U.S. patent application number 15/058046 was filed with the patent office on 2017-01-26 for nanosized carotenoid cyclodextrin complexes.
This patent application is currently assigned to NSE Products, Inc.. The applicant listed for this patent is NSE Products, Inc.. Invention is credited to Mark Bartlett, Angela Mastaloudis, Stephen J. Poole, Carsten Smitdt.
Application Number | 20170021035 15/058046 |
Document ID | / |
Family ID | 37943453 |
Filed Date | 2017-01-26 |
United States Patent
Application |
20170021035 |
Kind Code |
A1 |
Bartlett; Mark ; et
al. |
January 26, 2017 |
NANOSIZED CAROTENOID CYCLODEXTRIN COMPLEXES
Abstract
Methods for the preparation of nanosized nutrient formulations
for enhanced absorption of nutritional agents. The methods include
the complexation of cyclodextrin with carotenoids and incorporation
of the complexes into the nutritional supplements without
intermediate collection, isolation, and drying steps.
Inventors: |
Bartlett; Mark; (Orem,
UT) ; Mastaloudis; Angela; (Holladay, UT) ;
Smitdt; Carsten; (Sandy, UT) ; Poole; Stephen J.;
(Springville, UT) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
NSE Products, Inc. |
Provo |
UT |
US |
|
|
Assignee: |
NSE Products, Inc.
Provo
UT
|
Family ID: |
37943453 |
Appl. No.: |
15/058046 |
Filed: |
March 1, 2016 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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12784387 |
May 20, 2010 |
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15058046 |
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11538766 |
Oct 4, 2006 |
7781572 |
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12784387 |
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60724051 |
Oct 5, 2005 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 31/355 20130101;
A23V 2002/00 20130101; A61K 31/07 20130101; A61K 47/40 20130101;
A61P 35/00 20180101; A23V 2250/712 20130101; A61P 9/00 20180101;
A23L 33/115 20160801; A23V 2250/211 20130101; A23L 33/155 20160801;
A61K 31/015 20130101; A61K 47/6951 20170801; A61P 27/02 20180101;
A61P 27/12 20180101; A23L 33/12 20160801; A61K 31/724 20130101;
A61K 31/01 20130101; A23V 2250/1882 20130101; A23V 2002/00
20130101; A61K 47/44 20130101; A61K 9/4866 20130101; A61K 31/122
20130101; A61K 31/045 20130101; A23V 2250/5112 20130101; A61P 39/06
20180101; A23V 2250/702 20130101; A23V 2200/224 20130101 |
International
Class: |
A61K 47/48 20060101
A61K047/48; A61K 31/015 20060101 A61K031/015; A61K 31/01 20060101
A61K031/01; A23L 33/115 20060101 A23L033/115; A61K 31/045 20060101
A61K031/045; A61K 31/07 20060101 A61K031/07; A61K 31/355 20060101
A61K031/355; A23L 33/155 20060101 A23L033/155; A61K 47/44 20060101
A61K047/44; A61K 31/122 20060101 A61K031/122 |
Claims
1. A carotenoid containing composition comprising: at least one
carotenoid; a cyclodextrin; and fish oil, wherein the fish oil
comprises from 70 wt % to 90 wt % of the composition.
2. The composition of claim 1, wherein the cyclodextrin is
.gamma.-cyclodextrin.
3. The composition of claim 1, wherein the cyclodextrin is a
combination of .gamma.-cyclodextrin and .beta.-cyclodextrin.
4. The composition of claim 1, wherein the at least one carotenoid
is selected from the group consisting of astaxanthin, lycopene,
zeaxanthin, beta-carotene, lutein, and mixtures thereof.
5. The composition of claim 1, further including additional
nutritional components selected from the group consisting of
beeswax, vitamin A, vitamin E, D-limonene, and mixtures
thereof.
6. The composition of claim 1, wherein the fish oil is present
comprises from 75 wt % to 85 wt % of the composition.
7. The composition of claim 1, wherein the at least one carotenoid
is complexed with the cyclodextrin.
