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WO2016072992A1 - Supplément nutraceutique avec lactobacillus rhamnosus - Google Patents

Supplément nutraceutique avec lactobacillus rhamnosus Download PDF

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Publication number
WO2016072992A1
WO2016072992A1 PCT/US2014/064342 US2014064342W WO2016072992A1 WO 2016072992 A1 WO2016072992 A1 WO 2016072992A1 US 2014064342 W US2014064342 W US 2014064342W WO 2016072992 A1 WO2016072992 A1 WO 2016072992A1
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Prior art keywords
extract
dietary supplement
ginger
curcumin
cells
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PCT/US2014/064342
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English (en)
Inventor
Bruce E. HECK
Dong Hyun Kim
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Nwo Stem Cure LLC
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Nwo Stem Cure LLC
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Priority to CN201480083170.9A priority Critical patent/CN107073062A/zh
Priority to PCT/US2014/064342 priority patent/WO2016072992A1/fr
Priority to JP2017544271A priority patent/JP2017535289A/ja
Priority to KR1020177015272A priority patent/KR101971809B1/ko
Priority to CA2966487A priority patent/CA2966487A1/fr
Publication of WO2016072992A1 publication Critical patent/WO2016072992A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/906—Zingiberaceae (Ginger family)
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/15—Vitamins
    • A23L33/155—Vitamins A or D
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/29—Berberidaceae (Barberry family), e.g. barberry, cohosh or mayapple
    • A61K36/296—Epimedium
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/32—Burseraceae (Frankincense family)
    • A61K36/324—Boswellia, e.g. frankincense
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/82—Theaceae (Tea family), e.g. camellia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/906—Zingiberaceae (Ginger family)
    • A61K36/9066—Curcuma, e.g. common turmeric, East Indian arrowroot or mango ginger
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/906—Zingiberaceae (Ginger family)
    • A61K36/9068—Zingiber, e.g. garden ginger
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/02—Nutrients, e.g. vitamins, minerals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2400/00—Lactic or propionic acid bacteria
    • A23V2400/11—Lactobacillus
    • A23V2400/175—Rhamnosus

Definitions

  • the present technology relates to compositions and uses thereof to aid joint support, aging, and sports medicine recovery and performance that include Lactobacillus rhamnosus.
  • Osteoarthritis is a common disease resulting in inflammation that breaks down the lining of joints and cartilage.
  • Osteoarthritis is the most common form of arthritis. It is the result of aging "wear and tear" and trauma to the joint, such as sports injuries or fractures.
  • Major complaints of individuals with arthritis include joint pain, swelling, warmth, weakness, giving way of joint, instability, catching, popping, stiffness, poor sleep, muscle pain and fatigue.
  • Autoimmune arthritides such as rheumatoid arthritis, occurs when the body's immune system attacks itself. Osteoarthritis and rheumatoid arthritis are characterized by joint inflammation and cartilage degradation.
  • Mesenchymal stem cells can rebuild cartilage, where the stem cells are resident in the superficial zone of articular cartilage.
  • Treatment of arthritis has relied on relieving symptoms by exercise, braces, weight loss, medications, and surgery including total joint replacement.
  • Medications such as non-steroidal anti-inflammatory drugs (NSAIDs) have risks that include the stomach, cardiovascular system and kidneys leading to ulcers, heart attacks and kidney failure.
  • NSAIDs non-steroidal anti-inflammatory drugs
  • Osteoarthritis is accelerated with obesity/weight gain due to increased joint reactive forces.
  • Aging is a course of degeneration that is associated with the onset of many diseases.
  • systemic inflammation such as obesity
  • the body's ability to stimulate new bone marrow cells including mesenchymal stem cells decreases during aging, the result of which weakens the immune system and the ability to regenerate tissues.
  • Conditions currently identified with an increased prevalence with age and increased inflammation include osteoarthritis, rheumatoid arthritis, cardiovascular disease, diabetes, obesity, Alzheimer's, chronic kidney disease, autoimmune disease, cancer, and other diseases. Symptoms of aging are associated with the underlying oxidative stress, increased inflammation, weakened immune system and the body's decreased ability to form new cells and tissues.
  • Major symptoms of aging include fatigue, lethargy, changes in sleeping pattern, poor memory, poor vision, wrinkles, poor dentition, sexual dysfunction, decreased libido, type II diabetes, increased weight gain, fractures, constipation, skin changes including brown spots, loss of skin elasticity, menopause, hearing loss, increased bone fracture, arthritis, to name a few.
  • Injuries resulting from physical and athletic activities include muscle strains, joint sprains, ligament injuries, cartilage injuries, fractures and overuse conditions. Joints that are often attended to by an orthopedic surgeon for sports injury include the shoulder, knee, ankle, elbow, and wrist. Sports injuries can be accompanied by symptoms including pain, stiffness, swelling, feelings of instability, weakness, redness, crepitance, bruising, and/or mechanical symptoms such as locking or catching in a joint. Sports medicine has developed as a specialty for the prevention and treatment of sports-related injuries that occur at the ligament, muscle, tendon, and bone. Conventional treatment for sports injuries includes rest, ice, compression, elevation.
  • Additional treatments include physical therapy and sports medicine rehabilitation, medication such as NSAIDs to reduce inflammation that exacerbates the injury and leads to surgery.
  • medication such as NSAIDs to reduce inflammation that exacerbates the injury and leads to surgery.
  • NSAIDs include over the counter products, such as ibuprofen, acetaminophen, naproxen, and aspirin, and also include prescription formulations that of naproxen and celecoxib.
  • ibuprofen acetaminophen
  • naproxen naproxen
  • aspirin prescription formulations that of naproxen and celecoxib.
  • Several of these medications are associated with one or more side effects, some of which can be severe.
