U.S. patent application number 13/320507 was filed with the patent office on 2012-05-17 for lycopene and resveratrol dietary supplement.
This patent application is currently assigned to HSIEHS BIOTECH (SINGAPORE) PTE LTD. Invention is credited to Kun Lung Hsieh.
Application Number | 20120121699 13/320507 |
Document ID | / |
Family ID | 54398738 |
Filed Date | 2012-05-17 |
United States Patent
Application |
20120121699 |
Kind Code |
A1 |
Hsieh; Kun Lung |
May 17, 2012 |
LYCOPENE AND RESVERATROL DIETARY SUPPLEMENT
Abstract
A dietary supplement is disclosed comprising lycopene and
resveratrol in a range of ratio of lycopene:resveratrol from 1:10
to 10:1. Preferably, the ratio is 1:2 to 1:4. Lycopene is
preferably of .gtoreq.95% purity and resveratrol is of .gtoreq.98%
purity. Both lycopene and resveratrol may preferably comprise of
nano-sized particles in crystal powder to optimize oral intake in
the form of capsule or tablet. In small dosage, it should
preferably include a minimum of 5 mg of lycopene and 10 mg of
resveratrol. Various range of ratios of lycopene:resveratrol are
provided for specific therapeutic purposes including 1:4 for
symptomatic relief of arthritis, 1:2 for inhibiting melanoma or
carcinoma malignancy, and 1:3 for inhibiting hyperlipoidemia.
Generally, our dietary supplement composition may be used as an
agent for anti-ageing, anti-oxidative, inhibiting cardiovascular
diseases, relieving menopause symptoms and remission of
post-operative cancer patients.
Inventors: |
Hsieh; Kun Lung; (Ho Chi
Minh City, VN) |
Assignee: |
HSIEHS BIOTECH (SINGAPORE) PTE
LTD
Singapore
SG
|
Family ID: |
54398738 |
Appl. No.: |
13/320507 |
Filed: |
August 27, 2009 |
PCT Filed: |
August 27, 2009 |
PCT NO: |
PCT/SG2009/000300 |
371 Date: |
January 30, 2012 |
Current U.S.
Class: |
424/451 ;
514/733; 977/788; 977/915 |
Current CPC
Class: |
A61P 19/02 20180101;
A61P 39/06 20180101; A61P 17/00 20180101; A61P 3/06 20180101; A61K
9/48 20130101; A61K 9/20 20130101; A61K 45/06 20130101; A61P 35/00
20180101; A61K 31/01 20130101; A23L 33/105 20160801; A61P 9/00
20180101; A61K 31/05 20130101; A61P 43/00 20180101; A61P 15/12
20180101; A61K 31/01 20130101; A61K 2300/00 20130101; A61K 31/05
20130101; A61K 2300/00 20130101 |
Class at
Publication: |
424/451 ;
514/733; 977/788; 977/915 |
International
Class: |
A61K 9/48 20060101
A61K009/48; A61P 19/02 20060101 A61P019/02; A61P 35/00 20060101
A61P035/00; A61P 9/00 20060101 A61P009/00; A61P 15/12 20060101
A61P015/12; A61P 39/06 20060101 A61P039/06; A61K 31/05 20060101
A61K031/05; A61P 3/06 20060101 A61P003/06 |
Foreign Application Data
Date |
Code |
Application Number |
May 14, 2009 |
SG |
200903301-0 |
Claims
1. A dietary supplement composition comprising lycopene and
resveratrol in a range of ratio of lycopene : resveratrol from 1:10
to 10:1.
2. A dietary supplement composition according to claim 1 wherein
the ratio is 1:2 to 1:4.
3. A dietary supplement composition according to claim 1 wherein
the lycopene is of .gtoreq.95% purity.
4. A dietary supplement composition according to claim 3 wherein
the lycopene comprises nano-sized particles.
5. A dietary supplement composition according to claim 4 wherein
the lycopene comprises crystal powder.
6. A dietary supplement composition according to claim 1 wherein
the resveratrol is of .gtoreq.98% purity.
7. A dietary supplement composition according to claim 6 wherein
the resveratrol comprises nano-sized particles.
8. A dietary supplement composition according to claim 7 wherein
the resveratrol comprises crystal powder.
9. A dietary supplement composition according to claim 2 comprising
lycopene:resveratrol in the range of 1:4 for symptomatic relief of
arthritis.
