these compounds. Extracts that mask one or more
unpleasant characteristics of a compound of formula (1) or (2) can
be obtained from, for example and without limitation, oolong tea,
puerh tea, roasted adlay tea, eucommia leaves, jasmine flower, banzakuro
(guava fruit), barley, mate tea (Paraguay tea), rooibos tea, tinpi
(matured peal of Citrus unshiu), juemingzi, sanzashi (Crataegus),
soybean germ, ginger, ginseng, kouki tea, and yucca. The extracts
may be used in compositions of the invention individually, or in
combination. The compositions comprising a compound of formula (1)
and/or formula (2) and an extract may be added to or formulated
as a food, beverage, dietary supplement, medical food, pet food,
or cosmetic. The forgoing are non-limiting examples.
[0053] Whole plants or their leaves, fruits (preferably, defatted
seeds), bark, root, branch, or fermented plants are either dried
and powdered, dried without powdering, or powdered without drying,
and then extracted with solvent at room temperature or with heating
or extracted using instruments, such as a soxhlet extractor. Solvents
used for extraction, include, but are not limited water, methanol,
ethanol, propanol, 1,3-butylene glycol, benzene, ethyl ether, chloroform,
ethyl acetate, butyl acetate, acetone, or any combination of any
of the foregoing.
[0054] Extractions that are liquid may be used directly in products.
Preferably, the extractions are used as powders after freeze drying
or spray drying. Extractions may be further purified by liquid-liquid
extractions or adsorption chromatography.
[0055] Preferably, the compositions of the invention comprise one
or more extracts of oolong tea, puerh tea, roasted adlay tea, eucommia
leaves, and jasmine flower. More preferably, the compositions of
the invention comprise a combination of these extracts. A combination
of extracts may comprise, for example and without limitation, 10
parts of oolong tea extract, 2-4 parts of puerh tea extract, 2-4
parts of roasted adlay tea extract, 1-3 parts of eucommia leaf extract,
and 1-3 parts of jasmine flower extract. These extracts are commercially
available, such as, for example, from KGPP-P1 (Life Food Research).
[0056] The extracts in the compositions of the invention are about
0.001-40.0 weight % of the total weight of the composition, which
is an optimal range for achieving sufficient masking of undesirable
taste and aroma characteristics of a compound of formula (1) or
(2). Preferably, the total amount of the extract is about 0.01-20.0
weight % of the total weight of the composition.
[0057] Unpleasant taste and aroma characteristics of compounds
of formula (1) and compounds of formula (2) may also be masked in
compositions by including specific compounds, e.g., one or more
compounds selected from the group consisting of malthol, ethyl maltol,
furaneol, furaneol derivatives, vanillin, and ethyl vanillin. The
compositions comprising a compound of formula (1) and/or formula
(2) and any of the foregoing compounds, alone or in combination,
may be added to or formulated as a food, beverage, dietary supplement,
medical food, pet food, or cosmetic. The forgoing are non-limiting
examples.
[0058] Clathrate Complexes
[0059] Unpleasant taste and aroma characteristics of compounds
of formula (1) and (2) may also be masked by including the compounds
in a clathrate. When present in clathrates, compounds of formula
(1) and (2) also exhibit increased solubility, facilitating formulating
compositions comprising increased amounts of compounds of formula
(1) and (2) and more uniform distribution of the compound.
[0060] Specifically, the invention provides clathrates of any of
hydroxyphenylbutan-2-ones of formula (1) or hydroxyphenylbutan-2-ols
of formula (2) included in cyclodextrin. The invention further provides
compositions that contain these clathrates in, for example and without
limitation, a food, beverage, dietary supplement, medical food,
pet food, cosmetic, bath salt, or the like.
[0061] Hence, in certain embodiments, the invention is directed
to compositions comprising a clathrate comprising of a compound
of formula (1) or formula (2). In a preferred embodiment, a compound
of formula (1) or formula (2) forms part of a clathrate with a CD.
CDs for use in the invention may be any .alpha.-CD, .beta.-CD, .gamma.-CD,
as well as branched CDs, such as those with one or two oligosaccharide
molecules of glucose, maltose, maltotriose, or the like .alpha.-1,6-bonded
thereto, and chemically-modified branched CD such as hydroxypropyl-CD.
Preferably, CD for use in the invention is .beta.-CD or branched
.beta.-CD. One or more different types of such CDs may be used in
the invention either singly or as combined.
[0062] CD compounds are known in the art (see, for example, Hileman
et al., Electrophoresis 1998, 19(15):2677-2681). The compounds are
generally defined as a cyclic ring of 1,4 linked glucose residues.
CD compounds are typically classified based on the number of 1,4
linked glucose residues present in the ring, with rings of between
6 and 12 glucose residues being preferred. Rings of 6, 7, and 8
glucose residues are particularly preferred. Thus, CD compounds
that comprise a ring of six 1,4 linked glucose residues (i.e., n=6)
are referred to as .alpha.-CD compounds. CD compounds that comprise
a ring of seven 1,4 linked glucose residues are referred to as .beta.-CD
compounds, and cyclodextrin compounds that comprise a ring of eight
1,4 linked glucose residues are referred to as .gamma.-cyclodextrin
compounds. The glucose residues may be substituted with chemical
moieties to form cyclodextrin derivative compounds such as, without
limitation, sulfated cyclodextrin or sulfonated cyclodextrins. CD
compounds are commercially available (e.g., from Sigma-Aldrich,
Milwaukee, Wis.) or may be synthesized using methods well known
to one of ordinary skill in the art (see, e.g., Easton et al., Modified
Cyclodextrins: Scaffolds and Templates for Supramolecular Chemistry,
304 pp., World Scientific, April 1999)
[0063] A clathrate of the invention may be produced by contacting
any of hydroxyphenylbutan-2-ones or hydroxyphenylbutan-2-ols of
formula (1) or formula (2) with CD in water to thereby form a clathrate
in CD. The resulting clathrate may be further processed by drying
and powdering, using methods well known in the art.