  • Acetaminophen-associated overdoses in particular, account for about 56,000 emergency room visits and about 26,000 hospitalizations yearly and more than 450 deaths from liver failure.
  • Acetaminophen is also the number one cause of acute liver failure and can result in kidney toxicity.
  • NSAIDs can further induce nausea, heartburn, ingestion, abdominal pain, bleeding ulcer (GI complaints), where approximately 16,500 people per year die as a result of NSAED-associated gastrointestinal complications and an estimated 107,000 patients are hospitalized annually for NSAID-related GI complications.
  • NSAIDs can further present complications relating to heart attack, stroke (cardiovascular events), congestive heart failure, atrial fibrillation, and kidney damage.
  • compositions and methods that relate to treatment of various health issues including musculoskeletal disorders and injuries.
  • a dietary supplement that includes
  • Lactobacillus rhamnosus a dietary supplement
  • ginger a dietary supplement
  • vitamin D a dietary supplement
  • a dietary supplement in another embodiment, includes Lactobacillus rhamnosus, ginger, vitamin D, curcumin, and Boswellia extract, where the dietaiy supplement can be administered to provide joint support and mitigate one or more effects of arthritis.
  • a dietary supplement includes Lactobacillus rhamnosus, ginger, vitamin D, Boswellia extract, and green tea extract, where the dietaiy supplement can be administered to mitigate one or more effects of aging.
  • a dietary supplement includes Lactobacillus rhamnosus, ginger, vitamin D, curcumin, and Epimedium extract, where the dietary supplement can be administered to mitigate one or more effects arising from physical or athletic activities.
  • compositions or processes specifically envisions embodiments consisting of, and consisting essentially of, A, B and C, excluding an element D that may be recited in the art, even though element D is not explicitly described as being excluded herein.
  • all natural supplements disclosed herein may be provided in the synthetic form and used within the scope of the present disclosure.
  • compositional percentages are by weight of the total composition, unless otherwise specified. Disclosures of ranges are, unless specified otherwise, inclusive of endpoints and include all distinct values and further divided ranges within the entire range. Thus, for example, a range of "from A to B" or “from about A to about B” is inclusive of A and of B. Disclosure of values and ranges of values for specific parameters (such as amounts, weight percentages, etc.) are not exclusive of other values and ranges of values useful herein. It is envisioned that two or more specific exemplified values for a given parameter may define endpoints for a range of values that may be claimed for the parameter.
  • Parameter X is exemplified herein to have value A and also exemplified to have value Z, it is envisioned that Parameter X may have a range of values from about A to about Z.
  • disclosure of two or more ranges of values for a parameter (whether such ranges are nested, overlapping or distinct) subsume all possible combination of ranges for the value that might be claimed using endpoints of the disclosed ranges.
  • Parameter X is exemplified herein to have values in the range of 1-10, or 2-9, or 3-8, it is also envisioned that Parameter X may have other ranges of values including 1-9, 1-8, 1-3, 1-2, 2-10, 2-8, 2-3, 3-10, 3-9, and so on.
  • compositions that include the probiotic organism Lactobacillus rhamnosus and methods of administering such compositions to aid various health issues, including joint support, aging, and sports medicine recovery and performance.
  • the compositions can include a member selected from the group consisting of curcumin, Boswellia extract, ginger, vitamin D, green tea extract, Epimedium extract, and combinations thereof. Curcumin can be provided by tumeric or extracted therefrom. Additionally, it should be appreciated that curcumin may be provided in a synthetic form and used within the scope of the present disclosure.
  • Boswellia extract can be obtained from Boswellia serrata (i.e., Indian
  • Ginger can be obtained from the root of Zingiber officinale.
  • Vitamin D can include cholecalciferol.
  • Green tea extract can be obtained from Camellia sinesnsis.
  • Epimedium extract can be obtained from Epimedium sagittatum (i.e., Horny Goat Extract).
  • the compositions can be formulated for oral administration, including one or more tablets or capsules, liquid or slurry form, or as a powder or granulate.
  • Other ingredients can be included, such as various excipients, including one or more antiadherents, binders, coatings, disintegrants, flavors, colors, lubricants, glidants, sorbents, preservatives, and sweeteners.
  • Particular excipient examples include one or more of hypromellose, rice flour, magnesium stearate, cellulose, inulin, and silicon dioxide.
  • compositions and uses thereof tailored to particular muscloskeletal disorders and/or injuries.
  • a composition for providing joint support and mitigating one or more effects of arthritis comprises
  • composition for mitigating the effects of aging comprises
  • a composition for mitigating issues arising from physical and athletic activities comprises Lactobacillus rhamnosiis, curcumin, ginger, vitamin D, and Epimedium extract.
  • the composition can be used to provide protection against oxidative stress, anti-inflammatory action, and immuno-modulatory effects.
  • the various components used in the compositions are approved by the U.S. Food and Drug Administration (FDA) for human use as food and diet supplements and can present limited or no side effects, such as gastric irritation, stomach ulcers, hypertension, cardiovascular diseases, and kidney dysfunction.
  • FDA U.S. Food and Drug Administration
  • Lactobacillus rhamnosiis is approved by FDA for human use and can provide one or more activities attending to various health issues, including musculoskeletal issues. Lactobacillus rhamnosiis can reduce the inflammatory symptoms of rheumatoid arthritis in humans. Oral ingestion of Lactobacillus can improve the Health Assessment Questionnaire (HAQ) score and reduce the levels of plasma inflammatory cytokines. Lactobacillus rhamnosiis can ameliorate arthritis in animals. Exopolysaccharide (EPS), the major component of Lactobacillus rhamnosus, has anti-arthritogenic properties. EPS or EPS- producing probiotics can suppress active arthritis. Lactobacillus rhamnosus can suppress inflammation in animals.
