111111
`
`1111111111111111111111111111111111111111111111111111111111111111111111111111
`US 20060078625Al
`
`(19) United States
`c12) Patent Application Publication
`Rockway
`
`(10) Pub. No.: US 2006/0078625 Al
`Apr. 13, 2006
`(43) Pub. Date:
`
`(54) COMPOSITIONS INCLUDING KRILL
`EXTRACTS AND CONJUGATED LINOLEIC
`ACID AND METHODS OF USING SAME
`
`(76)
`
`Inventor: Susie Rockway, Grayslake, IL (US)
`
`Correspondence Address:
`Bell, Boyd & Lloyd LLC
`P.O. Box 1135
`Chicago, IL 60690-1135 (US)
`
`(21) Appl. No.:
`
`10/961,578
`
`(22) Filed:
`
`Oct. 8, 2004
`
`Publication Classification
`
`(51)
`
`Int. Cl.
`A61K 35164
`(2006.01)
`A61K 311202
`(2006.01)
`(52) U.S. Cl. ............................................ 424/538; 514/560
`
`(57)
`
`ABSTRACT
`
`Methods and compositions for the prevention, therapy and/
`or treatment of several disease states. The methods comprise
`the administration of a therapeutically effective amount of a
`composition including krill extract and conjugated linoleic
`acid. In addition, the present invention provides new and
`improved therapeutic compositions including krill extracts
`and conjugated linoleic acid.
`
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`US 2006/0078625 AI
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`Apr. 13, 2006
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`1
`
`COMPOSITIONS INCLUDING KRILL EXTRACTS
`AND CONJUGATED LINOLEIC ACID AND
`METHODS OF USING SAME
`
`PRIORITY CLAIM
`
`[0001] This application claims the benefit of U.S. Provi(cid:173)
`sional Patent Application No. 60/309,456, filed Oct. 8, 2003,
`the disclosures of which are hereby incorporated by refer(cid:173)
`ence.
`
`BACKGROUND OF THE INVENTION
`
`[0002] This invention generally relates to compositions
`and methods for preventing and/or treating diseases.
`
`[0003] PCT Patent Application No. PCT/CA02/00843
`published on Dec. 27, 2002 and entitled "Krill and/or
`Marine Extracts for Prevention and/or Treatment of Cardio(cid:173)
`vascular Diseases, Arthritis, Skin Cancer, Diabetes, Premen(cid:173)
`strual Syndrome and Transdermal Transport" (the disclosure
`of which is incorporated herein by reference) discloses krill
`and/or marine extracts.
`
`[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 acids,
`which are well known for their health benefits.
`
`[0005] The PCT application states that 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 can(cid:173)
`cer.
`
`[0006]
`It is also stated to be known in the art that krill
`and/or marine oil may be used for the treatment of autoim(cid:173)
`mune murine lupus and other autoimmune diseases and can
`also be used for treating cardiovascular diseases.
`
`[0007] However, it is stated that 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. It is known to use
`conjugated linoleic acid for the treatment of diseases.
`
`[0009] Published PCT Patent Application Nos. PCT/
`US00/21050, PCT/US00/21047, PCT/US00/21046, and
`PCT/US00/21044, entitled "Method and Compositions for
`Preventing and/or Treatment of Diabetes and Glucose
`Modulation", "Methods and Compositions for Attenuation
`and/or Prevention of Stress/Catabolic Responses", "Meth(cid:173)
`ods and Compositions for the Prevention and Treatment of
`Inflammation, Osteoarthritis, and Other Degenerative Joint
`Diseases", and "Methods and Compositions for the Preven-
`
`tion and Treatment of Syndrome X", respectively, (the
`disclosures of all of which are incorporated by reference)
`relate to the use of conjugated linoleic acid. As disclosed
`therein, conjugated linoleic acid has been used for the
`treatment of disease states.
