US 20080207748A1

(19) United States

(12) Patent Application Publication (10) Pub. No.: US 2008/0207748A1
Perez (43) Pub. Date: Aug. 28, 2008
(54) VITAMINC PREPARATION filed on Mar. 2, 2007, provisional application No.
60/904,593, filed on Mar. 2, 2007.
(75) Inventor: Pedro P. Perez, Mount Sinai, NY
(US) Publication Classification
Correspondence Address: (51) Int. Cl.
DARBY & DARBY P.C. A 6LX 3L/375 (2006.01)
P.O. BOX 770, Church Street Station A6IP 25/00 (2006.01)
New York, NY 10008-0770 (52)
52) U.S. Cl. ........................................................ S14/474
(73) Assignee: INNOVATION LABS, INC.,
Mount Sinai, NY (US) (57) ABSTRACT
(21) Appl. No.: 12/035,987 The present invention relates to vitamin C preparations which
enhance absorption of vitamin C into cells, and prolong the
(22) Filed: Feb. 22, 2008 retention of vitamin C within the blood plasma and tissue of
O O mammals, such as humans. The vitamin C preparations of the
Related U.S. Application Data present invention include lipophilic molecules which
(60) Provisional application No. 60/902,762, filed on Feb. improve the absorption of vitamin C resulting in higher
22, 2007, provisional application No. 60/904,468, plasma and cellular levels.

6O

3O

O
60 90 120
Time(minutes)
Patent Application Publication Aug. 28, 2008 Sheet 1 of 2 US 2008/02O7748A1

Figure 1

mid- PWC
6O

3O

O 30 60 90 120
Time(minutes)

Figure 2

100

5O

1 2.5 5 10 20
Lipid metabolized vitamin C(ug/ml)
Patent Application Publication Aug. 28, 2008 Sheet 2 of 2 US 2008/02O7748A1

Figure 3

4O

O 12 24
Time (hours)

Figure 4
60

3O

AA CaA EsterC PWC

US 2008/02O7748 A1 Aug. 28, 2008

VITAMIN C PREPARATION present in an amount of at least 0.01% by weight. The vitamin

C preparation is preferably in the form of an oral dosage form,
Such as a tablet or capsule.
0001. The present application claims the benefit of (i) U.S. 0011 Preferably, the amount of the lipophilic molecules
Provisional Application No. 60/902.762, filed Feb. 22, 2007, in the vitamin C preparation ranges from 0.1 or 0.2 to 5% by
(ii) U.S. Provisional Application No. 60/904,468, filed Mar. weight, based upon the total weight of the preparation.
2, 2007, and (iii) U.S. Provisional Application No. 60/904, According to one preferred embodiment, the vitamin C
593, filed Mar. 2, 2007, all of which are hereby incorporated preparation contains about 0.8 to about 1.8% by weight of the
by reference. lipophilic molecules and even more desirably about 1 to about
1.5% by weight of the lipophilic molecules.
FIELD OF THE INVENTION 0012. The vitamin C preparation can be administered to a
0002 The present invention relates to vitamin C prepara person to (i) promote a healthy nervous system, (ii) prevent or
tions having enhanced bioavailability. decrease the risk of developing a neurodegenerative disease,
(iii) enhance NGF-mediated neurite outgrowth, (iv) promote
BACKGROUND OF THE INVENTION wound healing, (v) enhance fibroblast adhesion to and the
interaction with the extracellular matrix, (vi) protect the
0003. According to the National Institute of Health and the immune system from Xenobiotics, (vii) decrease the risk of
Food and Nutritional Board of the National Academy of developing an oxidative pathogenesis, and (viii) decrease the
Science, vitamin C is an essential nutrient involved in many risk of developing cancer, cardiovascular diseases, athero
biological functions. Vitamin C can only be acquired through Sclerosis, and other age-related diseases associated with cyto
diet (i.e., food or nutritional Supplement). toxic, genotoxic, and proinflammatory mechanisms. Accord
0004 Vitamin C has been implicated as an important ing to one embodiment, the method includes:
dietary component as it is required for physiological and 0013 (a) recognizing the vitamin C preparation as being
metabolic activities including the development of healthy effective for one of the aforementioned purposes (e.g., to
neurons (Zhou et al., 2003; Weeks & Perez, 2007), prevention promote a healthy nervous system) and optionally that the
of neurodegenerative diseases (Boothby & Doering, 2005; person is in need thereof, and
Landmark 2006), wound healing (Kaplanet al., 2004: Mari 0014 (b) after such recognition, orally administering to
onnet C et al., 2006; Weeks & Perez, 2007), and the mainte the human an effective amount of the vitamin C preparation.
nance of a healthy immune system (Fayet al., 1994; Lehr et
al., 1994; Weeks & Perez, 2007). BRIEF DESCRIPTION OF THE DRAWINGS
0005 Given the importance of vitamin C, the bioavailabil
ity of vitamin C has been the focus of intense research. An 0015 FIG. 1 is a graph of the concentration of vitamin C in
improvement in absorption and retention of vitamin C in H9 human T-cells as measured 15-120 minutes following
blood plasma or tissue would increase the beneficial effects of administration of the vitamin C preparation of Example 1
Vitamin C. Thus, there is a continuing need for vitamin C (PWC), ascorbic acid (AA), calcium ascorbate (CaA), or
preparations having enhanced bioavailability. calcium ascorbate-calcium threonate-dehydroascorbate (ES
ter-C) (commercially available as Ester-C(R) from Nature's
SUMMARY OF THE INVENTION Value of Coram, N.Y.) (Ester-C(R).
0016 FIG. 2 is a graph of the percentage inhibition of
0006. The present invention relates to vitamin C prepara 1,1-diphenyl-2-picryl hydrazyl (DPPH) reduction as mea
tions which enhance absorption of vitamin C into cells, and sured by the procedure described in Example 4 following
prolong the retention of vitamin C within the blood plasma administration of 1, 2.5, 5, 10, or 20 g/ml of the vitamin C
and tissue of mammals, such as humans. The vitamin C preparation of Example 1.
preparations of the present invention include lipophilic mol 0017 FIG. 3 is a graph of the percentage of cells exhibit
ecules which improve the absorption of vitamin Cresulting in ing neurite outgrowth over 24 hours following administration
higher plasma and cellular levels. of vehicle (-) or 0.5 LM of the vitamin C preparation of
0007. One embodiment of the invention is a vitamin C Example 1 (PWC), ascorbic acid (AA), calcium ascorbate
preparation comprising: (CaA), or calcium ascorbate-calcium threonate-dehy
0008 (a) at least about 90% by weight of vitamin C, droascorbate (EsterC) or a control, as measured by the pro
0009 (b) at least about 0.1% by weight of lipophilic cedure described in Example 5.
molecules comprising (i) one or more Saturated Straight 0018 FIG. 4 is a graph showing the percentage of fibro
Co-C fatty alcohols, (ii) one or more unsaturated (D-9 blasts adhered to fibronectin substrates following administra
Cs-C fatty acids, (iii) optionally one or more Satu tion of vehicle (-) or 50 uM of the vitamin C preparation of
rated straight Ca-Co fatty acids, (iv) optionally one or Example 1 (PWC), ascorbic acid (AA), calcium ascorbate
more unsaturated (0-3 C-C fatty acids, and (v) (CaA), or calcium ascorbate-calcium threonate-dehy
optionally one or more unsaturated co-6 Cs-C fatty droascorbate (EsterC) or a control as measured by the proce
acids; and dure described in Example 6.
0010 (c) optionally at least about 0.1% by weight of
bioflavonoids, DETAILED DESCRIPTION OF THE INVENTION
based upon 100% total weight of the vitamin C preparation.
The preparation preferably comprises at least 0.1% by weight Definitions
of component (b)(i) (e.g., about 0.5 to about 4% by weight of 0019. The term “vitamin C. unless otherwise stated,
component (b)(i)), and at least 0.01% by weight of compo refers to ascorbic acid and pharmaceutically acceptable salts
nent (b)(ii), and when the preparation includes one or more of thereof, including, but not limited to, mineral salts of ascorbic
components (b)(iii)-(b)(V), each included component is acid, effervescent vitamin C (e.g., a combination of ascorbic
US 2008/02O7748 A1 Aug. 28, 2008

