WO2007081729A2 - Treatment modalities for autoimmune diseases - Google Patents
Treatment modalities for autoimmune diseases Download PDFInfo
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- WO2007081729A2 WO2007081729A2 PCT/US2007/000137 US2007000137W WO2007081729A2 WO 2007081729 A2 WO2007081729 A2 WO 2007081729A2 US 2007000137 W US2007000137 W US 2007000137W WO 2007081729 A2 WO2007081729 A2 WO 2007081729A2
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Definitions
- the present invention relates generally to compositions and methods useful to treat autoimmune diseases. More specifically, the invention relates to compositions of reduced isoalpha acids, minerals and vitamins. Description of the Related Art
- autoimmune diseases and disorders occur when the body's own protective immune system becomes self destructive.
- the targets of autoimmune interaction can range anywhere from the cellular level (e.g., myelin basic protein in multiple sclerosis, or the thyrotropin receptor in Graves' disease) to organ specific effects in rheumatoid arthritis or Crohn's disease to system wide effects as seen in systemic lupus erythematosus.
- cytokine over expression for example TNF-04 JL-2, or JL-2 receptor in inflammatory bowel disease, or under expression (IL-10 under expression in Type 1 diabetes), to defects in allele expression (HLA Class I B27 in ankylosing spondylitis), to altered expression of apoptosis proteins (under expression of Fas in autoimmune lymphoproliferative syndrome type 1 (ALPS 1).
- cytokine over expression for example TNF-04 JL-2, or JL-2 receptor in inflammatory bowel disease
- IL-10 under expression in Type 1 diabetes
- HLA Class I B27 in ankylosing spondylitis
- Fas in autoimmune lymphoproliferative syndrome type 1 ALP1
- Inflammation while not causative of many autoimmune diseases, none the less is a symptom often associated with autoimmune diseases and disorders, such as, for example, rheumatoid arthritis, inflammatory bowel disease, Crohn's disease, or ulcerative colitis.
- anti-inflammatory agents are often incorporated into many autoimmune treatment modalities as a means of palliative relief.
- PG prostaglandin
- NSAIDs non-steroidal anti-inflammatory drugs
- Arachidonic acid serves as the primary substrate for the biosynthesis of all PGs.
- PGs are ubiquitous hormones that function as both paracrine and autocrine mediators to affect a myriad of physiological changes in the immediate cellular environment.
- the varied physiological effects of PGs include inflammatory reactions such as in rheumatoid arthritis and osteoarthritis, blood pressure control, platelet aggregation, induction of labor and aggravation of pain and fever.
- the macrophage is a potent mediator of immune reactions and that rheumatoid arthritis is characterized by a migration of activated phagocytes (and other immunoreactive cells) into synovial and periarticular tissue.
- the activated phagocytes upon reaching the synovia release numerous mediating substances that appear to both exacerbate and perpetuate the rheumatoid condition.
- Pharmacological doses of zinc may immobilize macrophages, thereby preventing or limiting their access to the synovial site and providing a potential means to reduce joint specific inflammation in rheumatoid arthritis. See, for example, Aaseth, J., et al., Analyst 123(1): 3-6, 1998).
- macrophage immobilization may play a role in reducing macrophage interaction and activation, thereby reducing possible participation in, or augmentation of, the autoimmune response.
- compositions and methods that would modulate prostaglandin levels and or regulate macrophage activity, thereby modulating the inflammatory response associated with many autoimmune diseases. Such modulation and use may require continual use for chronic conditions or intermittent use as needed. Additionally, supplementation with select trace metals may also serve a means towards restoring a more normal immune function, thereby offering an additional avenue for intervention in autoimmune diseases.
- the instant invention describes compounds, compositions and methods to treat inflammation and autoimmune diseases related symptoms with a concomitant increase in the quality of life.
- the invention relates to novel modalities useful for the treatment of inflammation and autoimmune diseases and related symptoms with a concomitant increase in the quality of life.
- An aspect of the invention relates to compositions comprising a reduced isoalpha acid compound, a mineral, and a vitamin.
- Reduced isoalpha acid compounds contemplated include dihydro-isohumulone, dihydro-isocohumulone, dihydro-adhumulone, tetrahydro-isohumulone, tetrahydro-isocohumulone, tetrahydro- adhumulone, hexahydro-isohumulone, hexahydro-isocohumulone, and hexahydro- adhumulone.
- Reduced isoalpha acids also encompass moieties also known as "rho" isoalpha acids.
- the invention also provides methods of using such compositions for the treatment of autoimmune diseases.
- a mammal may be treated by the administration of a therapeutically effective amount of a composition including a reduced isoalpha acid compound, a mineral, and a vitamin.
- Reduced isoalpha acid compounds contemplated include dihydro-isohumulone, dihydro- isocohumulone, dihydro-adhumulone, tetrahydro-isohumulone, tetrahydro- isocohumulone, tetrahydro-adhumulone, hexahydro-isohumulone, hexahydro- isocohumulone, and hexahydro-adhumulone.
- Reduced isoalpha acids also encompass moieties also known as "rho" isoalpha acids.
- Figure 1 shows an outline of fractions and compounds obtained from hops.
- FIG 3 is a graphical representation showing the inhibition of PGE2 secretion in LPS stimulated RAW 264.7 cells by various combinations of reduced isoalpha acids ("RIAA”), vitamin D, zinc and selenium.
- RIAA reduced isoalpha acids
- the present invention relates to the identification of compositions combining a reduced isoalpha acid, a mineral, and a vitamin which have been found to be effectual in the treatment of autoimmune diseases.
- An aspect of the invention relates to compositions comprising one ore more of each of (i) a reduced isoalpha acid compound, (ii) a mineral, and (iii) a vitamin.
- the terms are to be interpreted synonymously with the phrases “having at least” or “including at least”.
- the term “comprising” means that the process includes at least the recited steps, but may include additional steps.
- the term “comprising” means that the compound or composition includes at least the recited features or components, but may also include additional features or components.
- reduced isoalpha acid refers to alpha acids isolated from hops plant product and subsequently have been isomerized and reduced, including cis and trans forms.
- reduced isoalpha acids include, but are not limited to dihydro- ⁇ sohumulone, dihydro-isocohumulone, dihydr ⁇ -adhumulone, tetrahydro- isohumulone, tetrahydro-isocohumulone, tetrahydro-adhumulone, hexahydro- isohumulone, hexahydro-isocohumulone, and hexahydro-adhumulone.
- tetra-hydroisoalpha acid refers to a certain class of reduced isoalpha acid.
- tetra-hydroisoalpha acid include, but are not limited to, tetra-hydro-isohumulone, tetra-hydro-isocohumulone and tetrahydro-adhumulone.
- hexa-hydroisoalpha acid refers to a certain class of reduced isoalpha acid.
- HHIAA hexa-hydroisoalpha acids
- Reduced isoalpha acid compounds according to the invention may be synthesized or may be obtained as fractions or compounds isolated, extracted, derived from hops or spent hops (see Verzele, M. and De Keukeleire, D., Developments in Food - Science 27: Chemistry and Analysis of Hop and Beer Bitter Acids. Elsevier Science Pub. Co., 1991, New York, USA, herein incorporated by reference in its entirety, for a detailed discussion of hops chemistry).
- hop extract refers to the solid material resulting from (1) exposing a hops plant product to a solvent, (2) separating the solvent from the hops plant products, and (3) eliminating the solvent.
- solvent refers to a liquid of aqueous or organic nature possessing the necessary characteristics to extract solid material from the hop plant product. Examples of solvents would include, but not limited to, water, steam, superheated water, methanol, ethanol, hexane, chloroform, liquid CO 2 , liquid N 2 or any combinations of such materials.