`
`SUMMARY OF THE INVENTION
`
`[0010]
`In accordance with the present invention there are
`provided methods of prevention, therapy and/or treatment of
`several disease states. The methods comprise the adminis(cid:173)
`tration of a therapeutically effective amount of a composi(cid:173)
`tion including krill extract and conjugated linoleic acid with
`or without other active or inactive ingredients. In addition,
`the present invention provides new and improved therapeu(cid:173)
`tic compositions including krill extracts and conjugated
`linoleic acid.
`
`[0011] To this end, in an embodiment, the present inven(cid:173)
`tion provides a method for preventing the onset of a disease
`state in an individual comprising the step of administering a
`therapeutically effective amount of a composition including
`krill extract and conjugated linoleic acid.
`
`[0012]
`In an embodiment, approximately 1.0 mg to about
`15 g per day of krill extract and conjugated linoleic acid are
`administered.
`
`[0013]
`In an embodiment, the individual is at risk of a
`disease or ailment chosen from the group consisting of joint
`ailment, PMS, Syndrome X, cardiovascular disease, bone
`disease, immune deficiency, diabetes, stress related disease,
`and hormonal disease.
`
`[0014]
`In an embodiment, the conjugated linoleic acid is
`chosen from the group consisting of a pure isomer of
`octadecadienoic acid and a mixture of octadecadienoic acid
`isomers including: cis-8, cis-1 0; cis-8, trans-! 0; trans-8,
`cis-1 0; trans-8, trans-! 0; cis-9, cis-11; cis-9, trans-11; trans-
`9, cis-11; trans-9, trans-11; cis-10, cis-12; cis-9, trans-12;
`trans-9, cis-12; trans-10, trans-12; cis-11, cis-13; cis-11,
`trans-13; trans-11, cis-13; trans-11, trans-13 octadecadienoic
`acid; 18:3 cis-6, cis-9, trans-11; 18:3 cis-6, trans-10, cis-12;
`18:3 cis-8, trans-12, cis-14; 20:3 cis-8, cis-11, trans-13; 20:4
`cis-5, cis-8, cis-11, trans-13; 20:4 cis-5, cis-8, trans-12,
`cis-14; metabolites thereof; and precursors and derivatives
`thereof.
`
`[0015]
`flavor.
`
`In an embodiment, the composition includes a
`
`[0016]
`In an embodiment, the composition includes an
`artificial sweetener.
`
`[0017]
`In another embodiment of the present invention, a
`composition for treating a disease state or reducing the risk
`of a disease state in a patient is provided comprising an
`effective amount of krill oil in association with conjugated
`linoleic acid and a pharmaceutically acceptable carrier,
`wherein said krill oil is obtained from a process comprising
`the steps of: 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; separating the liquid and solid contents; recovering
`a first lipid rich fraction from the liquid contents by evapo(cid:173)
`ration of the solvent present in the liquid contents; placing
`said solid contents in an organic solvent selected from the
`group of solvents consisting of alcohol, preferably ethanol,
`
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`2
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`isopropanol or t-butanol and esters of acetic acid, preferably
`ethyl acetate to achieve extraction of the remaining soluble
`lipid fraction from said marine and/or aquatic animal mate(cid:173)
`rial; separating the liquid and solid contents; recovering a
`second lipid rich fraction by evaporation of the solvent from
`the liquid contents; and recovering the solid contents.
`
`In yet another embodiment of the present inven(cid:173)
`[0018]
`tion, a therapeutic composition is provided comprising an
`effective amount of krill oil and conjugated linoleic acid in
`association with a pharmaceutically acceptable carrier,
`wherein said krill oil comprises Eicosapentanoic acid,
`Docosahexanoic acid, Phosphatidylcholine, Phosphatidyli(cid:173)
`nositol, Phosphatidylserine, Phosphatidylethanolamine,
`Sphingomyelin, a-tocopherol, Astaxanthin, and flavonoid.
`
`[0019] Still further, the present invention provides a
`method of treating a disease state comprising the steps of
`administering a therapeutically effective amount of a com(cid:173)
`position including conjugated linoleic acid and a krill
`extract.