10. A dietary supplement composition according to claim 2
comprising lycopene:resveratrol in the range of 1:2 for inhibiting
carcinoma malignancy.
11. A dietary supplement composition according to claim 10 for
inhibiting melanoma malignancy.
12. A dietary supplement composition according to claim 2
comprising lycopene:resveratrol in the range of 1:3 for inhibiting
hyperlipoidemia.
13. A dietary supplement composition according to claim 9, wherein
the lycopene and resveratrol act synergistically.
14. A dietary supplement composition according to claim 1,
formulated for oral intake.
15. A dietary supplement composition according to claim 14
formulated in a capsule or tablet.
16. A dietary supplement composition according to claim 15
comprising at least 5 mg of lycopene and 10 mg of resveratrol.
17. A dietary supplement composition according to claim 15
formulated in a capsule or tablet form comprising a unit weight of
a range taken from 190 to 400 mg.
18. A dietary supplement composition according to claim 1, for use
as an agent for anti-ageing, anti-oxidative, inhibiting development
of cardiovascular diseases, relieving menopause symptoms and
remission of post-operative cancer patients.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This United States utility patent application is the
.sctn.371 national phase of PCT international patent application no
PCT/SG2009/000300, having an international filing date of Aug. 27,
2009, which claims benefit of priority to Singapore Patent
Applications Serial Nos. SG 200903301-0, filed May 14, 2009. The
aforementioned applications are expressly incorporated herein by
reference in their entirety and for all purposes.
TECHNICAL FIELD
[0002] This invention generally relates to dietary supplement. It
relates specifically to such dietary supplement compositions
comprising lycopene and resveratrol exhibiting certain therapeutic
effects, including anti-oxidant, anti-arthritis, suppressing
carcinoma growth and mitigating hyperlipoidemia.
BACKGROUND ART
[0003] Lycopene, with a molecular formula of C.sub.40H.sub.56 and
molecular weight of 536.85, has a molecular structure shown
below.
##STR00001##
[0004] It is a carotenoid and the major target organs and tissues
of lycopene in the human body are testis, prostate, liver and
intestines. It is found to reduce incidence of prostatic carcinoma,
metrocarcinoma, and pancreatic carcinoma more effectively than
.beta.-carotene (Giovannucci E., 1999, Gann P. H., 1999). As early
as 1989, lycopene has been found to have the highest activity in
quenching oxygen-singlet among all carotenoids including
.beta.-carotene (Di Mascio P.). The anti-oxidative activity of
lycopene is found to be about 3.2-fold of that of .beta.-carotene,
and 100 times of that of vitamin E. Applied orally and absorbed
through the intestinal tract, lycopene quenches free-radicals and
thus protects tissues, cells, and DNA from oxidation by the
free-radicals.
[0005] Previous studies have revealed a number of functions of
lycopene: anti-ageing, enhancing immune health, reducing risk of
cardiovascular diseases and incidence of malignancies, especially
oral, throat, gastric, colon and uterus carcinomas. A meta-analysis
carried out at Harvard University including 47,000 participants
over a period of 6 years found that the incidence of prostatic
carcinoma was over 30% lower in the lycopene group (Giovannucci,
E., 1995). Furthermore, clinical trials revealed activity of
lycopene in suppressing tumor growth and metastasis, especially
effective for pancreatic, lung and gastric carcinomas (Giovannucci
E., 1999; Gann R. H., 1999)
[0006] Because of its multiple beneficial effects, lycopene is now
recognized as a star healthy food supplements in the 21st century
and is gaining in popularity world-wide. Especially in developed
countries including the U.S., Western Europe, Japan and Israel,
huge wealth and efforts have been invested in related researches
and in development of lycopene-containing drugs, food supplements,
foods and cosmetics since 1990.
[0007] Resveratrol, with a molecular formula
C.sub.14H.sub.12O.sub.3 and a molecular weight of 228.25, is a
terpenoid which is mainly contained in grape skin, peanut,
pineapple and knotweed rhizome. This compound appears as an
insipidity white crystal powder, slightly soluble in water but
soluble in organic solvents such as ethanol and acetone. The
structural formula of resveratrol is shown below.
