U.S. patent application number 10/481040 was filed with the patent office on 2004-12-02 for krill and/or marine extracts for prevention and/or treatment of cardiovascular diseases arthritis, skin cancer diabetes, premenstrual syndrome and transdermal transport.
Invention is credited to Sampalis, Tina.
Application Number | 20040241249 10/481040 |
Document ID | / |
Family ID | 23150259 |
Filed Date | 2004-12-02 |
United States Patent
Application |
20040241249 |
Kind Code |
A1 |
Sampalis, Tina |
December 2, 2004 |
Krill and/or marine extracts for prevention and/or treatment of
cardiovascular diseases arthritis, skin cancer diabetes,
premenstrual syndrome and transdermal transport
Abstract
The present invention relates to a method of treatment and/or
prevention of cardiovascular disease, rheumatoid arthritis, skin
cancer, premenstrual syndrome, diabetes and transdermal transport
enhancement. The method comprises the administration of a
therapeutically effective amount of krill and/or marine oil to a
patient. The present invention also relates to a composition for
the treatment and/or prevention of these diseases.
Inventors: |
Sampalis, Tina; (Laval,
CA) |
Correspondence
Address: |
CROWELL & MORING LLP
INTELLECTUAL PROPERTY GROUP
P.O. BOX 14300
WASHINGTON
DC
20044-4300
US
|
Family ID: |
23150259 |
Appl. No.: |
10/481040 |
Filed: |
July 9, 2004 |
PCT Filed: |
June 7, 2002 |
PCT NO: |
PCT/CA02/00843 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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60298383 |
Jun 18, 2001 |
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Current U.S.
Class: |
424/520 ;
424/523 |
Current CPC
Class: |
A61K 31/23 20130101;
A61P 3/06 20180101; A61P 9/06 20180101; A61K 31/122 20130101; A61K
31/20 20130101; A61K 31/232 20130101; A61P 3/08 20180101; A61K
31/683 20130101; A61P 3/10 20180101; A61P 15/08 20180101; A61P 9/10
20180101; A61P 17/00 20180101; A61K 2300/00 20130101; A61K 31/685
20130101; A61K 2300/00 20130101; A61P 15/00 20180101; A61K 31/07
20130101; A61P 37/06 20180101; A61P 17/02 20180101; A61K 33/00
20130101; A61K 31/575 20130101; A61P 7/02 20180101; A61K 31/202
20130101; A61K 31/23 20130101; A61P 5/24 20180101; A61P 9/00
20180101; A61P 29/00 20180101; A61P 19/02 20180101; A61K 35/612
20130101; A61K 31/201 20130101; A61K 35/612 20130101; A61P 9/12
20180101; A61K 9/0053 20130101; A61K 31/355 20130101; A61K 33/30
20130101; A61K 31/688 20130101; A61K 9/48 20130101; A61K 31/015
20130101; A61P 35/00 20180101 |
Class at
Publication: |
424/520 ;
424/523 |
International
Class: |
A61K 035/12; A61K
035/60 |
Claims
1-83. (Cancelled)
84. A composition comprising an amount of krill oil effective for
decreasing cholesterol, inhibiting platelet adhesion, inhibiting
artery plaque formation, preventing hypertension, controlling
arthritis symptoms, preventing skin cancer, enhancing transdermal
transportation of dermatological topical therapeutic applications,
enhancing transdermal transportation of dermatological cosmetic
applications, reducing symptoms of premenstrual syndrome, or
controlling blood glucose level in a patient, and a
pharmaceutically acceptable carrier, wherein said krill oil is
obtained from a process comprising the steps of: a) placing marine
or aquatic krill in a ketone solvent, to obtain a first extraction
of a soluble lipid fraction from said marine or aquatic krill; b)
separating the extraction into a first liquid and a first solid
contents; c) evaporating the ketone solvent present in the first
liquid contents to recover a first lipid rich fraction; d) placing
said first solid contents in an organic solvent selected from the
group of consisting of alcohol and esters of acetic acid, to
achieve a second extraction of soluble lipid fraction; e)
separating the second extraction into a second liquid and a second
solid contents; f) evaporating the organic solvent from the second
liquid contents to recover a second lipid rich fraction; and g)
recovering the solid contents.