[0064] To form clathrates, typically CD is dissolved in water and
a compound of formula (1) or formula (2) is added thereto and then
vigorously stirred or shaken for a period of from a few seconds
to a few hours, for example, in a stirrer or a homogenizer. Alternative
means of forming clathrates include, without limitation, shaking
in a closed vessel or ultrasonic treatment. During the process,
crystals of a compound of formula (1) or formula (2) may be added
to the CD solution directly in solid form. Alternatively, a compound
of formula (1) or (2) may be added in solution, by first dissolving
the compound in a suitable organic solvent and then adding the solution
comprising the dissolved compound to the CD solution. Examples of
suitable organic solvents for forming solutions comprising a compound
of formula (1) or (2) are, without limitation, acetone, ethanol,
methanol, isopropanol, tetrahydrofuran, and ethyl acetate. Especially
preferred is acetone. The amount of the organic solvent to be used
is that amount sufficient to dissolve the particular compound of
formula (1) or formula (2) to be added to CD. The ratio of a compound
of formula (1) or formula (2) to be added to CD generally ranges
from about 0.1:1 to about 2:1 (mol/mol). Preferably, the ratio of
a compound of formula (1) or formula (2) to be added to CD is in
the range of about 0.5:1 to about 1:1 (mol/mol). The contact reaction
temperature generally ranges from about 0 to about 100.degree. C.,
preferably from about 5 to about 70.degree. C. The clathrate comprising
a compound of formula (1) and/or formula (2) thus obtained is typically
dried and powdered.
[0065] The clathrates of the invention are not a mere admixture
but are an inclusion bodies of a compound of formula (1) and/or
formula (2) in CD. Formation of the inclusion body can be confirmed
using methods well known in the art such as, for example and without
limitation, differential calorimetry with a differential scanning
calorimeter (DSC).
[0066] Clathrates comprising a compound of formula (1) or formula
(2) do not have the unpleasant aroma peculiar to un-complexed forms
of compounds of formula (1) and/or formula (2). Accordingly, formation
of clathrates comprising compounds of formula (1) and/or formula
(2) can be determined through organoleptic testing.
[0067] The CD-clathrates of the invention of any of a compound
of formula (1) and/or formula (2) in CD may be used in various forms.
For example, they may be used as a powder or may also be used in
a solution or suspension.
[0068] Encapsulation Methods
[0069] The invention is also drawn to a composition comprising
one or both of a compound of formula (1) and a compound of formula
(2) wherein the composition is encapsulated with a coating effective
to mask the taste of the composition. Such encapsulated compositions
may be added to or formulated as, for example and without limitation,
a food, beverage, dietary supplement, medical food, pet food, or
cosmetic.
[0070] In preferred embodiments, compositions comprising a compound
of formula (1) and/or (2) is encapsulated by one of spray drying,
agglomeration, spray cooling, glass-like encapsulation, entrapping
the material in a sugar melt or sugar alcohol melt, formation of
a gelatin coating via formation of a coascervate, absorption, or
entrapping in a liposome. In a further preferred embodiment, the
coating comprises one or more extract selected from extracts of
oolong tea, puerh tea, roasted adlay tea, eucommia leaves, jasmine
flower, banzakuro (guava fruit), barley, mate tea (Paraguay tea),
rooibos tea, tinpi (matured peal of Citrus unshiu), juemingzi, sanzashi
(Crataegus), soybean germ, ginger, ginseng, kouki tea, and yucca.
More preferred, the coating comprises one or more extract selected
from extracts of oolong tea, puerh tea, roasted adlay tea, eucommia
leaves, and jasmine flower. In another preferred embodiment, the
coating comprises one or more of malthol, ethyl maltol, furaneol,
furaneol derivatives, vanillin, and ethyl vanillin. Preferably,
the coating further comprises a sugar alcohol. Preferably, the coating
further comprises one or both of L-histidine and proline.
[0071] Compositions
[0072] It is desirable that the ratio of compounds of formulas
(1) and/or (2) to extract is in the range of about 10:1 to about
1:20. More preferably, the ratio is in the range of about 1:1 to
about 1:5. For compositions that are included in beverages and chewable
food, the preferred ratio is from about 5:1 to about 1:1 to suppress
the bitter and harsh taste of the compounds.
[0073] The compositions of the invention may include other ingredients.
For instance, sugars may be added to enhance the masking effect.
There is no limitation to the amount of the sugar added if the composition
is used in food. Sugars that may be added include, but are not limited
to, monosaccharides (for example, galactose and glucose), disaccharides
(for example, sugar and trehalose), and sugar alcohols (for example,
xylitol, lactitol, mannitol, sorbitol, maltitol, and erythrytol).
In order to further sweeten the composition, one or more of these
sugars may be used in combination. Appropriate sugars may be selected
by sweetness, solubility, and texture. Preferably, sugar alcohols
are used. In solid foods, the sugar content is preferably from about
15 to about 95 weight % and more preferably from about 50 to about
80 weight %, based on the weight of the composition. In liquids
or gels, the sugar content is preferably from about 1 to about 20
weight % and more preferably from about 2 to about 10% weight %,
based on the weight of the total composition. In this range, appropriate
sweetness is obtained and balance of flavor is good.
[0074] It is further desirable to include an additional ingredient
effective for weight loss. For example, materials to inhibit sugar
and fat absorption may be added, which include, but are not limited
to, gymunema extract, garcinia extract, banaba extract, salacia,
albumin extracted form wheat, chitosan, "asia" polyphenol,
rice germ extract, forskohlii powder, saponin, or any combination
of any of the foregoing. Materials to enhance fat deposition may
be added, which include, but are not limited to, conjugate linoleic
acid, citrus, arurentium extract, or any combination of the foregoing.
Materials to enhance fat burning may be added, which include, but
are not limited to, soybean peptide, arginine, caffeine, capsaicin,
ephedrine, piperine, carnitine, proline, or any combination of the
forgoing. Materials to suppress appetite may be added, which include,
but are not limited to, L-histidine, extracts from citrus such as
grapefruit, or any of the foregoing. Materials to activate metabolism
and enhance weight loss may be added, which include, but are not
limited to, melilot extract, hucus extract, grape seed extract,
ginkgo extract, adlay extract, or any of the foregoing.