- Reduced isoalpha acids also encompass moieties also known as “rho” isoalpha acids. Compositions thus, may include rho isoalpha acid compounds. As used herein, “rho” refers to those reduced isoalpha acids wherein the reduction is a reduction of the carbonyl group in the 4-methyl-3-pentenoyl side chain. This subset of reduced isoalpha acids encompass any compound which is part of the supragenus structure shown below:
- R' is selected from the group consisting of carbonyl, hydroxyl, OR, and OCOR, wherein R is alkyl; wherein R" is selected from the group consisting of CH(CHa) 2 , CH 2 CH(CH 3 ) 2 , and CH(CH 3 )CH 2 CH 3 ; and wherein R, T, X, and Z are independently selected from the group consisting of H, F, Cl, Br, I, and x orbital, with the proviso that if one of R, T, X, or Z is a x orbital, then the adjacent R, T, X, or Z is also a ⁇ orbital, thereby forming a double bond.
- Certain embodiments of the invention include one or more reduced alpha acid compounds which fall within the scope of the Genus A structure:
- R' is selected from the group consisting of carbonyl, hydroxyl, OR, and OCOR, wherein R is alkyl; and wherein R" is selected from the group consisting of CH(CHa) 2 , CH 2 CH(CH 3 ) 2 , and CH(CH 3 )CH 2 CH 3 .
- Reduced isoalpha acid compounds also include compounds within the scope of the Genus B structure:
- R' is selected from the group consisting of carbonyl, hydroxyl, OR, and OCOR, wherein R is alkyl; and wherein R" is selected from the group consisting of CH(CHs) 2 , CH 2 CH(CH 3 ) 2 , and CH(CH 3 )CH 2 CH 3 .
- Minerals useful according to the invention include calcium, selenium, zinc, copper, iron, chromium, magnesium, manganese, vanadium, molybdenum, and boron.
- the minerals are zinc and selenium.
- Vitamins useful according to the invention include Vitamin A, Vitamin B, Vitamin C, Vitamin D, Vitamin E, Vitamin K, biotin, folate, pantothenic acid, para- aminobenzoic acid, and betaine.
- the vitamin is vitamin D.
- Compositions of the invention may include (a) one or more reduced isoalpha acid (dihydro-isohumulone, dihydro-isocohumulone, dihydro-adhumulone, tetrahydro-isohumulone, tetrahydro-isocohumulone, tetrahydro-adhumulone, hexahydro- isohumulone, hexahydro-isocohumulone, and hexahydro-adhumulone), (b) one or more rho reduced isoalpha acid compound of the Supragenus having the formula as shown and as described above; as well as (c) a vitamin, and (d) a mineral.
- reduced isoalpha acid dihydro-isohumulone, dihydro-isocohumulone, dihydro-adhumulone, tetrahydro-isohumulone, tetrahydro-adhumulone, hexa
- the rho reduced isoalpha acid compound is part of the Genus A having the formula as shown and as described above. In yet additional embodiments, the rho reduced isoalpha acid compound is part of the Genus B having the formula as shown and as described above.
- the minerals and vitamins for these compositions are as described above. In representative non limiting embodiments of the invention exemplified herein, the minerals are zinc and selenium and the vitamin is vitamin D.
- compositions of the invention may further include at least one member selected from the group consisting of rosemary, an extract or compound derived from rosemary, a triterpene species or derivatives or conjugates thereof, a diterpene lactone species or derivatives or conjugates thereof, and tryptanthrin or conjugates thereof.
- the terms "derivatives" or a matter "derived” refer to a chemical substance related structurally to another substance and theoretically obtainable from it, i.e., a substance that can be made from another substance. Derivatives can include compounds obtained via a chemical reaction.
- conjugates of compounds means compounds covalently bound or conjugated to a member selected from the group consisting of mono- or di- saccharides, amino acids, sulfates, succinate, acetate, and glutathione.
- the mono- or di- saccharide is a member selected from the group consisting of glucose, mannose, ribose, galactose, rhamnose, arabinose, maltose, and fructose.
- the amount of reduced isoalpha acid compound(s) in the compositions may be from about 0.5 to about 10,000 mg. In certain embodiments, the reduced isoalpha acid compound amount is from about 50 to about 7,500 mg. In certain embodiments exemplified herein, the unit dose comprises 225 mg of reduced isoalpha acids, 500 IU of vitamin D (as cholecalciferol), 5 mg of zinc (as zinc citrate) and 50 ⁇ g of selenium (as selenomethionine). As used herein, the recitation of a numerical range for a variable is intended to convey that the invention may be practiced with the variable equal to any of the values within that range.
- variable which is inherently discrete can be equal to any integer value of the numerical range, including the end-points of the range.
- variable variable which is inherently continuous can be equal to any real value of the numerical range, including the end-points of the range.
- a variable which is described as having values between 0 and 2 can be 0, 1 or 2 for variables which are inherently discrete, and can be 0.0, 0.1, 0.01, 0.001, or any other real value for variables which are inherently continuous.
- compositions according to the invention may further comprise a pharmaceutically acceptable carrier.
- a pharmaceutically acceptable carrier Any suitable materials and/or methods known to those of skill can be utilized in carrying out the present invention. However, preferred materials and methods are described. Materials, reagents and the like to which reference is made in the following description and examples are obtainable from commercial sources, unless otherwise noted.
- compositions according to the invention are optionally formulated in a pharmaceutically acceptable vehicle with any of the well known pharmaceutically acceptable carriers, including diluents and excipients (see Remington's Pharmaceutical Sciences, 18 th Ed., Gennaro, Mack Publishing Co., Easton, PA 1990 and Remington: The Science and Practice of Pharmacy. Lippincott, Williams & Wilkins, 1995). While the type of pharmaceutically acceptable carrier/vehicle employed in generating the compositions of the invention will vary depending upon the mode of administration of the composition to a mammal, generally pharmaceutically acceptable carriers are physiologically inert and non-toxic. Formulations of compositions according to the invention may contain more than one type of compound of the invention), as well any other pharmacologically active ingredient useful for the treatment of the symptom/condition being treated.
- composition include any and all possible compositions suitable for the administration of the combinations encompassed by the invention and thus include for example dietary supplement compositions and generally neutraceutical as well as pharmaceutical compositions.
- compositions and methods of using the same according to the inventions have been found to be effective in the inhibition OfPGE 2 .
- the invention provides compositions and methods of inhibiting PGE 2 .
- applicants postulate that these compositions and methods are effective in the treatment of inflammation and autoimmune disease by a PGE 2 mediated mechanism.
- the compositions of the invention are believed to modulate prostaglandin levels and or regulate macrophage activity, thereby modulating the inflammatory response associated with autoimmune diseases.
- the invention also provides methods of using such compositions for the treatment of inflammation and autoimmune diseases and related symptoms in a patient with a concomitant increase in the quality of life.
- autoimmune disorder refers to those diseases, illnesses, or conditions engendered when the host's systems are attacked by the host's own immune system.
- autoimmune diseases include alopecia areata, ankylosing spondylitis, arthritis, antiphospholipid syndrome, autoimmune Addison's disease, autoimmune hemolytic anemia, autoimmune inner ear disease (also known as Meniers disease), autimmune lymphoproliferative syndrome (ALPS), autoimmune thrombocytopenic purpura, autoimmune hemolytic anemia, autoimmune hepatitis, Bechet's disease, Crohn's disease, diabetes mellitus type 1, glomerulonephritis, Graves' disease, Guillain-Barre syndrome, inflammatory bowel disease, lupus nephritis, multiple sclerosis, myasthenis gravis, pemphigus, pernicous anemia, polyarteritis nodosa, polymyos
- mammals or “mammal in need” include humans as well as non-human mammals, particularly domesticated animals including, without limitation, cats, dogs, and horses.
- a mammal may be treated by the administration of a therapeutically effective amount of a composition including a reduced isoalpha acid compound, a mineral, and a vitamin.
- compositions useful for the treatment according to this aspect of the invention encompass compositions comprising one ore more of each of (i) a reduced isoalpha acid compound, (ii) a mineral, and (iii) a vitamin.
