U.S. patent application number 13/840810 was filed with the patent office on 2014-09-18 for method for preparing nanolipids with encapsulated alcohol.
This patent application is currently assigned to DERMAZONE SOLUTIONS, INC.. The applicant listed for this patent is Michael W. Fountain. Invention is credited to Michael W. Fountain.
Application Number | 20140271782 13/840810 |
Document ID | / |
Family ID | 51528029 |
Filed Date | 2014-09-18 |
United States Patent
Application |
20140271782 |
Kind Code |
A1 |
Fountain; Michael W. |
September 18, 2014 |
METHOD FOR PREPARING NANOLIPIDS WITH ENCAPSULATED ALCOHOL
Abstract
A method for preparing ethanol-containing nanolipid particles,
which can be used in food products, frozen desserts, or beverages.
The method comprises nanolipidic vehicles in which
ethanol-containing substances are encapsulated, said
ethanol-containing nanolipidic vehicles can be combined with food
products, desserts or beverage ingredients including those that are
subsequently frozen, The food product, dessert or beverage can
remain in a frozen state during consumption by an individual. A
composition comprising ethanol-containing nanolipid particles,
which can be used in food products, frozen desserts, or
beverages.
Inventors: |
Fountain; Michael W.; (Pilot
Point, TX) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Fountain; Michael W. |
Pilot Point |
TX |
US |
|
|
Assignee: |
DERMAZONE SOLUTIONS, INC.
St. Petersburg
FL
|
Family ID: |
51528029 |
Appl. No.: |
13/840810 |
Filed: |
March 15, 2013 |
Current U.S.
Class: |
424/439 ;
426/100; 426/592; 426/89 |
Current CPC
Class: |
A61K 9/5192 20130101;
C12G 3/00 20130101; A61K 9/51 20130101; A23P 10/35 20160801; C12G
3/04 20130101; A23G 9/485 20130101; A23L 33/10 20160801; C12G 3/05
20190201; A23G 9/48 20130101; A23V 2002/00 20130101; A61K 9/5123
20130101; A23G 9/32 20130101 |
Class at
Publication: |
424/439 ;
426/592; 426/89; 426/100 |
International
Class: |
C12G 3/00 20060101
C12G003/00; A23G 9/32 20060101 A23G009/32; A61K 9/48 20060101
A61K009/48; A23G 9/48 20060101 A23G009/48 |
Claims
1. A method for making nanolipid particles (NLPs) having ethanol
encapsulated within said nanolipidic particles, comprising the
steps of: a) providing a precursor solution; b) diluting said
precursor solution with an ethanol solvent to produce a
solvent-diluted precursor solution; c) adding an ethanol-containing
substance having an ethanol content of 0.2%-50.0% to an aqueous
solvent to produce an aqueous-ethanol monophase; and c) mixing said
solvent-diluted precursor solution with said aqueous-ethanol
monophase wherein said mixing produces one or more populations of
ethanol-loaded NLPs or NLP assemblies.
2. The method of claim 1 wherein said precursor solution is a
monophasic optically-clear solution.
3. The method of claim 1 wherein said diluting of said precursor
solution with said ethanol solvent is at a ratio ranging from about
1 part precursor to about 20 parts solvent to a ratio ranging from
about 1 part precursor to about 0.3 parts solvent.
4. The method of claim 1 wherein said NLP assembly has a population
formed having a mean particle diameter from about 20 nm-300 nm.
5. The method of claim 1 wherein the concentration of said solvent
in said NLPs is from about 0.5% to about 14%.
6. The method of claim 1 wherein the said concentration of ethanol
encapsulated within the nanolipidic particles is from about 0.1% to
15.0%.
7. The method of claim 1 wherein said diluting of said precursor
solution with said ethanol solvent is at a ratio ranging from about
1 part precursor to about 20 parts solvent to a ratio ranging from
about 1 part precursor to about 0.3 parts solvent; and; wherein
said NLP assembly population is formed having a mean particle
diameter from about 20-300 nm; and wherein the concentration of
said solvent in said NLPs is from about 0.5% to about 14%, and
wherein the said concentration of ethanol encapsulated within the
nanolipidic particles is from about 0.1 to 15.0%.
8. The method of claim 1, wherein said ethanol-containing substance
is selected from the group comprising vodka, gin, rum, bourbon,
grain alcohol, and liqueurs containing vodka, gin, rum, bourbon, or
grain alcohol.
9. The method of claim 1, wherein the concentration of ethanol in a
frozen food product containing ethanol-loaded NLPs is from about
0.1% to 15.0% by volume.
10. The method of claim 1, wherein said nanolipidic particles with
said encapsulated ethanol-containing substance is combined with
ingredients suitable for consumption in a frozen food product, and
the mixture is frozen at an appropriate temperature such that an
ethanol-containing frozen food results.
11. The method of claim 1, wherein said ethanol-containing frozen
food remains in the frozen state for a period of time sufficient
for an individual to consume said frozen food.