acid, citric acid and sodium bicarbonate), chelates of ascorbic 0060 about 0.1-0.9% behenic acid,
acid, and alkaline salts of ascorbic acid. 0061 about 0.1-0.9% tricosanoic acid,
0062) about 0.01-0.9% lignoceric acid,
Lipophilic Molecules 0063 about 0.05-0.9% cerotic acid,
0020 Suitable lipophilic molecules include, but are not 0064 about 0.1-1.0% heptacosanoic acid,
limited to, those derived from natural waxes such as, but is not 0065 about 0.05-1.5% montanic acid,
limited to, Sugar cane wax, rice bran wax, carnauba wax, 0.066 about 0.2-2.6% melissic acid,
candelilla wax, japan wax, ouricury wax, bayberry wax, shel 0067 about 0.05-1.6% docosahexaenoic acid,
lac wax, Sunflower wax, orange wax, and beeswax. Accord 0068 about 0.05-0.9% docosapentaenoic acid,
ing to one preferred embodiment, the lipophilic molecules are 0069 about 0.05-1.9% docosatetraenoic acid,
derived from rice bran wax, carauba wax, cadelilla wax, and 0070 about 0.05-0.9% docosadienoic acid,
beeswax. According to a more preferred embodiment, the (0071 about 0.01-1.8% erucic acid,
lipophilic molecules are derived from rice bran wax. Suitable 0072 about 0.01-0.09% nervonic acid,
lipophilic molecules extracted from natural waxes include, 0073 about 0.01-8.0% cetyl alcohol-hexadecanol-palmi
but are not limited to, palmitic acid, linoleic acid, linolenic tyl alcohol,
acid, oleic acid, and steric acid. (0074) about 0.01-5.0% 1-heptadecanol,
0021. According to one preferred embodiment, the vita (0075 about 0.01-1.0% 1-eicosanol-arachidyl alcohol,
min C preparation includes one or more or all of the following (0076 about 0.01-3.0% 1-docosanol-behenyl alcohol,
lipophilic molecules at the recited weight ratios: 0077 about 1.0-15.0% lignoceryl alcohol-1-tetracosanol,
0022 about 0.1-3.0 units (by weight) palmitic acid, 0078 about 1.0-12.0% 1-hexacosanol-ceryl alcohol,
0023 about 0.1-20.0 units linoleic acid, (0079 about 0.01-2.0% 1-heptacosanol,
0024 about 0.1-6.0 units alpha linolenic acid, 0080 about 0.5-20.0% 1-octacosanol,
0.025 about 0.1-4.0 units oleic acid, I0081 about 15.0-40.0% 1-triacontanol-melissyl alcohol,
0026 about 0.1-8.0 units steric acid, 0082 about 10.0-20.0% dotriacontanol, and
0027 about 0.1-0.9 units arachidic acid, I0083) about 5.0-15.0% tetratriacontanol, based upon
0028 about 0.1-0.9 units heneicosanoic acid, 100% total weight of the lipophilic molecules in the vitamin
0029 about 1.0-9.0 units behenic acid, C preparation.
0030 about 1.0-9.0 units tricosanoic acid, I0084. The mixture of lipophilic molecules can be obtained
0031) about 0.1-9.0 units lignoceric acid, by (1) saponification of a wax (e.g., a natural wax), (2) solidi
0032 about 0.5-9.0 units cerotic acid, fying and grinding the saponified wax to a do less than 2000
0033 about 1.0-10.0 units heptacosanoic acid, microns (e.g., 100-500 microns or 500-2000 microns), (3)
0034 about 0.5-15.0 units montanic acid, extracting the ground material with acetone or an alcohol
0035 about 2.0-26.0 units melissic acid, (e.g., ethanol or isopropanol), and (4) optionally solidifying
0.036 about 0.5-16.0 units docosahexaenoic acid, and grinding the extracted material to a do less than 2000
0037 about 0.5-9.0 units docosapentaenoic acid, microns (e.g., 100-500 microns or 500-2000 microns).
0038 about 0.5-19.0 units docosatetraenoic acid, I0085. The natural waxes undergo saponification or
0.039 about 0.5-9.0 units docosadienoic acid, hydrolysis before the extraction procedure. For saponifica
0040 about 0.1-18.0 units erucic acid, tion, the natural waxes are heated using a jacketed kettle at
0041 about 0.1-0.9 units nervonic acid, 90°C. for 3 hours until the wax was completely melted, KOH
0042 about 0.1-80.0 units cetyl alcohol-hexadecanol is added, and the mixture is held at 90° C. for 1 hour with
palmityl alcohol, stirring. For hydrolysis, the natural waxes are heated using a
0043 about 0.1-50.0 units 1-heptadecanol, jacketed kettle at 90° C. for 3 hours until the wax was com
0044) about 0.1-10.0 units 1-eicosanol-arachidyl alcohol, pletely melted, Sulfuric acid aqueous solution is added, and
0045 about 0.1-30.0 units 1-docosanol-behenyl alcohol, mixture is held at 90° C. for 1 hour with stirring. After 1 hour
0046) about 10.0-150.0 units lignoceryl alcohol-1-tetra of stirring the Saponified or hydrolyzed wax is poured into
cosanol, cart trays and dried at 21.1° C. before undergoing the extrac
0047 about 10.0-120.0 units 1-hexacosanol-ceryl alco tion procedure.
hol, I0086. The extraction of the natural waxes may be per
0048 about 0.1-20.0 units 1-heptacosanol, formed by either dispersed-solids extraction or immersion
0049 about 5.0-200.0 units 1-octacosanol, type percolation extraction. For the dispersed-solids extrac
0050 about 150.0-400.0 units 1-triacontanol-melissyl tion, the natural waxes are ground to a particle mesh size of
alcohol, 100 to 425 microns and subjected to liquid extraction in a
0051 about 100.0-200.0 units dotriacontanol, and dispersed-solids extraction system. In the case of immersion
0052 about 50.0-150.0 units tetratriacontanol. type percolation extraction, the natural waxes are ground to a
In one embodiment, the vitamin C preparation includes one or particle mesh size of 500 to 2000 microns and subjected to
more orall of the following lipophilic molecules at the recited liquid extraction in a solid-liquid immersion type percolating
weight percentages: extractor System. In both types of extraction equipment, the
0053 about 0.01-0.3% (by weight) palmitic acid, natural mixture of aliphatic alcohols, Saturated fatty acids,
0054 about 0.01-2.0% linoleic acid, and omega-3, omega-6, omega-9 fatty acids is selectively
0055 about 0.01-0.6% alpha linolenic acid, extracted with adequate hot organic solvents such as acetone
0056 about 0.01-0.4% oleic acid, and ethanol with a temperature range of 55° C. to 75°C. The
0057 about 0.1-0.8% steric acid, extractions are purified with hot organic solvents such as
0058 about 0.01-0.09% arachidic acid, hexane, heptane, and acetone; recovered; and dried. The
0059 about 0.01-0.09% heneicosanoic acid, extractions contain a mixture of aliphatic alcohols having 17
US 2008/02O7748 A1 Aug. 28, 2008