85. A composition according to claim 84, wherein the ketone solvent
is acetone.
86. A composition according to claim 84, wherein the organic
solvent is ethanol, isopropanol, t-butanol, or ethyl acetate
87. A composition according to claim 84, wherein the composition
comprises Eicosapentanoic acid, Docosahexanoic acid,
Phosphatidylcholine, Phosphatidylinositol, Phosphatidylserine,
Phosphatidylethanolamine, Sphingomyelin, a-tocopherol, Astaxanthin,
and flavonoid.
88. A composition of claim 87, further comprising at least one of
the group consisting of Linoleic acid, Alpha-linoleic acid,
arachidonic acid, oleic acid, palmitic acid, palmitoleic acid,
stearic acid, cholesterol, triglycerides, monoglycerides, all-trans
retinol, canthaxanthin, .beta.-carotene, zinc, selenium, nervonic
acid, sodium, potassium and calcium.
89. A composition of claim 84, wherein the composition comprising
an effective amount for decreasing cholesterol in a patient.
90. A composition of claim 84, wherein the composition comprising
an effective amount for inhibiting platelet adhesion or artery
plaque formation in a patient.
91. A composition of claim 84, wherein the composition comprising
an effective amount for preventing hypertension in a patient.
92. A composition of claim 84, wherein the composition comprising
an effective amount for controlling arthritis symptoms in a
patient.
93. A composition of claim 92, wherein the arthritis is rheumatoid
arthritis or osteoarthritis.
94. A composition of claim 84, wherein the composition comprising
an effective amount for preventing skin cancer in a patient.
95. A composition of claim 84, wherein the composition comprising
an effective amount for enhancing transdermal transportation of
dermatological topical therapeutic applications, or enhancing
transdermal transportation of dermatological cosmetic applications
decreasing cholesterol in a patient.
96. A composition of claim 84, wherein the composition comprising
an effective amount for reducing symptoms of premenstrual syndrome
in a patient.
97. The composition of claim 84, wherein the composition comprising
an effective amount for controlling blood glucose level in a
patient.
98. A method for decreasing cholesterol, inhibiting platelet
adhesion, inhibiting artery plaque formation, preventing
hypertension, controlling arthritis symptoms, preventing skin
cancer, enhancing transdermal transportation of dermatological
topical therapeutic applications, enhancing transdermal
transportation of dermatological cosmetic applications, reducing
symptoms of premenstrual syndrome, or controlling blood glucose
level in a patient in need thereof, said method comprising
administering an effective amount of the composition of claim 84 to
said patient.
99. A method of claim 98, wherein said administering is effected
orally.
100. A method of claim 99, wherein a quantity in a range of about 1
to almost 4.8 grams per day of krill oil is administered.
101. A method of claim 100, wherein said quantity is about 4.8
grams.
102. A method of claim 98, which is for decreasing cholesterol in a
patient.
103. A method of claim 98, which is for inhibiting platelet
adhesion and artery plaque formation in a patient.
104. A method of claim 98, which is for preventing hypertension in
a patient.
105. A method of claim 98, which is for controlling arthritis
symptoms in a patient.
106. A method of claim 105, wherein the arthritis is rheumatoid
arthritis or osteoarthritis.
107. A method of claim 98, which is for preventing skin cancer in a
patient.
108. A method of claim 98, which is for enhancing transdermal
transportation of dermatological topical therapeutic applications,
or enhancing transdermal transportation of dermatological cosmetic
applications decreasing cholesterol in a patient.
109. A method of claim 98, which is for reducing symptoms of
premenstrual syndrome in a patient.
110. A method of claim 98, which is for controlling blood glucose
level in a patient.
Description
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] This invention relates to multi-therapeutic extracts derived
from krill and/or marine, which can prevent and/or treat several
diseases.
[0003] 2. Description of Prior Art
[0004] Krill is the common name for small, shrimp-like crustaceans,
however not shrimp, that swarm in dense shoals, especially in
Antarctic waters. It is one of the most important food source for
fish, some kind of birds and especially for baleen whales as being
an important source of protein. Krill is also a good source of
omega-3 fatty acid, which are well known for their health
benefits.