  • EPS Exopolysaccharide
  • Lactobacillus rhamnos s can reduce inflammatory signaling in immature intestines in animals. Thus, it can be expected to suppress intestinal inflammatory syndromes that present in newborns or children, such as necrotizing enterocolitis (NEC), idiopathic inflammatory bowel diseases (IBD), or infectious enteritis. Lactobacillus rhamnosus can reduce GI and respiratoiy infections. Lactobacillus rhamnosus can reduce the risk for gastrointestinal and respiratory tract infections in pediatric patients. Mice treated with Lactobacillus rhamnos s showed attenuated weight gain on a high fat diet (HD) (not normal diet [ND]) compared to those with PBS (P). Mice receiving Lactobacillus rhamnosus showed faster glucose clearance (higher insulin sensitivity) on HD.
  • HD high fat diet
  • PBS normal diet
  • Lactobacillus rhamnosus can protect human colonic muscle. Lactobacillus rhamnos s can attenuate lipopolysaccharide (LPS)-caused inflammation that produces higher IL-6, lower IL- 10 (anti-inflammatory) and can restore the contractility of muscle tissue and cells under inflammation. Lactobacillus rhamnosus can increase insulin sensitivity. Lactobacillus rhamnos s can reduce oxidative stress in athletes during intense exercise. Treatment with Lactobacillus rhamnosus can decrease the plasma levels of reactive oxygen metabolites (dROM) and biological antioxidant potential (BAP) in athletes who took intense exercise training. Lactobacillus rhamnos s can decrease the incidence of UV-induced tumor formation.
  • LPS lipopolysaccharide
  • Lactobacillus rhamnosas Hairless mice treated with Lactobacillus rhamnosas showed a delay in tumor expansion in both number and size. Lactobacillus rhamnosus can enhance both natural and acquired immunity. Treatment with Lactobacillus rhamnosus can increase the plasma levels of peripheral leucocytes and peritoneal macrophages (phagocytic activities) and antibody, which suggests that Lactobacillus rhamnosus increases both innate and acquired immunity.
  • Lactobacillus rhamnosus provides several benefits, including the following. Lactobacillus rhamnosus is a unique probiotic strain. Lactobacillus rhamnosus can attenuate various types of arthritis. Lactobacillus rhamnosus functions as antioxidant which may make healthy cartilage cells. Lactobacillus rhamnosus can decrease the inflammatory cytokines that damage cartilage and joints. Lactobacillus rhamnosus can suppress the expression of inflammatory genes that cause pain and stiffness accompanied with arthritis. Lactobacillus rhamnosus can ameliorate rheumatoid arthritis. Lactobacillus rhamnosus can reduce oxidative stress and increases lifespan in the worm model, C.
  • Lactobacillus rhamnosus can decrease inflammation. Lactobacillus rhamnosus can improve insulin-sensitivity and reduce fat accumulation. Lactobacillus rhamnosus can provide photoprotection against UV radiation. Lactobacillus rhamnosus shows anti-oxidant benefits in athletes during intense exercise training. Lactobacillus rhamnosus can decrease the risk of gastrointestinal and respiratoiy infections. Lactobacillus rhamnosus can reduce adiposity in animals on high fat diet. Lactobacillus rhamnosus can protect against UV-induced carcinogenesis. Lactobacillus rhamnosus is anti-inflammatory and immuno-modulatory.
  • Compositions including Lactobacillus rhamnosus and uses thereof can have various physical amounts of Lactobacillus rhamnosus and various amounts of colony forming units (CFU) of Lactobacillus rhamnosus.
  • CFU colony forming units
  • Examples include physical amounts ranging from 1 mg to 1000 mg, 10 mg to 500 mg, 50 mg to 100 mg, and 67 mg.
  • Examples further include CFU values ranging from 100 million to 1 trillion, 1 billion to 100 billion, 5 billion to 50 billion, and 10 billion.
  • Other amounts for the Lactobacillus rhamnosus may also be selected by one of ordinary skill in the art, as desired. These amounts can be provided and administered as a composition comprising a single dose or as multiple doses, can be provided as a single capsule or as multiple capsules, and can be admixed with other components, for example.
  • Curcumin is approved by FDA for human use and can provide one or more activities attending to various health issues, including musculoskeletal issues. As noted, curcumin can be provided by tumeric or extracted therefrom. Additionally, it should be appreciated that curcumin may be provided in a synthetic form and used within the scope of the present disclosure. Curcumin can have the same analgesic effect as ibuprofen in osteoarthritis patients. Curcumin can be as effective as ibuprofen for the treatment of knee osteoarthritis while it has fewer side effects than ibuprofen. Curcumin can suppress the activity of human synoviocytes that cause rheumatoid arthritis.
  • Curcumin can suppress the production of inflammatory cytokines from synoviocytes that cause rheumatoid arthritis in patients. It can also suppress the expansion of human synoviocytes. Curcumin can suppress inflammation and arthritis in animals. Curcumin can suppress not only the production of inflammatory cytokines but also collagen-induced arthritis (CIA) in animals. Curcumin can enhance muscle regeneration after traumatic injury. Systemic treatment with curcumin can increase muscle mass (embryonic myosin heavy chain [EMHC]) and muscle cells in two different injured muscle sites (Masseter & tibialis anterior [TA]). Curcumin can increase cardiac muscle repair and can ameliorate cardiac failure. Curcumin can suppress the production of malondialdehyde (MDA [A]), a lipid peroxide, and matrix metalloproteases (MMPs) that damage cardiac muscle, in an animal model of myocardial infarction.
  • MDA [A] malondialdehyde
  • MMPs matrix metalloproteases
  • Curcumin can suppress oxidative stress that causes muscle damage. Curcumin can suppress the production of oxidants (hydrogen peroxide & NADPH-oxidase) and muscle damage markers (MCP-1 & CXCL14) in the muscle of animals that underwent extensive exercise.