`
`In an embodiment, the individual suffers from a
`[0020]
`disease or ailment chosen from the group consisting of joint
`ailment, PMS, Syndrome X, cardiovascular disease, bone
`disease, immune deficiency, diabetes, stress related disease,
`and hormonal disease.
`
`In a further embodiment of the present invention, a
`[0021]
`method of producing a therapeutic composition is provided
`comprising preparing a krill extract obtained from a process
`comprising the steps of: 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; separating the liquid and solid contents;
`recovering a first lipid rich fraction from the liquid contents
`by evaporation of the solvent present in the liquid contents;
`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 remain(cid:173)
`ing soluble lipid fraction from the marine and/or aquatic
`material; separating the liquid and solid contents; recovering
`a second lipid rich fraction by evaporation of the solvent
`from the liquid contents; recovering the solid contents; and
`adding the solid contents to a conjugated linoleic acid
`containing composition.
`
`[0022] Additional features and advantages of the present
`invention are described in, and will be apparent from, the
`following Detailed Description of the Invention.
`
`DETAILED DESCRIPTION OF THE
`INVENTION
`
`In accordance with the present invention, there is
`[0023]
`provided therapeutic compositions comprising krill extract
`and conjugated linoleic acid for the prevention and/or treat(cid:173)
`ment and/or therapy of diseases. A variety of treatments and
`compositions are possible pursuant to the present invention.
`The compositions can also be used prophylactically to
`prevent the onset of diseases as well as to maintain a healthy
`individual.
`
`It is believed that there are synergistic effects
`[0024]
`achieved by combining conjugated linoleic acid and krill oil
`extract in a single composition or treatment. These benefits
`are derived from the two oils that have different composi-
`
`tions but produce enhanced or synergistic benefits through
`shared eicosanoid mechanisms. These mechanisms include
`changing membrane composition through phospholipid
`incorporation, longer chain fatty acid incorporation and
`conjugated linoleic acid incorporation. In addition to these
`synergistic shared mechanisms the ability of conjugated
`linoleic acid to activate peroxisome peroxidation activation
`receptors (PPAR), which are thought to be involved with
`glucose and lipid metabolism as well as adipocyte apoptosis
`produces a synergistic effect. These combined oils are
`believed to be beneficial in indications, applications and
`compositions listed below.
`
`[0025] Various combinations of the oils can be used. The
`oils can be topically applied or, parenterally and/or orally
`delivered. By way of example, a daily dosage can provide as
`little as 1 mg of the oils or as much as 15 g of the oils; in
`an embodiment, between 100 mg to 12 g of oil is provided
`daily. Efficacious doses will depend on the condition being
`addressed. By way of example, combinations of either oil
`can be used in a 1:1 ratio or a ratio of0.05: 1 to 1:0.05. These
`oils can be combined with other organic or inorganic com(cid:173)
`pounds known to further enhance the conditions being
`addressed.
`
`[0026] With respect to the krill extract, 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:
`
`(a) placing marine and/or aquatic krill and/or
`[0028]
`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;
`
`(c) recovering a lipid rich fraction from the liquid
`[0030]
`phase obtained at step (b) by evaporation of the solvent
`present in the liquid phase;
`
`(d) placing the solid phase in an organic solvent,
`[0031]
`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
`
`(f) recovering a lipid rich fraction from the liquid
`[0033]
`phase obtained at step (e) by evaporation of the solvent
`present in the liquid phase.
`
`[0034] As set forth in PCT Application No. PCT/CA02/
`00843, 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
`
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`US 2006/0078625 AI
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`3
`
`[0039]
`
`iii. Linoleic acid: 0.10 g/100 g
`
`[0040]
`
`iv. Alpha-linolenic acid: >0.3 g/100 g
`
`[0041] The PCT application states that in the preferred
`embodiment, the Omega-3 fatty acids are found in more than
`30 g/100 g
`
`[0042]
`
`ii) Omega-6:
`
`[0043]
`
`i. Linoleic acid: >0.9 g/100 g
`
`[0080] The PCT application sets forth that after charac(cid:173)
`terization 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.