[0005] It is known in the art to use krill and/or marine enzymes
for the treatment of a great variety of diseases in human and
animals such as infections, inflammations, cancers, HIV/AIDS, pain,
polyps, warts, hemorrhoids, plaque, wrinkles, thin hairs, allergic
itch, anti-adhesion, eye disease, acne, cystic fibrosis and immune
disorders including autoimmune disease and cancer.
[0006] It is also known in the art that krill and/or marine oil may
be used for the treatment of autoimmune murine lupus and other
autoimmune diseases and can also be used for treating
cardiovascular diseases.
[0007] However, the krill and/or marine oil used for these
treatments has only conserved its omega-3 fatty acids as active
ingredients, which is a very small part of all the active
ingredients of the krill and/or marine itself. This fact reduces
the potential of the krill and/or marine oil as a treatment for
these diseases.
[0008] There is an increasing demand for treatments using products
derived from a natural source, therefore, it would be highly
desirable to be provided with a krill and/or marine extract having
an enhanced potential for prevention and/or treatment and/or
management of disease.
SUMMARY OF THE INVENTION
[0009] In accordance with the present invention there is provided a
method of prevention, therapy and/or treatment of several disease,
the method comprising the administration of a therapeutically
effective amount of krill and/or marine oil to a patient.
[0010] In a preferred embodiment of the present invention the krill
and/or marine oil is obtained from a process comprising the steps
of:
[0011] (a) placing krill and/or marine material in a ketone
solvent, preferably acetone to achieve extraction of the soluble
lipid fraction from the marine and/or aquatic animal material;
[0012] (b) separating the liquid and solid contents;
[0013] (c) recovering a first lipid rich fraction from the liquid
contents by evaporation of the solvent present in the liquid
contents;
[0014] (d) placing the solid contents in an organic solvent
selected from the group of solvents consisting of alcohol,
preferably ethanol, isopropanol or t-butanol and esters of acetic
acid, preferably ethyl acetate to achieve extraction of the
remaining soluble lipid fraction from the marine and/or aquatic
material;
[0015] (e) separating the liquid and solid contents;
[0016] (f) recovering a second lipid rich fraction by evaporation
of the solvent from the liquid contents; and
[0017] (g) recovering the solid contents.
[0018] In a preferred embodiment of the present invention, the
krill and/or marine oil comprises Eicosapentanoic acid,
Docosahexanoic acid, Phosphatidylcholine, Phosphatidylinositol,
Phosphatidylserine, Phosphatidylethanolamine, Sphingomyelin,
a-tocopherol, all-trans retinol, Astaxanthin and flavonoid.
[0019] In another embodiment of the present invention, the krill
and/or marine oil comprises Eicosapentanoic acid, Docosahexanoic
acid, Linolenic acid, Alpha-linolenic acid, Linoleic acid,
Arachidonic acid, Oleic acid, palmitic acid, palmitoleic acid,
stearic acid, nervonic acid, Phosphatidylcholine,
Phosphatidylinositol, Phosphatidylserine, Phosphatidylethanolamine,
Sphingomyelin, Cholesterol, Triglycerides, Monoglycerides,
a-tocopherol, all-trans retinol, Astaxanthin, Canthaxanthin,
.beta.-carotene, flavonoid, Zinc, Selenium, sodium, potassium and
calcium.
[0020] In another embodiment of the present invention, the krill
and/or marine oil comprises Eicosapentanoic acid, Docosahexanoic
acid, Linolenic acid, Alpha-linolenic acid, Linoleic acid,
Arachidonic acid, Oleic acid, palmitic acid, palmitoleic acid,
stearic acid, Phosphatidylcholine, Phosphatidylinositol,
Phosphatidylserine, Phosphatidylethanolamine, Sphingomyelin,
Cholesterol, Triglycerides, Monoglycerides, a-tocopherol, all-trans
retinol, Astaxanthin, Canthaxanthin, .beta.-carotene, Zinc and
Selenium.
[0021] The diseases that can be treated and/or prevented by the
method of the present invention are cardiovascular diseases,
arthritis, skin cancer, diabetes, premenstrual syndrome and
transdermal transport enhancement.
[0022] In accordance with the present invention there is also
provided a composition for the treatment and/or prevention and/or
therapy of the previously mentioned diseases, the composition
comprising a therapeutically effective amount of krill and/or
marine oil in association with a pharmaceutically acceptable
carrier.