  • oxidants hydrogen peroxide & NADPH-oxidase
  • MCP-1 & CXCL14 muscle damage markers
  • curcumin provides several benefits, including the following. Curcumin can be as safe and effective as an NSAH) in the treatment of knee osteoarthritis. Curcumin can be anti-inflammatory. Curcumin can reduce inflammatory cytokines in cartilage. Curcumin can show an anti-arthritic effect in animals. Curcumin can promote cartilage formation from mesenchymal stem cells. Curcumin can reduce inflammation in the synovial lining of human joints. Curcumin can suppress collagen-induced arthritis in animals. Curcumin can show a therapeutic effect for the treatment of osteoarthritis.
  • Curcumin can promote muscle repair. Curcumin may prevent loss of muscle mass and stimulate muscle regeneration after traumatic injury. Curcumin can reduce inflammation and can enhance eccentric exercise-induced muscle damage. Curcumin can promote cardiac repair. Curcumin can decrease oxidative stress following downhill running-induced muscle damage. Curcumin can have a therapeutic effect for the treatment of osteoarthritis.
  • compositions including curcumin and uses thereof can employ various amounts. Examples include amounts ranging from 1 mg to 1000 mg, 10 mg to 700 mg, 100 mg to 500 mg, and 350 mg. Other amounts for the curcumin may also be selected by one of ordinary skill in the art, as desired. These amounts can be provided and administered as a composition comprising a single dose or as multiple doses, can be provided as a single capsule or as multiple capsules, and can be admixed with other components, for example.
  • Boswellia extract is approved by FDA for human use and can provide one or more activities attending to various health issues, including musculoskeletal issues.
  • Boswellia extract can include Boswellia serrata extract.
  • Boswellia extract can reduce osteoarthritis symptoms. Osteoarthritis patients who received Boswellia plant extract reported decreased knee pain and swelling, increased knee flexion, and increased walking distance. Boswellia plant extract reduced osteoarthritis-related pain and physical functions (visual analog scale), Lequesne's functional index, and WOMAC pain and stiffness.
  • Boswellia extract can reduce arthritis and inflammation in animals. Boswellia extract can reduce arthritic scores, paw edema, and the local tissue pro-inflammatory cytokines tumor necrosis factor alpha (TNF-a) and interleukin-1 beta (IL- ⁇ ) in a Lewis rat adjuvant arthritis animal model. Boswellia extract can restore memory in animals. Orally ingested
  • Boswellia extract can reduce the escape latency and distance traveled but had no influence on swimming speed in the Morris water maze, suggesting that it enhances spatial memory in animals. Boswellia extract can have anti-tumor and anti-hyperlipidemic effects in animals. Orally ingested Boswellia plant extract can reduce TPA-induced skin inflammation and edema formation.
  • Boswellia Extract provides several benefits, including the following.
  • Boswellia Extract significantly improves pain score and physical function in osteoarthritis patients.
  • Boswellia extract can suppress the activation of the inflammatory immune system.
  • Boswellia extract can block cartilage matrix breakdown and can increase type II collagen and aggrecan in human osteoarthritis chondrocytes.
  • Boswellia extract can reduce cartilage-degrading enzymes and inflammation in osteoarthritis patients.
  • Boswellia extract can be anti-inflammatory, anti-arthritic, and analgesic.
  • Boswellia extract can decrease knee pain and can increase knee flexion and walking distance.
  • Boswellia extract can decrease joint inflammation and spinal arthritis.
  • Boswellia Extract can improve memory in an aging animal model.
  • Boswellia extract can have anti-oxidant and antithrombotic effects.
  • Boswellia extract can increase the elasticity of photo-aged skin.
  • Boswellia extract can exert anti-tumor and anti-hyperlipidemic effects.
  • compositions including Boswellia extract and uses thereof can have various physical amounts of Boswellia extract and various amounts of boswellic acid. Examples include physical amounts ranging from 1 mg to 1000 mg, 10 mg to 800 mg, 100 mg to 600 mg, and 500 mg. Additionally, it should be appreciated that Boswellia extract may be provided in a synthetic form and used within the scope of the present disclosure. Other amounts for the Boswellia extract may also be selected by one of ordinary skill in the art, as desired. Examples further include where the physical amount includes various percentages of boswellic acid, including 1% to 100%, 10% to 90%, 25% to 75%, and 65%. These physical amounts and percentages can be provided and administered as a composition comprising a single dose or as multiple doses, can be provided as a single capsule or as multiple capsules, and can be admixed with other components, for example.
  • Ginger is approved by FDA for human use and can provide one or more activities attending to various health issues, including musculoskeletal issues.
  • ginger can be obtained from the root of Zingiber officinale.
  • Ginger can be as effective as an NSAID in reducing arthritic pain without gastropathy in patients.
  • a ginger-containing supplement (Zinaxin) reduced arthritic pain (visual analogue scale [VAS]) to the same extent as diclofenac, an NSAID.
  • Zinaxin does not cause gastropathy that accompanies NSAID.
  • Ginger can relieve osteoarthritis symptoms. Osteoarthritis patients treated with ginger showed a marked relief of osteoarthritis symptoms (based on Health Assessment Questionnaire) and progressing improvement without showing any sign of negative effects.
  • Ginger can reduce inflammation and muscle soreness caused by exercise in patients. In 98 patients treated with ginger for 6 weeks, there was a significant decrease in muscle soreness and inflammation.
  • ginger provides several benefits, including the following.
  • Ginger therapy can demonstrate a marked relief of osteoarthritis symptoms with few side effects.
  • Ginger can suppress joint inflammation by reducing inflammatory cytokines in rheumatoid arthritis.