- compositions useful for the methods of the invention may comprise rho reduced isoalpha acids of Supragenus structure as described and as shown above for the first aspect of the invention.
- compositions may comprise reduced isoalpha acids of Genus A and/or Genus B as described and as having the formulae shown above for the first aspect of the invention.
- compositions suitable according to the methods of the invention may include (a) one or more reduced isoalpha acid (dihydro-isohumulone, dihydro- isocohumulone, dihydro-adhumulone, tetrahydro-isohumulone, tetrahydro- isocohumulone, tetrahydro-adhumulone, hexahydro-isohumulone, hexahydro- isocohumulone, and hexahydro-adhumulone), (b) one or more rho reduced isoalpha acid compound of the Supragenus having the formula as shown and as described above; as well as (c) a vitamin, and (d) a mineral.
- reduced isoalpha acid dihydro-isohumulone, dihydro- isocohumulone, dihydro-adhumulone, tetrahydro-isohumulone, tetrahydro- isocohumul
- the rho reduced isoalpha acid compound is part of the Genus A having the formula as shown and as described above. In yet additional embodiments, the rho reduced isoalpha acid compound is part of the Genus B having the formula as shown and as described above.
- the minerals and vitamins for these compositions are as described above. In representative non limiting embodiments of the invention exemplified herein, the minerals are zinc and selenium and the vitamin is vitamin D.
- compositions of the invention may further include at least one member selected from the group consisting of rosemary, an extract or compound derived from rosemary, a triterpene species or derivatives or conjugates thereof, a diterpene lactone species or derivatives or conjugates thereof, and tryptanthrin or conjugates thereof.
- rosemary extract compounds derived from rosemary, triterpene species (including derivatives or conjugates thereof), diterpene lactone species or derivatives or conjugates thereof, and tryptanthrin or conjugates thereof see e.g., U.S. Patent Application Serial No. 10/689,856 hereby incorporated in its entirety.
- the term "effective amount” means an amount necessary to achieve a selected result. Such an amount can be readily determined without undue experimentation by a person of ordinary skill in the art. As used herein, the term “substantial” means being largely but not wholly that which is specified.
- compositions of the invention have been found too produce a synergistic effect as exemplified in Figure 3 infra.
- the terms “synergy” and “synergistic effect” indicate that the effect produced from the aggregate compounds administered in toto is greater than would be predicted based on the effects produced when combinations of compounds less than the total aggregate are co-administered.
- the selected dosage level will depend upon activity of the particular composition, the route of administration, the severity of the condition being treated or prevented, and the condition and prior medical history of the patient being treated. However, it is within the skill of the art to start doses of the composition at levels lower than required to achieve the desired therapeutic effect and to gradually increase the dosage until the desired effect is achieved. If desired, the effective daily dose maybe divided into multiple doses for purposes of administration, e.g., two to four separate doses per day. It will be understood, however, that the specific dose level for any particular patient will depend upon a variety of factors including body weight, general health, diet, time and route of administration, combination with other compositions and the severity of the particular condition being treated or prevented.
- Certain embodiments include delivering an effective amount of a reduced isoalpha acid with other active ingredients.
- a daily dose of preferred compositions would be formulated to deliver about 0.5 to 10,000 mg of reduced isoalpha acid per day. More preferably, an effective daily dose of preferred compositions would be formulated to deliver about 50 to 7,500 mg of reduced isoalpha acid per day.
- the effective daily dose is administered once or twice a day.
- Daily dosages of from about 0.5 to about 800 mg of reduced isoalpha acid, more preferably about 50 to 400 mg of reduced isoalpha acid per day are contemplated by the inventors.
- Another certain embodiment provides a composition comprising about 10 to 3,000 mg of reduced isoalpha acid per day, more preferably about 50 to 2,000 mg of reduced isoalpha acid per day.
- Preferred embodiments include delivering an effective amount of tryptanthrin or conjugates thereof alone or with in combination with other active ingredients.
- a daily dose of preferred compositions would be formulated to deliver about 0.0005 to 50 mg tryptanthrin/kg body weight per day. More preferably, an effective daily dose of preferred compositions would be formulated to deliver about 0.01 to 10 mg tryptanthrin/kg body weight per day.
- a daily dose of preferred compositions would be formulated to deliver about 0.035 to 3500 mg of tryptanthrin per day. More preferably, an effective daily dose of preferred composition would be formulated to deliver about 0.7 to 700 mg of tryptanthrin per day.
- the effective daily dose is administered once or twice a day.
- Preferred embodiments include delivering an effective amount of rosemary or an extract or compound derived from rosemary in combination with other active ingredients.
- a daily dose of preferred compositions would be formulated to deliver about 0.5 to 5,000 mg of rosemary, an extract of rosemary, or rosemary-derived compound per day. More preferably, an effective daily dose of preferred composition would be formulated to deliver about 5 to 2,000 mg of rosemary, an extract of rosemary, or rosemary-derived compound per day.
- the effective daily dose is administered once or twice a day.
- a certain embodiment provides a composition comprising about 75 mg of rosemary extract or rosemary-derived compound or derivative, to be administered once or twice a day.
- Preferred embodiments include delivering an effective amount of a triterpene or diterpene lactone species or derivatives or conjugates thereof in combination with other active ingredients.
- a daily dose of preferred compositions would be formulated to deliver about 0.0005 to 50 mg triterpene or diterpene lactone/kg body weight per day. More preferably, an effective daily dose of preferred compositions would be formulated to deliver about 0.01 to 10 mg triterpene or diterpene lactone/kg body weight per day.
- a daily dose of preferred compositions would be formulated to deliver about 0.035 to 3,500 mg of triterpene or diterpene lactone species per day. More preferably, an effective daily dose of preferred composition would be formulated to deliver about 0.7 to 700 mg of triterpene or diterpene lactone species per day.
- the effective daily dose is administered once or twice a day.
- an embodiment provides a composition containing an extract of rosemary and a triterpene, such as oleanolic acid, along with an active ingredient, such as a reduced isoalpha acid or tryptanthrin or conjugate thereof.
- an embodiment provides a composition comprising about 0.01 to 500 mg of rosemary extract and about 0.01 to 500 mg of oleanolic acid.
- an embodiment provides a composition capable of producing concentrations in target tissues of 0.1 to lO ⁇ g/g tissue of rosemary extract and about 0.1 to 25 ⁇ g/g tissue of oleanolic acid.
- a composition of preferred embodiments for topical application would contain about 0.001 to 10 weight percent, preferably about 0.1 to 1 weight percent of a reduced isoalpha acid or derivative or tryptanthrin or conjugate thereof.
- Preferred embodiments would produce serum concentrations in the ranges of about 0.0001 to 10 ⁇ M, preferably about 0.01 to 1 ⁇ M of a reduced isoalpha acid or tryptanthrin or conjugate thereof.
- the preferred embodiments for topical application can further comprise an additional ingredient selected from rosemary, an extract or compound derived from rosemary, a triterpene species or derivatives or conjugates thereof, a diterpene lactone species or derivatives or conjugates thereof, a fraction isolated or derived from hops or tryptanthrin or conjugates thereof, at concentrations of each component of 0.001 to 10 weight percent, preferably 0.1 to 1 weight percent. Preferred embodiments would produce serum concentrations in the ranges of about 0.
- compositions can be administered in the form of a dietary supplement or therapeutic composition.
- the compositions may be administered orally, topically, transdeimally, transmucosally, parenterally, rectally, etc., in appropriate dosage units, as desired.
- compositions for dietary application may include various additives such as other natural components of intermediary metabolism, vitamins and minerals, as well as inert ingredients such as talc and magnesium stearate that are standard excipients in the manufacture of tablets and capsules.
- one embodiment comprises active ingredients of preferred compositions in combination with glucosamine or chondrotin sulfate.