to 34 carbon atoms, saturated fatty acids having 16 to 30 0110. According to another embodiment, the vitamin C
saturated carbon atoms, and omega-3, omega-6, omega-9 preparation includes about 200 to 40,000 IU vitamin C.
fatty acids with melting point between 70 and 80°C. The ratio
of the natural wax particles to hot liquid extractants is from 1 Dosage Forms
to 4 and 1 to 10. According to one preferred embodiment, the 0111. The vitamin C preparation is preferably in the form
extractions with hot organic solvents at 60°C., and the ratio of of an oral dosage form, such as beads, pellets, granules,
natural wax particles to hot liquid extractants is 1 to 8. capsules (soft or hard), Sachets, tablets, powders, dispersible
Bioflavonoids
powders capable of effervescing upon addition of water,
aqueous or oily suspensions, emulsions, syrups, elixirs, or
0087 Suitable bioflavonoids include, but are not limited lozenges. For example, the oral dosage form can bean chew
to, rutin, naringin, hesperidin, neohesperidin, neohesperidin able tablet or gum, oral liquid dosage form, Such as a Suspen
dihydrochalcone, maringenin, hersperitin, nomilin, and gallic sion in an aqueous or non-aqueous liquid solution, or an
acid. According to one preferred embodiment, the vitamin C emulsion which can be a soft drink, tea, milk, coffee, juice,
preparation contains hesperidin, gallic acid, and optionally sports drink, or water. The vitamin C preparation can also be
other bioflavonoids. incorporated into various products, such as nutritional
0088 According to one preferred embodiment, the vita Supplements (including vitamins and multi-vitamins), foods
min C preparation includes one or more or all of the following (including health food products such as nutrition bars), and
bioflavonoids at the recited weight ratios: drinks (including fruit juices such as energy drinks).
0112 Generally, the daily dosage of the vitamin C prepa
I0089 about 20-120 units (by weight) rutin, ration on a vitamin C weight basis can range from 30 mg to 2
0090 about 25-100 units naringin, g. For instance, the daily dosage can be 60 mg to 1 g or 60 mg
0091) about 7000-20000 units hesperidin, to 500 mg. Desirably, the daily dosage ranges from 60 mg to
0092) about 5-100 units neohesperidin, 500 mg (e.g., the daily dosage can be 400 mg). According to
0093 about 10-100 units neohesperidin dihydrochalcone, one preferred embodiment, the daily dosage ranges from 60
0094) about 5-100 units naringenin, mg to 200 mg (e.g., the daily dosage can be 60, 100, or 200
0095 about 5-100 units hersperitin, mg). The daily dose can be achieved by administration of a
0096 about 50-150 units nomilin, and single dosage form of the invention or alternatively, two or
0097 about 120,000-1,000,000 units gallic acid. more such dosage forms. Preferably, the daily dose is
In one embodiment, the vitamin C preparation includes one or achieved by administration of only one or two dosage forms
more or all of the following bioflavonoids at the recited (e.g., once daily dosing or b.i.d.). Therefore, the present
weight percentages: invention includes, but is not limited to, dosage forms con
0098 about 20-120 ppm rutin, taining 30, 60, 100, 200, 400, 500, or 1000 mg of the vitamin
C preparation (on a vitamin C weight basis).
0099 about 25-100 ppm naringin, 0113. The vitamin C preparation may include one or more
0100 about 7000-20000 ppm hesperidin, excipients or additives. Suitable excipients and additives
0101 about 5-100 ppm neohesperidin, include, but are not limited to, additional antioxidants (e.g.,
0102) about 10-100 ppm neohesperidin dihydrochalcone, phenolic compounds), inert diluents (such as lactose, sodium
0103) about 5-100 ppm maringenin, carbonate, calcium phosphate, and calcium carbonates),
0104 about 5-100 ppm hersperitin, granulating and disintegrating agents (such as corn starch and
0105 about 50-150 ppm nomilin, and algenic acid), binders (such as starch), lubricants (such as
0106 about 120-1000 mg/g gallic acid, magnesium Stearate, Stearic acid and talc), preservatives
(such as ethyl or propyl p-hydroxybenzoate), colorants, fla
based on 1 g of the bioflavonoid mixture. Voring agents, release modifying agents, thickeners, and any
0107 According to one embodiment, the vitamin C prepa combination of any of the foregoing. Suitable antioxidants
ration includes vitamin C and the lipophilic molecules at a include, but are not limited to, bioflavonoids, flavonoids, fla
weight ratio ranging from about 1000:1 to about 10:1. Vonols, flavanones, flavones, flavonals, flavanolols, and fla
According to a preferred embodiment, the weight ratio ranges Vanols.
from about 100:1 to about 8:1. 0114 Suitable inert solid diluents include, but are not lim
0108. According to a preferred embodiment, the vitamin ited to, calcium carbonate, calcium phosphate and kaolin.
C preparation includes at least about 90% by weight of vita Suitable diluents for soft capsules include, but are not limited
min C and about 0.1% by weight of the lipophilic molecules to, water and oils such as peanut oil, liquid paraffin, corn oil,
based upon 100% total weight of the vitamin C preparation. wheat germ oil, soybean oil, and olive oil.
More preferably, the vitamin C preparation includes from 0115 Aqueous Suspensions or dispersions contain the
about 90 to about 99% by weight of vitamin C and from about Vitamin C preparation, for example, in fine powder form
1 to about 8% by weight of lipophilic molecules. According to together with one or more Suspension or dispersion (or wet
another embodiment, the Vitamin C preparation includes ting) agents. Suitable Suspension agents include, but are not
from about 90 to about 98% by weight of vitamin C and from limited to, sodium carboxymethylcellulose, methylcellulose,
about 2 to about 7% (e.g., about 5%) by weight of lipophilic hydroxypropylmethylcellulose, sodium alginate, polyvinyl
molecules. pyrrolidone, gum tragacanth and gum acacia. Suitable dis
0109 According to a preferred embodiment, the vitamin persing or wetting agents include, but are not limited to,
C preparation includes at least about 90% by weight of vita lecithin, condensation products of an alkylene oxide with
min C, from about 0.1 to about 9% by weight of lipophilic fatty acids, condensation products of ethylene oxide with
molecules, and from about 0.1 to about 5% by weight of long chain aliphatic alcohols, condensation products of eth
bioflavonoids. ylene oxide with partial esters derived from fatty acids and a
US 2008/02O7748 A1 Aug. 28, 2008