  • Ginger can be as effective as the powerful steroid, betamethasone, in reducing osteoarthritis and rheumatoid arthritis.
  • Ginger can reduce arthritis pain as much as diclofenac (NSAID) does in patients.
  • NSAID diclofenac
  • Ginger can have antioxidant and protective effects against acetaminophen in animals.
  • Ginger can have anti-oxidative, anti-inflammatory, anticancer, and anti-diabetic effects. Ginger can reduce muscle pain caused by exercise.
  • Ginger can reduce muscle soreness caused by exercise. Long-term treatment with ginger can relieve osteoarthritis symptoms with few side effects.
  • compositions including ginger and uses thereof can have various physical amounts of ginger where the physical amounts can include various concentration ratios. Examples include physical amounts ranging from 1 mg to 1000 mg, 10 mg to 800 mg, 100 mg to 600 mg, and 500 mg. Examples further include where the physical amount relates to a ginger concentrate range, including 1.5:1 to 20:1, 2:1 to 15:1, 5:1 to 10:1, and 8:1. Equivalent concentrations of gingeroles (active ingredients of ginger) may also be employed. Additionally, it should be appreciated that ginger may be provided in a synthetic form and used within the scope of the present disclosure. Other amounts for the ginger may also be selected by one of ordinary skill in the art, as desired. These amounts can be provided and administered as a composition comprising a single dose or as multiple doses, can be provided as a single capsule or as multiple capsules, and can be admixed with other components, for example.
  • Vitamin D is approved by FDA for human use and can provide one or more activities attending to various health issues, including musculoskeletal issues. As noted, vitamin D can include cholecalciferol. Vitamin D can decrease the effects of osteoarthritis in humans. Sunlight exposure and serum Vitamin D (25[OH]D) levels are positively correlated with a decrease in knee cartilage loss. Thus, achieving vitamin D sufficiency may prevent and/or retard cartilage loss in knee osteoarthritis. Vitamin D (l,25(OH)2D3) can reduce the arthritic production of matrix metalloprotease-9 and prostaglandin E2 (PGE2) in human articular chondrocytes.
  • PGE2 prostaglandin E2
  • Vitamin D can increase proper bone formation and can decrease unwanted aortic calcification on a high phosphate diet. In chronic kidney disease, patients lose their production of proper bone-forming factors and gain unnecessary aortic calcification. Paricalcitol containing Vitamin D can reverse both. Vitamin D can increase bone formation. Vitamin D (l,25(OH)2D3) can increase the expression of protein factors (type I collagen, osteopontin, sialoprotein, osteocalcin, alkaline phosphatase, and BMP-2) that enhance bone formation.
  • protein factors type I collagen, osteopontin, sialoprotein, osteocalcin, alkaline phosphatase, and BMP-2
  • vitamin D provides several benefits, including the following. Vitamin D levels are positively associated with improvement in knee cartilage volume.
  • Vitamin D can suppress inflammation in osteoarthritis and rheumatoid arthritis. Vitamin D can exert anti-inflammatory action on synovial lining cells. Vitamin D levels can be associated with bone mineral density and protection of cartilage in osteoarthritic knee.
  • Vitamin D-deficient athletes can have a smaller heart size. Vitamin D-deficiency can be associated with lower body mass in professional football players. Vitamin D directly affects skeletal muscle structure and function. Vitamin D can prevent overuse-caused injuries such as stress fracture. Vitamin D can modulate the age-related decline in muscle function and benefits the aging athlete. Vitamin D can be used for DNA repair, thus exerting an anti- aging effect. Vitamin D can have protective effects on cardiovascular disease, diabetes, auto-immune disease and cancer. Vitamin D can be important for anti-aging of the bone. Vitamin D can increase the expression of anti-aging genes. Vitamin D can induce bone formation in mesenchymal stem cells.
  • compositions including vitamin D and uses thereof can have various amounts of vitamin D, including various ranges of international units (IU). Examples include IU values ranging from 1 IU to 10,000 IU, 10 IU to 7,500 IU, 100 IU to 5,000 IU, 500 IU to 2,000 IU, and 1,000 IU. Additionally, it should be appreciated that vitamin D may be provided in a synthetic form and used within the scope of the present disclosure. Other amounts for the vitamin D may also be selected by one of ordinary skill in the art, as desired. These amounts can be provided and administered as a composition comprising a single dose or as multiple doses, can be provided as a single capsule or as multiple capsules, and can be admixed with other components, for example.
  • IU international units
  • Green tea extract is approved by FDA for human use and can provide one or more activities attending to various health issues, including musculoskeletal issues.
  • green tea extract can be obtained from Camellia sinesnsis and can include various weight percentages of polyphenols, catechins, and epigallocatechin gallate (EGCG).
  • Green tea extract can suppress skin damage and aging caused by UV light. Cream containing green tea extract can reduce UV-induced photo-aging and subsequent immunosuppression.
  • Green tea extract can increase learning and memory in old rats. Both young and old rats treated with green tea extract showed shorter time to find a safe place (closed [dark] arm) and to take a proper avoiding action to a pain-inducing condition.
  • Green tea extract can have bone-forming and anti-fat effects.
  • Green tea extract can increase the activity of bone- forming alkaline phosphatase (ALP) and suppresses the proliferation of fat cells (adipocytes).
  • ALP alkaline phosphatase
  • green tea extract provides several benefits, including the following.
  • Green tea extract can be effective in enhancing learning and memory.
  • Green tea extract can have bone-forming and anti-obesity effects.
  • Green tea extract can have antioxidant and anti-aging effects.
  • Green tea extract can have a UV protective effect.
  • Green tea extract can protect blood cells from aging-induced oxidative stress.
  • Compositions including green tea extract and uses thereof can have various physical amounts of green tea extract and various amounts of polyphenols, catechins, and epigallocatechin gallate.