[0075] Additional ingredients include, but are not limited to,
gymunema extract, forskohlii powder, soybean peptide, arginine,
adlay extract, L-histidine, and proline. Preferred additional ingredients
are L-histidine and proline. The ratio of compounds of formulas
(1) and/or (2) and total additional ingredients typically ranges
from about 10:1 to about 1:5 and preferably, from about 5:1 to about
1:5.
[0076] It is further desirable to include vitamin C plant extracts,
which are effective to reduce and inhibit melanin synthesis and
to promote collagen synthesis, and hyaluronic acid and derivatives
thereof for improvement of rough skin. Vitamin C is additionally
desirable due to its role in the synthesis of adrenal cortical hormone
and inhibition of mental stress.
[0077] Water soluble ascorbic acid and derivatives are the preferred
forms of vitamin C used in the compositions of the invention. Water
soluble ascorbic acid includes L-ascorbic acid and its sodium salt,
potassium salt, magnesium salt, calcium salt, barium salt, ammonium
salt, monoethanolamine salt, diethanolamine salt, triethanolamine
salt, monoisopropanolamine salt, triisopropanolamine salt; L-ascorbic
acid-2-phosphoric acid sodium salt, potassium salt, magnesium salt,
calcium salt, barium salt, ammonium salt, monoethanolamine salt,
diethanolamine salt, triethanolamine salt, monoisopropanolamine
salt, triisopropanolamine salt; L-ascorbic acid-2-sulfuric acid
sodium salt, potassium salt, magnesium salt, calcium salt, barium
salt, ammonium salt, monoethanolamine salt, diethanolamine salt,
triethanolamine salt, monoisopropanolamine salt, triisopropanolamine
salt; and ascorbic acid sugar derivative such as L-ascorbic acid-2-o-glucoside.
Water soluble ascorbic acid derivatives, L-ascorbic acid phosphoric
acid sodium ester, L-ascorbic acid phosphoric acid magnesium ester,
L-ascorbic acid-2-o-glucoside are also preferred. To increase the
stability of vitamin C, it is preferred to use it with an organic
acid, such as citric acid, malic acid, fumaric acid, malonic acid,
succinic acid, tartaric acid, lactic acid, or any combination of
any of the foregoing.
[0078] Additional ingredients that may be added to compositions
of the present invention include plant extracts that reduce and
inhibit melanin synthesis and promote collagen synthesis. Preferred
extracts include extracts from licorice, camellia, peach, ziou,
otogirisou (Hypericum erectum), loquat, or any combination of any
of the foregoing. These extracts may be obtained from leaves, fruits,
seeds (defatted), roots, or rhizome, through extraction by water,
1,3-butylene glycol, or mixture of these solvents. Hydrophobic extracts
may be extracted by ethanol, concentrated, and then further extracted
by squalane.
[0079] Further ingredients that may be added to the compositions
of the invention include other vitamins and minerals. Vitamins include,
but are not limited to vitamin B1, vitamin B2, niacin, pantothenic
acid, vitamin B6, vitamin B12, folic acid, biotin, and inositol.
Minerals include, but are not limited to, zinc, iron, calcium, magnesium,
chromium, selenium, potassium, and sodium. Minerals that chelate
with either an amino acid, such as aspartic acid, or an organic
acid, such as gluconic acid or picric acid are preferred to enhance
absorption.
[0080] The compositions may additionally contain royal jelly, salmon
milt extract (DNA Na), yeast extract (RNA), or any combination of
any of the foregoing, in an amount of from about 0.1 to about 10
weight % and more preferably, from about 1 to about 5 weight %,
based upon the total weight of the composition.
[0081] Additional ingredients include organic acids such as, for
example and without limitation, citric acid, malic acid, fumaric
acid, malonic acid, succinic acid, tartaric acid, and lactic acid;
dyes; synthetic or natural flavors such as, for example and without
limitation, vanillin, linalool, raspberry flavor, apple flavor,
and coffee flavor; drying agents; food fibers; electrolytes; antioxidants;
preservatives; moisturizers; and any combination of any of the foregoing.
[0082] Food, Beverage, Dietary Supplement, Medical Food, Pet Food,
or Cosmetic
[0083] Foods, beverages, dietary supplements, medical foods, and
pet foods may be in the form of a tablet, granule, capsule, chewing
gum, jelly, chocolate, candy, beverage, soup, ice cream, pasta,
or baked good. The food is not particularly limited and may be a
gel, powder, liquid, granule, cream, paste, or solid food. Cosmetics
may be in the form of, for example, creams, milky lotions, lotions,
essences, packs, cataplasms, foundations, face powders, lipsticks,
and bath agents. Cosmetics include, but are not limited to, creams,
lotions, pastes, gels and cakes that are suitable for application
to the skin.
[0084] In a preferred embodiment, compounds of formulas (1) and/or
(2) are formulated in a gel pack composition. The gel pack composition
is applied to a release sheet to form a slimming sheet pack. The
slimming sheet pack has superior properties, both as a cosmetic
product and in terms of the ability to effect weight loss a fat
loss compared to other forms of applying compounds of formulas (1)
and/or (2). Hence, subjects that apply compounds of formulas (1)
or (2) in the form of a gel pack experience greater fat loss and
slimming, compared to subjects that apply compounds of formulas
(1) or (2) in the form of paste.
[0085] Test Methods for Evaluation of Taste and Bitterness
[0086] Taste and bitterness can be evaluated using a panel of trained
panelists ("flavorists"). A panel of potential flavorists
is screened for their abilities to taste bitter substances. The
panel is then trained to scale various bitter substances. The scaling
requires that substances such as caffeine are used at various levels
in a water solution. The panel is required to indicate the relative
levels of bitterness in each solution. The panelists who can best
scale the bitter substances are selected as flavorists to assess
the bitterness of compounds and the masking capabilities of compounds
and compositions.