hexitol Such as polyoxyethylene Sorbitol monooleate, or con tioned so that the vitamin C preparation is released in a
densation products of ethylene oxide with partial esters therapeutically effective amount to a targeted site such as a
derived from fatty acids and hexitol anhydrides. diseased or injured tissue or organ. The device can be intro
0116 Dispersible powders and granules suitable for duced temporarily or permanently into a mammal (e.g., a
preparation of an aqueous Suspension by the addition of water human) for the prophylaxis ortherapy of a medical condition,
contain the vitamin C preparation, for example, together with or to augment the immune system. The device can be intro
a dispersing agent, Wetting agent, or Suspending agent. Suit duced subcutaneously, percutaneously, or Surgically. The
able dispersing agents, wetting agents, and Suspending agents medical device can be selected from Stents, synthetic grafts,
include those mentioned above. artificial heart valves, artificial hearts and fixtures to connect
0117 Oily suspensions may be formulated by suspending the prosthetic organ to the vasculature, venous valves,
the vitamin C preparation in an oil. Such as an vegetable oil or abdominal aortic aneurysm grafts, inferior venal caval filters,
a mineral oil. The oily Suspensions may also contain a thick catheters including permanent drug infusing catheters, embo
ening agent such as carnauba wax, candelilla wax, rice bran lic coils, embolic materials used in vascular embolization
wax, beeswax, hard paraffin, or cetyl alcohol. mesh repair materials, a Dracon Vascular particle orthopedic
0118. The vitamin C preparation may be in the form of an metallic plates, rods, screws, and vascular Sutures.
oil-in-water emulsion. The oily phase may be a vegetable I0123. The vitamin C preparation may be formulated to
based oil or a mineral based oil. Suitable emulsifying agents provide immediate release or controlled release (e.g., Sus
include, for example, naturally occurring gums such as acacia tained release) of the vitamin C preparation, for example, to
and tragacanth gum, naturally occurring phosphatides such as provide effective doses of vitamin Cover extended periods of
soybean, lecithin, esters and partial esters derived from fatty time to prolong the biological activity and beneficial bio
acids and hexitol anhydrides and condensation products of chemical functions of vitamin C. One embodiment of the
partial esters with ethylene oxide, Such as polyoxyethylene invention is a controlled release dosage form (such as a solid
Sorbitan monooleate. dosage form) containing about 200 to 40,000 IU vitamin C,
0119 Syrups and elixirs may be formulated with Sweet about 1 to 100 mg of lipophilic molecules, and 1 to 500 mg of
ening agents such as glycerol, propylene glycol, Sorbitol, bioflavanoids. For example, the controlled release dosage
aspartame, or Sucrose, and may also contain a demulcent, form may release about 10 to about 35% by weight of the total
preservative, flavoring, or coloring agent. vitamin C preparation within about 2 hours in an in vitro
0120. The vitamin C preparation may be also in a form dissolution test, and about 40 to about 70% by weight of the
suitable for administration by inhalation (e.g., as a finely total vitamin C preparation within about 8 hours. According
divided powder or a liquid aerosol), or for parenteral admin to another embodiment, the controlled release dosage form
istration (e.g., as a sterile aqueous or oily solution for intra may release about 50% by weight of the total vitamin C
venous, Subcutaneous, intramuscular dosing or as a Supposi preparation within about 2 hours in an invitro dissolution test,
tory for rectal dosing). Administration of the vitamin C and more than 90% by weight of the total vitamin C prepa
preparation by these non-oral routes avoids gastrointestinal ration within about 6 or 8 hours. Any type of controlled
side effects, which may accompany high doses of vitamin C release system known in the art can be used. The in vitro
released in the stomach. dissolution test is conducted using the Basket Method (Appa
0121 The vitamin C preparation can also be delivered ratus 1) with 900 ml 0.1N HCl as the medium run at 100 RPM
topically, for example, to protect the skin from free radicals, at a temperature of 37°C. The samples are filtered through
promote wound healing (for instance, for healing cuts, abra Whatman filter paper #1 and the amount of vitamin C is
sions, Sun damage (e.g., Sunburn), wrinkles, and Scars), and/ calculated based on the equivalence to standard
or reduce inflammation. The vitamin C preparation of the dicholorophenol-indophenol solutions.
invention provides Superior penetration of vitamin C through 0.124 Solid controlled release dosage forms (e.g., tablets)
the skin than vitamin C alone. Transdermal delivery of the can beformulated (e.g., coated) so as to prolong the release of
Vitamin C preparation permits systemic delivery of the Vita the vitamin C preparation into the gastrointestinal tract, or to
min C while avoiding gastrointestinal side effects. The topical prevent the release of the vitamin C preparation in the stom
formulation containing the vitamin C preparation can be in ach in order to prevent or attenuate the gastrointestinal side
the form of a solution, Suspension, lotion, emulsion, oint effects which can accompany high doses of vitamin C
ment, cream, or gel. According to a preferred embodiment, released in the stomach. For example, the vitamin C prepa
the topical formulation is a cream or lotion. The formulation ration can be enteric coated so as to prevent significant release
may include additional active ingredients. These formula of the preparation in the stomach. Controlled release of the
tions may prepared by methods known in the art, and typically Vitamin C preparation can prolong therapeutic and/or immu
include a topically acceptable vehicle. One embodiment is a noprotective systemic concentrations of vitamin C in a per
topical formulation containing about 0.5 to about 25% by SO.
weight of the vitamin C preparation of the present invention, 0.125 One embodiment of the invention is a three layer
based upon 100% total weight of the topical formulation. For controlled release dosage form (e.g., a tablet) where each
instance, the topical formulation can contain 0.5-2%, 1-2%. layer contains a vitamin C preparation of the invention. The
1-5%. 1-10%, 5-15%, 5-20%, or 10-20% by weight of the Vitamin C preparation of each layer can be the same or dif
Vitamin C preparation. ferent. At least one of the layers provides controlled release of
0122) The vitamin C preparation could be used to coat a the vitamin C preparation. For example, the dosage form can
medical device that is then positioned to a desired target include (i) a first layer, (ii) a second layer, and (ii) an outer
location within the body, whereupon the vitamin C prepara layer Surrounding the first and second layers, where the first
tion elutes from the medical device. Preferably, the coating layer and outer layer provide controlled release of the vitamin
includes a therapeutically effective amount of the vitamin C C preparation(s) and the second layer provides immediate
preparation. In one embodiment, the medical device is posi release of the vitamin C preparation.
US 2008/02O7748 A1 Aug. 28, 2008