12. The method of claim 3, wherein said diluting of said precursor
solution with said ethanol solvent is at a ratio of about 1 part
precursor to about 10 parts solvent to about 1 part loaded
nanolipidic population to about 0.5 parts solvent.
13. The method of claim 1, wherein the stability of said
ethanol-encapsulated nanolipidic particles is such that said
particles will maintain structural integrity through multiple
freeze-thaw cycles.
14. The method of claim 1, wherein said precursor solution
comprises phospholipids selected from the group consisting of
phosphatidylcholine (PC), phosphatidylethanolamine (PE),
phosphatidic acid (PA) and phosphatidylinositol (PI) and mixtures
thereof.
15. The method of claim 1, comprising making one or more additional
serial dilutions of said precursor solution with said ethanol
solvent, wherein said additional dilutions form distinct
populations of nanolipidic particles, and wherein said nanolipidic
particle populations decrease in size as ethanol concentration in
precursor solution increases.
16. The method of claim 1, comprising making one or more additional
dilutions of said precursor solution with said ethanol solvent in
order to provide a desired number of nanolipidic particles per unit
volume
17. The method of claim 1, wherein said aqueous solvent further
comprises an additional water-soluble passenger molecule.
18. The method of claim 1, wherein one or more lipophilic or
amphipathic passenger molecules are added to said precursor
solution to form a loaded nanolipidic particle population, wherein
said nanolipidic particles encapsulate admixed passenger
molecules.
19. The method of claim 10, wherein said frozen food is a frozen
beverage or dessert having a final ethanol concentration up to
0.2%-15.0% by volume.
20. The method of claim 10, wherein said nanolipidic particles with
said encapsulated ethanol-containing substance is in a topping for
a frozen dessert, said topping having a final ethanol concentration
of 0.2%-15.0% by volume.
21. The method of claim 1, wherein said nanolipidic particles with
encapsulated ethanol are admixed with nanolipidic particles
encapsulating a pharmaceutical product, said admixture is added to
ingredients suitable for a frozen food, wherein said frozen mixture
is a delivery device for said pharmaceutical.
22. A composition with nanolipidic particles having
alcohol-encapsulated within, comprising: a precursor solution, an
ethanol solvent that dilutes said precursor solution and forms a
solvent-diluted precursor solution; an ethanol-containing substance
having an ethanol concentration of 0.2%-50.0%; an aqueous solvent
added to the ethanol-containing substance to produce an
aqueous-ethanol monophase; alcohol encapsulated nanolipid particles
formed by the mixture of said solvent-diluted precursor solution
with said aqueous-ethanol monophase.
23. The composition of claim 22 wherein said precursor solution is
a monophasic optically-clear solution.
24. The composition of claim 22 wherein said precursor solution
with said ethanol solvent is at a ratio ranging from about 1 part
precursor to about 20 parts solvent to a ratio ranging from about 1
part precursor to about 0.3 parts solvent.
25. The composition of claim 22 wherein said NLP assembly has a
population formed having a mean particle diameter from about 20
nm-300 nm.
26. The composition of claim 22 wherein the concentration of said
solvent in said NLPs is from about 0.5% to about 14%.
27. The composition of claim 22 wherein the said concentration of
ethanol encapsulated within the nanolipidic particles is from about
0.2% to 15.0%.
28. The composition of claim 22 wherein said precursor solution
with said ethanol solvent is at a ratio ranging from about 1 part
precursor to about 20 parts solvent to a ratio ranging from about 1
part precursor to about 0.3 parts solvent; and wherein said NLP
assembly population is formed having a mean particle diameter from
about 20 nm-300 nm; and wherein the concentration of said solvent
in said NLPs is from about 0.5% to about 14%, and wherein the said
concentration of ethanol encapsulated within the nanolipidic
particles is from about 0.2% to 15.0%.
29. The composition of claim 22, wherein said ethanol-containing
substance is selected from the group comprising vodka, gin, rum,
bourbon, grain alcohols, and liqueurs containing vodka, gin, rum,
bourbon, or grain alcohols.
30. The composition of claim 22, wherein the concentration of
ethanol-containing substance in a frozen food product is from about
0.2% to 15.0% by volume.
31. The composition of claim 22, wherein said nanolipidic particles
with said encapsulated ethanol-containing substance are combined
with ingredients suitable for consumption in a frozen food product,
and the mixture is frozen at an appropriate temperature such that
an ethanol-containing frozen food results.
32. The composition of claim 22, wherein said ethanol-containing
frozen food remains in the frozen state for a period of time
sufficient for an individual to consume said frozen food.
33. The composition of claim 22, wherein said precursor solution
with said ethanol solvent is at a ratio of about 1 part precursor
to about 10 parts solvent to about 1 part loaded nanolipidic
population to about 0.5 parts solvent.
34. The composition of claim 22, wherein the stability of said
ethanol-encapsulated nanolipidic particles that said particles will
maintain structural integrity through multiple freeze-thaw
cycles.