`
`[0081] The oil has the following stability indexes:
`
`[0082] Peroxide value: <0.1 (mEq/kg)
`
`[0083] Oil Stability index: <0.1 after 50 hours at 97.8° C.
`
`[0044]
`g/100 g
`
`ii. Arachidonic acid: <0.45 g/100 g, preferably <0.6
`
`[0084] Saponification index: 7-180
`
`[0045]
`
`iii) Omega-9:
`
`[0046]
`
`i. Oleic acid: >5 g/100 g
`
`[0047]
`
`iv) palmitic acid: >10 g/100 g
`
`[0048] v) palmitoleic acid: 0.08 g/100 g
`
`[0049] vi) stearic acid: >0.5 g/100 g
`
`[0050] Phospholipids
`
`[0051] Phosphatidylcholine: >4.5 g/100 g
`
`[0052] Phosphatidylinositol: >107 mg/100 g
`
`[0053] Phosphatidylserine: > 75 mg/100 g
`
`[0054] Phoshatidylethanolamine: >0.5 g/100 g
`
`[0055] Sphingomyelin: >107 mg/100 g
`
`[0056] Neutral lipids
`
`[0057] Cholesterol: <3 g/100 g
`
`[0058] Triglycerides: <55 g/100 g
`
`[0059] Monoglycerides: >0.5 g/100 g
`
`[0060] As set forth in the PCT application, the neutral
`lipids of the krill and/or marine extract also comprises:
`
`[0061] Diglycerides: >0.5 g/100 g
`
`[0062] Antioxydants
`
`[0063] A-tocopherol (vitamin E): >1.0 IU/100 g
`
`[0064] All-trans retinol (vitamin A): >1500 IU/100 g
`
`[0065] B-carotene: >3000 flg/100 ml
`
`[0066] Pigments
`
`[0067] Astaxanthin: >20 mg/100 g
`
`[0068] Canthaxanthin: >2 mg/100 g
`
`[0069] Metals
`
`[0070] Zinc: >0.1 mg/100 g
`
`[0071] Selenium: >0.1 mg/100 g
`
`[0072] The PCT application states in another embodiment,
`the krill and/or marine extract also comprises:
`
`[0073] Flavonoids: >0.5 mg/100 g
`
`[0074] Sodium: <500 mg/100 g
`
`[0075] Calcium: >0.1 mg/100 g
`
`[0076] Potassium: >50 mg/100 g
`
`[0077] Aluminum: <8.5 mg/100 g
`
`[0078] Protein: >4 g/1 00 g
`
`[0079] Moisture and volatile matter: <0.8%
`
`[0085]
`
`Iodine value: 60-130%
`
`[0086] Pursuant to the present invention, the method and
`composition comprises administering krill extract and con(cid:173)
`jugated linoleic acid. If desired, the composition can include
`non-active ingredients and/or agents such as flavors, artifi(cid:173)
`cial sweeteners, excipients, etc. The product of the present
`invention is intended to provide a physiologically based
`means to aid in maintaining normal physiological homeo(cid:173)
`stasis.
`
`[0087] Conjugated linoleic acid refers to a group of
`dienoic derivatives of linoleic acid that occur naturally in
`milk and meat of ruminating animals. It can be synthesized
`in the laboratory and in commercial scale and is currently
`available commercially as a dietary supplement.
`
`[0088] Conjugated linoleic acid is believed to be absorbed
`efficiently into the body in a manner similar to that of other
`fatty acids, e.g., linoleic acid. The safety of conjugated
`linoleic acid has been demonstrated in detailed toxicological
`assessments and through extensive use in humans, both as a
`naturally occurring substance and as a dietary supplement. It
`is believed that conjugated linoleic acid is safe for human
`consumption.