- pharmaceutically acceptable carrier includes any and all solvents, dispersion media, coatings, isotonic and absorption delaying agents, sweeteners and the like. These pharmaceutically acceptable carriers may be prepared from a wide range of materials including, but not limited to, diluents, binders and adhesives, lubricants, disintegrants, coloring agents, bulking agents, flavoring agents, sweetening agents and miscellaneous materials such as buffers and absorbents that may be needed in order to prepare a particular therapeutic composition.
- diluents binders and adhesives
- lubricants disintegrants
- coloring agents coloring agents
- bulking agents flavoring agents
- sweetening agents sweetening agents
- miscellaneous materials such as buffers and absorbents that may be needed in order to prepare a particular therapeutic composition.
- the use of such media and agents for pharmaceutically active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active ingredients, its use in preferred compositions is contemplated.
- talc, and magnesium stearate are included in the formulation.
- Other ingredients known to affect the manufacture of this composition as a dietary bar or functional food can include flavorings, sugars, amino-sugars, proteins and/or modified starches, as well as fats and oils.
- Dietary supplements, lotions or therapeutic compositions of preferred embodiments can be formulated in any manner known by one of skill in the art. Ih one embodiment, the composition is formulated into a capsule or tablet using techniques available to one of skill in the art. In capsule or tablet form, the recommended daily dose for an adult human or animal would preferably be contained in one to six capsules or tablets. However, preferred compositions can also be formulated in other convenient forms, such as an injectable solution or suspension, a spray solution or suspension, a lotion, gum, lozenge, food or snack item.
- Food, snack, gum or lozenge items can include any ingestible ingredient, including sweeteners, flavorings, oils, starches, proteins, fruits or fruit extracts, vegetables or vegetable extracts, grains, animal fats or proteins.
- preferred compositions can be formulated into cereals, snack items such as chips, bars, gumdrops, chewable candies or slowly dissolving lozenges. Preferred embodiments
- H contemplate treatment of all types of inflammation-based diseases, both acute and chronic.
- Preferred formulations reduce the inflammatory response and thereby promotes healing of, or prevents further damage to, the affected tissue.
- a pharmaceutically acceptable carrier can also be used in the preferred compositions and formulations.
- This example demonstrates the effect of combinations of reduced isoalpha acids (RIAA), zinc, selenium, and vitamin D3 on prostaglandin E2 (PGE2) release.
- RIAA reduced isoalpha acids
- PGE2 prostaglandin E2
- Test compounds were prepared in dimethyl sufoxide (DMSO).
- RIAA and sodium selenite was supplied by Metagenics (San Clemente, CA).
- Zinc Chloride and Vitamin D3, 1 -alpha, 25-dihydroxy were purchased from EMD Biosciences (San Diego, CA).
- Lipopolysaccharide was purchased from Sigma-Aldrich (St. Louis, MO).
- Murine macrophage RAW 264.7 cell line was purchased from ATCC (Manassas, VA) and maintained according to their instructions. Cells treated with either sodium selenite (2 ⁇ M) or zinc chloride (169 nM) were grown in serum rich media (10% FBS) in T-75 flasks for two days prior to seeding in 96-well plates. Cells were subcultured in 96-well plates at a density of 1 x 10 5 cells per well and allowed to reach 90% confluence. RIAA (20 to 1 ⁇ g/ml) and vitamin D3 (355 nM) were added to the cells in serum free media at a final concentration of 0.1% DMSO.
- PGE2 Determination -A commercial, non-radioactive procedure for quantification of PGE2 was employed (Cayman Chemical, Ann Arbor, MI). The recommended manufacturer procedure was used without modification. Briefly, 50 ⁇ l of the medium, along with a serial dilution of PGE2 standard samples, were mixed with appropriate amounts of PGE2-acetylcholinesterase tracer conjugate, and incubated at 4°C overnight. Fresh Ellman's was prepared and the color development reaction was allowed to progress for 75 minutes at room temperature. The absorbance was measured at 405 nm. The PGE2 concentration was represented as picograms per ml as calculated from the standard curve. The average of four wells was determined for each treatment.
- f a is the factional inhibition of the reaction.
- IC 50 median inhibitory concentration
- RAW 264.7 cells were stimulated treated for 24 hours with LPS (1 ⁇ g/mL) at various concentrations of RIAA, sodium selenite, zinc chloride, or vitamin D3.
- the medium from the cell culture was recovered and the secreted concentration of PGE2 was determined by ELISA.
- the percent inhibition of PGE2 was then determined. The values are seen in Table 1 with the average of four wells represented at the PGE2 amount in pg/ml and the standard deviation (SD).
- Figure 3 depicts the percent inhibition graphically and the calculated IC50 ( ⁇ g/ml) values.
- Results indicate the following rank of IC50 values for PGE2 inhibition in the RAW 264.7 cell model after 24 hour stimulation: RIAA+VD3 (17.54 ⁇ g/ml)>RIAA (9.83 ⁇ g/rnl)>RIAA+zinc (5.06 ⁇ g/ml)>RIAA+selenium+zinc (4.55 ⁇ g/ml)>RIAA+selenium (3.23 ⁇ g/ml)>RIAA+selenium+VD3 (1.84)>RIAA+zinc+VD3 (1.38 ⁇ g/ml)>RIAA+selenium+zinc+VD3 (1.35 ⁇ g/ml).
- This case shows the positive effect that a protocol combining an inflammatory-modulating medical food, RIAA, vitamin D, Zn, and Se, and diet, had on a patient presenting with a history of Crohns' disease and several other symptoms relating to immune-inflammatory conditions.
- the MSQ is a clinical tool for the evaluation of general physical symptoms. Total scores above 75 are generally associated with substantial symptomatology and disability; scores below 30 generally indicate few or low intensity symptoms f
- the MOS SF-36 is a well-validated general quality of life questionnaire that summarizes health outcome in two reliable reproducible scores: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). On a scale of 0-100, 50 is the mean for the US. Higher scores are associated with healthier individuals.
- SIBDQ is a shortened version of the Inflammatory Bowel Disease Questionnaire (IBDQ), which has been valuable in assessing important clinical changes in the health and outcomes of patients with IBD.
- the 10 items in the SIBDQ provide information in four categorical scores: bowel, systemic, social, and emotional. A higher score indicates a better quality of life, while a lower score indicates a poorer quality of life.
- RA with negative rheumatoid factor. Obesity. Iron deficiency.
- the patient was instructed to begin inflammatory-modulating medical food with added reduced iso-alpha-acids from hops (RIAA) and Vitamin D, working up to 2 scoops bid. (UltralnflamX AT). 5— through 7- Week Results
- This case shows the positive effect that a protocol combining an inflammatory-modulating medical food, RIAA, vitamin D, Zn and Se and diet had on a patient presenting with rheumatoid arthritis and other inflammation-related symptoms.
- MSQ is a clinical tool for the evaluation of general physical symptoms. Total scores above 75 are generally associated with substantial symptomatology and disability; scores below 30 generally indicate few or low intensity symptoms.
- the MOS SF-36 is a well-validated general quality of life questionnaire that summarizes health outcome in two reliable reproducible scores: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). On a scale of 0-100, 50 is the mean for the US. Higher scores are associated with healthier individuals. Table 5: AIMS2-A* Questionnaire Scores
- the A1MS2-Abridged questionnaire is a clinical toot for the evaluation of health status and outcomes of individuals with rheumatic diseases.
- a low score value indicates a high health status, while a high score value indicates poor health.
- MSQ is a clinical tool for the evaluation of general physical symptoms. Total scores above 75 are generally associated with substantial symptomatology and disability; scores below 30 generally indicate few or low intensity symptoms Table 6: Laboratory Values
- the MSQ is a clinical tool for the evaluation of general physical symptoms. Total scores above 75 are generally associated with substantial symptomatology and disability: scores below 30 generally indicate few or low intensity symptoms. f
- the MOS SF-36 is a well-validated general quality of life questionnaire that summarizes health outcome in two reliable reproducible scores: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). On a scale of 0-10O, 50 is the mean for the US. Higher scores are associated with healthier individuals.