8. A method of enhancing bioavailability of a carotenoid,
comprising: co-administering to a subject in need thereof an a
carotenoid and a combination of a cyclodextrin and fish oil.
9. The method of claim 8, wherein the carotenoid and the
cyclodextrin are complexed together.
10. The method of claim 8, wherein the cyclodextrin is
.gamma.-cyclodextrin.
11. The method of claim 8, wherein the cyclodextrin is a
combination of .gamma.-cyclodextrin and .beta.-cyclodextrin.
12. The method of claim 8, wherein the carotenoid is selected from
the group consisting of astaxanthin, lycopene, zeaxanthin,
beta-carotene, lutein, and mixtures thereof.
13. The method of claim 8, wherein additional nutritional
components are co-administered, said additional nutritional
components selected from the group consisting of beeswax, vitamin
A, vitamin E, D-limonene, and mixtures thereof.
14. The method of claim 8, wherein the carotenoid, cyclodextrin,
and the fish oil are administered in a single dosage form.
Description
PRIORITY DATA
[0001] This application is a continuation of U.S. patent
application Ser. No. 12/784,387, filed May 20, 2010, which is a
divisional of U.S. patent application Ser. No. 11/538,766 filed on
Oct. 4, 2006, which claims the benefit of U.S. Provisional Patent
Application Ser. No. 60/724,051 filed on Oct. 5, 2005, each of
which is incorporated herein by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to compositions and related
processes which increase the bioavailability of carotenoids
provided by nutritional supplement formulations containing such
nutrients. Accordingly, the present invention involves the fields
of chemistry, food science, biology and nutrition.
BACKGROUND OF THE INVENTION
[0003] Carotenoids are highly colored fat-soluble plant pigments
that are well known for their nutritional and health benefits.
Benefits associated with carotenoids include antioxidant activity
as well as conversion to vitamin A. Studies indicate that higher
dietary intake of carotenoids offers protection against developing
certain cancers, macular degeneration, cataracts, heart disease,
and other health conditions linked with oxidative or free radical
damage. Because of the significant and desirable health benefits
associate with carotenoids, nutritional companies have been quick
to place carotenoid containing products on the market.
Unfortunately, carotenoids are not readily soluble in intestinal
fluid and therefore their absorption into the body is often quit
low.
[0004] Therefore, methods and systems for improving carotenoid
absorption and bioavailability, as well as that of other nutrients,
continues to be sought.
SUMMARY
[0005] Accordingly, the present invention provides methods and
compositions for improving the bioavailability of nutrients,
particularly, carotenoids, primarily through specific manufacturing
techniques.
[0006] In one embodiment the invention includes a method for
manufacturing a carotenoid containing nutritional supplement. The
method includes mixing an amount of cyclodextrin with water to form
a water/cyclodextrin slurry at 50.degree. C., admixing an amount of
at least one carotenoid to the water/cyclodextrin slurry to form a
preblend composition including cyclodextrin carotenoid complexes,
pulling a vacuum over the preblend composition and thoroughly
mixing the preblend composition for a minimum of 1 hour, forming a
final blend by mixing under a vacuum the undried preblend
composition with additional nutritional components at a temperature
of about 40-45.degree. C. milling the final blend in a vacuum,
encapsulating the milled final blend.
[0007] In one aspect of the invention the cyclodextrin is a
gamma-cyclodextrin. In another aspect of the invention the at least
one carotenoid is selected from a group consisting of astaxanthin,
lycopene, zeaxanthin, beta-carotene, and combinations thereof
[0008] In a further aspect of the invention additional nutritional
components can be incorporated into the composition including fish
oil, beeswax, vitamin A, vitamin E, lutein, limonene, krill oil,
and combinations thereof.