`
`[0089] Pursuant to the present invention, the conjugated
`linoleic acid can be conjugated linoleic acid such as that set
`forth in U.S. Pat. No. 5,986,116 the disclosure of which is
`incorporated herein by reference.
`
`[0090]
`In an embodiment, the conjugated linoleic acid is
`either a pure isomer of octadecadienoic acid, or a mixture of
`octadecadienoic acid isomers selected from the group con(cid:173)
`sisting of: cis-8, cis-1 0; cis-8, trans-! 0; trans-8, cis-1 0;
`trans-8, trans-10; cis-9, cis-11; cis-9, trans-11; trans-9, cis-
`11; trans-9, trans-11; cis-10, cis-12; cis-9, trans-12; trans-9,
`cis-12; trans-10, trans-12; cis-11, cis-13; cis-11, trans-13;
`trans-11, cis-13; trans-11, trans-13 octadecadienoic acid;
`metabolites thereof, including but not limited to 18:3 cis-6,
`cis-9, trans-11; 18:3 cis-6, trans-10, cis-12; 18:3 cis-8,
`trans-12, cis-14; 20:3 cis-8, cis-11, trans-13; 20:4 cis-5,
`cis-8, cis-11, trans-13; 20:4 cis-5, cis-8, trans-12, cis-14; as
`well as precursors or derivatives thereof.
`
`[0091] Pursuant to the present invention, the composition
`can be taken as a dietary supplement or a pharmacological
`product.
`
`[0092] By way of example and not limitation, contempla(cid:173)
`tive examples of indications/applications that can be treated
`benefit from the present invention are as follows:
`
`INDICATIONS/ APPLICATIONS
`
`[0093] 1. Joint
`
`[0094] 2. PMS
`
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`4
`
`[0095] 3. Syndrome X
`
`[0096] 4. Body Composition
`
`[0097] 5. Cardiovascular
`
`[0098] 6. Bone Content (Health)
`
`[0099] 7. Immune enhancement
`
`[0100] 8. Diabetes
`
`[0101] 9. Anticarcinogen
`
`[0102] 10. Hormonal Fluctuations
`
`[0103] 11. Quality of Life-feel good
`
`[0104] 12. Stress Catabolic Response
`
`[0105] 13. Skin, hair and nails
`
`[0106] 14. Anti-inflammatory
`
`[0107] 15. Antioxidant
`
`[0108] 1. Joint
`
`[0109] Anti-inflammatory
`reactions: Both conjugated
`linoleic acid and krill oil reduce the adverse effects that
`occur when the eicosanoid pathway through COX-1 and
`COX-2 enzymatic reactions leading to prostaglandin syn(cid:173)
`thesis, such as PGE-2, PGE-1, leukotrienes and thrombox(cid:173)
`anes, are extended beyond normal, physiological needs from
`those signals initially produced by stress or injury. The
`continuation of eicosanoid production leads to chronic
`inflammation as indicated in osteoarthritis, joint pain, car(cid:173)
`tilage breakdown, increased adipose deposition, bone break(cid:173)
`down. In addition, involvement of those eicosanoids (proin(cid:173)
`flammatory) known to increase platelet aggregation and
`eventual plaque formation when endothelial injury has
`occurred-all involved with cardiovascular disease.
`
`[0110] 2. PMS
`
`[0111] The most probable cause of the physical symptoms
`of PMS seems to be the combined interaction of hormones
`and essential nutrients leading to an increased inflammatory
`response.
`
`[0112] The emotional symptoms of PMS seem to be
`propagated by an exaggerated response of neurotransmitters
`to psychosocial stresses. Reducing arachidonic incorpora(cid:173)
`tion or its release from phospholipids (SN-2 position)
`decreases formation of prostaglandin E2 which when
`elevated continues inflammatory response. By increasing the
`ratio of Omega-3 fatty acids to Omega-6 (as in the case of
`krill oil): and by reducing the synthesis of arachidonic acid
`(by decreasing linoleic acid, its precursor) (both conjugated
`linoleic acid and krill oil accomplish this by two different
`mechanisms) will lead to reduced inflammatory responses.