- the AIMS2-Abridged questionnaire is a clinical toot for the evaluation of health status and outcomes of individuals with rheumatic diseases. A low score value indicates a high health status, while a high score value indicates poor health.
- Erythromelalgia Raynaud's phenomenon. Dysbiosis. Fatigue probably from sleep apnea and restless leg syndrome. Asthma and migraine headaches possibly exacerbated by food allergies.
- the patient was instructed to begin inflammatory- modulating medical food with added reduced iso-alpha-acids from hops (RIAA) and Vitamin D, working up to 2 scoops bid. (UltralnflamX AI) 2- through 5-Week Results
- the MSQ is a clinical tool for the evaluation of general physical symptoms. Total scores above 75 are generally associated with substantial symptomatology and disability; scores below 30 generally indicate few or low intensity symptoms f
- the MOS SF-36 is a well-validated general quality of life questionnaire that summarizes health outcome in two reliable reproducible scores: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). On a scale of 0-100, SO is the mean for the US. Higher scores are associated with healthier individuals.
- This case shows the positive effect that a protocol combining an inflammatory-modulating medical food, RIAA, vitamin D, Zn, and Se, and diet, had on a patient presenting with a history of SLE and related GI symptoms.
- the MSQ is a clinical tool for the evaluation of general physical symptoms. Total scores above 75 are generally associated with substantial symptomatology and disability; scores below 30 generally indicate few or low intensity symptoms f
- the MOS SF-36 is a well-validated general quality of life questionnaire that summarizes health outcome in two reliable reproducible scores: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). On a scale of 0-100, 50 is the mean for the US. Higher scores are associated with healthier individuals.
- Cell culture - RAW 264.7 cells obtained from American Type Culture Collection (Catalog #TIB-71, Manassas, VA), were grown in Dulbecco's Modification of Eagle's Medium (DMEM, Mediatech, Herndon, VA) and maintained in log phase.
- the DMEM growth medium was made by adding 50 mL of heat inactivated FBS and 5 mL of penicillin/streptomycin to a 500 mL bottle of DMEM and storing at 4 ° C. The growth medium was warmed to 37 ° C in water bath before use.
- test materials were prepared as IOOOX stock in DMSO.
- 1 mL DMEM without FBS was added for test concentrations of 0.05, 0.10, 0.5, and 1.0 ⁇ g/mL.
- Two ⁇ L of the IOOOX DMSO stock of the test material was added to the 1 mL of medium without FBS.
- the tube contained the final concentration of the test material concentrated 2-fold and the tube placed in an incubator for 10 minutes to equilibrate to 37°C.
- Cells A549 (human pulmonary epithelial) Cells were obtained from the American Type Culture Collection (Manassas, VA) and sub-cultured according to the instructions of the supplier. The cells were routinely cultured at 37°C with 5% CO 2 in RPMI 1640 containing 10% FBS, with 50 units penicillin/mL, 50 ⁇ g streptomycin/mL, 5% sodium pyruvate, and 5% L-glutamine. On the day of the experiments, exponentially growing cells were harvested and washed with serum-free RPMI 1640.
- interleukin-l ⁇ (10 ng/mL) was added to induce the expression of COX-2.
- the cells were washed with serum- free RPMI 1640 and the test materials, dissolved in DMSO and serum-free RPMI, were added to the wells to achieve final concentrations of 25, 5.0, 0.5 and 0.05 ⁇ g/mL. Each concentration was run in duplicate.
- DMSO was added to the control wells in an equal volume to that contained in the test wells.
- A23187 50 ⁇ M was added to the wells to release arachidonic acid. Twenty-five ⁇ L of media were sampled from the wells 30 minutes later for PGE 2 determination.
- Results At the doses tested, the experimental protocol failed to capture a median effective concentration of any of the hops extracts or derivatives. Since the protocol requires the stimulation of COX-2 expression prior to the addition of the test compounds, the likely answer to the failure of the test materials to inhibit PGE 2 synthesis is that their mechanism of action is to inhibit the expression of the COX-2 isozyme and not activity directly. While some direct inhibition can be observed using the WHMA- COX-2 protocol, this procedure is inappropriate in evaluating the anti-inflammatory properties of hops compounds or derivatives of hops compounds.
- AGS cells were grown and used for testing hops compounds and derivatives.
- PGE 2 was determined and reported as previously described in Example 1.
- the median inhibitory concentrations (IC50) for PGE2 synthesis from AGS cells were calculated.
- Sensitivity to allergens is a problem for an increasing number of consumers. This issue has been complicated by a surprising increase in asthma over the past few years. Asthma suffers are especially sensitive to airborne allergens. Allergy rates are also on the rise. This gives rise to increased awareness of the causes of allergy symptoms and how to decrease the associated discomfort. Approximately 10% of the population become hypersensitized (allergic) upon exposure to antigens from a variety of environmental sources. Those antigens that induce immediate and/or delayed types of hypersensitivity are known as allergens. These include products of grasses, trees, weeds, animal dander, insects, food, drugs, and chemicals. Genetic predisposition of an individual is believed to play a role in the development of immediate allergic responses such as atopy and anaphylaxis whose symptoms include hay fever, asthma, and hives.
- allergens are protein-based molecules, and these protein allergens can originate from many sources. It has been know for some time that one of the most common sources of allergens in a house is from dust mites. Of course, as is the case with all allergens, only certain people are allergic to dust mite allergens. But this group of people can be quite large in many areas, especially in hot humid areas. For example, in the southeastern United States of America, where it is both hot and humid for much of the year, the incidence of house dust mite allergies in the general population can be as high as 25%. House dust mites thrive in plush carpets, overstuffed upholstery, cushy bed comforters and the like. Methods
- Mite dust allergen isolation - Dermatophagoides farinae are the American house dust mite.
- D. farinae were cultured on a 1:1 ratio of Purina Laboratory Chow (Ralston Purina, Co, St. Louis, MO) and Fleischmann's granulated dry yeast (Standard Brands, Inc. New York, NY) at room temperature and 75% humidity.
- Live mites were aspirated from the culture container as they migrated from the medium, killed by freezing, desiccated and stored at 0% humidity.
- the allergenic component of the mite dust was extracted with water at ambient temperature.
- mite powder Five-hundred mg of mite powder were added to 5 mL of water (1:10 w/v) in a 15 mL conical centrifuge tube (VWR, Rochester, NY), shaken for one minute and allowed to stand overnight at ambient temperature. The next day, the aqueous phase was filtered using a 0.2 ⁇ m disposable syringe filter (Nalgene, Rochester, NY). The filtrate was termed mite dust allergen and used to test for induction of PGE2 biosynthesis in A549 pulmonary epithelial cells.
- PGE2 assay Determination of PGE2 in the culture medium was performed as previously described in Example 1.
- test materials included Hops fractions (1) alpha hop (1% alpha acids; AA), (2) aromahop OE (10% beta acids and 2% isomerized alpha acids , (3) isohop (isomerized alpha acids; IAA), (4) beta acid solution (beta acids BA), (5) hexahop gold (hexahydro isomerized alpha acids; HHIAA), (6) redihop (reduced isomerized-alpha acids; RIAA), and (7) tetrahop (tetrahydro-iso-alpha acids THIAA). Test materials at a final concentration of 10 ⁇ g/mL were added 60 minutes prior to the addition of the mite dust allergen. Results
- Table 15 depicts the extent of inhibition OfPGE 2 biosynthesis by hops derivatives in A549 pulmonary cells stimulated by mite dust allergen. All hops derivatives were capable of significantly inhibiting the stimulatory effects of mite dust allergens.
- a preferred embodiment comprises compositions containing at least one fraction isolated or derived from hops ⁇ Humulus lupulus).
- fractions isolated or derived from hops are alpha acids, isoalpha acids, reduced isoalpha acids, tetra-hydroisoalpha acids, hexa-hydroisoalpha acids, beta acids, and spent hops.