[0009] In another embodiment of the invention a method for
manufacturing a carotenoid containing nutritional supplement
includes heating an amount of water to 50.degree. C. in a blending
apparatus, mixing an amount of cyclodextrin with water to form a
water/cyclodextrin slurry, admixing an amount of at least one
carotenoid to the water/cyclodextrin slurry to form a preblend
composition including cyclodextrin carotenoid complexes, pulling a
vacuum over the preblend composition and thoroughly mixing the
preblend composition for a minimum of 1 hour in a separate mixing
container, forming a fish oil blend by mixing an amount of fish oil
at a temperature of 60.degree. C. until thoroughly mixed and then
allowing to cool to 40-45.degree. C., forming a final blend by
mixing under a vacuum the undried preblend composition with the
fish oil/beeswax blend a temperature of about 40-45.degree. C.
optionally admixing additional nutritional components to the final
blend, cooling final blend mixture to 25-28.degree. C., milling the
final blend in a vacuum to reduce particle size, encapsulating the
milled final blend.
DETAILED DESCRIPTION
[0010] Definitions
[0011] In describing and claiming the present invention, the
following terminology will be used in accordance with the
definitions set forth below.
[0012] The singular forms "a," "an," and, "the" include plural
referents unless the context clearly dictates otherwise. Thus, for
example, reference to a nutritional supplement containing "a
cyclodextrin component" includes one or more cyclodextrin
components and reference to "the carotenoid" includes reference to
one or more carotenoids.
[0013] As used herein, "subject" refers to a mammal that may
benefit from the administration of a nutritional supplement or
method of this invention. Examples of subjects include humans, and
may also include other animals such as horses, pigs, cattle, dogs,
cats, rabbits, and aquatic mammals.
[0014] As used herein, the terms "formulation" and "composition"
are used interchangeably and refer to a mixture of two or more
compounds, elements, or molecules.
[0015] As used herein, "single dose" refers to one or multiple
capsule delivery units capable of delivering the desired amount of
carotenoid to a subject.
[0016] As used herein, an "effective amount," and "sufficient
amount" may be used interchangeably and refer to an amount of an
ingredient which, when included in a chew composition, is
sufficient to achieve an intended compositional or physiological
effect. For example, a "sufficient amount" of carotenoid extract
would be the minimum amount needed to have a nutritional affect.
Further, a "therapeutically effective amount" refers to an amount
of a carotenoid which is sufficient to achieve a desired
physiological effect. The determination of an effective amount is
well within the ordinary skill in the art of pharmaceutical,
neutraceutical, herbaceutical, cosmetic, and medical sciences. See,
for example, Meiner and Tonascia, "Clinical Trials: Design,
Conduct, and Analysis," Monographs in Epidemiology and
Biostatistics, Vol. 8 (1986), incorporated by reference in its
entirety.
[0017] The term "admixed" means that the drug and/or enhancer can
be dissolved, dispersed, or suspended in the carrier. In some
cases, the drug may be uniformly admixed in the carrier.
[0018] As used herein, a plurality of items, structural elements,
compositional elements, and/or materials may be presented in a
common list for convenience. However, these lists should be
construed as though each member of the list is individually
identified as a separate and unique member. Thus, no individual
member of such list should be construed as a de facto equivalent of
any other member of the same list solely based on their
presentation in a common group without indications to the
contrary.
[0019] Concentrations, amounts, and other numerical data may be
expressed or presented herein in a range format. It is to be
understood that such a range format is used merely for convenience
and brevity and thus should be interpreted flexibly to include not
only the numerical values explicitly recited as the limits of the
range, but also to include all the individual numerical values or
sub-ranges encompassed within that range as if each numerical value
and sub-range is explicitly recited. As an illustration, a
numerical range of "about 1 to about 5" should be interpreted to
include not only the explicitly recited values of about 1 to about
5, but also include individual values and sub-ranges within the
indicated range. Thus, included in this numerical range are
individual values such as 2, 3, and 4 and sub-ranges such as from
1-3, from 2-4, and from 3-5, etc.
[0020] This same principle applies to ranges reciting only one
numerical value. Furthermore, such an interpretation should apply
regardless of the breadth of the range or the characteristics being
described.
[0021] Invention
[0022] The present invention encompasses a process for preparing a
carotenoid containing nutritional supplement including the
formation of a carotenoid-cyclodextrin complex. Carotenoids are
well known in the nutritional arts for providing a variety of
health benefits. The present invention provides for methods of
manufacturing a readily absorbable carotenoid containing
nutritional supplement that is easy to perform, is time and cost
effective, and results in a product in which the carotenoid is both
highly stable and readily bioavailable.