35. The composition of claim 22, wherein said precursor solution
comprises phospholipids selected from the group consisting of
phosphatidylcholine (PC), phosphatidylethanolamine (PE),
phosphatidic acid (PA) and phosphatidylinositol (PI) and mixtures
thereof.
36. The composition of claim 22 further comprising one or more
additional serial dilutions of said precursor solution, wherein
said additional dilutions form distinct populations of nanolipidic
particles, and wherein said nanolipidic particle populations
decrease in size as ethanol concentration in precursor solution
increases.
37. The composition of claim 22 further comprising one or more
additional dilutions of said precursor solution with said ethanol
solvent in order to provide a desired number of nanolipidic
particles per unit volume.
38. The composition of claim 22, wherein said aqueous solvent has
an additional water-soluble passenger molecule.
39. The composition of claim 22, further comprising one or more
lipophilic or amphipathic passenger molecules added to said
precursor solution to form a loaded nanolipidic particle population
wherein said nanolipidic particles encapsulate admixed passenger
molecules.
40. The composition of claim 31, wherein said nanolipid particles
are added to a frozen beverage or dessert having a final ethanol
concentration from 0.1%-15.0% by volume.
41. The composition of claim 31, wherein said nanolipid particles
are added to a food product, said food product having a final
ethanol concentration of from 0.1-15.0% by volume.
42. The composition of claim 40, wherein the ethanol encapsulated
in said nanolipidic particles is in a concentration of 0.1% to
15.0%.
43. The composition of claim 22, wherein said nanolipidic particles
with encapsulated ethanol are admixed with nanolipidic particles
encapsulating a pharmaceutical product, said admixture is added to
ingredients suitable for a frozen food, wherein said frozen mixture
is a delivery device for said pharmaceutical
44. A nanolipidic particle (NLP) having encapsulated ethanol, made
by a process comprising the steps of: a) providing a precursor
solution; b) diluting said precursor solution with an ethanol
solvent to produce a solvent-diluted precursor solution; c) adding
an ethanol-containing substance having an ethanol content of
0.2%-50.0% to an aqueous solvent to produce an aqueous-ethanol
monophase; and c) mixing said solvent-diluted precursor solution
with said aqueous-ethanol monophase wherein said mixing produces
one or more populations of ethanol-loaded nanolipids (NLPs) or NLP
assemblies.
45. Nanolipidic particles of claim 44 wherein said precursor
solution is a monophasic optically-clear solution.
46. Nanolipidic particles of claim 44 wherein said diluting of said
precursor solution with said ethanol solvent is at a ratio ranging
from about 1 part precursor to about 20 parts solvent to a ratio
ranging from about 1 part precursor to about 0.3 parts solvent.
47. Nanolipidic particles of claim 44 wherein said NLP assembly has
a population formed having a mean particle diameter from about 20
nm-300 nm.
48. Nanolipidic particles of claim 44 wherein the concentration of
said solvent in said NLPs is from about 0.5% to about 14%.
49. Nanolipidic particles of claim 44 wherein the said
concentration of ethanol encapsulated within the nanolipidic
particles is from about 0.1% to 15.0%.
50. Nanolipidic particles of claim 44 wherein said diluting of said
precursor solution with said ethanol solvent is at a ratio ranging
from about 1 part precursor to about 20 parts solvent to a ratio
ranging from about 1 part precursor to about 0.3 parts solvent;
and; wherein said NLP assembly population is formed having a mean
particle diameter from about 20 nm-300 nm; and wherein the
concentration of said solvent in said NLPs is from about 0.5% to
about 14%, and wherein the said concentration of ethanol
encapsulated within the nanolipidic particles is from about 0.1% to
15.0%.
51. Nanolipidic particles of claim 44, wherein said
ethanol-containing substance is selected from the group comprising
vodka, gin, rum, bourbon, grain alcohol, and liqueurs containing
vodka, gin, rum, bourbon, or grain alcohol.
52. Nanolipidic particles of claim 44, wherein the concentration of
ethanol in said ethanol-loaded NLPs is from about 0.1% to 15.0% by
volume.
53. Nanolipidic particles of claim 44, wherein said nanolipidic
particles encapsulated with said ethanol-containing substance are
combined with ingredients suitable for consumption in a frozen food
product, and the mixture is frozen at an appropriate temperature
such that an ethanol-containing frozen food results.
54. Nanolipidic particles of claim 44, wherein said
ethanol-containing frozen food remains in the frozen state for a
period of time sufficient for an individual to consume said frozen
food.
55. Nanolipidic particles of claim 46, wherein said diluting of
said precursor solution with said ethanol solvent is at a ratio of
about 1 part precursor to about 10 parts solvent to about 1 part
loaded nanolipidic population to about 0.5 parts solvent.
56. Nanolipidic particles of claim 44, wherein the stability of
said ethanol-loaded nanolipids is such that said ethanol-loaded
nanolipids will maintain structural integrity through multiple
freeze-thaw cycles.