- Preferred compounds of fractions isolated or derived from hops include, but are not limited to, humulone, cohumulone, adhumulone, isohumulone, isocohumulone, isoadhumulone, dihydro-isohumulone, dihydro-isocohumulone, dihydro-adhumulone, tetrahydro- isohumulone, tetrahydro-isocohumulone, tetrahydro-adhumulone, hexahydro- isohumulone, hexahydro-isocohumulone, and hexahydro-adhumulone.
- Preferred compounds can also bear substituents, such as halogens, ethers, and esters.
- Another embodiment comprises composition containing tryptanthrin and conjugates thereof.
- compositions that include, as a first component, an active ingredient isolated or derived from an extract of hops and as a second component at least one member selected from the group consisting of rosemary ⁇ Rosmarinus officinalis L.), an extract or compound derived from rosemary, a triterpene species or derivatives or conjugates thereof, and tryptanthrin or conjugates thereof.
- compositions that include, as a first component, tryptanthrin or conjugates thereof and as a second component at least one member selected from the group consisting of an active ingredient isolated or derived from an extract of hops, rosemary, an extract or compound derived from rosemary, and a triterpene species or derivatives or conjugates thereof.
Abstract
Description
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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US8410179B2 (en) | 2010-10-30 | 2013-04-02 | Kindex Therapeutics, Llc | Cis, 3,4-dihydroxy-2-(3-methylbutanoyl)-5-(3-methylbutyl)-4-(4-methylpentanoyl)cyclopent-2-en-1-derivatives, substantially enantiomerically pure compositions and methods |
Families Citing this family (33)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7901713B2 (en) * | 2001-06-20 | 2011-03-08 | Metaproteomics, Llc | Inhibition of COX-2 and/or 5-LOX activity by fractions isolated or derived from hops |
US20040115290A1 (en) * | 2001-06-20 | 2004-06-17 | Tripp Matthew L. | Modulation of inflammation by hops fractions and derivatives |
US8168234B2 (en) | 2001-06-20 | 2012-05-01 | Metaproteomics, Llc | Compositions that treat or inhibit pathological conditions associated with inflammatory response |
US8206753B2 (en) * | 2001-06-20 | 2012-06-26 | Metaproteomics, Llc | Anti-inflammatory botanical products for the treatment of metabolic syndrome and diabetes |
US7901714B2 (en) * | 2001-06-20 | 2011-03-08 | Metaproteomics, Llp | Treatment modalities for autoimmune diseases |
US7815944B2 (en) * | 2001-06-20 | 2010-10-19 | Metaproteomics, Llc | Anti-inflammatory pharmaceutical compositions for reducing inflammation and the treatment of prevention of gastric toxicity |
US8142819B2 (en) | 2002-10-21 | 2012-03-27 | Metaproteomics, Llc | Synergistic compositions that treat or inhibit pathological conditions associated with inflammatory response |
US8158160B2 (en) | 2001-11-13 | 2012-04-17 | Eric Hauser Kuhrts | Anti-inflammatory cyclooxygenase inhibitors |
KR20050071605A (en) * | 2002-10-21 | 2005-07-07 | 메타프로테오믹스, 엘엘씨 | Compositions that treat or inhibit pathological conditions associated with inflammatory response |
KR20060105429A (en) | 2003-05-22 | 2006-10-11 | 메타프로테오믹스, 엘엘씨 | Anti-inflammatory pharmaceutical compositions for reducing inflammation and the treatment or prevention of gastric toxicity |
US7914831B2 (en) * | 2004-02-27 | 2011-03-29 | Metaproteomics, Llc | Synergistic anti-inflammatory pharmaceutical compositions and related methods using curcuminoids or methylxanthines |
US20050192356A1 (en) * | 2004-02-27 | 2005-09-01 | Babish John G. | Synergistic anti-inflammatory pharmaceutical compositions and methods of use |
AU2005304317A1 (en) * | 2004-11-13 | 2006-05-18 | Metaproteomics, Llc | Compositions exhibiting inhibition of cyclooxygenase-2 |
WO2007021694A2 (en) * | 2005-08-09 | 2007-02-22 | Metaproteomics, Llc | Protein kinase modulation by hops and acacia products |
NZ568860A (en) * | 2005-12-09 | 2012-09-28 | Metaproteomics Llc | Protein kinase modulation by hops and acacia products |
US20080051466A1 (en) * | 2006-06-20 | 2008-02-28 | Metaproteomics, Llc | Isoalpha acid based protein kinase modulation cancer treatment |
WO2007149482A2 (en) * | 2006-06-20 | 2007-12-27 | Metaproteomics, Llc | Xanthohumol based protein kinase modulation cancer treatment |
US8227437B2 (en) * | 2006-06-22 | 2012-07-24 | Tai June Yoo | Restoration of hearing loss |
AU2008229110A1 (en) * | 2007-03-19 | 2008-09-25 | Metaproteomics, Llc | Methods and compositions for promoting bone and joint health |
US8241674B2 (en) | 2007-05-11 | 2012-08-14 | Metaproteomics, Llc | Methods and compositions for heavy metal detoxification |
US20090060878A1 (en) * | 2007-09-04 | 2009-03-05 | The Procter & Gamble Company | Oral Compositions, Products And Methods Of Use |
EP2229178A4 (en) * | 2007-12-10 | 2011-03-09 | Metaproteomics Llc | Substituted 1,3-cyclopentadione multi-target protein kinase modulators of cancer, angiogenesis and the inflammatory pathways associated therewith |
AU2009231723B2 (en) * | 2008-04-02 | 2014-04-17 | Metaproteomics, Llc. | Substituted 1,3-cyclopentadione attenuated endothelial inflammation and endothelial-monocyte interactions |
AU2011227202A1 (en) * | 2010-03-17 | 2012-10-04 | Arbonne International Llc | Oral supplement |
AU2011268342B2 (en) | 2010-06-16 | 2014-12-04 | IRR, Inc. | Use of levocetirizine and montelukast in the treatment of influenza, common cold and inflammation |
WO2013026558A2 (en) * | 2011-08-19 | 2013-02-28 | Joy Development Ug | Combined therapeutic agent |
EP2787988A4 (en) * | 2011-12-08 | 2016-11-02 | Metaproteomics Llc | Supplemented oil compositions and methods for improved health |
ES2660494T3 (en) | 2013-03-13 | 2018-03-22 | 14779507 | Use of levocetirizine and montelukast in the treatment of a traumatic injury |
JP6441888B2 (en) | 2013-03-13 | 2018-12-19 | インフラマトリー・レスポンス・リサーチ・インコーポレイテッド | Use of levocetirizine and montelukast in the treatment of autoimmune disorders |
CA2901413A1 (en) | 2013-03-13 | 2014-10-09 | Bruce Chandler May | Use of levocetirizine and montelukast in the treatment of vasculitis |
WO2016044095A1 (en) | 2014-09-15 | 2016-03-24 | Inflammatory Response Research, Inc. | Levocetirizine and montelukast in the treatment of inflammation mediated conditions |
CN105126005A (en) * | 2015-09-29 | 2015-12-09 | 成都倍加特生物科技有限公司 | Internal administration medicament for treating alopecia areata and preparation method thereof |
WO2018106921A1 (en) * | 2016-12-09 | 2018-06-14 | Balchem Corporation | Essential nutrients and related methods |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040151792A1 (en) * | 2001-06-20 | 2004-08-05 | Tripp Matthew L. | Compositions that treat or inhibit pathological conditions associated with inflammatory response |