##STR00002##
[0008] Resveratrol is known as an antioxidant, and has been found
to decrease blood viscidity, suppress platelet-coagulation, enhance
vasodilation and thus promote blood circulation. Because of its
hypolipidemic feature, resveratrol plays an important role in
preventing atherosclerosis and ischemic heart diseases. Resveratrol
also has antineoplastic effect and is a natural substitute of
estrogen. Further functionalities of resveratrol include
anti-ageing effect, preventing oxidation of low-density lipoprotein
(LDL) cholesterol, anti-inflammation and anti-allergic effect.
[0009] The main application of resveratrol is directed to acute
infectious hepatitis, menostasis, rheumatism, bone and muscle pain,
bronchitis, cholecystolithiasis, hypercholesterol and
hypertriglyceride condition. The major target organs and tissues of
resveratrol in human body are heart, blood vessels and skins.
[0010] There exist a number of patents either one of lycopene and
resveratrol as the essential compound with optionally the other
compound, or with both compounds in specific range of ratios which
are claimed to be therapeutic for various ailments. New Zealand
Patent No. 526350 (al-Shakarchi) disclosed lycopene in 0.1-2% w/v
and resveratrol in 0.05-1.5% w/v in a preferred combination of a
main complex composition which comprises metal salts, amino acids,
amino alcohol and vitamin B complex. The lycopene resveratrol
disclosed is in the range of 1:15-40:1.
[0011] In U.S. patent publication No. 2008/0262081 (Raederstorff)
lycopene with resveratrol is disclosed for anti-aging effect in
form of a dietary supplement in wide-ranging ratios from about
1:1430-24:1. International patent publication No. WO 07131767 (DSM)
discloses combination of lycopene and genistein for therapy of
prostate carcinoma wherein in one of the embodiments resveratrol is
preferably added such that lycopene: resveratrol range is about 1:2
to 1:33/4.
[0012] In International patent publication No. WO 2004/000043
(Perani) a food supplement is disclosed with both lycopene and
resveratrol as antioxidants at 1:1 ratio. Another publication No.
WO 2005/107729 (Kang) disclosed a skin disorder therapeutic
composition comprising lycopene plus optionally resveratrol at a
ratio of about 4:1.
[0013] Most commercially available preparations contain extracted
lycopene as crystals which are water-insoluble and can not be
efficiently absorbed in human intestinal tract. Natural lycopene is
sourced from intracellular microsomes of plant cells and is
similarly difficult to be absorbed directly by human body through
oral intake, a problem not addressed by the prior art.
[0014] While the prior art also made wide therapeutic claims which
have largely been speculative, our present invention endeavours to
disclose certain combination ratios of lycopene to resveratrol for
therapeutic use in specific ailments including arthritis, carcinoma
generally and melanoma specifically, and in mitigating
hyperlipoidemia.
SUMMARY OF DISCLOSURE
[0015] In the general embodiment of our invention, we disclose a
dietary supplement composition comprising lycopene and resveratrol
in a range of ratio of lycopene:resveratrol from 1:10 to 10:1.
Preferably, the ratio is 1:2 to 1:4. In a first aspect of our
composition, the lycopene is preferably of .gtoreq.95% purity and
resveratrol is of .gtoreq.98% purity. Both lycopene and resveratrol
may preferably comprise of nano-sized particles. Preferably, the
particles are in the form of crystal powder to optimize intestinal
absorption upon oral intake in the form of capsule or tablet. In
small dosage, it should preferably include a minimum of 5 mg of
lycopene and 10 mg of resveratrol.
[0016] In a second aspect of our composition, various range of
ratios of lycopene:resveratrol are provided for specific
therapeutic purposes including 1:4 for symptomatic relief of
arthritis, 1:2 for inhibiting melanoma or carcinoma malignancy, and
1:3 for inhibiting hyperlipoidemia. Generally, our dietary
supplement composition may be used as an agent for anti-ageing,
anti-oxidative, inhibiting development of cardiovascular diseases,
relieving menopause symptoms and remission of post-operative cancer
patients.
LIST OF ACCOMPANYING DRAWINGS
[0017] The drawings accompanying this specification as listed below
may provide a better understanding of our invention and its
advantages when referred in conjunction with the detailed
description the follows as exemplary and non-limiting embodiments
of our composition, in which:
[0018] FIG. 1: is a column chart showing pain index of arthritis
patients in placebo group, group treated with resveratrol only,
group treated with lycopene only and group treated with combination
of both resveratrol and lycopene;
[0019] FIG. 2 is a line graph illustrating growth of melanoma graft
in nude mice: untreated control, treated only with resveratrol,
treated only with lycopene and combination of both resveratrol and
lycopene;
[0020] FIG. 3 is a column chart showing triglycerides levels in
untreated control group, group treated with resveratrol only, group
treated with lycopene only and group treated with combination of
both resveratrol and lycopene.
DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS
[0021] Our new composition is formulated based on the results of
our research over years which revealed synergistic and
complementary effects of the two potent anti-oxidative compounds,
i.e. lycopene and resveratrol, as active ingredients. One main
aspect of our findings concerns the bioavailability of these two
compounds upon oral intake, and their respective distribution or
deposition upon uptake in the human body.
[0022] After oral intake, over 90 percent of lycopene that is able
to be adsorbed goes to the prostate and other internal organs while
resveratrol is mainly distributed in the heart, circulation system,
along respiratory tract and skin. From the following trials and
results, it may be shown that the combination of the two compounds
appears to show synergistic effects and to possess significantly
higher activities in mitigating a number of diseases and
malignancies and in improving conditions of some disorders than
those of each of the compounds on its own.
[0023] In the broad, general embodiment of our dietary supplement
composition, lycopene and resveratrol are to be admixed in a range
of ratio of lycopene:resveratrol from 1:10 to 10:1 with the range
of 1:2 to 1:4 considered as optimal ratio.
[0024] The bio-absorption of the two compounds following oral
intake may be increased with the compounds provided in a certain
high levels of purity and specific microscopic structural form. [By
"microscopic" we mean particle size of a scale lower than
micrometer, i.e. including nanometer and .ANG. scale.]
[0025] Lycopene is preferably provided in purity .gtoreq.95% while
resveratrol is preferably provided in purity .gtoreq.98%. Both
compounds are also preferably provided in form of nano-sized
particles, particularly micro-crystalline particles, or
nano-crystals. These microscopic crystalline forms of lycopene and
resveratrol may be produced with suitable conventional controlled
recrystallization techniques such as single or multi-solvent
solvent recrystallization, hot filtration recrystallization, and
seeding, or a proprietary technology such as Elan Pharmaceutical's
NanoCrystal.TM. technology for synthesizing nano-scale crystals
optimized for water-solubility.
[0026] Examples of preparation of the composition comprising
lycopene and resveratrol in various ratio are given in the
following:
Preparation Example 1
Lycopene Resveratrol Composition in 1:2 Ratio
[0027] 100 grams of lycopene with a purity of 95% and 200 g of
resveratrol with a purity of 98% were mixed and sieved through a
100-mesh filter. The mixture was then capsulated, yielding a total
of 1580 capsules with an average weight of 190 mg each.
Preparation Example 2
Lycopene Resveratrol Composition in 1:1 Ratio
[0028] 200 g of lycopene with a purity of 95% and 200 g of
resveratrol with a purity of 98% were mixed and sieved through a
100-mesh filter. The mixture was then capsulated, yielding a total
of 2000 capsules, averaging 200 mg each.
Preparation Example 3
Lycopene Resveratrol Composition in 2:1 Ratio
[0029] 200 g of lycopene with a purity of 95% and 100 g of
resveratrol with a purity of 98% were mixed and sieved through a
100-mesh filter. The mixture was then capsulated, yielding a total
of 1200 capsules, averaging 250mg each.
[0030] For smaller dosages, our dietary supplement may be
formulated as having, for example, 5 mg of lycopene and 10 mg of
resveratrol in a 15 mg capsule or tablet. Conventional methods may
be employed to make tablets such as the use of binding agent such
as starch and/or magnesium stearate. For an example of lycopene
resveratrol composition in 1:3 ration 100 grams of lycopene with a
purity of 95% and 300 g of resveratrol with a purity of 98% may be
mixed with 40 g starch, and then mixed with 200 g starch slurry
before tablet-making.
[0031] The second major aspect of our present invention concerns
certain combination ratios of lycopene to resveratrol for
therapeutic use in specific ailments including arthritis, carcinoma
generally and melanoma specifically, and in mitigating
hyperlipoidemia.
Trial 1
Symptomatic Relief of Arthritis
[0032] Forty subjects chosen for having a history of over 10 years
suffering from knee joints pain. They were divided into 4 groups.
Each group was served with placebo capsules, resveratrol (e.g. 400
mg/person/day) or lycopene (e.g. 100 mg/person/day), or the
combination of both, respectively as indicated in FIG. 1. Five
grades (as pain index) were designed for patients to define their
painfulness.