[0023] It is well known in the nutritional supplement arts that
carotenoids have poor solubility in intestinal fluids. This poor
solubility leads to poor absorption or uptake of the carotenoids
into systemic circulation. Another factor contributing to poor
absorption of carotenoids is that carotenoids tend to aggregate
into large particles which are not readily digested or absorbed.
Cyclodextrins can encapsulate the poorly soluble compounds
increasing their solubility and inhibiting the aggregation which
typically occurs. The smaller encapsulated compounds are often
referred to as nano-particles because of their extremely small
size.
[0024] The present invention provides a streamlined method for the
manufacture of nutritional supplements containing
carotenoid-cyclodextrin complexes. In particular the method
provides for the production and subsequent direct incorporation of
carotenoid-cyclodextrin complexes into a nutritional supplement
without the intermediary steps of collection, isolation, and
drying. Because the carotenoid-cyclodextrin complexes can be
directly incorporated into nutritional supplements without
intermediary steps, costs are reduced.
[0025] The method of the present invention includes creating a
cyclodextrin slurry by combining an amount of cyclodextrin with
water. The preferred temperature for the manufacture of the slurry
is from to 50.degree. C. All types of cyclodextrins and
combinations thereof may be used in the present invention including
.alpha.-cyclodextrin, .gamma.-cyclodextrin, and
.beta.-cyclodextrin. In one embodiment the cyclodextrin used is
.gamma.-cyclodextrin. In another embodiment the cyclodextrin is a
mixture of .gamma.-cyclodextrin, and .beta.-cyclodextrin. The
cyclodextrin and water mixture should be mixed for a period of
about 20 minutes or until a caramel color is observed. The role of
the water is to hydrate the cyclodextrin. Hydrated cyclodextrin can
than better complex with the carotenoids. Once the cyclodextrin
slurry is formed carotenoids can be admixed therein. The mixing of
the carotenoid/cyclodextrin mixture should continue for a minimum
of 1 hour at a temperature of from about 40.degree. C. to about
50.degree. C. Mixing the carotenoid/cyclodextrin mixture at high
shear can enhance or increase the rate of reaction and thereby the
rate of formation of the carotenoid-cyclodextrin complex. However,
such lower shear values generated by lower mixing speeds can also
be used effectively to form the carotenoid-cyclodextrin
complexes.
[0026] The carotenoids which can be used in the present invention
include any carotenoid known in the art to have positive health
benefits. The preferred carotenoids for use in the present
invention are astazanthin, lycopene, zeaxanthin, beta-carotenes,
lutein, and mixtures thereof When possible, it is preferred that a
vacuum should be pulled over the carotenoid containing compositions
of the present invention so as to slow or inhibit the degradation
of the carotenoids. Another acceptable method of maintaining the
stability of the carotenoid is to keep the carotenoids containing
mixtures under nitrogen.
[0027] As the carotenoid/cyclodextrin composition is mixed,
carotenoid-cyclodextrin complexes begin to precipitate out of
solution making the solution more viscous. This increase in
viscosity can be used as an indicator of successful formation of
the carotenoid-cyclodextrin complex. In traditional
carotenoid-cyclodextrin complex manufacturing methods the
precipitated complexes are collected, isolated and dried at this
point in the process. By so doing the water originally present in
the cyclodextrin slurry is eliminated. In the method of the present
invention the complexes are maintained in the preblend slurry,
including the water. The ability of the manufacturing process of
the present invention to eliminate the drying process reduces both
the time and cost associated with the process.
[0028] After formation of the carotenoid-cyclodextrin complexes,
the preblend slurry can then be admixed with additional nutritional
components at a temperature of 40.degree. C. to 45.degree. C. to
form a final blend. The final blend is mixed thoroughly for a
minimum of 20 minutes. Examples of additional nutritional
components which can be used in the present invention include but
are not limited to vitamin A, vitamin E, lutein, fish oil,
limonene, beeswax, and combinations thereof It is preferred that
the final blend be mixed with fish oil. Any type of fish oil known
to one skilled in the art can be used with the present invention.