Family Cites Families (79)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2175340A (en) | 1936-03-27 | 1939-10-10 | New Discoveries Inc | Vitaminizing malted liquors |
US3933919A (en) | 1964-12-15 | 1976-01-20 | Geoffrey Wilkinson | Hydroformylation of mono-α-olefins and mono-α-acetylenes |
GB1140545A (en) | 1965-03-01 | 1969-01-22 | Kalamazoo Spice Extract Co | Hop flavours for malt beverages and the like |
US3451821A (en) * | 1965-03-01 | 1969-06-24 | Kalamazoo Spice Extract Co | Increasing the utilization of hops and improving flavor control of malt beverages and the like |
US3720517A (en) | 1970-12-21 | 1973-03-13 | Hamm T Brewing Co | Preparation of a fermented malt champagne |
US3932603A (en) | 1971-05-28 | 1976-01-13 | General Foods Corporation | Oral preparations for reducing the incidence of dental caries |
GB1372932A (en) | 1971-03-15 | 1974-11-06 | Gen Foods Corp | Anti-caries compositions |
US3965188A (en) | 1972-01-10 | 1976-06-22 | Miller Brewing Company | Hop extract process and product |
CH617326A5 (en) | 1975-12-04 | 1980-05-30 | Siegfried Ag | |
US4170638A (en) | 1976-11-05 | 1979-10-09 | S. S. Steiner, Inc. | Method for producing a deodorant |
US4148873A (en) | 1976-11-05 | 1979-04-10 | S. S. Steiner, Inc. | Method for treating the skin with extracts of hops |
US4123561A (en) | 1977-02-01 | 1978-10-31 | S.S. Steiner, Inc. | Method for processing hops for brewing |
US4401684A (en) | 1981-10-01 | 1983-08-30 | Australian Hop Marketers Pty. Ltd. | Preservation of hops utilizing ascorbic acid |
BE896610A (en) | 1982-05-06 | 1983-08-16 | Hop Developments Ltd | EXTRACTION OF PLANT MATERIAL USING CARBONIC ANHYDRIDE |
US4473551A (en) | 1982-08-23 | 1984-09-25 | Faxon Pharmaceuticals, Inc. | Anti-inflammatory composition |
US4644084A (en) | 1984-01-25 | 1987-02-17 | Miller Brewing Company | Preparation of tetrahydroisohumulones |
GB2187755B (en) | 1984-02-28 | 1990-03-28 | Kalamazoo Holdings Inc | Separation of the constituents of co2 hop extracts |
SU1247011A1 (en) | 1985-02-20 | 1986-07-30 | Специальное Конструкторское Бюро Химизации Научно-Производственного Объединения "Аэрозоль" | Agent for hair care |
US4767640A (en) | 1985-10-29 | 1988-08-30 | Miller Brewing Company | Light stable hop extracts and method of preparation |
US4692280A (en) | 1986-12-01 | 1987-09-08 | The United States Of America As Represented By The Secretary Of Commerce | Purification of fish oils |
JP2594787B2 (en) | 1987-02-27 | 1997-03-26 | 大洋香料株式会社 | Caries prevention agent |
US4778691A (en) | 1987-04-03 | 1988-10-18 | Kalamazoo Holdings, Inc. | Removal of deleterious odor-forming impurities from hop flavors |
US5041300A (en) | 1987-04-03 | 1991-08-20 | Kalamazoo Holdings, Inc. | Hop flavor which is odor forming impurity free |
US4956195A (en) | 1987-04-03 | 1990-09-11 | Kalamazoo Holdings, Inc. | Hop flavors wherein deleterious odor-forming impurities have been removed |
DE3712986A1 (en) | 1987-04-16 | 1988-10-27 | Marbert Gmbh | MEDICAL PREPARATIONS BASED ON TREASURE EXTRACT, METHOD FOR THE PRODUCTION THEREOF AND USE OF TREATMENT EXTRACT FOR THE PRODUCTION OF COSMETIC PREPARATIONS AND A SPECIAL TREATMENT EXTRACT |
US4857554A (en) | 1987-08-17 | 1989-08-15 | Georgios Kallimanis | Method for the treatment of psoriasis |
US5082975A (en) | 1988-08-15 | 1992-01-21 | Kalamazoo Holdings, Inc. | Synthesis of hexahydrolupulone, novel forms thereof, and its use as a selective inhibitor of cell growth and multiplication |
US5166449A (en) | 1988-08-15 | 1992-11-24 | Kalamazoo Holdings, Inc. | Synthesis of hexahydrolupulone, novel forms thereof, and its use as a selective inhibitor of cell growth and multiplication |
DE3931147A1 (en) | 1989-09-19 | 1991-03-28 | Solong Natural Ltd | New nerve tonic contg. extract of avena sativa - used to treat frigidity and increase libido in women |
US5013571A (en) | 1990-01-31 | 1991-05-07 | Pfizer Inc. | Methods for making tetrahydroisoalpha and hexahydroisoalpha acids |
DE59010282D1 (en) | 1990-09-10 | 1996-05-15 | Fromm Mayer Bass Ltd | A process for isomerizing humulon in a carbon dioxide hop extract and a process for obtaining isohumulone therefrom |
JP3155003B2 (en) | 1990-11-06 | 2001-04-09 | サントリー株式会社 | Method for producing hop extract and hop extract obtained by the method |
JP2514860B2 (en) | 1990-11-30 | 1996-07-10 | アサヒビール株式会社 | Hop extract used for elimination of active oxygen and its utilization |
RU2045995C1 (en) | 1991-03-19 | 1995-10-20 | Акционерное общество открытого типа "Волжский научно-исследовательский институт целлюлозно-бумажной промышленности" | Drinking water filtering shell and method for production of this shell |
TW199905B (en) | 1992-02-03 | 1993-02-11 | J E Siebel Sons Company Inc | Method and composition for enhancing foam properties of fermented malt beverages |
NZ254859A (en) | 1992-07-29 | 1997-02-24 | Drymed A S | Composition comprising fertilised, incubated shelled (avian or reptilian) eggs |
US5286506A (en) | 1992-10-29 | 1994-02-15 | Bio-Technical Resources | Inhibition of food pathogens by hop acids |
US5296637A (en) | 1992-12-31 | 1994-03-22 | Kalamazoo Holdings, Inc. | Production of odor-free tetrahydroisohumulates from alpha acids via their tetrahydrohumulates and subsequent isomerization |
JPH06312924A (en) | 1993-04-28 | 1994-11-08 | Asahi Breweries Ltd | Utilization of humulones having antioxidant action |
JP3431250B2 (en) | 1993-12-28 | 2003-07-28 | 日本臓器製薬株式会社 | Beverage and method for producing the same |
JP2677762B2 (en) * | 1994-04-08 | 1997-11-17 | 株式会社神戸製鋼所 | Oil-cooled compressor |
ES2129691T3 (en) | 1994-04-12 | 1999-06-16 | Hoechst Marion Roussel Ltd | PHARMACEUTICAL COMPOSITION TO TREAT OSTEOPOROSIS. |
JPH0873369A (en) | 1994-09-01 | 1996-03-19 | Fuairudo:Kk | Tea for health |
JPH0967245A (en) | 1995-08-28 | 1997-03-11 | Asahi Breweries Ltd | Bathing agent |
US5827895A (en) | 1996-02-27 | 1998-10-27 | Regents Of The University Of Minnesota | Hexahydrolupulones useful as anticancer agents |
US6020019A (en) | 1996-03-26 | 2000-02-01 | Miller Brewing Company | Hydrogenation of hop soft resins using CO2 |
JPH1025247A (en) | 1996-07-10 | 1998-01-27 | Asahi Breweries Ltd | Preventive and therapeutic agent for gastritis and gastric and duodenal ulcer |
US6589994B1 (en) | 1996-08-30 | 2003-07-08 | Nps Pharmaceuticals, Inc. | Treating a variety of pathological conditions, including spasticity and convulsions, by effecting a modulation of CNS activity with isovaleramide, isovaleric acid, or a related compound |
JP4083831B2 (en) | 1996-11-20 | 2008-04-30 | 株式会社カネボウ化粧品 | Skin preparation |
US5968539A (en) | 1997-06-04 | 1999-10-19 | Procter & Gamble Company | Mild, rinse-off antimicrobial liquid cleansing compositions which provide residual benefit versus gram negative bacteria |