[0087] When testing for bitterness in a food or beverage product,
the following is standard procedure:
[0088] a. The sample of product with known bitterness is evaluated
against a sample with a masking compound.
[0089] b. The expert panel evaluates the two samples for their
degree of bitterness.
[0090] c. Typically the panel indicates if the bitterness is totally
removed or significantly attenuated.
[0091] d. The panel may also be asked to indicate the quality of
the flavor.
[0092] Methods
[0093] In certain embodiments, the invention is drawn to a method
of reducing or controlling weight, by administering a clathrate
including a compound of formula (1) and/or (2), or a composition
comprising a compound of formula (1) and/or (2) and a component
that masks unpleasant taste and aroma characteristics of these compounds.
In preferred embodiments, the clathrate or composition is added
to or formulated as a food, beverage, dietary supplement, medical
food, pet food cosmetic or bath salt that is administered to a mamma,
preferably a human, dog, or cat, to reduce or control weight or
fat.
[0094] Effective amounts of the compounds of formulas (1) and/or
(2) are tailored to the user's condition. There is no particular
upper limit for consumption amount and frequency per day, however
preferably, a range of about 50 to about 300 mg/day/ 70 kg body
weight (adult) is administered. There is also no limitation on time
of administration, however, preferably, the administration occurs
before a meal.
[0095] The following Examples are provided for a further illustration
of the invention, but are not intended to be limiting thereof. Unless
otherwise indicated, all parts and percentages are by weight of
the final composition.
EXAMPLE 1
[0096] Granule samples, Sample 1, Sample 2, and Sample 3, were
made based on the formulas listed in Table 1 by conventional procedure.
The ingredients shown in Table 1 were mixed with alcohol. The resulting
mixture was granulated through an extrusion granulator having a
0.8 mm diameter extrusion orifice. The resulting granules were dried
in a batch-type flow drier with charge air temperature of 70.degree.
C. and exhaust gas temperature of 50.degree. C. for 10 min, until
the water content of the dried granules was reduced to 7% or less.
1TABLE 1 Formulations of Sample 1, Sample 2, and Sample 2 by weight
%. Materials Sample 1 Sample 2 Sample 3 Raspberry ketone 6 6 6 Oolong
tea (dry) 1.2 0.3 39 Puerh tea (dry) 0.3 0.1 9.75 Roasted adlay
tea (dry) 0.3 0.1 9.75 Eucommia leaves (dry) 0.1 0.025 3.25 Jasmine
flower (dry) 0.1 0.025 3.25 Maltitol 76.4 77.85 13.4 Suclarose 0.1
0.1 0.1 Raspberry flavorant 5 5 5 Excipient ("seorasu")
10 10 10.0 Flavor 0.5 0.5 0.5 Total 100 100 100
[0097] Sample 1 and comparative samples, Sample 2 and Sample 3,
were tasted by 18 volunteers. Bitter and harsh flavor was evaluated
by trained volunteers, and the results were summarized in Table
2.
2TABLE 2 Results of taste test. Sample 1 Sample 2 Sample 3 Bitter,
harsh .largecircle. X .DELTA. taste reported
[0098] Flavor improvement key:
[0099] 9 or more volunteers answered they tasted a bitter, harsh
taste--X
[0100] 5-8 volunteers answered they tasted a bitter, harsh taste--.DELTA.
[0101] 1-4 volunteers answered they tasted a bitter, harsh taste--O
EXAMPLE 2
[0102] A chewable type tablet, Sample 4, was formulated based on
the ingredients of Table 3. The ingredients shown in Table 3 were
mixed uniformly. Using a tabletting machine, the resulting mixture
powder was directly continuously tabletted into tablets having a
weight of 0.5 g. The tabletting speed was 12 tablets/min and pressure
was 2 t/m.sup.2. A total of approximately 180,000 (approximately
9 kg) tablets were produced.
3TABLE 3 Formulation of Sample 4 by weight %. Materials Sample
4 Raspberry ketone 5.6 Oolong tea (dry) 0.72 Puerh tea (dry) 0.2
Roasted adlay tea (dry) 0.2 Eucommia leaves (dry) 0.16 Jasmine flower
(dry) 0.16 "Banzakuro" (dry) 0.11 Barleyl (dry) 0.08 Mate
tea (dry) 0.08 Rooibos tea (dry) 0.08 "Tinpi" (dry) 0.06
Juemingzi (dry) 0.05 "Sanzashi" (dry) 0.03 Soybean germ
(dry) 0.03 Ginger (dry) 0.02 Ginseng extract (dry) 0.01 "Kouki"
tea extract (dry) 0.01 Yucca extract (dry) 0.01 gymunema extract
(dry) 1 Yucca saponin (dry) 1 Adlay extract powder (dry) 1 L-histidine
0.5 Forskohlii powder (dry) 0.1 Vitamin C 34.5 Hyaluronic acid 0.1
Vitamin B6 0.1 Vitamin P 0.5 Inositol 11.2 maltitol 20.5 Sucrose
0.5 Salmon milt extract (DNA Na) 0.1 Yeast extract (RNA) 0.1 excipient
("seorasu") Rest Raspberry flavor 5.7 total 100
[0103] The flavor of the chewable tablet was tested according to
the procedures given in Example 1. The number of testers indicating
bitterness and acridity was 2 out of 18.
EXAMPLE 3
[0104] The ingredients in Table 4 were put into a chewing gum mixer
and mixed for 15 min, until homogeneous. The mixture was rolled
and cut into chewing gum weighing 3 g (20.times.14.times.11 mm).
4TABLE 4 Formulation of Sample 5 by weight %. Materials Sample
5 Gum base 20 Maltitol 62 Raspberry ketone 5 Jasmine flower (dry)
0.9 Roasted adlay (dry) 1.1 gymunema extract (dry) 0.5 Adlay extract
powder (dry) 0.5 Vitamin C 5 Reduced maltose starch syrup 4 Raspberry
flavor 1 Total 100
[0105] The flavor of the chewing gum (3 g/stick) was tested according
to the procedures given in Example 1. Test results were good, the
number of testers indicating bitterness and acridity were 0 out
of 18.