0126. According to one preferred embodiment, the outer Preparation of the Vitamin C Preparation:
layer releases substantially all (>90%) of the vitamin C prepa
ration in a controlled manner within 60, desirably 30, and 0.134 Ajacketed mixer was charged withdry powder of 58
even more desirably 20 minutes, as determined by the afore kg of vitamin C, 0.75 kg of the lipid metabolites prepared
mentioned in vitro dissolution test. The second layer provides above and 1.5 kg of bioflavonoids (AnMar International Ltd;
immediate release of the vitamin C preparation contained Bridgeport, Conn.). The mixer was then turned on (agitation
therein. Finally, the first layer releases the vitamin C prepa is initiated plows) to create a homogenous mixture of dry
ration contained therein in a controlled manner over at least 6 powder. The high speed shearing devices (choppers) were
hours (e.g., Substantially of the vitamin C preparation may be initiated for 1 minute. Hot water was then pumped through the
released within 6-10 hours or 6-8 hours), as determined by the jacket of the mixer to heat the mixture to 80°C. with continu
aforementioned in vitro dissolution test. ous mixing (plows only) for 15 minutes for complete encap
0127 Transdermal patch devices can also provide con Sulation. The encapsulated mixture was cooled by running
trolled administration (e.g., continuous or other Sustained chilled water (10° C.) through the jacket under continuous
administration) of the vitamin C preparation. Methods for mixing for 1 hour until a free-flowing powder was formed.
preparing controlled release transdermal formulations are The powder was discharged into a double polyethylene-lined
known in the art. For example, the transdermal device may container and then passed through a comminuting mill run
contain an impermeable backing layer which defines the ning at approximately 2500 rpm equipped with a 0.15 mm
outer Surface of the device and a permeable skin attaching screen. The milled powder was collected into appropriately
membrane, Such as an adhesive layer, sealed to the outer layer labeled, double polyethylene-lined drums and reconciled.
in Such a way as to create a reservoir between them wherein
the therapeutic agent is placed (e.g., a bandage or patch (in TABLE 1
cluding a time released patch)).
The formulation of a of the invention is shown below:
0128. Other suitable controlled release systems include,
but are not limited to, long-term Sustained implants, aqueous Ingredients Amount
or oily Suspensions, emulsions, syrups, elixirs, or lozenges,
chewable tablet or gum, foods, beverages, osmotic systems, Vitamin C 90-99%
and dissolution system (e.g., effervescent oral dosage form). Lipophilic Molecules O. 1-5%
palmitic acid 0.1-3.0 mg/g
0129. The vitamin C preparation of the present invention linoleic acid (O-6 fatty acid) 0.1-20.0 mgg
is preferably administered orally to a mammal (e.g., a alpha linolenic acid (c)-3 fatty acid) 0.1-6.0 mg/g
human), but it can also be administered by other routes of oleic acid (c)-9 fatty acid) 0.1-4.0 mgg
Stearic acid 0.1-8.0 mgg
administration, such as intravenously or Subcutaneously. arachidic acid 0.1-0.9 mgg
heneicosanoic acid 0.1-0.9 mgg
Preparation of Formulation behenic acid 1.0-9.0 mgg
tricosanoic acid 1.0-9.0 mgg
lignoceric acid 0.1-9.0 mgg
0130. The vitamin C preparation of the present invention cerotic acid 0.5-9.0 mg/g
may be prepared by methods well known in the art, such as heptacosanoic acid 1.0-10.0 mgg
mixing the vitamin C, lipophilic molecules, optionally biofla montanic acid
melissic acid
0.5-15.0 mg/g
2.0-26.0 mgg
Vanoids, and any desired excipients. Docosahexaenoic acid (DHA) (c)-3 fatty acid) 0.5-16.0 mg/g
0131 The following examples illustrate the invention docosapentaenoic acid (DPA) (c)-3 fatty acid) 0.5-9.0 mg/g
without limitation. Docosatetraenoic acid (DTA) (c)-6 fatty acid) 0.5-19.0 mg/g
docosadienoic acid (co-6 fatty acid) 0.5-9.0 mg/g
erucic acid (O-9 fatty acid) 0.1-18.0 mgg
EXAMPLE1 nervonic acid (c)-9 fatty acid) 0.1-0.9 mgg
cetyl alcohol-hexadecanol-palmityl alcohol 0.1-80.0 mg/g
1-heptadecanol 0.1-50.0 mg/g
Lipid Metabolite Extraction: 1-eicosanol-arachidyl alcohol 0.1-10.0 mgg
0132 Saponification: 25 kg of rice bran wax was heated 1-docosanol-behenyl alcohol 0.1-30.0 mgg
lignoceryl alcohol-1-tetracosanol 10.0-150.0 mg/g
using a jacketed kettle at 90° C. for 3 hours until the wax was 1-hexacosanol-ceryl alcohol 10.0-120.0 mg/g
completely melted. 4.67 L of 8.0 M KOH (450 g/l) in water 1-heptacosanol 0.1-20.0 mgg
was slowly added with continuous stirring and heating. The 1-octacosanol
1-triacontanol-melissyl alcohol
5.0-200.0 mg/g
mixture was held at 90° C. for 1 hour with stirring. After 1 150.0-400.0 mg/g
Dotriacontanol 100.0-200.0 mg/g
hour the Saponified wax was poured into cart trays and dried Tetratriacontanol 50.0-150.0 mg/g
at 21.1° C. The 32.1 kg of cooled dried saponified wax was Bioflavonoids (optional) O. 1-5%
then ground to a powder (100-425 or 500-2000 microns). Rutin
Naringin
20-120
25-100
ppm *
ppm
0.133 Extraction: 9.6 kg of the saponified wax was placed Hesperidin 7000-20000 ppm
in 8 extraction thimbles (1.2 kg of saponified wax per extrac Neohesperidin 5-100 ppm
tion thimble). 100 L of acetone were pumped into a 200 L neohesperidin dihydrochalcone 10-100 ppm
cylindrical-bottom flask and connected to a SOXhlet system. Naringenin 5-100 ppm
Hersperitin 5-100 ppm
The system was refluxed for approximately 24 hours, and the Nomilin 50-150 ppm
extract was pumped to a jacketed reactor. The extract was gallic acid At least 120 mg/g
chilled to approximately 10° C. with 20 rpm agitation (20 (q.S.)
rpm) for 10 hours. The chilled extract was then centrifuged in *mg/g = mg of component per g of total lipophilic molecules
a vertical basket centrifuge. The collected solid was poured **ppm or mg g = ppm or mg of component per g of total bioflavonoid mix
into trays and vacuum dried for 16 hours. The dried solid was ture
then ground to a powder.
US 2008/02O7748 A1 Aug. 28, 2008