[0023] In accordance with the present invention, it is further
provided the use of krill and/or marine oil for the treatment
and/or prevention and/or therapy of the previously mentioned
diseases.
[0024] In accordance with the present invention, it is also
provided the use of krill and/or marine oil for the manufacture of
a medicament for the treatment and/or prevention and/or therapy of
the previously mentioned diseases.
DETAILED DESCRIPTION OF THE INVENTION
[0025] In accordance with the present invention, there is provided
krill and/or marine extract for prevention and/or treatment and/or
therapy of several diseases.
[0026] A multi-therapeutic oil extract free of enzyme is derived
from krill and/or marine, found in any marine environment around
the world, for example, the Antarctic ocean (euphasia superba), the
Pacific ocean (euphasia pacifica), the Atlantic ocean, the Indian
ocean, in particular coastal regions of Mauritius Island and/or
Reunion Island of Madagascar, Canadian West Coast, Japanese Coast,
St-Lawrence Gulf and Fundy Bay, and this oil extract is a free
fatty acid lipid fraction.
[0027] The extraction process can be described as the
following:
[0028] (a) Placing marine and/or aquatic krill and/or marine in a
ketone solvent, preferably acetone, to achieve the extraction of
grease from the krill and/or marine;
[0029] (b) Separating the liquid and the solid phases;
[0030] (c) Recovering a lipid rich fraction from the liquid phase
obtained at step (b) by evaporation of the solvent present in the
liquid phase;
[0031] (d) Placing the solid phase in an organic solvent, which can
be alcohol, preferably ethanol, isopropanol or t-butanol, or esters
of acetic acid, preferably ethyl acetate. This in order to extract
the remaining soluble lipid fraction from the solid phase;
[0032] (e) Separating the liquid and the solid phases; and
[0033] (f) Recovering a lipid rich fraction from the liquid phase
obtained at step (e) by evaporation of the solvent present in the
liquid phase.
[0034] The active components of the enzyme-free krill and/or marine
oil extract are:
[0035] Lipids
[0036] i) Omega-3:
[0037] i. Eicosapentanoic acid: >8 g/100 g
[0038] ii. Docosahexanoic acid: >2 g/100 g
[0039] iii. Linolenic acid: >0.10 g/100 g
[0040] iv. Alpha-linolenic acid: >0.3 g/100 g
[0041] In the preferred embodiment of the present invention, the
Omega-3 are found in more than 30 g/100 g.
[0042] ii) Omega-6: i. Linoleic acid: >0.9 g/100 g
[0043] ii. Arachidonic acid: <0.45 g/100 g, preferably <0.6
g/100 g
[0044] iii) Omega-9: i. Oleic acid: >5 g/100 g
[0045] iv) palmitic acid: >10 g/100 g
[0046] v) palmitoleic acid: 0.08 g/100 g
[0047] vi) stearic acid: >0.5 g/100 g
[0048] Phospholipids
[0049] Phosphatidylcholine: >4.5 g/100 g
[0050] Phosphatidylinositol: >107 mg/100 g
[0051] Phosphatidylserine: >75 mg/100 g
[0052] Phosphatidylethanolamine: >0.5 g/100 g
[0053] Sphingomyelin: >107 mg/100 g
[0054] Neutral Lipids
[0055] Cholesterol: <3 g/100 g
[0056] Triglycerides: <55 g/100 g
[0057] Monoglycerides: >0.5 g/100 g
[0058] In another embodiment of the present invention, the neutral
lipids of the krill and/or marine extract also comprises:
[0059] Diglycerides: >0.5 g/100 g
[0060] Antioxydants
[0061] .alpha.-tocopherol (vitamin E): >1.0 IU/100 g
[0062] all-trans retinol (vitamin A): >1500 IU/100 g
[0063] .beta.-carotene: >3000 .mu.g/100 ml
[0064] Pigments
[0065] Astaxanthin: >20 mg/100 g
[0066] Canthaxanthin: >2 mg/100 g
[0067] Metals
[0068] Zinc: >0.1 mg/100 g
[0069] Selenium: >0.1 mg/100 g
[0070] In another embodiment of the present invention, the krill
and/or marine extract also comprises:
[0071] Flavonoids: >0.5 mg/100 g
[0072] Sodium: <500 mg/100 g
[0073] Calcium: >0.1 mg/100 g
[0074] Potassium: >50 mg/100 g
[0075] Aluminum: <8.5 mg/100 g
[0076] Protein: >4 g/100 g
[0077] Moisture and volatile matter: <0.8%
[0078] After characterization of the krill and/or marine oil
extract, it was determined that the extract contains less than 25
ppm of solvent residue from the extraction process.