EXAMPLE 3B
[0106] Raspberry flavor can also be added sugarless gums according
to the following compositions:
5 Fruit Fruit Acid Acid Stick Bubble Stick Bubble Gum Gum Gum Gum
Dreyfus Base 25.0 25.0 Dreyfus bubble base 26.0 26.0 70% Sorbitol
solution 15.0 17.0 15.0 17.0 100-Mesh Powdered Sorbitol 47.5 48.3
47.0 47.3 Glycerine 5.0 2.0 5.0 2.0 Fruit acid 1.0 1.0 Flavor 1.3
0.5 0.8 0.5 Raspberry ketone 6.0 6.0 6.0 6.0 Aspartame 0.2 0.2 0.2
0.2 100.0% 100.0% 100.0% 100.0%
[0107] The sugarless gum formulations set forth above are put into
a chewing gum mixer and mixed for 15 min, until homogeneous. The
mixture is rolled and cut into chewing gum weighing 3 g (20.times.14.times.11
mm). The flavor of the sugarless gum is tested according to the
procedures given in Example 1.
EXAMPLE 4
[0108] Gel beverage (200 ml/pack), Sample 6, was formulated based
on the ingredients listed in Table 5 using a conventional method.
The ingredients given in Table 5 were mixed and homogenized to prepare
a gel dispersion. The dispersion was cooled to about 10.degree.
C. and was filled into 200 ml pouches which were then sealed. The
pouches were then thermally sterilized by showering with hot water
(67.degree. C., 35 min), and then were cooled to 35.degree. C. or
lower. The process yields a jelly drink.
6TABLE 5 Formulation of Sample 6 by weight %. Materials Sample
6 Raspberry ketone 0.3 Puerh tea (dry) 0.04 Eucommia tea (dry) 0.02
Garcinia extract (dry) 1 Maltodextrin 1.5 Reduced maltose starch
syrup 1.25 Galactose 1 Carrageenan 0.9 Concentrated fruit 0.5 Citric
acid 0.4 Suclarose 0.003 Flavor 0.1 Water 92.987 Total 100
[0109] The flavor of the jelly drink (200 ml) was tested according
to the procedures given in Example 1. Test results were good, the
number of testers indicating bitterness and acridity were 1 out
of 18.
EXAMPLE 5
[0110] Beverage (100 ml), Sample 7, was formulated based on the
ingredients listed in Table 6. The ingredients listed in Table 6
were added into 50 mL of water. Once the ingredients dissolved,
water was added to 100 mL total beverage.
7TABLE 6 Formulation of Sample 7 by weight %. Materials Sample
7 Raspberry ketone 0.2 Oolong tea (dry) 0.03 Jasmine flower (dry)
0.005 Mate tea (dry) 0.005 L-histidine 1 Adlay extract powder (dry)
0.1 Citric acid 1 Sodium citrate 0.5 Vitamin B2 0.01 Vitamin B6
0.01 Pantothenic acid 0.01 Nicotinic acid 0.005 Maltitol 5 Saccharin
0.02 Sucrose fatty acid ester 10 Flavor Small amount Water Rest
Total 100
[0111] The flavor of the beverage (100 ml) was tested according
to the procedures given in Example 1. Test results were good, the
number of testers indicating bitterness and acridity were 0 out
of 18.
EXAMPLE 6
[0112] Hard candy, Sample 8, was formulated based on the ingredients
listed in Table 7 using a conventional method. Reducing palatinose
and trehalose were heated in a still with sufficient water until
completely dissolved. The mixture was then boiled in a cooker until
water content was reduced to 2.5%. The reduced mixture was then
mixed with the ingredients listed in Table 7. The resulting mixture
was then cooled, sized in a batch former, and stamped into hard
candies.
8 TABLE 7 Material Sample 8 Raspberry ketone 6 Roasted adlay 3.5
Jasmine flower 2.5 Reduced paratinose 40 Trehalose 43 Lemon juice
3 Citric acid 1.5 Sweetener (stevia) 0.2 Flavor 0.3 Total 100
[0113] The hard candy is tested according to the procedures given
in Example 1. Test results were good, with 0 out of 18 testers indicating
bitterness or acridity.
[0114] In the following examples, Proton Nuclear Magnetic Resonance
Spectrum (.sup.1H-NMR) was determined using an AM-400 apparatus(400
MHz; Bruker) with tetramethylsilane for external standard. Differential
Scanning Calorimeter (DSC) was performed using a DSC-220 apparatus
(Seiko Electronic Industry).
EXAMPLE 7
[0115] Preparation of 4-(4-hydroxyphenyl)butan-2-one (hereinafter
referred to as raspberry ketone)/.beta.-CD clathrate
[0116] In a nitrogen atmosphere, 69.1 g (60.9 mmol) of .beta.-CD
(Nihon Shokuhin Kako) and 800 ml of pure water were put into a 2-liter
four-neck flask equipped with a Dimroth condenser and a thermometer,
and dissolved by stirring at about 60.degree. C. After it was confirmed
that the system gave a clear solution, 10 g (60.9 mmol) of raspberry
ketone (Takasago International) dissolved in acetone (30 ml) was
dropwise added thereto, and stirred for 30 minutes at that temperature.
Heating was stopped, and the solution was gradually cooled still
with stirring, then cooled with ice, and further stirred at a temperature
not higher than 5.degree. C. for 1 hour. Thus deposited, the resulting
clathrate was taken out through filtration under reduced pressure,
washed with 200 ml of water cooled with ice, and then dried. The
process gave 63.2 g of a white powder, raspberry ketone/.beta.-CD
clathrate.
[0117] The proton nuclear magnetic resonance spectrum (.sup.1H-NMR)
of the thus-obtained clathrate (in a solvent of dimethylsulfoxide
deuteride, (CD.sub.3).sub.2SO) was measured. This confirmed that
the molar ratio of .beta.-CD/raspberry ketone in the clathrate was
about 1:0.91 and that 1000 mg of the clathrate contained 108 mg
of raspberry ketone.