  • Examples include physical amounts ranging from 1 mg to 1000 mg, 10 mg to 800 mg, 100 mg to 600 mg, and 500 mg. Examples further include where the physical amount includes polyphenols at 1% to 100 %, 10% to 100%, 50% to 100%, and 98%. Examples further include where the physical amount includes catechins at 1% to 100 %, 10% to 100%, 50% to 100%, and 80%. Examples further include where the physical amount includes epigallocatechin gallate at 1% to 100 %, 10% to 90%, 25% to 75%, and 50%.
  • green tea extract may be provided in a synthetic form and used within the scope of the present disclosure.
  • Other amounts for the green tea extract may also be selected by one of ordinary skill in the art, as desired. These amounts can be provided and administered as a composition comprising a single dose or as multiple doses, can be provided as a single capsule or as multiple capsules, and can be admixed with other components, for example.
  • Epimedium extract is approved by FDA for human use and can provide one or more activities attending to various health issues, including musculoskeletal issues.
  • Epimedium extract can be obtained from Epimedium sagittatum (i.e., Horny Goat Extract) and can have various weight percentages of icariin.
  • Epimedium extract can increase the formation of bone cells.
  • Treatment with epimedium extract increased the formation of bone cells from mesenchymal stem cells.
  • Epimedium extract has a vasorelaxant effect in animals. Icarrin, a major component of epimedium extract, can reduce blood pressure by relaxing coronary arterial vessel and increasing the activity of the antioxidant enzyme, eNOS, in the vessel.
  • Epimedium extract can enhance peripheral nerve regeneration.
  • Epimedium extract (Icarrin: major component) can promote peripheral nerve regeneration and improve the function of damaged nerves in a crush injury animal model. Epimedium extract can mimic one or more effects of testosterone. Icarrin (ICA - a major component of epimedium extract) can increase the levels of circulating serum testosterone and serum bone Gla-protein (BGP), a marker of bone growth.
  • ICA Icarrin
  • BGP serum bone Gla-protein
  • Epimedium extract provides several benefits, including the following.
  • Epimedium extract can be a testosterone-mimetic.
  • Epimedium extract can enhance the activities of the anti-oxidant enzymes, eNOS and NO.
  • Epimedium extract can enhance the formation of bone cells from mesenchymal stem cells.
  • Epimedium extract can improve bone formation and decrease bone absorption.
  • Epimedium extract can have cardiovascular therapeutic effects.
  • Epimedium extract can restore the function of damaged nerves and promote peripheral nerve regeneration.
  • compositions including Epimedium extract and uses thereof can have various physical amounts of Epimedium extract with various weight percentages of icariin.
  • Examples include physical amounts ranging from 1 mg to 1000 mg, 10 mg to 800 mg, 100 mg to 600 mg, and 500 mg. Examples further include where the physical amount includes various weight percentages of icariin, including 0.1 % to 100%, 1% to 90%, 1% to 50%, 5% to 20%>, and 10%.. Additionally, it should be appreciated that Epimedium extract may be provided in a synthetic form and used within the scope of the present disclosure. Other amounts for the Epimedium extract may also be selected by one of ordinary skill in the art, as desired. These amounts can be provided and administered as a composition comprising a single dose or as multiple doses, can be provided as a single capsule or as multiple capsules, and can be admixed with other components, for example.
  • compositions can be formulated in various ways, typically for oral administration. Examples include forming the compositions into various tablets or capsules, providing the compositions in a liquid or slurry form, or providing the compositions as powders or granulates.
  • the composition components can be entirely admixed together into a single portion, each provided as a separate portion, or various components can be admixed where the whole composition is provided by more than one portion but where a total number of portions is less than the number of components.
  • Other dosage forms suitable for oral administration can be used.
  • compositions can be included in the present compositions, such as various excipients, including one or more antiadherents (e.g., magnesium stearate), binders (e.g., saccharides, gelatin, polymers), coatings (e.g., hydroxypropyl methylcellulose, enterics such as waxes, plastics, fibers etc.), disintegrants (e.g., polyvinylpyrrolidone, carboxymethyl cellulose, modified starches), flavors, colors, lubricants (e.g., talc, silica, fats), glidants (e.g., fumed silica, talc, magnesium carbonate), sorbents, preservatives (e.g., antioxidants such as vitamins A, E, and C), and sweeteners.
  • antiadherents e.g., magnesium stearate
  • binders e.g., saccharides, gelatin, polymers
  • coatings e.g.,
  • the present compositions and methods of administering such compositions can impact the way a body's stem cells respond to various health issues, including musculoskeletal issues.
  • Stem cells include unique types of cells that have a remarkable potential to develop many different cell types.
  • Stem cells can differentiate into other cell types, including fat, muscle, bone, cartilage, nerve, blood vessel, etc. They are important in early life during growth and repairing/replenishing tissues. Once a stem cell develops into specific cells, such as a fat cell, it typically can not form other tissues such as bone, cartilage, and muscle.
  • the present compositions can impact stem cells and thereby reduce the inflammatory process and improve underlying symptoms. Keeping tissues healthy also leads to the possibility of disease modification and reducing symptoms/progression of health conditions.