57. Nanolipidic particles of claim 44, wherein said precursor
solution comprises phospholipids selected from the group consisting
of phosphatidylcholine (PC), phosphatidylethanolamine (PE),
phosphatidic acid (PA) and phosphatidylinositol (PI) and mixtures
thereof.
58. Nanolipidic particles of claim 44, comprising making one or
more additional serial dilutions of said precursor solution with
said ethanol solvent, wherein said additional dilutions form
distinct populations of nanolipidic particles, and wherein said
nanolipidic particle populations decrease in size as ethanol
concentration in precursor solution increases.
59. Nanolipidic particles of claim 44, comprising making one or
more additional dilutions of said precursor solution with said
ethanol solvent in order to provide a desired number of nanolipidic
particles per unit volume
60. Nanolipidic particles of claim 44, wherein said aqueous solvent
further comprises an additional water-soluble passenger
molecule.
61. Nanolipidic particles of claim 44, wherein one or more
lipophilic or amphipathic passenger molecules are added to said
precursor solution to form a loaded nanolipidic particle population
wherein said nanolipidic particles encapsulate admixed passenger
molecules.
62. Nanolipidic particles of claim 53, wherein said frozen food is
a frozen beverage or dessert having a final ethanol concentration
of 0.1% to 15.0% by volume.
63. Nanolipidic particles of claim 53, wherein said nanolipidic
particles with encapsulated ethanol are in a topping for a frozen
dessert, said topping having a final ethanol concentration of up to
of 0.1% to 15.0% by volume.
64. Nanolipidic particles of claim 44, wherein said nanolipidic
particles with encapsulated ethanol are admixed with nanolipidic
particles encapsulating a pharmaceutical product, said admixture is
added to ingredients suitable for a frozen food, wherein said
frozen mixture is a delivery device for said pharmaceutical.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] Not Applicable
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
[0002] Not applicable.
TECHNICAL FIELD OF INVENTION
[0003] This invention relates to the field of encapsulation of
ethanol in nanolipidic particles.
BACKGROUND OF THE INVENTION
[0004] Frozen foods, particularly frozen desserts and frozen
beverages, are very popular with consumers. Frozen desserts, such
as ice creams and sorbets are consumer favorites, and are
frequently flavored with liqueurs such as Grand Marnier.RTM. and
Kahlua.RTM.. Frozen beverages, such as margaritas and pina coladas,
are also popular. Attempts to provide such frozen desserts and
beverages with an ethanol content comparable to the non-frozen
counterparts has been met with limited success due to the
substantially lower freezing point of ethanol as compared to
water-based products.
[0005] The freezing point of pure water is 0.degree. C. (32.degree.
F.). The freezing point of pure ethanol is -114.degree. C.
(-173.2.degree. F.). The freezing point of ethanol containing
products will fall into the range between these two limits, with
the freezing point of an alcohol-containing food product depending
upon the percentage of alcohol (ethanol) in the final product.
Practical and physical limitations prevent the use of commercial
freezing mechanisms capable of maintaining high-ethanol content
foods at temperatures low enough to stay frozen. Most freezing
apparatuses have a functional range for freezing a food product,
and consumer safety will also dictate a temperature range wherein
frozen foods may be safely ingested. Freezing food products with
alcohol ranging up to 15% in the final concentration requires
freezing at temperatures substantially below the freezing point of
water.
[0006] This decreased freezing point has long been understood to a
limiting factor in the ability to make products containing ethanol
which can remain frozen long enough for an individual to reasonably
consume the product while it remains in the frozen state. Various
means have been employed to overcome this obstacle, most of which
have involved the addition of stabilizing materials, such as gels
or agar, to the food product. Even then, there has been limited
success.
[0007] Incorporating passenger molecules, such as pharmaceutical
active ingredients, in lipid vesicles such as liposomes has been
reported in the prior art. An amphipathic carrier structure denoted
as a Solvent Dilution Microcarrier ("SDMC") was disclosed in U.S.
Pat. No. 5,269,979. In general, the '979 patent described making a
plurality of SDMC vehicles by solubilizing an amphipathic material
and a passenger molecule in a first quantity of a non-aqueous
solvent. Following this, a first quantity of water was added,
forming a turbid suspension. In a subsequent step, a second
quantity of non-aqueous solvent was added to form an optically
clear solution. The final step of a preferred embodiment was to
organize the optically clear solution into SDMC vehicles by mixing
with air or a second quantity of water.
[0008] In U.S. Pat. No. 5,879,703, a method for preparing a
shelf-stable precursor solution useful for remote encapsulation of
active ingredients was described. In '703, the precursor solution
was made by solubilizing an amphipathic material in a non-aqueous
solvent. A quantity of water was added to the first mixture to form
a precursor solution characterized by optical clarity and being
monophasic at room temperature. The precursor solution could be
stored for an extended period of time--and the desired active
ingredient added at a later time, perhaps at a remote location, to
form a loaded precursor solution. SDMCs could be formed, in
preferred embodiments, from the loaded precursor solution by
diluting with water or mixing with air. SDMCs ranged from about 230
to about 412 nanometers in size.