[0118] To confirm that the compound obtained herein was not a mere
mixture but was a true clathrate body, a mixture of .beta.-CD and
raspberry ketone was prepared in a ratio of 9:1 by weight. Four
samples, raspberry ketone alone, .beta.-CD alone, the mixture of
the two, and the clathrate of the two were compared through differential
scanning calorimetry. FIGS. 1 to 4 are DSC patterns of the samples
heated at 10.degree. C./min. FIG. 1 is a DSC pattern of raspberry
ketone alone; FIG. 2 is a DSC pattern of .beta.-CD alone; FIG. 3
is a DSC pattern of the mixture of .beta.-CD and raspberry ketone
in a ratio of 9:1 by weight; and FIG. 4 is a DSC pattern of the
clathrate obtained in this Example 7.
[0119] FIGS. 1-4 were compared with each other. An endothermic
peak (at 78 to 80.degree. C.) is seen in FIG. 3 but not in FIG.
4. This confirms that the compound prepared in this Example was
a clathrate of raspberry ketone in .beta.-CD.
[0120] FIGS. 5 and 6 each are .sup.1H-NMR spectra [in (CD.sub.3).sub.2SO]
of raspberry ketone alone and that of the compound prepared in this
Example (that is, raspberry ketone/.beta.-CD clathrate), respectively,
relative to an external standard, tetrainethylsilane (TMS). The
clathrate was processed with chloroform to extract the included
raspberry ketone, and the extracted raspberry ketone was analyzed
using .sup.1H-NMR. Raspberry ketone extracted from clathrate had
the same .sup.1H-NMR pattern as raspberry ketone that had not been
included and exracted from clathrates. These results indicated that
incorporation of raspberry ketone into clathrate complexes did not
lead to its degradation.
EXAMPLE 8
[0121] Preparation of 4-(3,4-dihydroxyphenyl)butan-2-one/.beta.-CD
clathrate
[0122] In a nitrogen atmosphere, 62.4 g (55 mmol) of .beta.-CD
(Nihon Shokuhin Kako) and 720 ml of pure water were put into a 2-liter
four-neck flask equipped with a Dimroth condenser and a thermometer,
and dissolved by stirring at about 60.degree. C. After it was confirmed
that the system gave a clear solution, 9.0 g (50 mmol) of 4-(3,4-dihydroxyphenyl)butan-2--
one dissolved in acetone (27 ml) was dropwise added thereto, and
stirred for 30 minutes at that temperature. Heating was stopped,
and this was gradually cooled still with stirring, then cooled with
ice, and further stirred at a temperature not higher than 1 to 3.degree.
C. for 1 hour. Thus deposited at that temperature, the resulting
clathrate was taken out through filtration under reduced pressure,
washed with 200 ml of water cooled with ice, and then dried. The
process gave 57.5 g of a white powder. The proton nuclear magnetic
resonance spectrum (.sup.1H-NMR) of the thus-obtained clathrate
(in a solvent of dimethylsulfoxide deuteride, (CD.sub.3).sub.2SO)
was measured. This confirmed that the molar ratio of .beta.-CD/4-(3,4-dihydroxyphenyl)butan-2-one
in the clathrate is about 1/0.88 and 1000 mg of the clathrate contains
121 mg of 4-(3,4-dihydroxyphenyl)butan-2-one.
EXAMPLE 9
[0123] Sample 9 and Comparative Samples 9a and 9b
[0124] Using the clathrate of raspberry ketone/.beta.-CD that had
been prepared in Example 7, gum (Sample 9) was produced as in Table
8 that indicates its formulation (% by weight). For comparison,
non-clathrated raspberry ketone alone (Comparative sample 9a), and
a mixture of raspberry ketone and ,.beta.-CD (Comparative sample
9b) was used in place of the clathrate in producing other samples
of gum as in Table 8. Ten expert panelists tried all these gum samples
to organoleptically evaluate them. The test results are given in
Table 8.
9 TABLE 8 Sample 9 Comp. Sample 9a Comp. Sample 9b Gum Base 20
20 20 Lactitol 60 60 60 Maltitol 12 15.3 12 Reducing Glutinous 3
3 3 Starch Syrup Fragrance 1.2 1.2 1.2 Grape Skin Dye 0.1 0.1 0.1
Raspberry Ketone 3.7 -- -- Clathrate Raspberry Ketone -- 0.4 0.4
.beta.-cyclodextrin -- -- 3.3 Evaluation (taste) good strong smell
of strong smell of raspberry ketone raspberry ketone
EXAMPLE 10
[0125] Sample 10 and Comparative Samples 10a and 10b
[0126] Using the clathrate of raspberry ketone/.beta.-CD that had
been prepared in Example 7, tablet candies (Sample 10) were produced
from the formulations in Table 9, using a continuous tabletting
machine. For comparison, non-clathrated raspberry ketone alone (Comparison
sample 10a), and a mixture of raspberry ketone and .beta.-CD (Comparison
sample 10b) were used in place of the clathrate in producing other
tablet candies as in Table 9. In the same manner as in Example 9,
the tablet candies were organoleptically evaluated by panelists.
In the process of producing the tablet candies, the starting material
was checked for its flowability in the hopper of the tabletting
machine used, and, in addition, the tablet candies were checked
for separation of raspberry ketone therein. The test results are
given in Table 9.
10 TABLE 9 Sample 10 Comp. Sample 10a Comp. Sample 10b Sorbitol
45 90 45 Sucrose Ester 3 3 3 Fragrance 1.3 1.3 1.3 Sour Seasoning
0.7 0.7 0.7 Raspberry Ketone 50 -- -- Clathrate Raspberry Ketone
-- 5 5 .beta.-cyclodextrin -- -- 45 Evaluation (taste) good strong
smell of strong smell of raspberry ketone raspberry ketone (workability,
.largecircle. .DELTA. .DELTA. flowability) good bridges formed in
bridges formed in hopper hopper (workability, no separation found
separation found separation of separation raspberry ketone in tablets)
EXAMPLE 11
[0127] Sample 11 and Comparative Samples 11a and 11b
[0128] Using the clathrate of raspberry ketone/.beta.-CD that had
been prepared in Example 7, powder for drink (Sample 11) was produced
as in Table 10 that indicates its formulation (% by weight). For
comparison, non-clathrated raspberry ketone alone (Comparative sample
11a), and a mixture of raspberry ketone and .beta.-CD (Comparative
sample 11b) were used in place of the clathrate in producing other
samples of powder for drink as in Table 10. 20 g of each powder
was dissolved in 150 ml of water, and panelists tried the resulting
drinks to organoleptically evaluate them in the same manner as in
Example 9. While dissolved in water, each powder was visually checked
for its solubility. The test results are given in Table 10.