For the purposes of the present invention krill oil is included as
a fish oil.
[0029] In addition to the health benefits which are inherent in
fish oil, the addition of the fish oil to the preblend slurry helps
to stabilize and solubilize any uncomplexed carotenoids found in
the preblend slurry and further enhances the bioavailability of
both the complexed and uncomplexed carotenoids. It has been
determined that when the carotenoid-cyclodextrin complexes of the
present invention are co-administered with a minimum amount of fish
oil the bioavailability of the carotenoids is increased above that
of the carotenoid-cyclodextrin complex alone. Without being limited
by theory, it is believed that this increase in bioavailability is
due, at least in part, to fish oils stimulation of lipase enzymes
in the gut which in turn facilitate the absorption of the
carotenoids. In a preferred embodiment the fish oil comprises from
about 70 wt % to about 90 wt % of the final blend composition. In
another embodiment the fish oil can comprise from about 75 wt % to
about 85 wt % of the final blend composition. When other
nutritional components, particularly readily oxidizable components
such as Vitamin A and vitamin E, are included in the final blend
composition the fish oil also acts to stabilize and protect those
components.
[0030] Once the final blend composition is complete, it is milled
to assure small particle size of the complexed carotenoids. After
milling the final blend can be directly encapsulated or stored in
an air tight container under nitrogen. In a preferred embodiment of
the present invention, the final blend is encapsulated into soft
gelatin capsules. The compositions produced by the methods of the
present invention are intended to be delivered to subjects so as to
provide therapeutically effective amounts of carotenoids to the
subject. Such amounts are readily determinable by one of ordinary
skill in the art based on the concentrations of the carotenoids in
the invention compositions.
[0031] In addition to the method, the present invention provides a
composition and related method for providing enhanced
bioavailability of carotenoids. Specifically, it has been found
that when fish oil is included in the final blend composition as
described above, the bioavailability of the carotenoids is
unexpectedly increased above the bioavailability of the
carotenoid/cyclodextrin complex alone and a fish oil/carotenoid
mixture alone. As discussed above, it is believed that the
unexpected increase of bioavailability is due, at least in part, to
fish oils stimulation of lipase enzymes in the gut which in turn
facilitate the absorption of the carotenoids.
[0032] The example provided below is illustrative of only one
embodiment of making a carotenoid containing nutritional supplement
of the present invention. While the processing conditions and
ingredients may be preferred, no limitation thereto is to be
inferred.
Example 1
[0033] A stable carotenoid containing nutritional supplement is
preparing according to the following steps.
[0034] 1. 5.640 kg of water is added to a blender and heated to
50.degree. C. Temperature is confirmed before adding
cyclodextrin.
[0035] 2. Blades of blender are removed from blender container and
4.070 kg of gamma-cyclodextrin (Cavamax V Wacker Biochem) is added
and initially hand mixed, and then mechanically mixed for at least
30 minutes or until a cyclodextrin water slurry is formed. The
slurry is caramel in color.
[0036] 3. The following carotenoids are added in the amounts shown
in the following table:
TABLE-US-00001 Activity (% Carotenoid or IU/mg) kg Beta-Carotene
(30% Fluid Suspension, B.trispora) 500.00 IU 0.273 Beta-Carotene
(Caromin 13% b 6.5% a; oil; palm fruit) 13.000% 0.689 Astaxanthin,
5% OIL BioAstin (H. pluvialis) 5.000% 0.224 Lycopene (20% Oil
Susp.) LycoVit synthetic 20.000% 0.560 Zeaxanthin (20% Fluid Susp.)
20.000% 0.056
[0037] 4. A vacuum is pulled over the mixing container and the
composition is mixed on a low speed (9.6 rpm) for at least 1 hour
at a temperature of 4-45.degree. C. and carotenoid cyclodextrin
complexes form. (Note: as the carotenoids react with the
cyclodextrins the compound will precipitate and the mixture
increases in viscosity which is an indication of a successful
complexation reaction.)