[0079] The oil has the following stability indexes:
[0080] Peroxide value: <0.1 (mEq/kg)
[0081] Oil Stability index: <0.1 after 50 hours at 97.8.degree.
C.
[0082] Saponification index: 70-180
[0083] Iodine value:60-130%
[0084] The present invention will be more readily understood by
referring to the following examples which are given to illustrate
the invention rather than to limit its scope.
EXAMPLE 1
Cardiovascular Disease Prevention and/or Treatment
[0085] Krill and/or marine oil has been shown to decrease
cholesterol in vivo. It also inhibits platelet adhesion and plaque
formation and reduces vascular endothelial inflammation in a
patient. It can offer hypertension prophylaxis. It prevents
oxidation of low-density lipoprotein. It may have an inhibitory
effect on the secretion of VLDL due to increased intracellular
degradation of apo B-100. It also offers a post-myocardial
infarction prophylaxis because of its ability to decrease CIII
apolipoprotein B, to decrease CIII non-apolipoprotein B
lipoproteins and to increase antithrombin III levels. Krill and/or
marine oil is suitable for prophylactic usage against
cardiovascular disease in human where cardiovascular disease
relates to coronary artery disease, hyperlipidemia, hypertension,
ischemic disease (relating to angina, myocardial infarction,
cerebral ischemia, shock without clinical or laboratory evidence of
ischemia, arrhythmia)
[0086] To evaluate the effects of krill and/or marine oil on the
course of arteriosclerotic coronary artery disease and
hyperlipidemia, a study was performed (prospective clinical trial,
statistical significance p<0.05) with patients with known
hyperlipidemia.
[0087] A group of 13 patients took krill and/or marine oil
concentrate gelules. Both fish oil and krill and/or marine oil
contained equal amounts of omega-3 fatty acids. Recommended dosage
is of 1 to 6 capsules per day, each capsule containing 800 mg of
oil. In this study, each patient took 6 capsules per day.
[0088] The patients were tested for LDL, HDL, Triglycerides, vital
signs, CBC, SGOT/SGPT, .gamma.-GT, ALP, Urea, Creatine, Glucose,
K.sup.+, Na.sup.+, Ca.sup.2+ and total indirect bilirubin
cholesterol before treatment and also at 2 months.
[0089] Table 1 is showing the results obtained from the previously
described tests:
1TABLE 1 Paired Samples Test Paired Differences 95% Confidence Std.
Interval of the Parameter Error Difference Sig. (2- tested Mean SD.
Mean Lower Upper t-value df tailed) Cholesterol .4954 .55800 .15476
.1582 .8326 3.201 12 .008 Triglycerides .3538 .54543 .15127 .0242
.6834 2.339 12 .037 HDL -.2108 .29859 .08281 -.3912 -.0303 -2.545
12 .026 LDL .2846 .47333 .13128 -.0014 .5706 2.168 12 .051 Chol/HDL
.3600 .53446 .14823 .0370 .6830 2.429 12 .032
[0090] From the above, it was shown that a daily uptake of 1 to 4.8
g of krill extract was providing to the patients a cholesterol
decrease in the range of 15%, a triglycerides decrease in the range
of 15%, a HDL increase in the range of 8%, a LDL decrease in the
range of 13% and a Cholesterol/HDL ratio decrease of 14%.
[0091] This shows that an uptake of krill extract has a beneficial
effect on patient suffering from hyperlipidemia, which is known to
be the primary causative factor of atherosclerosis.
EXAMPLE 2
Arthritis Treatment
[0092] Krill and/or marine oil offers symptomatic relief for
Arthritis where arthritis relates to adult arthritis, Still's
disease, polyarticular or pauciarticular juvenile rheumatoid
arthritis, rheumatoid arthritis, osteoarthritis because it has been
shown that it provides a clinical improvement in decreasing the
number of tender joints and of analgesics consumed daily by
decreasing the production of Interleukin-8 and Interleukin-1 in
human patients. Patients with a bleeding tendency or severe
psychiatric disease were excluded from the study.