[0009] Although SDMCs and the shelf-stable precursor solution
provided for making vehicles suitable for delivering active
ingredients in a variety of applications, a need remained for
improved vehicles for delivery of passenger molecules.
[0010] It has now been found that the shelf-stable precursor
solution such as described in the '703 patent can be used as a
starting material in a novel method which results in vehicles of a
smaller size than previously reported. The starting material is
manipulated by dilution with a non-aqueous solvent, either before
or after loading with a passenger molecule, to provide one or more
defined populations of nanolipidic particles ("NLPs") which range
in size from about 1 nanometer to about 20 nanometers.
[0011] NLP assemblies are formed from the NLPs which range in size
from about 30 nanometers to about 200 nanometers. In addition, it
has been found that NLPs can be used in a method for making carrier
vehicle preparations which are mixed smaller and larger carrier
vehicles, or having a larger mean size of about 200-300 nanometers,
but improved encapsulation of passenger molecules.
SUMMARY OF THE INVENTION
[0012] A means has now been found by which ethanol can be
effectively, efficiently and economically encapsulated in a
nanolipid particle for possible consumer consumption, such as
encapsulation of ethanol maintained at percentages not previously
possible for consumer ingestion.
[0013] A method for preparing ethanol-containing food products,
frozen desserts and beverages is disclosed using alcohol
encapsulated in nanolipid particles and assemblies. The method
comprises nanolipidic vehicles in which ethanol-containing
substances are encapsulated, said ethanol-containing nanolipidic
vehicles are combined with dessert or beverage ingredients which
can subsequently consumed or incorporated into food products, such
as frozen foods, desserts or beverages. These food items can remain
in a frozen state during consumption by an individual without
losing the characteristics of the alcohol encapsulated in nanolipid
particles and assemblies.
[0014] The method of the claimed invention provides for the
encapsulation of various ethanol-containing substances in
lipid-based vesicles, said vesicles being preferably soy-based,
which may be added to ingredients appropriate for consumption in a
food product, such as a dessert or beverage, and the combination
may then be frozen by established means available in food service
to produce an ethanol-containing food product or frozen food
product capable of maintaining a frozen state at consumer-safe
temperatures for a period of time sufficient for consumption of
said product. Additional stabilizing materials do not need be added
to the food product to achieve this result.
DETAILED DESCRIPTION
Preparation of Nanolipidic Particles (NLPs) and NLP Assembly
Populations
[0015] Nanolipidic particles (NLPs) are prepared according to the
techniques set forth in United States Patent Application
Publication No. 2010/0239686 A1, published Sep. 23, 2010, and
United States Patent Application Publication. No. 2012/00195940 A1,
published Aug. 2, 2012, which are both herein incorporated by
reference. NLPs are prepared from a Shelf-Stable Precursor Stock,
prepared according to U.S. Pat. No. 5,879,703 which is also
incorporated by reference as if fully set forth herein.
[0016] NLPs are made from a precursor solution as described in U.S.
Pat. No. 5,879,703. As stated in the '703 patent, a precursor
solution may be made by solubilizing an amphipathic material in a
first quantity of a non-aqueous solvent appropriate to solubilize
the amphipathic material to form a first mixture. The amphipathic
material preferably comprises phospholipids (PL). Preferred
phospholipids comprise one or more of the following phosphatides:
phospatidylcholine (PC), phospatidylethanolamine (PE), phosphatidic
acid (PA) and phosphatidylinositol (PI). In a preferred embodiment,
PC, PE, PA and PI are combined. A preferred ratio of PLs useful in
the invention is PC:PE:PA:PI of 6.5:2.5:0.7:0.3 in ethanol.
Preferably, one gram of PL is solubilized in 5.0-7.5 mL of ethanol
solvent.
[0017] After dissolution of the amphipathic material, a quantity of
water is added to form a turbid suspension. The amount of water to
add is approximately 9 kg of water to 31 kg of dissolved
amphipathic material, but the amount of water can be varied to
result in the desired turbid suspension. A second quantity of
non-aqueous solvent, such as ethanol, is added until the turbid
suspension is monophasic and has optical clarity at room
temperature. This resulting product is a precursor solution which
is shelf-stable over time.
[0018] In the '703 patent, it was disclosed that a precursor
solution made according to the process disclosed therein was shelf
stable at least up to two years, and perhaps longer, as long as it
remains in a monophasic condition. It has been recently determined
that precursor solutions made by this method are stable for at
least eight years, independent of manufacturing, location, season,
year and lot.
[0019] It has now been found that a precursor solution such as
disclosed in '703 can be used as a starting material to make
nanolipidic particles (NLPs) and NLP assemblies. In '703, the
precursor solution was disclosed as being useful for making SDMCs
(Solvent Dilution Microcarriers) at a later point in time and,
perhaps, a remote location. SDMCs have a diameter of from about 230
to about 412 nm. In contrast, NLPs have a mean diameter of from
about 1 nm to about 20 nm and NLP assemblies have a mean diameter
from about 30 nm to about 200 nm.