EXAMPLE 2 pesticide mediated T-cell hyperactivation. Given that the for

mulation of the current invention has greater ability to prevent
0135. The rate of vitamin C absorption in H9 cells, a pesticide-induced T-cell aggregation than other vitamin C
human T-cell line, was determined for the formulation of formulations, Suggests that the formulation of the present
Example 1 and other vitamin C formulations. invention will provide greater protection against other delete
0.136 Cells from the human T-lymphoblastic H9 cell line rious Xenobiotics.
were starved of vitamin C for 18 hours in serum-free media
and subsequently suspended in 50 uM of (1) ascorbic acid TABLE 2
(AA), (2) calcium ascorbate (CaA), (3) calcium ascorbate
calcium threonate-dehydroascorbate (commercially avail The vitamin C preparation of Example 1 inhibits xenobiotic
induced homotypic aggregation in human T-lymphocytes more
able as Ester-C(R) from Nature's Value of Coram, N.Y.) (Ester effectively than calcium ascorbate-calcium
C(R), or (4) the vitamin C preparation of Example 1 (PWC). threonate-dehydroascorbate Ester-C(R).
At the times indicated in FIG. 1, cells were harvested and Activators of T-cell Aggregation
measured for vitamin C and protein content. The cellular Wit. CAdded None PHA Bifenthrin
vitamin C levels of the cells were measured using the 2,4-
dinitrophenylhydrazine spectrophotometric technique None 105 1701S 3OO 13
(Bessey et al., 1947). AA
CaA
94
124
7S 12
110 - 10
1305
1378
0137. Over a two hour period, the level of vitamin C EsterC 82 12O 17 2008
uptake from Example 1 was consistently higher than that *PWC 11 6 2O 9 SO 10
observed with ascorbic acid, calcium ascorbate, and calcium
ascorbate-calcium threonate-dehydroascorbate (See FIG. 1).
At fifteen minutes, cellular vitamin C levels ranged from EXAMPLE 4
7+1.4 nmol/mg cellular protein with ascorbic acid, to over
double that amount (15+2.4 nmol/mg protein) with the vita
min C preparation of Example 1. The absorbed vitamin C 0143. The antioxidant and free radical scavenging activity
levels rose significantly with time, peaking at approximately was determined for the vitamin C preparation of Example 1
two hours with cellular levels ranging from 31 nmol/mg pro and known dietary antioxidants.
tein for ascorbic acid and 50 nmol/mg protein for the vitamin 0144 Briefly, 200 ml of a 1, 2.5, 5, 10, or 201g/ml solution
C preparation of Example 1. of the vitamin C preparation of Example 1 was mixed with 50
0138. In order for vitamin C to exert its beneficial effects, ul of a 659 uM 1,1-diphenyl-2-picryl hydrazyl (DPPH) solu
it must be taken up into the cell. To date, vitamin-C lipid tion and incubated at 25° C. for 20 minutes. Free radical
metabolites exhibits the greatest amount of vitamin Cuptake Scavenging activity of the vitamin C preparation of Example
and retention as compared to all other vitamin C formula 1 was measured by the reduction of 1,1-diphenyl-2-picryl
tions. hydrazyl (DPPH) to 1,1-diphenyl-2-picryl hydrazine at an
absorbance of 510 nm. The results are shown in FIG. 2.
EXAMPLE 3 0145 The vitamin C preparation dose dependently scav
enged DPPH free radicals. The vitamin C preparation dem
0.139. The ability to inhibit pesticide-induced T-lympho onstrated excellent scavenging ability by reducing the DPPH
cyte aggregation was determined for the formulation of induced free radical concentration by 93% at its maximum
Example 1 and other vitamin C formulations. concentration.
0140. The human T-lymphoblastic H9 cell line was incu 0146 The peroxyl radical oxygen reactive species
bated with vehicle (-) or with one of two activators of T-lym (ORAC) scavenging ability of the vitamin C preparation was
phocyte aggregation, phytohemagglutinin (PHA; 10 um) or also determined. The ORAC assay detects free radical dam
bifenthrin (10 mM). The cells were immediately treated with age to fluorescein induced by 2.2"-Asobix dihydrochloride
0.5 LM of (1) ascorbic acid (AA), (2) calcium ascorbate (AAPH; 153 mM), and the change is measured by fluores
(CaA), (3) calcium ascorbate-calcium threonate-dehy cence spectrophotometry. Antioxidants inhibit the free radi
droascorbate (Ester-C(R), or (4) the vitamin C preparation of cal range damage to the fluorescent compound and prevent
Example 1 (PWC) for 30 minutes at 37° C. After treatment, the reduction in fluorescence. The results are shown in Table
the ability of each formulation to inhibit homotypic aggrega 3. The results from different concentrations of the vitamin C
tion was measured by counting aggregate size at 400x mag preparation of Example 1 were compared to the known anti
nification. oxidant TroloxR). The ORAC results are expressed as
0141. The vitamin C preparation of Example 1, inhibited Trolox(R) equivalents (6-Hydroxy-2,5,7,8-tetramethylchro
the aggregation of the T-lymphocytes induced by the pesti man-2-carboxylic Acid; TE) per gram of sample.
cide PHA or the pesticide bifenthrin by 88% and 84% respec 0147 Vitamin C is a chemical reducing agent for many
tively (Table 2). The reduction in T-lymphocyte aggregation intracellular and extracellular reactions such as oxidative
was greater following treatment with the vitamin C prepara DNA or protein damage, low-density lipoprotein oxidation,
tion of Example 1 than any of the other formulations. lipid peroxidation, oxidants, the formation of nitrosamines in
0142 Leukocyte cell-cell adhesion is associated with gastric juice, extracellular oxidants from neutophils, and
Xenobiotic induced hyperactivation and inflammatory dam endothelium dependent vasodilation. The vitamin C prepara
age, and vitamin C has been shown to prevent cigarette tion of the present invention, which exhibits potent antioxi
Smoke-induced leukocyte aggregation and attachment to vas dant and free radical scavenging effects in vitro, can serve as
cular endothelium (Lehret al., 1994; Weber et al., 1996). As a good vitamin C preparation to prevent such damage thus
shown in Table 2, vitamin C has also been shown to reduce contributing to the protection against cancer, cardiovascular
US 2008/02O7748 A1 Aug. 28, 2008

diseases, atherosclerosis, and other age-related diseases EXAMPLE 6

caused by cytotoxic, genotoxic, and proinflammatory mecha
nisms. 0151. The ability to promote fibroblast adhesion to
fibronectin was determined for the formulation of Example 1
TABLE 3 and other vitamin C formulations.
ORAC values comparing the antioxidant activity of the vitamin C 0152 NIH3T3 fibroblastoma cells were seeded onto
preparation of Example 1 with known dietary antioxidants. fibronectin coated plates pretreated with either vehicle (-) or
Nutrient ORAC
various 50 mM of (1) ascorbic acid (AA), (2) calcium ascor
SOUCC (MTEg) Reference
bate (CaA), (3) calcium ascorbate-calcium threonate-dehy
droascorbate (Ester-C(R), or (4) the vitamin C preparation of
The vitamin C preparation 1343 Example 4 Example 1 (PWC). The plates were incubated for 15 minutes
of Example 1 at 37° C. The unattached cells were removed by aspiration
trial #1 1062
trial #21394 and the attached cells were fixed, stained, and counted in
trial #31402 triplicate. Results are shown in FIG. 4.
trial #41440 0153. The vitamin C preparation of Example 1 enhanced
Cinnamon 1243 Sua et al., 2007
Freeze-Dried 1027 Schauss et al., 2006 fibroblast adhesion to fibronectin by over three-fold. In addi
Acai tion to adhesion, fibroblast spreading on fibronectin is an
Green and 76.1.1 Prior and Cao, 1999 important next step to migration and wound healing perfor
black teas (235-1526) aCC.
Chokeberry 161 Wu et al., 2004
Broccoli 65.8 to 1216 Kurilich et al., 2002
Soft wheat 32-48 Moore et al., 2005 EXAMPLE 7
Careless 21 Wu et al., 2004
gooseberry
0154 The human serum vitamin C, plasma C-reactive
protein, oxidized LDL, and urine uric and oxalate levels were
determined for the formulation of Example 1 and other vita
EXAMPLE 5 min C formulations.
0155 Healthy volunteers maintained a low vitamin C diet
0148. The ability to promote neurite outgrowth was deter for 14 days. Following an overnight fast, Volunteers received
mined for the formulation of Example 1 and other vitamin C a single oral dose of 1000 mg or either (1) ascorbic acid (AA),
formulations. (2) calcium ascorbate (CaA), (3) calcium ascorbate-calcium
0149 PC12 cells were treated with 100 ng/ml of Nerve threonate-dehydroascorbate (commercially available as
Growth Factor (NGF) and incubated for a 24 hour period Ester-C(R) from Nature's Value of Coram, N.Y.) (Ester-CR)),
followed by treatment with either vehicle (-) or various 50LM or (4) the vitamin C preparation of Example 1 (PWC). Blood
of (1) ascorbic acid (AA), (2) calcium ascorbate (CaA), (3) samples were collected immediately prior to the oral dose
calcium ascorbate-calcium threonate-dehydroascorbate (ES administration and at various time points post ingestion.
ter-C(R), or (4) the vitamin C preparation of Example 1 Urine was collected over a 24-hour time period and saved for
(PWC). The formation of neurites were measured at hours 1, oxalate and uric acid assays. Serum vitamin C levels were
3, 6, 9, 12, and 24. The results are shown in FIG. 3. measured by HPLC with coulometric electrochemical detec
0150 PC12 cells responded to NGF treatment by extend tion. Plasma C-reactive protein and oxidized LDL were mea
ing neurites. The vitamin C preparation of Example 1 signifi sured by enzyme linked immunosorbent assay (ELISA) and
cantly enhanced the NGF-induced neurite outgrowth in 12% urine uric acid and oxalate levels were measured by enzy
of the cells by the first hour. In fact, the vitamin C preparation matic methods.
was the only formulation that resulted in a significant aug 0156 The vitamin C preparation of Example 1 is more
mentation of NGF-induced neurite outgrowth, Suggesting rapidly absorbed and leads to higher serum vitamin Clevels
that this is the only formulation that would aid in protection and greater reduction of plasma levels of inflammatory and
against neurodegenerative diseases. oxidative stress markers than other forms of vitamin C.