  • Cells and tissues can be damaged with stress, lack of sleep, travel, certain medications, smoking, injury, aging, a poor diet, toxins, autoimmune diseases and many other causes. Stem cells can participate in the healing and repair of these damaged cells and tissues. Stem cells offer a renewable source of cells and tissues to treat multiple diseases, and conditions including arthritis, aging, and sports medicine injuries. Damaged cells and tissue can lead to accelerated aging and injury, including sports injuries. Currently, obesity is an epidemic resulting in stem cells forming more fat leading to lack of bone, cartilage, and blood vessels resulting in diabetes, hypertension, osteoporosis, arthritis,
  • the present compositions and uses thereof involve a paradigm shift in the thought of addressing the aging process. To slow the aging process, it is felt that keeping the cells that replenish the tissues (e.g., mesenchymal and hematopoietic stem cells) healthy is important. Aging declines the number of stem cells. Multiple scientific studies demonstrate the individual supplements in the present compositions can protect such cells. However, the combinations used in the present compositions revolutionize the current thought and approach to supporting joint health, anti-aging, and sports medicine
  • the present compositions and methods of using such compositions may direct a person's own stem cells to form muscle, bone, cartilage, nerve, blood vessel over fat.
  • individual supplements of the present compositions have demonstrated marked improvement of anti-oxidant function and the ability to down regulate inflammatory chemicals and genes responsible for contributing to the disease process. These effects have been demonstrated through extensive research, including clinical studies involving patients with various conditions.
  • Individual components in the present compositions have demonstrated the ability to protect cells and promote chondrogenic differentiation of mesenchymal stem cells (MSCs).
  • MSCs mesenchymal stem cells
  • compositions for providing joint support and mitigating one or more effects of arthritis comprises Lactobacillus rhan osus, vitamin D, curcumin, Boswellia extract, and ginger.
  • the composition is formulated as capsules, with a serving size of two capsules that contain ingredients or components as shown in the following TABLE 1.
  • Vitamin D3 (as cholecalciferol) 1000 IU 250%
  • Boswellia Serrata Gum Extract 500 mg n/a
  • Curcumin as Tumeric Root Extract 350 mg n/a
  • Lactobacillus rhamnosus 10 billion CFU n/a n/a Daily Value not established.
  • Hypromellose Capsule
  • Rice Flour Magnesium Stearate.
  • Frozen bone marrow mononuclear cells were purchased from Allcells
  • MSCs When the MSCs were confluent, the cells were recovered by the addition of 0.25% trypsin/EDTA (Invitrogen, Carlsbad, CA). MSCs (Passage 2-3) were plated in either a 75-cm 2 flask or a 24 well plate and cultured in a-MEM with 20% FBS up to a density of 2.0X10 4 cells/cm 2 . The medium was replaced with adipogenic medium, and the cells were cultured for an additional 14 days. The adipogenic media consisted of complete culture medium supplemented with DMEM- high glucose, 10% (v/v) FBS, 10 ⁇ g/ml insulin, 0.5 mM dexamethasone (Sigma-Aldrich, St.
  • adipocytes were fixed in 10% formaldehyde, washed in Oil-red O for 10 min, rinsed with 60% isopropanol (Sigma- Aldrich, St. Louis, MO), and the Oil red O eluted by adding 100% isopropanol for 10 min and OD measured at 490 nm, for 0.5 sec reading.
  • LIVE/DEAD ⁇ Viability/Cytotoxicity Assay Kit (Life Technologies). Briefly, human MSC were plated on 24 wells plate. On, next day cells were treated with ingredients and 100 ⁇ H 2 0 2 for 12hr. The supernatant media from each well was collected into microtubes and cells were washed with IX PBS, followed by collection of washes into respective microtubes to collect any floating or dead cells. The cells attached to the bottom of the plate were incubated in IX PBS in a 37 °C incubator. The microtubes were centrifuged at 2000 rpm for 3 min to get the cell pellet.
  • cell pellet was resuspended into IX PBS containing 2 ⁇ calcein AM and 4 ⁇ ethidium / homodimer. Re-suspended cells were again poured into their respective wells and the plate was incubated at 37 °C for 15 min. The cells were then imaged under 10X objective using fluorescence microscope (Olympus 1X71).
  • TABLE 1 It is also believed that the formulation of TABLE 1 will have a beneficial effect on chondrogenic and osteogenic differentiation of human MSC. Inflammation is detrimental to chondrogenesis and chondrocyte formation from human MSC.
  • the formulation of TABLE 1 demonstrates anti-inflammatory effects, as inferred by the significant decrease in adipogenesis in the above-described experiments.
  • An embodiment of a composition for mitigating the effects of aging comprises Lactobacillus rhanmosns, Boswellia extract, ginger, green tea extract, and vitamin D.
  • the composition is formulated as capsules, with a serving size of two capsules that contain ingredients or components as shown in the following TABLE 2.
  • Vitamin D (as cholecalciferol) 1000 IU 250%
  • Green Tea (leaf) Extract (Camellia sinensis) 500 mg n/a (standardized to 98% polyphenols, 80% catechins,
  • Boswellia Serrata Extract 500 mg n/a (standardized to 65% boswellic acid)
  • Ginger root (from 8: 1 concentrate) (Zingiber 500 mg n/a officinale)
  • Lactobacillus rhamnosus 10 billion CFU n/a n/a Daily Value not established.
  • Frozen bone marrow mononuclear cells were purchased from Allcells
  • MSCs When the MSCs were confluent, the cells were recovered by the addition of 0.25% trypsin EDTA (Invitrogen, Carlsbad, CA). MSCs (Passage 2-3) were plated in either a 75-cm 2 flask or a 24 well plate and cultured in a-MEM with 20% FBS up to a density of 2.0X10 4 cells/cm 2 . The medium was replaced with adipogenic medium, and the cells were cultured for an additional 14 days. The adipogenic media consisted of complete culture medium supplemented with DMEM- high glucose, 10% (v/v) FBS, 10 ⁇ g/ml insulin, 0.5 mM dexamethasone (Sigma-Aldrich, St.
  • LIVE DEAD® Viability/Cytotoxicity Assay Kit (Life Technologies). Briefly, human MSC were plated on 24 wells plate. On, next day cells were treated with ingredients and 100 ⁇ H 2 0 2 for 12hr. The supernatant media from each well was collected into microtubes and cells were washed with IX PBS, followed by collection of washes into respective microtubes to collect any floating or dead cells. The cells attached to the bottom of the plate were incubated in IX PBS in a 37 °C incubator. The microtubes were centrifuged at 2000 rpm for 3 min to get the cell pellet.