[0020] Various populations of NLP assemblies may be made for
various applications. Preferred populations range from about 40-60
nm; about 60-80 nm; about 80-110 nm; about 110-140 nm; and about
150-200 nm. NLP assembly populations are generally 20-30% smaller
in diameter than SDMCs for the same passenger molecule.
[0021] A slightly larger population or mixed population of carrier
vehicles is referred to herein as ECVs or encapsulating carrier
vehicles. Although overlapping the mean diameter of SDMCs, the ECV
is made using a different method employing NLPs and the result is a
carrier vehicle population which has been found to exhibit a higher
encapsulating efficiency. The ECVs are described as having a mean
diameter from about 200 nm to 300 nm.
[0022] To make carriers for passenger molecules, such as NLP
populations, NLP assemblies, or ECVs according to the method
disclosed in United States Patent Application Publications No.
2010/0239686 and 2012/0195940, the precursor solution as previously
described in the '703 patent is diluted with a suitable solvent or
mixed solvent system which is compatible with the solvent system
used in the precursor solution. This dilution is performed either
before or after addition of the passenger molecule as will be
further described in detail below.
[0023] The solvent is selected for biocompatibility if the end use
of the carriers will require that characteristic. The solvent or
mixed solvent system used for dilution must be miscible with the
solvents in the precursor solution and should be effective to
disperse rather than dissolve the carriers. Most preferably, the
solvent used for dilution is ethanol, since it possesses the
desired qualities. Ethanol is the solvent of choice for any end use
wherein the particles are for ingestion. The dilution is preferably
conducted in a sequential or serial manner. For example, a first
dilution of 1:10 provides a population of carriers, and further
serial dilution to about 1:0.5 provides a series of populations of
carriers.
[0024] The size of the carriers in each dilution can be determined
by laser light scattering. Mixed populations of NLPs and larger
vesicles may be created at lower dilutions with the non-aqueous
solvent. An appropriate instrument for this purpose is the
Zetasizer 1000 manufactured by Malvern Instruments, (Worcestershire
United Kingdom). Diameters of particles reported herein were
determining using the Multimodal Analysis Mode of the Zetasizer
1000 to determine particle size by peak intensities. Other
techniques may be used to analyze particle size, which results can
be correlated to the numerical values obtained with the light
scattering technique described herein.
[0025] Addition of the desired passenger molecule occurs prior to
dilution with the solvent if the passenger molecule is lipophilic
or amphipathic. Addition occurs after dilution if the passenger
molecule is water soluble.
[0026] Thus, in the case of a lipophilic or amphipathic passenger
molecule, the NLP loaded populations form upon dilution with the
solvent. NLP assembly populations or ECVs are formed by dilution of
the NLP loaded population into water.
[0027] In the case of a water soluble passenger molecule, the
precursor solution is mixed with a passenger molecule dissolved in
water. NLP assembly populations or ECVs are formed upon dilution
with the non-aqueous solvent. If a serial dilution technique is
used, distinct populations are formed.
[0028] Based on curves observed from different classes of
compounds, ranges for the finished NLP assembly population can be
established for each NLP population used to form the final NLP
assembly population. The more non-aqueous solvent that is used to
dilute the NLPs, the smaller the NLP assembly populations.
[0029] Various NLP loaded populations may be mixed and matched to
provide a multifunctional NLP assembly product. The different NLP
loaded populations within the NLP assembly could provide a
preparation which allows one active ingredient to be preferentially
absorbed over the other, thus allowing a control of the rates of
release of different ingredients in a single preparation.
Alternatively, a single NLP population could be loaded with more
than one passenger molecule to provide the multifunctionality.
[0030] Another advantage to the NLP technology is that an optically
clear solution containing NLPs loaded with passenger molecules can
be made by selecting conditions where the NLPs are less than about
150 nm in size. It is many times important that a product appear
optically clear or it will fail to gain consumer acceptance. For
example, loaded NLPs in an optically clear solution have
application in the beverage industry and the pharmaceutical
industry for liquid products. As one example, a mouthwash can be
prepared that contains NLPs which encapsulates an ingredient for
time-release in the mouth. A consumer prefers to purchase an
optically clear mouthwash rather than a cloudy one.
[0031] The passenger molecules suitable for use in forming a NLP
loaded population are numerous. In one embodiment, passenger
molecules can be selected which exhibit lipid solubility or are
amphipathic. These molecules have solubility profiles ideally
suited for loading into NLPS. In another embodiment, water soluble
molecules may be incorporated into NLPs by solubilization into the
aqueous solution used to form the finished NLP product. Using these
two approaches virtually any molecule may be incorporated as a
passenger molecule into NLP products of defined sizes. An
innovative use of both approaches may be used to incorporate both
lipid and water soluble compounds into a NLP assembly product by
first incorporating lipid soluble compounds into NLPs prior to
dilution with ethanol and second incorporating water soluble
molecule(s) into the water solution used to form the finished NLP
product of defined size.