[0033] Upon completion of the trial, they experienced complete
relief or near complete relief from knee joint pain within one
month. The best daily dose is speculated to be 100 mg of lycopene
and 400 mg of resveratrol, i.e. lycopene resveratrol in the ratio
of 1:4 for efficacious symptomatic relief of arthritis. As is
apparent from the bar chart of FIG. 1, the combination of
resveratrol and lycopene showed synergistic effect on providing
symptomatic relief of rheumatic knee joint pain.
Trial 2
Inhibition of Melanoma Malignancy
[0034] Inhibition of melanoma growth is shown in FIG. 2 where the
subjects are C57 mouse which are grafted with B16 murine melanoma
tumour cells. From the line graph of FIG. 2, it is apparent that
the combination of both lycopene and resveratrol has synergistic
effect in suppressing growth of melanoma grafts. The optimal ratio
of lycopene: resveratrol is suggested to be in the range of 1:2 for
efficacious suppression of growth of carcinoma including
melanoma.
[0035] In one specific case, a man with a tonsil tumor sized
3.times.3 cm, reported shrinkage of the tumor a size below the
detectable range of magnetic resonance imaging after three-month
intake of our dietary supplement comprising lycopene and
resveratrol according to the aforesaid ratio. As is apparent from
the bar chart of FIG. 2, the combination of resveratrol and
lycopene showed synergistic effect in suppressing growth of
tumor.
Trial 3
Lowering of Triglyceride Levels in Hyperlipoidemia
[0036] Forty volunteer patients with hyperlipoidemia or having
symptoms of high levels of triglyceride were enrolled in a
one-month experiment. They were divided into 4 groups, and each
group was given a different formulation of lycopene and/or
resveratrol or none (control). The results are shown in FIG. 3. The
group taking 600 mg resveratrol plus 200 mg lycopene achieved
complete relief of hyperlipoidemia. Accordingly, the composition of
these 2 phytochemicals in the ratio of lycopene:resveratrol at 1:3
may be considered optimal for inhibiting hyperlipoidemia. The
combination of resveratrol and lycopene showed synergistic effect
in lowering the level of triglycerides in blood.
[0037] Further health promoting effects of our preparation of
lycopene and resveratrol may be expected to include anti-ageing,
anti-oxidative, inhibiting cardiovascular diseases, relieving
menopause symptoms and remission of post-operative cancer
patients.
[0038] It would be apparent to a person skilled in the art that the
suggested methods of obtaining the 2 active ingredients, i.e.
lycopene and resveratrol, in their respective purity and
nano-crystalline form may be obtained from alternative or modified
techniques. The aforementioned ratios of lycopene and resveratrol
are suggestive based on our trial results and the respective
experimental conditions and may be subject to variance or
tolerances. Many of the formulation or dosage techniques described
above may also be similarly achieved with other conventional
methods known to the notional skilled person. These modifications,
adaptations and alternatives are to be considered as equivalents to
our invention and fall within the scope and letter of the following
claims.
LIST OF REFERENCES
[0039] Giovannucci, E. L., Ascherio, A., Rimm, E. B., Stampfer, M.
J., Colditz, G. A., and Willett, W. C. Intake of carotenoids and
retinol in relationship to risk of prostate cancer. J. Natl. Cancer
Inst. 1995; 87; 1767-1776.
[0040] Giovannucci E. Tomatoes, tomato-based products, lycopene,
and cancer: Review of the epidemiologic literature. Journal of the
National Cancer Institute 1999; 91: 317-331.
[0041] Di Mascio P., Kaiser S., Sies H. Lycopene as the most
efficient biological carotenoid singlet oxygen quencher. Arch
Biochem Biophys. 1989; 274(2): 532-538.
[0042] Gann P H, Ma J, Giovannucci E, Willett W, Sacks F M,
Hennekens C H, Stampfer M J. Lower prostate cancer risk in men with
elevated plasma lycopene levels: results of a prospective analysis.
Cancer Res. 1999 Mar 15;59(6)1225-30.
[0043] Edward Giovannucci, Eric B. Rimm, Yan Liu, Meir J. Stampfer,
Walter C. Willett, A Prospective Study of Tomato Products,
Lycopene, and Prostate Cancer Risk, J. Natl Cancer Inst. 2002 Mar
6;94(5)391-8.
* * * * *