TABLE 4
Clinical data comparing the serum vitamin Clevels, plasma C-reactive protein,
oxidized LDL levels, and urine uric acid and oxalate levels of the vitamin C preparation
of Example 1 with other vitamin C formulations.
Serum Vitamin C Levels
(mg/dl)
Hrs Post-Admin:

Vitamin C O 1 2 4 6 24

AA O56 OO6 12 O.10 1.64 O.18 151 0.22 1460.13 O.80 O.O9
CaA O.S.O. O.OS O.88. O.10 1.12 O.17 1.03 - 0.13 1.O. O.13 O.59 O.O9
EsterC O56 O.O9 1.3 O.O8* 2.17 O.19* 1.54 - 0.14* 1.51 O.19* 0.85 0.08
1.22 + 0.11* 1.69 0.27 1.52 + 0.16* 1.17 0.12 O.73 O.O7
US 2008/02O7748 A1 Aug. 28, 2008

TABLE 4-continued
Clinical data comparing the serum vitamin Clevels, plasma C-reactive protein,
oxidized LDL levels, and urine uric acid and oxalate levels of the vitamin C preparation
of Example 1 with other vitamin C formulations.
Plasma C-Reactive Protein Plasma OxLDL Urine Markers
(ng ml) (U/ml) (mg/dl)
O 24 Change O 24 Change Uric Acid Oxalate

AA 129.75 - 26 117.00 33 12.75 68.78 6 67.89 S O.89 SO.85 8.8 18.82.7

CaA 18917 - 41 180.83 43 8.34 60.56 S 57.67 6 3.78 39.751O.S 17.82.6
EsterC 15230 19 128.60 - 19 23.7 62.56 S S7.3O4 S.26** 48.737.1 13.7 1.5
*PWC 2006338 18O.OO-52 20.63 50.51 - 4 48.20 4 2.31 40.96 7.O 17.91.9

*Statistically significant deference compared to Calcium Ascorbate. At one hour p = 0.0026 for PWC and p =
0.049 for Ester-C. At two hours, p = 0.0009. At four hours p = 0.0278 for PWC and 0.0477 for Ester C. At six
hours, p = 0.0470
**Statistically significant difference from Ascorbic Acid (p = 0.045). Note that the reductions in OxLDL were not
significantly different for any vitamin C Supplementation with a before-and-after comparison; however, the drop
observed with PWC was significantly greater than the drop observed with Ascorbic Acid.
Note:
All statistically significant differences are noted. Data are presented as the mean + S.E.M. All 0 time points were
immediately prior to oral administration of the vitamin C formulation

REFERENCES (0167 Schauss AG, Xianli W., Prior RL, Ou B, Huang D,

Owens J. Agarwal A, Jensen G. S. Hart A. N. Shanbrom E:
(O157 Bessey O, Lowry O, Brock M: The quantitative Antioxidant capacity and other bioactivities of the freeze
determination of ascorbic acid in Small amount of white dried Amazonian palm berry, Euterpe Oleraceae Mart.
blood cells and platelets. JBC 1947, 168(1):197-205 (Acai). J. Agric Food Chem. 2006, 54(22):8604-10
0158 Boothby LA, Doering PL: Vitamin Cand vitamin E (0168 Su L, Yin J-J, Charles D, Zhou K, Moore J, and Yu L:
for Alzheimer's disease. Ann. Pharmacotherapy 2005, Total phenolic contents, chelating capacities and radical
39(12):2073-80 Scavenging properties of black peppercorn, nutmeg, rose
0159 Fay M.J, Bush MJ, Verlangieri AJ. Effect of aldonic hip, cinnamon and oregano leaf. Food Chem. 2007, 100
acids on the uptake of ascorbic acid by 3T3 mouse fibro (3):990-97
blasts and human T lymphoma cells. Gen. Pharmacol. (0169 Weber C, Erl W. Weber K, Weber PC: Increased
1994, 25(7): 1465-69 adhesiveness of isolcated monocytes to endothelium is
(0160 Kaplan B, Gonul B, Dincer S, Dincer Kaya F N, prevented by vitamin C intake in smokers. Circulation
Babul A: Relationships between tensile strength, ascorbic 1996, 93(8): 1488-92
acid, hydroxyproline, and Zinc levels of rabbit full-thick (0170 Weeks BS and Perez PP: A novel vitamin C prepa
ness incision wound healing. Surg. Today 2004, 34(9):747 ration enhances neurite formation and fibroblast adhesion
51 and reduces Xenotiotic-induced T-cell hyperactivation.
(0161 Kurilich A C, Jefferey E. H. Juvik JA, Wallig MA, Med. Sci. Monit. 2007, 13(3):BR51-58
and Klein B P: Antioxidant capacity of different broccoli (0171 Wu X, Gu L, Prior RL, McKay S: Characterization
(Brassica oleracea) genotypes using the oxygen radical of anthocyanins and proanthocynaidins in Some cultivars
absorbance capacity (ORAC) assay.J. Agric. Food Chem. of Ribes, Aronia, and Sambucus and their antioxidant
2002, 50(18):5053-57 capacity. J. Agric. Food Chem. 2002, 52(26):7846-56
0162 Landmark K: Could intake of vitamins C and E 0172 Zhou X, TaiA, Yamamotol: Enhancement of neurite
inhibit development of Alzheimer dementia? Tidsskr Nor outgrowth in PC12 cell stimulated with cyclic AMP and
NGF by 6-acylated ascorbic acid 2-O-alpha-glucosides
Laegeforen 2006, 15 (8): 159-61 (6-Acyl-AA-2G), novel lipophilic ascorbate derivatives.
(0163 Lehr H A, Frei B, Arfors K E: Vitamin C prevents Biol. Pharm. Bull. 2003, 26(3):341-46.
cigarette Smoke-induced leukocyte aggregation and adhe We claim:
sion to endothelium in vivo. PNAS 1994, 91 (16):7688-92 1. A vitamin C preparation comprising:
0164 Marionnet C, Vioux-Chagnoleau C, Pierrard C. Sok (a) at least about 90% by weight of vitamin C,
J, Asselineau D, Bernerd F: Morphogenesis of dermal (b) at least about 0.1% by weight of lipophilic molecules
epidermal junction in a model of reconstructed skin: ben comprising (i) one or more Saturated Straight Co-Ca
eficial effects of vitamin C. Exp. Dermatol. 2006, 15(8): fatty alcohols, (ii) one or more unsaturated co-9Cs-Ca
625-33 fatty acids, (iii) optionally one or more saturated Straight
0.165 Moore J. Hao Z, Zhou K Luther M, Costa J. Y L: Ca-Co fatty acids, (iv) optionally one or more unsatur
Carotenoid, tocopherol, phenolic acid, and antioxidant ated c)-3 C-C fatty acids, and (v) optionally one or
properties of Maryland-grown soft wheat. J. Agric. Food more unsaturated (D-6Cs-C fatty acids; and
Chem. 2005, 53(17):6649-57 (c) optionally at least about 0.1% by weight of biofla
0166 Prior R L. Cao G: Antioxidant capacity and vonoids, based upon 100% total weight of the vitamin C
polyphenolic components of teas: implications for altering preparation.
in vivo antioxidant status. Proc. Soc. Exp. Biol. Med. 1999, 2. The vitamin C preparation of claim 1, wherein the vita
220(4):255-61 min C preparation comprises (i) at least about 0.1% by weight
US 2008/02O7748 A1 Aug. 28, 2008