[0032] NLPs may also be used in the food and beverage industry. For
example, NLPs incorporating caffeine may be used in dietary
supplements for appetite suppression. Encapsulation in NLPs has
been found to be effective to mask the taste of the passenger
molecule if it is desired that tasting of such be bypassed upon
ingestion.
[0033] Another application in the food and beverage industry is the
incorporation of substances into NLPs which will be tasted, rather
than masked. Flavorings such as peppermint oil and other oils are
appropriately incorporated into NLPs. The encapsulation of
oil-containing substances may lead to increased shelf life in that
the encapsulated substance is protected from oxidation. In
addition, the encapsulation of substances would permit additional
options for manufacturers and consumers.
[0034] As just one example, a manufacturer of a beverage could
prepare and bottle one base flavor. The consumer would then have
the option of adding NLP packets to the beverage to meet the taste
preferences of the consumer or to enrich it with vitamins. A
consumer that prefers a strong peppermint flavoring in a chocolate
drink could add NLPs containing peppermint oil to his or her
beverage. Substances that are meant to be tasted can also be
loosely associated with the exterior of the NLP by providing such
substances in the aqueous phase of the procedure. For example, an
NLP containing a vitamin that preferably should not be tasted can
have a pleasant taste on the outside thereof.
[0035] If it is desired that the NLPs remain in the mouth so that
their contents can be tasted, a natural carbohydrate or sugar can
be linked to the NLP by merely providing it in the aqueous
solution. This will stick to the inside of the mouth for a period
of time, and normal mouth chemistry and mastication will release
the contents of the NLPs to provide the desired effect. The NLPs
can also be subjected to agitation and shear such as in a blender
or heavy industrial equipment at a manufacturing site to provide
flavorings to foods and beverages.
[0036] If the desired passenger molecule is water soluble, the
passenger molecule should first be dissolved in water. The
incorporation step, or loading of the passenger molecule into the
NLP, is accomplished when the NLP product is formed by adding the
dissolved passenger molecule to the precursor solution.
[0037] The nanolipidic particles with encapsulated ethanol of the
invention have a softer "mouth feel" than a preparation containing
free ethanol. The encapsulation process leads to the ethanol being
sequestered inside the nanolipid such that the ethanol does not
immediately contact the mucosa in the mouth. Other passengers
molecules which may in the preparation, such as vitamins and
pharmaceutical substances, are similarly sequestered within the
nanolipidic particles.
Sample Preparation of NLPs and NLP Assembly Populations with
Encapsulated Ethanol-Containing Substances
[0038] NLPs encapsulating ethanol-containing substances were
prepared as follows:
[0039] Solvent-diluted precursor stock was prepared by adding 1
part shelf-stable precursor stock to 0.3 part ethanol to form a
solvent-diluted precursor.
[0040] An ethanol-containing substance is dissolved in an aqueous
solvent to form an aqueous-ethanol monophase.
[0041] An aliquot of solvent-diluted precursor stock added to an
aliquot of the aqueous-ethanol monophase. This solution is stirred
at room temperature resulting in a loaded NLP population with the
desired ethanol-containing substance encapsulated within the
nanolipid particles to yield a liposomal concentrate comprising
ethanol in the amount of about 0.1% to 15.0% by volume.
[0042] The size of the loaded NLPs may be determined by using the
Malvern 1000 Zetasizer Laser Light Scattering Instrument set to
analyze populations using multimodal analysis mode. The size of the
finished preparation was determined to be 20 nm-150 nm.
[0043] Nanolipid particle sizes useful for the preparation of the
invention can be increased or decreased by adjusting the ratio of
ethanol to Solvent Dilution Microcarrier (SDMC) used in preparation
of the precursor stock solution. Particle sizes can range from
approximately 60 nm using 20 parts ethanol: 1 part SDMC up to 170
nm using 0.3 part ethanol: 1 part SDMC. Sizes of NLP and NLP
assembly populations useful for the method of the invention are 20
nm to 300 nm, preferably 20 nm to 170 nm.
[0044] One or more additional dilutions of the precursor solution
may be made with ethanol solvent in order to provide a desired size
of NLPs and number of NLPs per unit volume. The more ethanol
solvent that is used to dilute the NLPs, the smaller the resulting
NLP assembly populations will be.
[0045] In one embodiment, nanolipid particles having ethanol
encapsulated at a concentration of 5.0%-8.0%, is added to base
ingredients for gelato. This gelato mixture is then frozen by a
commercially acceptable process to produce a frozen gelato for
consumption.