[0093] To evaluate the effects of krill and/or marine oil
supplementation on the clinical course of osteoarthritis, a study
was performed (prospective clinical trial, statistical significance
p<0.05) with patients diagnosed with and treated for
osteoarthritis which is Active class I, II or III and having
treatment with NSAIDs and/or analgesics for at least 3 months
before enrollment.
[0094] A group of 13 patients took krill and/or marine oil
concentrate capsules at a daily rate of 6 capsules of 800 mg krill
oil per capsule. The recommended dosage varies between 1 and 4.8
grams of pure krill extract per day. Patients were asked to follow
a normal healthy diet consisting of 20% fat (less than 10% animal
fat), 40% protein and 40% carbohydrates.
[0095] The inclusion criteria for the study are being aged between
50 and 65 years, both genders being admissible, having a clinical
diagnosis of primary osteoarthritis (mild to moderate) 6 to 12
months prior to study enrollment including pain and stiffness,
radiographic confirmation of illness prior to enrollment. It also
include evidence of measurable symptoms of OA for at least 3 months
prior to study enrollment requiring the use of acetaminophen,
anti-inflammatory agents or opioid analgesics. Patients were asked
to stop the use of all "pain-killers" the week prior to initiation
of the trial for wash-out purposes.
[0096] The Exclusion criteria were a severe osteoarthritis,
unavoidable sustained use of NSAID's, aspirin or other medicines
for anti-inflammatory use, use of topical analgesics within 4 weeks
of randomization visit, steroid injection into either knee within
past 3 months, initiation of physical therapy or muscle
conditioning within 3 months, seafood allergies, use of
anticoagulants or salicylates, alcohol consumption exceeding 3
mixed drinks per day, concurrent medical/arthritic disease that
could confound or interfere with the evaluation of pain, prior
surgery (including arthroscopy) of either knee, a known "secondary"
cause of osteoarthritis.
[0097] Evaluation was based on daily dose of NSAIDs and/or
analgesics and/or SAARDs, number of painful joints, number or
swollen joints, duration of morning stiffness, visual analog scale
(0-100) WOMACscale and SF36. Preliminary results have been obtained
after 2 months. The number of NSAIDs and/or analgesics and/or
SAARDs required for daily functioning has been recorded at
initiation and at 2 months after initiation.
[0098] Results shown at Table 2 demonstrate the effect of an uptake
of krill extract on the relief of arthritis.
2 TABLE 2 Frequency % Valid % Cumulative % No change 3 23.1 23.1
23.1 Pain relief 10 76.9 76.9 100.0 Total 13 100.0 100.0
[0099] This shows that ten out of 13 (76.9%) people reported a
significant pain relief and improvement of flexibility of large
joints (lower back, knees, shoulders)
EXAMPLE 3
Skin Cancer Prophylaxis
[0100] Krill and/or marine oil has been shown to be a skin cancer
prophylactic because of its retinol anti-carcinogenic effect,
Astaxanthin anti-carcinogenic effect and its phopholipid
anti-carcinogenic effect.
[0101] To evaluate the photoprotective potential of krill and/or
marine oil against UVB-induced skin cancer, a study was performed
on nude mice, preferably on C57BL6 Nude Congenic Mice-B6NU-T
(heterozygotes) because of their proven susceptibility to skin
cancer.
[0102] Groups were formed as follows: 48 fish oil: 16 with oral
supplementation (po) 16 with local application, 16 with po and
local application; 48 krill and/or marine oil: 16 with po, 16 with
local application, 16 with po and local application. In order to
establish efficacy of krill and/or marine oil for the prevention of
skin cancer, the test was conducted as a randomized blind
controlled trial (statistical significance p<0.05). Half of the
mice have been treated orally or topically or both with oil
containing 100% by weight krill and/or marine oil and the other
half have been treated the same way with fish oil.
[0103] Nutrition was fat-free chow for the first week and was
modified accordingly with the assigned group as described below for
the following 2-20 weeks in the quantity of 1 ml of oil per
day.