`
`[0113] 3. Syndrome X
`
`[0114] Metabolic syndrome encompasses specific abnor(cid:173)
`malities such as elevated plasma TG's, low levels of HDL,
`increased blood pressure, fasting glucose and increased
`abdominal adipose tissue. Having three or more of these
`conditions constitutes Syndrome X. Conjugated linoleic acid
`decreases elevated glucose levels, decrease elevated TG
`levels and decrease high blood pressure. Krill oil lowers
`elevated glucose and reduce plasma cholesterol, TG and
`simultaneously elevate HDL levels. The combination of
`
`these two oils should have a pos1tJve impact on those
`specific parameters involved with this syndrome.
`
`[0115] 4. Body Composition
`
`[0116] Conjugated linoleic acid reduces fat accumulation
`in humans by decreasing lipoprotein lipase (LPL) synthesis,
`hormone lipase synthesis, decrease adipose cell number by
`apopotosis at early cell development, and increase fat as a
`fuel source (beta-oxidation). In addition, conjugated linoleic
`acid increases muscle mass (LBM) even under catabolic
`conditions such as calorie reduction via weight loss. Krill
`increases energy level, feelings of wellness and energy
`levels, skin, hair and nails improvement, which combined
`with fat loss will give physical and emotional benefits in
`those using these oils.
`
`[0117] 5. Cardiovascular Health
`
`[0118] Cardiovascular health can be improved via the
`present invention due to the ability of the compositions to
`achieve the following:
`
`[0119] LDL cholesterol lowering (conjugated linoleic
`acid, krill oil)
`
`[0120] HDL elevation or maintenance (krill oil)
`
`[0121] TG lowering (conjugated linoleic acid and krill oil)
`
`[0122] Reducing elevated glucose (conjugated linoleic
`acid and krill oil)
`
`[0123] Reducing abdominal adipose (conjugated linoleic
`acid)
`
`[0124]
`Increasing elasticity of endothelial lining and
`reducing platelet aggregation precursors (anti-inflammatory
`response) (conjugated linoleic acid and krill oil)
`
`[0125] 6. Bone Health
`
`[0126] Reducing the chronic stress catabolic response and
`inflammatory response by intake of both conjugated linoleic
`acid and krill oil should dramatically favor an environment
`of bone synthesis and reduce bone degradation. The
`Omega-3 present in krill oil improves the ability of conju(cid:173)
`gated linoleic acid to increase bone mineral content possibly
`by conjugated linoleic acid's ability to decrease inflamma(cid:173)
`tory prostaglandins. Krill oil also contains other compounds
`such as antioxidants and flavonoids that would likely
`improve the micro-environment surrounding bone cells and
`joints.
`
`[0127] 7. Immune Enhancement
`
`[0128] Conjugated
`increases antibody
`linoleic acid
`response to viral invasion. Combined with the antioxidants,
`Omega-3, vitamin and mineral profile and phospholipids
`present in krill oil, enhancing macrophage ability to respond
`to immune challenge.
`
`[0129] 8. Diabetes
`
`[0130] Conjugated linoleic acid decreases elevated glu(cid:173)
`cose and increase insulin sensitivity. Krill oil decreases
`elevated glucose; combining these oils will strengthen their
`ability to promote glucose utilization and favor a healthier
`glucose plasma level.
`
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`US 2006/0078625 AI
`
`Apr. 13, 2006
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`5
`
`such as asthma, rheumatoid arthritis, allergies, etc. could all
`possibly be improved by reducing the eicosanoids respon(cid:173)
`sible for the continuation of inflammation and the cytokines
`involved in perpetuating those chronic disorders. Both con(cid:173)
`jugated linoleic acid and krill oil are shown to reduce these
`inflammatory compounds.