11TABLE 10 Comp. Comp. Sample 11 Sample 11a Sample 11b Sugar 75
79.5 75 Sour Seasoning 7 7 7 Fragrance 4 4 4 Branched Amino Acid
8 8 8 Vitamin C 1 1 1 Raspberry Ketone 5 -- -- Clathrate Raspberry
Ketone -- 0.5 0.5 .beta.-cyclodextrin -- -- 4.5 Evaluation (taste)
good strong smell of strong smell of raspberry ketone raspberry
ketone (solubility OO x x in water) good raspberry ketone raspberry
ketone remained remained undissolved undissolved
EXAMPLE 12
[0129] Sample 12 and Comparative Samples 12a and 12b
[0130] Using the clathrate of raspberry ketone/.beta.-CD that had
been prepared in Example 7, drink (Sample 12) was produced as in
Table 11 that indicates its formulation (% by weight). For comparison,
non-clathrated raspberry ketone alone (Comparative sample 12a),
and a mixture of raspberry ketone and .beta.-CD (Comparative sample
12b)were used in place of the clathrate in producing other samples
of drink as in Table 11. Panelists tried the drink samples to organoleptically
evaluate them in the same manner as in Example 9. In addition, the
drink samples were visually checked as to whether or not raspberry
ketone was completely dissolved therein. The test results are given
in Table 11.
12TABLE 11 Comp. Sample 12 Sample 12a Comp. Sample 12b Erythritol
90 90.9 90 Raspberry Juice 7 7 7 Vitamin C 0.3 0.3 0.3 Fragrance
0.9 0.9 0.9 Sour Seasoning 0.8 0.8 0.8 Raspberry Ketone 1 -- --
Clathrate Raspberry Ketone -- 0.1 0.1 .beta.-cyclodextrin -- --
0.9 Evaluation (taste) good strong smell of strong smell of raspberry
ketone raspberry ketone (appear- OO x x ance) clear raspberry ketone
raspberry ketone remained remained undissolved undissolved
EXAMPLE 13
[0131] Sample 13 and Comparative Samples 13a and 13b
[0132] Using the clathrate of raspberry ketone/.beta.-CD that had
been prepared in Example 7, dog food (Sample 13) was produced as
in Table 12 that indicates its formulation (% by weight). For comparison,
non-clathrated raspberry ketone alone (Comparative sample 13a),
and a mixture of raspberry ketone and .beta.-CD (Comparative sample
13b) were used in place of the clathrate in producing other samples
of dog food as in Table 12. Panelists tried the dog food samples
to organoleptically evaluate them in the same manner as in Example
9. The test results are given in Table 12.
13TABLE 12 Example of Dog Food Comp. Comp. Sample 13 Sample 13a
Sample 13b Cereals (wheat, corn) 50.0 50.0 50.0 Meat (meat meal)
45.0 45.0 45.0 Premix (vitamins, 3.0 3.0 3.9 minerals) Fragrance
1.0 1.0 1.0 Raspberry Ketone 1.0 -- -- Clathrate Raspberry Ketone
-- 0.1 0.1 .beta.-cyclodextrin -- 0.9 -- Evaluation (taste) good
strong smell of strong smell of raspberry ketone raspberry ketone
EXAMPLE 14
[0133] Sample 14 and Comparative Samples 14a and 14b
[0134] Using the clathrate of raspberry ketone/.beta.-CD that had
been prepared in Example 7, cat food (Sample 14) was produced as
in Table 13 that indicates its formulation (% by weight). For comparison,
non-clathrated raspberry ketone alone (Comparison sample 14a), and
a mixture of raspberry ketone and .beta.-CD (Comparison sample 14b)
were used in place of the clathrate in producing other samples of
cat food as in Table 13. Panelists tried the cat food samples to
organoleptically evaluate them in the same manner as in Example
9. The test results are given in Table 13.
14TABLE 13 Example of Cat Food Sample 14 Sample 14a Sample 14b
Cereals (wheat, corn) 50.0 50.0 50.0 Meat (fish meal, meat 45.0
45.0 45.0 meal) Premix (vitamins, 3.0 3.0 3.9 minerals) Fragrance
1.0 1.0 1.0 Raspberry Ketone 1.0 -- -- Clathrate Raspberry Ketone
-- 0.1 0.1 .beta.-cyclodextrin -- 0.9 -- Evaluation (taste) good
strong smell of strong smell of raspberry ketone raspberry ketone
EXAMPLE 15
[0135] Nutrient Functional Drink, 50 ml Mini-drink
[0136] The constitutive components of the formulation of Table
14 above were prepared. The weight of each component is 100 times
in Table 14. Except raspberry ketone clathrate and peach flavor,
all the components were dissolved in about 3000 ml of pure water
under heat. After heating the resulting composition was stopped,
raspberry ketone clathrate was added to it and dissolved, and pure
water was added thereto to be about 5000 ml in total. This was cooled,
and peach flavor was added thereto at about 50.degree. C., and pure
water was further added thereto to be 5000 ml in total. This was
filled into 50-ml glass vials.