[0104] The mice were divided in six groups as follows:
[0105] Group A: fat-free chow with supplementation of fish oil (20%
of total calories)
[0106] Group B: fat-free chow (100% of calories)+local application
of fish oil 2 times per day
[0107] Group C: fat free chow with supplementation of fish oil (20%
of total calories)+local application of soy oil 2 times per day
[0108] Group D: fat-free chow with supplementation of krill and/or
marine oil (20% of total calories)
[0109] Group E: fat free chow (100% of calories)+local application
of krill and/or marine oil 2 times per day
[0110] Group F: fat-free chow with supplementation or krill and/or
marine oil (20% of total calories)+local application of krill
and/or marine oil 2 times per day
[0111] The mice had been submitted to UVB radiation using a
fluorescent test lamp, emission spectrum 270400 nm during weeks
2-20. The essay were performed during 30 minutes of UVB exposure
per day and the test lamp was at a distance of 30 cm from the mice.
At the end of the 20 weeks, or when malignant tumors had formed,
mice were anesthetized with ether and sacrificed. Skin was examined
blind by pathologists for signs of carcinogenesis.
[0112] The following tables (Tables 3-8) are showing the results
obtained about the incidence of cancer when ultra-violet radiations
are administered to mice's skin during 5 weeks.
3TABLE 3 Krill extract Oral uptake Cumulative Frequency Percent
Valid Percent Percent Valid Benign 14 87.5 87.5 87.5 Cancer 2 12.5
12.5 100.0 Total 16 100.0 100.0
[0113]
4TABLE 4 Control Oral uptake Cumulative Frequency Percent Valid
Percent Percent Valid Benign 14 87.5 87.5 87.5 Cancer 2 12.5 12.5
100.0 Total 16 100.0 100.0
[0114]
5TABLE 5 Krill extract topical uptake Cumulative Frequency Percent
Valid Percent Percent Valid BENIGN 16 100.0 100.0 100.0
[0115]
6TABLE 6 Control topical uptake Cumulative Frequency Percent Valid
Percent Percent Valid BENIGN 5 31.3 31.3 31.3 Cancer 11 68.8 68.8
100.0 Total 16 100.0 100.0
[0116]
7TABLE 7 Krill extract topical and oral uptake Cumulative Frequency
Percent Valid Percent Percent Valid BENIGN 16 100.0 100.0 100.0
[0117]
8TABLE 8 Control topical and oral uptake Cumulative Frequency
Percent Valid Percent Percent Valid BENIGN 10 62.5 62.5 62.5 Cancer
6 37.5 37.5 100.0 Total 16 100.0 100.0
[0118] The results obtained shows that both oral and topical use of
krill oil is effective for the protection of the skin against the
harmful effects fo UVB radiation induced skin cancer.
EXAMPLE 4
Transdermal Transport in Therapeutic Applications
[0119] Krill and/or marine oil enhances transdermal transportation
as a substrate for dermatological topical therapeutic applications.
It may be used in dermatological treatments via creams, ointments,
gels, lotions and oils. It may also be used in various therapeutic
applications such as relating to anesthesic, corticosteroids,
anti-inflammatory, antibiotic and ketolytic functions.
[0120] To evaluate the efficacy of krill and/or marine oil as a
substrate for topical treatments and the speed of transdermal
absorption of krill and/or marine alone or as a substrate, a study
was performed as a randomized blind controlled trial on C57BL6 nude
Congenic Mice-B6NU-T (heterozygotes).
[0121] The results appearing in tables 5 and 6 are showing that
topical treatment with krill oil faciliate the absorption of
retinol and other antioxydants through the dermis which in turn
result in significant photoprotective potential which in turn
results in 100% protection from UVB induced skin cancer. In
contrast, fish oil application with all-trans retinol resulted in
68.8% incidence of cancer.
EXAMPLE 5
Transdermal Transport for Dermatological Topical Cosmetic
Applications
[0122] Krill and/or marine oil can be used to enhance transdermal
transportation as a substrate for dermatological topical cosmetic
applications where cosmetic applications relate to skin hydration,
anti-wrinkle, keratolytics, peeling and mask via creams, ointments,
gels, lotions or oils.
[0123] To evaluate the effects of Krill and/or marine oil in aging
and facial wrinkles, a study was conducted as a prospective
clinical trial on patients concerned about facial dryness and
wrinkles. Those patients had no prognosis severely limited by other
dermatological or non-dermatological condition, bleeding tendency
or severe psychiatric disease.