`
`[0144] 15. Antioxidant
`
`[0145] Conjugated linoleic acid behaves as a weak anti(cid:173)
`oxidant. Krill oil is a potent anti-oxidant. Thus, both oils will
`have a beneficial impact in cell's ability to reduce free(cid:173)
`radical damage associated with cell death, aging, neurologi(cid:173)
`cal damage, and cardiovascular disease by specific reduction
`in LDL oxidation.
`
`It should be understood that various changes and
`[0146]
`modifications
`to
`the presently preferred embodiments
`described herein will be apparent to those skilled in the art.
`Such changes and modifications can be made without
`departing from the spirit and scope of the present invention
`and without diminishing its intended advantages. It is there(cid:173)
`fore intended that such changes and modifications be cov(cid:173)
`ered by the claims.
`
`[0131] 9. Anticarcinogen
`
`[0132] Conjugated linoleic acid is a naturally occurring
`anticarcinogen. Krill oil protects against free radical damage
`from sunlight and environmental toxins. Both oils will have
`a favorable impact in reducing risk of cancer, especially
`those cancers induced by free radical damage.
`
`[0133] 10. Hormonal Fluctuations
`
`[0134] Significant improvement in female mood swings
`occur prior and during menstruation. This suggests that there
`will likely be overall benefit in reducing hormonal changes
`that naturally occur during each month by increasing the
`Omega-3 portion oftriglycerides and phospholipids that are
`part of brain cells. Increasing membrane fluidity by increas(cid:173)
`ing long chain fatty acids (Omega-3) enhances the ability of
`protein receptors to respond to substrate interaction and
`therefore, should be improved general cell health by the
`addition of krill oil and conjugated linoleic acid.
`
`[0135]
`In addition, cell membrane composition will be
`improved by the naturally occurring phospholipids existing
`in krill oil. The unique chemical composition appears to
`allow the molecule to be absorbed quickly and is easily
`incorporated into cell membranes, which could explain the
`neurological and hormonal aspects of the observed benefits
`seen in women taking this product. The existence of these
`unique phospholipids with a phosphate group in SN-2
`position, allows greater effects of conjugated linoleic acid to
`act as a COX-2 inhibitor since the conjugated linoleic acid
`molecule would not have to be released by phospho lipases
`within the cell, thus more conjugated linoleic acid will exist
`in the free form and more should be available for either
`PPAR activation or further synthesis of conjugated linoleic
`acid elongated and desaturated products. Therefore, the
`combination of the two oils will have an enhanced and
`perhaps synergistic responses in reducing the ill effects of
`inflammatory eicosanoids, as well as increasing the fluidity
`of cell membranes.
`
`[0136] 11. Quality of Life-Enhanced Wellness
`
`[0137] Subjective data from clinical study supports the
`overall feelings of increased mental focus, more energy, less
`fatigue and less mood swings.
`
`[0138] 12. Stress Catabolic Response
`
`[0139] The anti-inflammatory response of both conjugated
`linoleic acid and krill oil will reduce stress catabolic
`response (hormonally induced reaction to stressors in life)
`and will enhance the bodies ability to maintain homeostasis.
`
`[0140] 13. Skin, Hair and Nails
`
`[0141] Krill oil improves women's perception ofhealthier
`skin, hair and nails, which is likely do to the improved ratio
`of Omega-3 to Omega-6 fatty acids in addition to the
`antioxidant properties of Vitamin A and Vitamin B, fla(cid:173)
`vonoids and astathanxine. Conjugated linoleic acid may also
`help these factors by displacing arachidonic acid and allow(cid:173)
`ing more Omega-3 to compete with COX enzymes and
`increase odd numbered eicosanoids.
`
`[0142] 14. Anti-Inflammatory
`
`[0143] Aging and many chronic diseases in humans is
`related indirectly if not directly to the ability of cells to
`reduce chronic inflammatory responses. Thus, conditions
`
`The invention is claimed as follows:
`1. A method for preventing the onset of a disease state in
`an individual comprising the step of administering a thera(cid:173)
`peutically effective amount of a composition including krill
`extract and conjugated linoleic acid.