15 TABLE 14 Formulation (in 50 ml): Raspberry ketone clathrate
500 mg Gymnema extract 150 mg Betaine 500 mg Inositol 500 mg Hardly-digestible
dextrin 2 g Soybean oligosaccharide 500 mg Royal jelly 100 mg Sodium
riboflavin phosphate 12.5 mg Pyridoxine hydrochloride 50 mg Ascorbic
acid 30 mg Nicotinamide 10 mg Erythritol 2 g Sucralose (trichlorogalactose)
10 mg Citric acid 140 mg Malic acid 100 mg Sodium benzoate 20 mg
Butyl parahydroxybenzoate 1.5 mg Ethyl parahydroxybenzoate 3.5 mg
Peach flavor 50 .mu.l Pure water to make 50 ml in all
EXAMPLE 16
[0137] Nutrient Functional Food, Packaged Jelly
[0138] The constitutive components of the formulation of Table
15 above were prepared. The weight of each component is 100 times
in Table 15. Except raspberry ketone clathrate and peach flavor,
all the components were dissolved in about 1000 ml of pure water
under heat. After heating the resulting composition was stopped,
raspberry ketone clathrate and peach flavor were added to it and
dissolved, and pure water was added thereto to be 1500 ml in total.
While hot, this was packaged into aluminum-laminate sticks.
16 TABLE 15 Formulation (in 15 g): Raspberry ketone clathrate 100
mg Hardly-digestible dextrin 2 g Betaine 500 mg Inositol 500 mg
Artichoke extract 350 mg Sodium riboflavin phosphate 3 mg Pyridoxine
hydrochloride 5 mg Ascorbic acid 50 mg Nicotinamide 10 mg Erythritol
1.25 g Sucralose (trichlorogalactose) 3 mg Sodium benzoate 10 mg
Gelling agent (premix of carrageenan, 90 .mu.g locust bean gum and
agar) Peach flavor 7.5 .mu.l Pure water to make 15 ml in all
[0139] As is obvious from the Tables mentioned above, the clathrate
of any of hydroxyphenylbutan-2-ones or hydroxyphenylbutan-2-ols
in CD has a mild smell and is highly soluble in water, and its processability
into preparations is good.
EXAMPLE 17
[0140] Slimming Sheets
[0141] Gel pack compositions were prepared from the ingredients
listed in Table 16. Gelatin was dissolved in 50 g of water, and
polyvinyl alcohol in 50 g of water. These solution were combined
and mixed with stirring while heating. Raspberry ketone and/or 4-(3',4'-dihydroxy-phenyl)butan-2--
ol was dissolved in a solution of 10 g of water and 10 g of ethanol.
Sodium polyacrylate was then mixed with glycerin, and the resulting
mixture and the other ingredients were mixed with stirring to obtain
1 kg of a gel pack composition. Gel pack compositions were then
spread on one surface of a sheet substrate of nonwoven polyester
fabric(100 mm.times.400 mm) having a weight of 100 g/m.sup.2 to
form a layer having a weight of 800 g/m.sup.2. A release sheet was
placed on the surface of the pack composition to complete the slimming
sheet pack. The slimming sheet packs were evaluated for slimming
activity and adhesiveness as described below.
[0142] Slimming sheet packs were evaluated by women subjects aged
30-49 (18 total). Each subject was given two different slimming
sheets chosen from sheets formulated from samples 101-104. Slimming
sheets were grouped in paired sets representing each of the six
possible pairs of sheets possible for samples 101-104. Each of the
six possible pairs for samples 101-104 was tested by three subjects.
Each subject was given a set of 20 sheets (i.e., 10 each of the
two different types of sheets in each paired set), to be applied
over a ten day period. Subjects placed one type of sheet pack from
the set they were given to the same site of the left thigh every
night before bed, and removed it every morning upon awakening. The
other type of sheet from the set was similarly applied and removed
from a site on the right thigh. Subjects applied the sheet packs
each night for 10 continuous days. At the end of the 10-day period,
subjects measured the circumference of their left and right thighs,
to evaluate the effect of slimming of the sheet pack they had tried.
Subjects also evaluated the adhesiveness of the sheet pack to their
skin, based on the criterion of whether the sheet pack remain attached
to the skin. Nine panelists tried each slimming sheet formulated
from samples 101-104.
[0143] Results are given in Table 16.
17TABLE 16 Sample Sample 101 102 Sample 103 Sample 104 Raspberry
ketone 1.0 1.0 1.0 0.8 4-(3',4'-Dihydroxy- -- -- -- 0.2 phenyl)butan-2-ol
Sodium polyacrylate 7.8 10.0 7.8 8.5 Polyvinyl alcohol 4.2 2.0 4.2
3.5 Carboxyvinyl polymer 1.0 1.0 1.0 1.0 Glycerin 28.0 28.0 28.0
28.0 Polyoxyethylene 0.4 -- 0.4 0.4 sorbitan monooleate (20 E.O.)
Titanium oxide 0.15 0.15 0.15 0.15 Anhydrous caffeine 0.1 0.1 --
0.1 Phaeophytes extract 0.1 0.1 -- 0.1 (in terms of dry residue)
Tea extract.sup.1 0.1 0.1 -- 0.1 (in terms of dry residue) Ethanol
2.0 2.0 2.0 2.0 Tartaric acid 0.05 0.05 0.05 0.05 Methylparaben
0.1 0.1 0.1 0.1 Ethylparaben 0.1 0.1 0.1 0.1 Fragrance 0.1 0.1 0.1
0.1 Pure water balance balance balance balance Masking effect.sup.2
A A C B Slimming effect.sup.3 A B B A .sup.1KGPP-P1 (Life Food Research)
.sup.2Slimming effect: A: 8 or 9 subjects reported a circumference
reduction of at least 0.5 cm. B: 5 to 7 subjects reported a circumference
reduction of at least 0.5 cm. .sup.3Masking effect: A: 8 or 9 subjects
reported masking of unpleasant odor of the sheet pack B: 5 to 7
subjects reported masking of unpleasant odor of the sheet pack C:
0 to 4 subjects reported masking of unpleasant odor of the sheet
pack
[0144] The present invention is not to be limited in scope by the
specific embodiments described herein. Various modifications of
the invention in addition to those described herein will become
apparent to those skilled in the art from the foregoing description.
Such modifications are intended to fall within the scope of the
appended claims.
[0145] All patents, applications, publications, test methods, literature,
and other materials cited herein are hereby incorporated by reference.
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