Example 1
[0046] Frozen alcohol-containing gelatos which have been prepared
by the claimed method of the invention include the following:
TABLE-US-00001 Gelato Flavor % Alcohol by volume Raspberry Cream
8.0% Orange Cream (Grand Marnier .TM.) 8.0% Bourbon Vanilla
5.0%
[0047] In another embodiment, nanolipidic particles having ethanol
encapsulated at a concentration of 5.0% are added to base
ingredients for a sorbet or frozen beverage. This sorbet or frozen
beverage mixture is then frozen by a commercially acceptable
process to produce a frozen sorbet, pops, or beverage for
consumption. Ice pops and other frozen products of a similar nature
can be prepared by the same method.
Example 2
[0048] Frozen alcohol-containing sorbets, pops, and beverages can
be been prepared by the claimed method of the invention include the
following:
TABLE-US-00002 Sorbet or Beverage Flavor % Alcohol by volume Pina
Colada 5.0% Mojito 5.0% Strawberry Margarita 5.0% Apple Martini
5.0%
[0049] In yet another embodiment, nanolipid particles having
ethanol encapsulated at a concentration of up to 15.0% is added to
base ingredients for a syrup or topping for a frozen dessert.
Example 3
[0050] Alcohol-containing syrups and toppings for frozen desserts
which have been prepared by the claimed method of the invention
include the following:
TABLE-US-00003 Syrup or Topping Flavor % Alcohol by volume Caffe
(Kahlua .RTM.) 15.0% Chocolate Mint 15.0% Caramel 15.0% Raspberry
15.0% Grand Marnier .RTM. 15.0% Limoncello 15.0%
Stability of NLPs in Commercially Available Alcoholic Beverage
Products
[0051] NLPs (1:10 Precursor to Ethanol, volume/volume) were
prepared and diluted 1:10 (NLP volume/volume) in commercially
available alcoholic beverage products and stored for one week at
Room Temperature. After one week the mixtures were vortexed,
diluted 1:10 (volume/volume) in distilled water, and the size of
the NLPs were analyzed using a Zetasizer 1000 (Malvern
Instruments). The results of the stability study were as
follows:
TABLE-US-00004 Citron .RTM. Vodka 1:10 NLP 150 nm Malibu .RTM.
Coconut Rum 1:10 NLP 130 nm Beefeater .RTM. Gin 1:10 NLP 150 nm
Stability of NLPs in 100 Proof (50% volume/volume in Distilled
Water) Ethanol Mixtures
[0052] NLPs (1:10 and 1:20 Precursor to Ethanol, volume/volume)
were prepared and diluted 1:10 in 100 proof mixtures of ethanol and
water (50% ethanol, volume/volume). The samples were placed in a
commercial freezer for 14 days, removed, allowed to thaw and warm
to Room Temperature. Both samples were homogenous and optically
clear, without any precipitation. The samples were vortexed and the
size of the NLPs were determined using a Zetasizer 1000 (Malvern
Instruments). The results of the analyses were:
TABLE-US-00005 100 Proof Ethanol in Distilled Water Containing NLPs
1:10 NLP 163 nm 1:20 NLP 142 nm
Stability of NLPs after Repeated Freeze Thaw Stored in 25 Proof
Ethanol in Distilled Water
[0053] NLPs (1:5, 1:10 and 1:20 Precursor to Ethanol volume/volume)
were prepared and added 1:10 (volume/volume) into solutions of 25
Proof Ethanol in Distilled Water (12.5% Ethanol in Distilled Water,
volume/volume). All mixtures were optically clear. The initial size
of the NLPs and subsequent size analyses conducted on days 7, 14
and 21 were performed using a Zetasizer 1000 (Malvern Instruments).
After the initial size determinations the samples were placed into
a commercial freezer for intervals of 7 days. On days 7, 14 and 21
the samples were removed from the freezer allowed to thaw and warm
to Room Temperature.
[0054] They were vortexed and subjected to size analyses after
which they were returned to the commercial freezer. At days 7, 14
and 21 all preparations after equilibrating to Room Temperature
were optically clear and free of any precipitation. The results of
the size analyses were:
TABLE-US-00006 NLP Time 0 7 Days 14 Days 21 Days 1:5 156 nm 160 nm
167 nm 162 nm 1:10 77 nm 82 nm 92 nm 94 nm 1:20 105 nm 100 nm 106
nm 116 nm
[0055] The NLPs and NLP assembly populations can also be used to
formulate a delivery vehicle for pharmaceuticals, such as
analgesics, as an admixed passenger with the NLPs with encapsulated
ethanol. The admixed passenger loaded NLPs can then be mixed with
ingredients suitable for making a frozen food product. The loaded
NLP-frozen food ingredient mixture can be frozen in a form such as
an ice pop to provide a delivery vehicle for the encapsulated
ingredients. One practical application of such a delivery device
would be in the treatment of sore throats in individuals.
[0056] The examples of ethanol encapsulation in NLPs and NLP
assemblies presented herein, are representative examples only. The
method of the invention is applicable to other types of ethanol
containing substances and these examples are not meant to
constitute the entire range of ethanol-containing substances that
may be used in the method disclosed herein.
* * * * *