of one or more saturated Straight Co-C fatty alcohols, (ii) at about 20-120 ppm rutin,
least about 0.01% by weight of component one or more about 25-100 ppm naringin,
unsaturated (D-9Cs-C fatty acids, (iii) optionally at least about 7000-20000 ppm hesperidin,
0.01% by weight of one or more saturated straight Cla-Co about 5-100 ppm neohesperidin,
fatty acids, (iv) optionally at least about 0.01% by weight of about 10-100 ppm neohesperidin dihydrochalcone,
one or more unsaturated co-3 C-C fatty acids, and (v) at
least about 0.01% by weight of one or more unsaturated (O-6 about 5-100 ppm maringenin,
Cs-C fatty acids, based upon 100% total weight of vitamin about 5-100 ppm hersperitin,
C preparation. about 50-150 ppm nomilin, and
3. The vitamin C preparation of claim 1, wherein the vita about 120-1000 mg/g gallic acid,
min C preparation comprises (a) at least 90% by weight of based upon 1 g of the bioflavonoids.
vitamin C, (b) 0.1 to 5% by weight of the lipophilic mol 10. The vitamin C preparation of claim 1, wherein the
ecules, and (c) 0.1 to 5% by weight of the bioflavonoids. Vitamin C is ascorbic acid or a pharmaceutically acceptable
4. The vitamin C preparation of claim 1, wherein the vita salt thereof.
min C preparation comprises about 200 to 40,000 IU vitamin
C. 11. A method of promoting a healthy nervous system in a
5. The vitamin C preparation of claim 1, wherein the vita human comprising:
min C preparation comprises the following lipophilic mol (a) recognizing the vitamin C preparation of claim 1 as
ecules: being effective to promote a healthy nervous system, and
about 0.01-0.3% (by weight) palmitic acid, (b) after Such recognition, orally administering to the
about 0.01-2.0% linoleic acid, human an effective amount of the vitamin C preparation
about 0.01-0.6% alpha linolenic acid, of claim 1.
about 0.01-0.4% oleic acid, 12. A method of decreasing the risk of a human of devel
about 0.1-0.8% steric acid, oping a neurodegenerative disease comprising:
about 0.01-0.09% arachidic acid, (a) recognizing the vitamin C preparation of claim 1 as
about 0.01-0.09% heneicosanoic acid, being effective to decrease the risk of a human of devel
about 0.1-0.9% behenic acid, oping a neurodegenerative disease, and
about 0.1-0.9% tricosanoic acid, (b) after Such recognition, orally administering to the
about 0.01-0.9% lignoceric acid, human an effective amount of the vitamin C preparation
about 0.05-0.9% cerotic acid, of claim 1.
about 0.1-1.0% heptacosanoic acid, 13. A method of enhancing NGF-mediated neurite out
about 0.05-1.5% montanic acid, growth in a human comprising:
about 0.2-2.6% melissic acid,
about 0.05-1.6% docosahexaenoic acid, (a) recognizing the vitamin C preparation of claim 1 as
about 0.05-0.9% docosapentaenoic acid, being effective to enhance NGF-mediated neurite out
about 0.05-1.9% docosatetraenoic acid, growth, and
about 0.05-0.9% docosadienoic acid, (b) after Such recognition, orally administering to the
about 0.01-1.8% erucic acid, human an effective amount of the vitamin C preparation
about 0.01-0.09% nervonic acid, of claim 1.
about 0.01-8.0% cetyl alcohol-hexadecanol-palmityl alco 14. A method of promoting wound healing in a human
hol, comprising:
about 0.01-5.0% 1-heptadecanol, (a) recognizing the vitamin C preparation of claim 1 as
about 0.01-1.0% 1-eicosanol-arachidyl alcohol, being effective to promote wound healing, and
about 0.01-3.0% 1-docosanol-behenyl alcohol, (b) after Such recognition, orally administering to the
about 1.0-15.0% lignoceryl alcohol-1-tetracosanol, human an effective amount of the vitamin C preparation
about 1.0-12.0% 1-hexacosanol-ceryl alcohol, of claim 1.
about 0.01-2.0% 1-heptacosanol, 15. A method of enhancing fibroblast adhesion to and the
about 0.5-20.0% 1-octacosanol, interaction with the extracellular matrix in a human compris
about 15.0-40.0% 1-triacontanol-melissyl alcohol, ing:
about 10.0-20.0% dotriacontanol, and (a) recognizing the vitamin C preparation of claim 1 as
about 5.0-15.0% tetratriacontanol
based upon 100% total weight of the lipophilic molecules in being effective to enhance fibroblast adhesion to and the
the Vitamin C preparation. interaction with the extracellular matrix, and
6. The vitamin C preparation of claim 1, wherein the lipo (b) after Such recognition, orally administering to the
philic molecules are extracted from a natural wax. human an effective amount of the vitamin C preparation
of claim 1.
7. The vitamin C preparation of claim 5, wherein the wax is
selected from Sugar cane wax, rice bran wax, carnauba wax, 16. A method of protecting the immune system from Xeno
candelilla wax, japan wax, ouricury wax, bayberry wax, shel biotics in a human comprising:
lac wax, Sunflower wax, orange wax, and beeswax. (a) recognizing the vitamin C preparation of claim 1 as
8. The vitamin C preparation formulation of claim 1, being effective to protect the immune system from Xeno
wherein the bioflavonoids are a mixture comprising hesperi biotics, and
din and gallic acid. (b) after Such recognition, orally administering to the
9. The vitamin C preparation of claim 7, wherein the vita human an effective amount of the vitamin C preparation
min C preparation comprises the following bioflavonoids: of claim 1.
US 2008/02O7748 A1 Aug. 28, 2008

17. A method of decreasing the risk of developing an oxi lated diseases associated with cytotoxic, genotoxic, and
dative pathogenesis in a human comprising: proinflammatory mechanisms in a human comprising:
(a) recognizing the vitamin C preparation of claim 1 as (a) recognizing the vitamin C preparation of claim 1 as
being effective to decrease the risk of a human of cancer,
being effective to decrease the risk of a human of devel cardiovascular diseases, atherosclerosis, and other age
oping an oxidative pathogenesis, and related diseases associated with cytotoxic, genotoxic,
(b) after Such recognition, orally administering to the and proinflammatory mechanisms, and
human an effective amount of the vitamin C preparation (b) after Such recognition, orally administering to the
of claim 1. human an effective amount of the vitamin C preparation
of claim 1.
18. A method of decreasing the risk of developing cancer,
cardiovascular diseases, atherosclerosis, and other age-re