  • cell pellet was resuspended into IX PBS containing 2 ⁇ calcein AM and 4 ⁇ ethidium / homodimer. Re-suspended cells were again poured into their respective wells and the plate was incubated at 37 °C for 15 min. The cells were then imaged under 10X objective using fluorescence microscope (Olympus 1X71).
  • TABLE 2 will have a beneficial effect on chondrogenic and osteogenic differentiation of human MSC. Inflammation is detrimental to chondrogenesis and chondrocyte formation from human MSC.
  • the formulation of TABLE 2 demonstrates anti-inflammatory effects, as inferred by the significant decrease in adipogenesis in the above-described experiments.
  • compositions for mitigating issues arising from physical and athletic activities comprises Lactobacillus rhamnosus, curcumin, ginger, vitamin D, and Epimedium extract.
  • the composition is formulated as capsules, with a serving size of two capsules that contain ingredients or components as shown in the following TABLE 3.
  • Vitamin D (as cholecalciferol) 1000 IU 250%
  • Epidmedium sagittatum 500 mg n/a (standardized to 10% icariin)
  • Ginger root (from 8:1 concentrate) (Zingiber 500 mg n/a officinale)
  • Lactobacillus rhamnosus 10 billion CFU n/a n/a Daily Value not established.
  • Hypromellose Capsule
  • Rice Flour Magnesium Stearate.
  • Frozen bone marrow mononuclear cells were purchased from Allcells
  • MSCs When the MSCs were confluent, the cells were recovered by the addition of 0.25% trypsin/EDTA (Invitrogen, Carlsbad, CA). MSCs (Passage 2-3) were plated in either a 75-cm 2 flask or a 24 well plate and cultured in a-MEM with 20% FBS up to a density of 2.0X10 4 cells/cm 2 . The medium was replaced with adipogenic medium, and the cells were cultured for an additional 14 days. The adipogenic media consisted of complete culture medium supplemented with DMEM- high glucose, 10% (v/v) FBS, 10 ⁇ g/ml insulin, 0.5 mM dexamethasone (Sigma- Aldrich, St.
  • adipocytes were fixed in 10% formaldehyde, washed in Oil-red O for 10 min, rinsed with 60% isopropanol (Sigma- Aldrich, St. Louis, MO), and the Oil red O eluted by adding 100% isopropanol for 10 min and OD measured at 490 nm, for 0.5 sec reading.
  • LIVE DEAD ⁇ Viability/Cytotoxicity Assay Kit (Life Technologies). Briefly, human MSC were plated on 24 wells plate. On, next day cells were treated with ingredients and 100 ⁇ H 2 0 2 for 12hr. The supernatant media from each well was collected into microtubes and cells were washed with IX PBS, followed by collection of washes into respective microtubes to collect any floating or dead cells. The cells attached to the bottom of the plate were incubated in IX PBS in a 37 °C incubator. The microtubes were centrifuged at 2000 rpm for 3 min to get the cell pellet.
  • cell pellet was resuspended into IX PBS containing 2 ⁇ calcein AM and 4 ⁇ ethidium / homodimer. Re-suspended cells were again poured into their respective wells and the plate was incubated at 37 °C for 15 min. The cells were then imaged under 10X objective using fluorescence microscope (Olympus 1X71).
  • TABLE 3 will have a beneficial effect on chondrogenic and osteogenic differentiation of human MSC. Inflammation is detrimental to chondrogenesis and chondrocyte formation from human MSC.
  • the formulation of TABLE 3 demonstrates anti-inflammatory effects, as inferred by the significant decrease in adipogenesis in the above-described experiments.
  • Example embodiments are provided so that this disclosure will be thorough, and will fully convey the scope to those who are skilled in the art. Numerous specific details are set forth such as examples of specific components, devices, and methods, to provide a thorough understanding of embodiments of the present disclosure. It will be apparent to those skilled in the art that specific details need not be employed, that example embodiments may be embodied in many different forms, and that neither should be construed to limit the scope of the disclosure. In some example embodiments, well-known processes, well-known device structures, and well-known technologies are not described in detail. Equivalent changes, modifications and variations of some embodiments, materials, compositions and methods can be made within the scope of the present technology, with substantially similar results.

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Abstract

Cette invention concerne des compositions et leurs utilisations comprenant un mélange d'un probiotique et d'agents phytochimiques naturels qui peuvent affecter les cellules souches d'un individu et le processus inflammatoire pour réduire les symptômes sous-jacents de divers problèmes de santé, dont l'arthrite, le vieillissement et les lésions physiques ou athlétiques, facilitant ainsi la cicatrisation et la réparation des tissus.
PCT/US2014/064342 2014-11-06 2014-11-06 Supplément nutraceutique avec lactobacillus rhamnosus Ceased WO2016072992A1 (fr)

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CN201480083170.9A CN107073062A (zh) 2014-11-06 2014-11-06 具有鼠李糖乳杆菌的营养医学补充剂
PCT/US2014/064342 WO2016072992A1 (fr) 2014-11-06 2014-11-06 Supplément nutraceutique avec lactobacillus rhamnosus
JP2017544271A JP2017535289A (ja) 2014-11-06 2014-11-06 ラクトバチルス・ラムノサス（ｌａｃｔｏｂａｃｉｌｌｕｓ ｒｈａｍｎｏｓｕｓ）を含む栄養補助食品
KR1020177015272A KR101971809B1 (ko) 2014-11-06 2014-11-06 락토바실러스 람노서스를 보유한 기능식품 보충제
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