`2. The method of claim 1 wherein approximately 1 mg to
`about 15,000 mg per day of krill extract and conjugated
`linoleic acid are administered.
`3. The method of claim 1 wherein the individual is at risk
`of a disease or ailment chosen from the group consisting of
`a joint ailment, PMS, Syndrome X, cardiovascular disease,
`bone disease, immune deficiency, diabetes, stress related
`disease, and hormonal disease.
`4. The method of claim 1 wherein the conjugated linoleic
`acid is chosen from the group consisting of a pure isomer of
`octadecadienoic acid and a mixture of octadecadienoic acid
`isomers including: cis-8, cis-1 0; cis-8, trans-! 0; trans-8,
`cis-1 0; trans-8, trans-! 0; cis-9, cis-11; cis-9, trans-11; trans-
`9, cis-11; trans-9, trans-11; cis-10, cis-12; cis-9, trans-12;
`trans-9, cis-12; trans-10, trans-12; cis-11, cis-13; cis-11,
`trans-13; trans-11, cis-13; trans-11, trans-13 octadecadienoic
`acid; 18:3 cis-6, cis-9, trans-11; 18:3 cis-6, trans-10, cis-12;
`18:3 cis-8, trans-12, cis-14; 20:3 cis-8, cis-11, trans-13; 20:4
`cis-5, cis-8, cis-11, trans-13; 20:4 cis-5, cis-8, trans-12,
`cis-14; metabolites thereof; and precursors and derivatives
`thereof.
`5. The method of claim
`includes a flavor.
`6. The method of claim
`includes an artificial sweetener.
`7. The method of claim 1 wherein the krill extract and
`conjugated linoleic acid are present at a ratio of 0.05:1 to
`1:0.05.
`8. The method of claim
`includes excipients.
`wherein the composition
`9. The method of claim
`includes other active ingredients.
`10. The method of claim 1 wherein the composition
`includes inactive ingredients.
`11. A composition for treating a disease state or reducing
`the risk of a disease state in a patient comprising an effective
`
`wherein the composition
`
`wherein the composition
`
`wherein the composition
`
`AKER EXHIBIT 2017 Page 6
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`US 2006/0078625 AI
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`Apr. 13, 2006
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`6
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`amount of krill oil in association with conjugated linoleic
`acid and a pharmaceutically acceptable carrier, wherein said
`krill oil is obtained from a process comprising the steps of:
`
`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;
`
`b) separating the liquid and solid contents;
`
`c) recovering a first lipid rich fraction from the liquid
`contents by evaporation of the solvent present in the
`liquid contents;
`
`d) placing said solid contents in an organic solvent
`selected from the group of solvents consisting of alco(cid:173)
`hol, preferably ethanol, isopropanol or t-butanol and
`esters of acetic acid, preferably ethyl acetate to achieve
`extraction of the remaining soluble lipid fraction from
`said marine and/or aquatic animal material;
`
`e) separating the liquid and solid contents;
`
`f) recovering a second lipid rich fraction by evaporation
`of the solvent from the liquid contents; and
`
`g) recovering the solid contents.
`12. A therapeutic composition comprising an effective
`amount of krill oil and conjugated linoleic acid in associa(cid:173)
`tion with a pharmaceutically acceptable carrier, wherein said
`krill oil comprises Eicosapentanoic acid, Docosahexanoic
`acid, Phosphatidylcholine, Phosphatidylinositol, Phosphati(cid:173)
`dylserine, Phosphatidylethanolamine, Sphingomyelin, a-to(cid:173)
`copherol, Astaxanthin, and flavonoid.
`
`13. A method of treating a disease state comprising the
`steps of administering a therapeutically effective amount of
`a composition including conjugated linoleic acid and a krill
`extract.
`14. The method of claim 13 wherein approximately 100
`mg to about 12,000 mg per day of krill