[0124] 13 Healthy Caucasian women with facial dryness or wrinkles
have been included in this study. Women have been asked to take 6
capsules a day, each capsule containing 800 mg of krill extract.
The recommended daily dosage is of about 1 to 4.8 g of krill
extract.
[0125] Table 9 shows results obtained on skin hydration following
the method previously described.
9TABLE 9 Changes in skin hydration Frequency % Valid % Cumulative %
No change 4 30.8 30.8 30.8 Hydration 9 69.2 69.2 100.0 Total 13
100.0 100.0
[0126] The results of the pilot study after 2 months indicate that
nine out of 13 (69.2%) people reported a significant improvement of
the hydration, texture and elasticity of the skin (face, hands and
arms) in human patients.
[0127] Moreover, these results are also indicative that krill
extract is useful for anti-wrinkle treatment. The mechanism of
all-trans retinol, which is included in the krill oil, as an
anti-wrinkle works as follows:
[0128] Regeneration and distinctive anti-inflammatory effects
[0129] Improve blood irrigation
[0130] Increases the epidermis regeneration by increasing the rate
of cell division and turnover
[0131] Accelerates the differentiation of keratin
[0132] Regenerates the collagen
[0133] Allows cells in the top layer of the skin, which are always
being replaces, to mature more normally than untreated sun-damaged
cells
[0134] Reduces the activation of enzymes that break down the
proteins collagen and elastin that provide structural support for
the skin.
[0135] The results obtained with krill extract administered on a
patent's skin show that the krill extract is having an anti-wrinkle
effect by increasing the hydration and the mechanism above
described.
EXAMPLE 6
Premenstrual Syndrome
[0136] Table 10 shows results obtained from the use of krill oil to
reduce the pain and mood changes associated with premenstrual
syndrome in women. Krill oil extract was administered to 7 women
during 2 months. The women were taking 6 capsules of krill extract
per day, each capsule containing 800 mg of krill oil. A recommended
daily intake of krill oil is of about 1 to 4.8 grams. All
participants were advised to continue with their usual nutrition
habits and to refrain from initiating any restrictions in their
diet. No serious side effects were reported.
[0137] All women enrolled reported noticeable emotional and/or
physical discomfort 7 to 10 days prior to menstruation. A
self-assessment visual analogue scale validated for the assessment
of the premenstrual syndrome, ranging from 0 (no symptoms) to 10
(unbearable) was used as a primary outcome in order to evaluate the
effect of krill extract on premenstrual discomfort.
[0138] Data analysis has been reported on 60% of the women
participating in the study who have completed a two months regimen.
The majority of the women (73.3%) showed a clinically significant
reduction in both emotional and physical distress prior to
menstruation (see Table 10).
10TABLE 10 Frequency distribution of the effect of krill extract on
premenstrual syndrome symptomatology PMS symptoms Frequency % Valid
% Cumulative % No change 26.7 26.7 26.7 Positive 73.3 73.3 100.0
Total 100.0 100.0
EXAMPLE 7
Diabetes
[0139] 8 human patients were taking krill extract at the dosage of
6 capsules a day, each capsule containing 800 mg of krill extract,
during 2 months. A recommended daily intake of krill oil is of
about 1 to 4.8 grams. The Table 11 is showing the variation in the
glucose tested for the patients after 2 months.
11TABLE 11 Variation in glucose in patients Paired Differences 95%
Confidence Para- Std. Interval Sig. meter Error of the t- (2-
tested Mean SD. Mean Difference value df tailed) Glucose .5778
.60369 .20123 .1137-1.0418 2.871 8 .021
[0140] A blood glucose decrease of 20% was obtained for the
patients taking krill extract, which shows that an uptake of krill
extract is controlling blood glucose content and therefore
controlling diabetes in human patients.
[0141] While the invention has been described in connection with
specific embodiments thereof, it will be understood that it is
capable of further modifications and this application is intended
to cover any variations, uses, or adaptations of the invention
following, in general, the principles of the invention and
including such departures from the present disclosure as come
within known or customary practice within the art to which the
invention pertains and as may be applied to the essential features
hereinbefore set forth, and as follows in the scope of the appended
claims.
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