WO1999044623A1 (en) | 1998-03-04 | 1999-09-10 | Nps Pharmaceuticals, Inc. | Compositions comprising valerian extracts, isovaleric acid or derivatives thereof with a nsaid |
DE19841615A1 (en) | 1998-09-11 | 2000-03-16 | Fritz Armin Mueller | Medicinal wine for alleviating pain and other symptoms of premenstrual syndrome, comprising mixture of extracts of different plants in dry white wine |
ES2147538B1 (en) | 1999-01-29 | 2001-04-01 | Revlon Consumer Prod Corp | A CAPILLARY LOTION WITH IMPROVED PROPERTIES IN ITS HAIR PROTECTIVE AND PREVENTIVE ACTION OF HIS FALL, AND REDUCTION OF THE EXTERNAL EFFECTS OF ANDROGENETIC ALOPECIA AND WITH THAT OF THE HAIR FALL. |
US6801860B1 (en) | 1999-02-15 | 2004-10-05 | Genetics Institute, Llc | Crystal structure of cPLA2 and methods of identifying agonists and antagonists using same |
US6383527B1 (en) | 1999-03-04 | 2002-05-07 | Nps Pharmaceuticals, Inc. | Compositions comprising valerian extracts, isovaleric acid or derivatives thereof with a NSAID |
US20010031305A1 (en) | 1999-05-07 | 2001-10-18 | Michael Smith | Hop extract of defined composition |
MXPA01012390A (en) | 1999-06-02 | 2003-10-14 | Oxford Natural Products Plc | Combination of glucosamine with herbal extracts of tripterygium, ligustrum and erycibe. |
US6129907A (en) | 1999-08-04 | 2000-10-10 | Colgate Palmolive Company | Stable hydrogenated lupulone antibacterial oral compositions |
US6200594B1 (en) | 1999-12-29 | 2001-03-13 | Vital Dynamics, Inc. | Breast-enhancing, herbal compositions and methods of using same |
US6953593B2 (en) | 2000-02-01 | 2005-10-11 | Lipoprotein Technologies, Inc. | Sustained-release microencapsulated delivery system |
US6583322B1 (en) | 2000-02-25 | 2003-06-24 | Kalamazoo Holdings, Inc. | Dihydro and hexahydro isoalpha acids having a high ratio of trans to cis isomers, production thereof, and products containing the same |
US20020086070A1 (en) | 2000-03-11 | 2002-07-04 | Kuhrts Eric Hauser | Anti-inflammatory and connective tissue repair formulations |
KR20030005252A (en) | 2000-03-31 | 2003-01-17 | 니신 오일 밀스 가부시키가이샤 | External preparation for the skin and beautifying agents |
US6440465B1 (en) | 2000-05-01 | 2002-08-27 | Bioderm, Inc. | Topical composition for the treatment of psoriasis and related skin disorders |
DE10031955A1 (en) | 2000-06-30 | 2002-01-17 | Deutsches Krebsforsch | Curcumin derivatives with improved water solubility compared to curcumin and medicaments containing them |
US20020076452A1 (en) | 2000-08-01 | 2002-06-20 | Ashni Naturaceuticals, Inc. | Combinations of sesquiterpene lactones and ditepene lactones or triterpenes for synergistic inhibition of cyclooxygenase-2 |
US6908630B2 (en) | 2000-08-01 | 2005-06-21 | Metaproteomics, Llc | Combinations of sesquiterpene lactones and ditepene triepoxide lactones for synergistic inhibition of cyclooxygenase-2 |
FR2815227B1 (en) | 2000-10-17 | 2003-04-11 | Schwartz Laboratoires Robert | ANTI-STRESS COMPOSITION FOR PRIMARY INCORPORATION IN NUTRITIONAL VEHICLES |
US6835199B2 (en) | 2001-01-31 | 2004-12-28 | Rex Medical, L.P. | Apparatus and method for resectioning gastro-esophageal tissue |
US6391346B1 (en) | 2001-04-05 | 2002-05-21 | Thomas Newmark | Anti-inflammatory, sleep-promoting herbal composition and method of use |
US7205151B2 (en) | 2001-06-20 | 2007-04-17 | Metaproteomics, Llc | Complex mixtures exhibiting selective inhibition of cyclooxygenase-2 |
US20040219240A1 (en) | 2001-06-20 | 2004-11-04 | Babish John G. | Anti-inflammatory pharmaceutical compositions for reducing inflammation and the treatment or prevention of gastric toxicity |
US8142819B2 (en) | 2002-10-21 | 2012-03-27 | Metaproteomics, Llc | Synergistic compositions that treat or inhibit pathological conditions associated with inflammatory response |
US7279185B2 (en) * | 2001-10-26 | 2007-10-09 | Metaproteonics, Llc | Curcuminoid compositions exhibiting synergistic inhibition of the expression and/or activity of cyclooxygenase-2 |
CA2464334C (en) | 2001-10-26 | 2012-01-10 | Metaproteomics, Llc | Curcuminoid compositions exhibiting synergistic inhibition of the expression and/or activity of cyclooxygenase-2 |
US7144590B2 (en) | 2003-01-09 | 2006-12-05 | Lipoprotein Technologies, Inc. | Bioactive compositions derived from humulus lupulus |
US20050192356A1 (en) * | 2004-02-27 | 2005-09-01 | Babish John G. | Synergistic anti-inflammatory pharmaceutical compositions and methods of use |
US7914831B2 (en) * | 2004-02-27 | 2011-03-29 | Metaproteomics, Llc | Synergistic anti-inflammatory pharmaceutical compositions and related methods using curcuminoids or methylxanthines |
NZ568860A (en) * | 2005-12-09 | 2012-09-28 | Metaproteomics Llc | Protein kinase modulation by hops and acacia products |
-
2006
- 2006-01-06 US US11/326,874 patent/US7718198B2/en not_active Expired - Fee Related
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2007
- 2007-01-04 AU AU2007205243A patent/AU2007205243A1/en not_active Withdrawn
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Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040151792A1 (en) * | 2001-06-20 | 2004-08-05 | Tripp Matthew L. | Compositions that treat or inhibit pathological conditions associated with inflammatory response |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8410179B2 (en) | 2010-10-30 | 2013-04-02 | Kindex Therapeutics, Llc | Cis, 3,4-dihydroxy-2-(3-methylbutanoyl)-5-(3-methylbutyl)-4-(4-methylpentanoyl)cyclopent-2-en-1-derivatives, substantially enantiomerically pure compositions and methods |
US8410178B2 (en) | 2010-10-30 | 2013-04-02 | Kindex Therapeutics, Llc | CIS 3,4-dihydroxy-2-(3-methylbutanoyl)-5-(3-methylbutyl)-4-(4-methylpentanoyl)cyclopent-2-en-1-derivatives, substantially enantiomerically pure compositions and methods |
US8829056B2 (en) | 2010-10-30 | 2014-09-09 | Kindex Pharmaceuticals, Inc. | Cis 3,4-dihydroxy-2-(3-methylbutanoyl)-5-(3-methylbutyl)-4-(4-methylpentanoyl) cyclopent-2-en-1-one derivatives, substantially enantiomerically pure compositions and methods |
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JP2009525952A (en) | 2009-07-16 |
WO2007081729A3 (en) | 2007-11-08 |
WO2007081710A2 (en) | 2007-07-19 |
AU2007205243A1 (en) | 2007-07-19 |
EP2604262A1 (en) | 2013-06-19 |
WO2007081710A3 (en) | 2008-02-14 |
NZ569513A (en) | 2012-03-30 |
MX2008008735A (en) | 2008-09-12 |
US20070020352A1 (en) | 2007-01-25 |
AU2007205224A1 (en) | 2007-07-19 |
AU2007205224B2 (en) | 2013-03-28 |
CA2636142A1 (en) | 2007-07-19 |
EP1993528A4 (en) | 2010-07-28 |
CA2635016A1 (en) | 2007-07-19 |
EP1993528A2 (en) | 2008-11-26 |
US7718198B2 (en) | 2010-05-18 |
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