[0038] 5. After at least one hour of mixing the mixer container
containing the carotenoid-cyclodextrin complex are immediately
removed and added to a main mixer containing a fish oil beeswax
blend. The fish oil and beeswax blend is made by adding
approximately 6.1 kg of beeswax and 73.2 kg of fish oil to the
mixer and blending at 60.degree. C. to until thoroughly mixed. The
composition is then cooled to 40-45.degree. C. before the
carotenoid-cyclodextrin complex is added. A small amount of the
fish oil/beeswax composition is used to rinse the
carotenoid-cyclodextrin complex into the mixer container.
[0039] 6. Additional components can then be added to the mixer. The
components and the amounts added are shown in the table below:
TABLE-US-00002 Activity (% Ingredient or IU/mg) kg Vitamin A
(Palmitate, liquid 1,700 USP) 1600.0 IU 0.043 Vitamin E
(d-alpha-tocopherol 1490 oil) 1.430 IU 2.988 Vitamin E, 60% g-t,
6.8% a-t, 20% d-t, 1.4% b-t, 60.000% 2.671 MTS-90G Oil Vitamin E
Tocotrienols (50% E&TT, Fr. Palm 38.000% 0.028 Oil) Lutein
(Ester, Xangold, oil susp, 15%) 15.000% 0.298 Krill Oil 100.000%
2.035 D-Limonene (liquid) 95.000% 1.071
[0040] 7. After the addition of the carotenoid/cyclodextrin complex
and the other ingredients the mixture a vacuum is pulled over the
mixer container and the mixture is mixed using high shear for 20
minutes at 20-45.degree. C. The mixture is then allowed to cool to
25-28.degree. C. and is removed from the mixer and milled to reduce
the particle size.
[0041] 8. After milling the mixture can be stored in a sealed
container under nitrogen or encapsulated immediately. Encapsulation
is done in a soft gelatin capsule. Each soft gelatin capsule
contains about 1.2 grams of the milled final composition.
Example 2
[0042] A study was performed to determine the effect of the
composition of claim 1 on the Skin Carotenoid Scores (SCS) of
subjects. The study involved the use of Raman Spectroscopy to
assess changes in Skin Carotenoid Scores over an eighteen week
period of supplementation with the Composition of example 1 in
comparison to a placebo.
[0043] Fifty two subjects between 18 and 65 years of age qualified
for the study participation. Food frequency and health history
questionnaires were used to screen inclusion criteria, and the
Pharmanex BioPhotonic Scanner was used to assess skin carotenoid
levels. Individuals taking antioxidant supplements, having high
exposure to sunlight or tanning bed use, pregnant women, or
individuals using sunless tanning products were excluded from the
study. All subjects were healthy non-smokers consuming typical U.S.
diets containing less than five daily servings of fruit and
vegetables, and had baseline Raman Intensity Scores between 13,000
and 35,000 Raman Intensity Counts. Participants were instructed to
maintain their dietary and exercise habits throughout the duration
of the study. Subjects (n=52) meeting study criteria were randomly
assigned in a double blind manner to one of two groups, composition
of example 1 (n=27) or placebo (n=25).
[0044] Subjects were given their respective capsules, placebo or
composition of Example 1, and were instructed to take them twice
daily (once with their morning meal and once with their evening
meal). The dosage amount for the Example 1 participants included
two softgel capsules twice daily. The placebo taken twice daily
included also included two softgel capsules which contained omega-3
fatty acids but no carotenoids.
[0045] The results of the study showed an unexpectedly high
increase of the Skin Carotenoid Scores. Specifically, the average
increase for those taking the composition of Example 1 was 17,757
Raman Intensity counts after the eighteen weeks compared to
approximately no change for the placebo participants. Throughout
the 18 week study the Carotenoid Scanner Score continually
increased with no apparent plateau effect.
[0046] While the forgoing example is illustrative of the principles
of the present invention in one or more particular applications, it
will be apparent to those of ordinary skill in the art that
numerous modifications in form, usage and details of implementation
can be made without the exercise of inventive faculty, and without
departing from the principles and concepts of the invention.
Accordingly, it is not intended that the invention be limited,
except as by the claims set forth below.
* * * * *