US20060183799A1 - Biologically active oils - Google Patents

Biologically active oils Download PDF

Info

Publication number
US20060183799A1
US20060183799A1 US10/559,599 US55959905A US2006183799A1 US 20060183799 A1 US20060183799 A1 US 20060183799A1 US 55959905 A US55959905 A US 55959905A US 2006183799 A1 US2006183799 A1 US 2006183799A1
Authority
US
United States
Prior art keywords
oil
disease
substrate
biologically active
biologically
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US10/559,599
Other languages
English (en)
Inventor
Athol Gillies Turner
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of US20060183799A1 publication Critical patent/US20060183799A1/en
Priority to US12/125,024 priority Critical patent/US8039512B2/en
Priority to US13/232,408 priority patent/US8329748B2/en
Priority to US13/671,401 priority patent/US8629181B2/en
Abandoned legal-status Critical Current

Links

Images

Classifications

    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P7/00—Preparation of oxygen-containing organic compounds
    • C12P7/64—Fats; Fatty oils; Ester-type waxes; Higher fatty acids, i.e. having at least seven carbon atoms in an unbroken chain bound to a carboxyl group; Oxidised oils or fats
    • 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
    • A61K36/06—Fungi, e.g. yeasts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • 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
    • 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
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
    • C11B1/00—Production of fats or fatty oils from raw materials
    • C11B1/02—Pretreatment
    • C11B1/025—Pretreatment by enzymes or microorganisms, living or dead
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
    • C11B1/00—Production of fats or fatty oils from raw materials
    • C11B1/06—Production of fats or fatty oils from raw materials by pressing
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
    • C11B1/00—Production of fats or fatty oils from raw materials
    • C11B1/10—Production of fats or fatty oils from raw materials by extracting
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
    • C11B1/00—Production of fats or fatty oils from raw materials
    • C11B1/10—Production of fats or fatty oils from raw materials by extracting
    • C11B1/102—Production of fats or fatty oils from raw materials by extracting in counter-current; utilisation of an equipment wherein the material is conveyed by a screw
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
    • C11B1/00—Production of fats or fatty oils from raw materials
    • C11B1/12—Production of fats or fatty oils from raw materials by melting out
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
    • C11B3/00—Refining fats or fatty oils
    • C11B3/006—Refining fats or fatty oils by extraction
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
    • C11B3/00—Refining fats or fatty oils
    • C11B3/008—Refining fats or fatty oils by filtration, e.g. including ultra filtration, dialysis
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
    • C11B3/00—Refining fats or fatty oils
    • C11B3/12—Refining fats or fatty oils by distillation
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P1/00—Preparation of compounds or compositions, not provided for in groups C12P3/00 - C12P39/00, by using microorganisms or enzymes
    • C12P1/02—Preparation of compounds or compositions, not provided for in groups C12P3/00 - C12P39/00, by using microorganisms or enzymes by using fungi
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P7/00—Preparation of oxygen-containing organic compounds
    • C12P7/64—Fats; Fatty oils; Ester-type waxes; Higher fatty acids, i.e. having at least seven carbon atoms in an unbroken chain bound to a carboxyl group; Oxidised oils or fats
    • C12P7/6436—Fatty acid esters
    • C12P7/6445—Glycerides
    • C12P7/6463—Glycerides obtained from glyceride producing microorganisms, e.g. single cell oil

Definitions

  • the present invention relates to fungal metabolism/transformation of lipid substrates to produce fats and more particularly oils and their extracts containing biologically-active chemical compounds for the treatment or prophylaxis of diseases, disorders or conditions in humans and other animals.
  • compositions formulated for administration by any route including without limitation, oral, buccal, sublingual, rectal, parenteral, topical, inhalational, injectable and transdermal, preferably oral or topical, including biologically-active oils and/or their extracts which demonstrate efficacy across a broad spectrum of diseases, disorders or conditions in humans and other animals, together with pharmaceutically acceptable excipients, carriers or adjuvants.
  • This invention is based on the identification of the major factor/s responsible for the variation in quality of plant and animal derived oils, namely the transformation of the lipid substrates by fungi growing in and on the lipid substrate.
  • the quality of the fat or oil produced depends on the type and number of fungi (enzymes), lipid substrate, temperature, humidity and length (time) of incubation prior to rendering.
  • the basis of this invention therefore relates to the controlled use of fungi to transform lipid substrate/s to produce oils which contain biologically-active chemical compounds. It has been established by the present inventor that exposure of the lipid substrate to fungi is responsible for the major variation in biological activity (efficacy) rather than temperature, oxygen and light during processing and storage, although these latter factors may have some minor influence.
  • a first aspect of the present invention provides a process for the production of fats or oils and their extracts containing biologically-active chemical compounds from a lipid substrate, the process comprising:
  • a related aspect of the present invention provides a process for the production of oils and their extracts containing biologically-active chemical compounds from a lipid substrate, the process comprising
  • step b) typically the period of incubation is between about 7 to 28 days at high humidity of between about 80-100%.
  • step c) if the lipid is animal derived, it is typical that the product is a biologically active oil obtained by rendering said inoculated substrate. Alternatively, if said lipid is plant or seed derived, the biologically active oil is obtained by cold pressing or solvent extraction of said inoculated substrate mixture.
  • Bacteria are not involved in the transformation process. While not wishing to be bound by any theory, it appears that the fungi penetrate the lipid cell and excrete enzymes that digest the lipid within the cell. Breakdown products are released and some are absorbed by the fungus and transformed internally while others appear in the supernatant.
  • the fungal mixture used to inoculate the lipid substrate and which is the source of the fungally-derived lipolytic enzymes may be intact/whole fungal organisms, pure fungi, single fungi or mixed fungi, active enzyme extracts thereof, genetically modified organisms or modified enzymes.
  • the process of the present invention transforms the lipids, resulting in fats or oils containing biologically-active chemical compounds which are suitable for treating a wide range of human and veterinary diseases. It is noted that using this method of producing oils and their extracts the amount of free fatty acids, mono and diglycerides are enriched, for example the level of total free fatty acids some plant animal and plant oils is up to or exceeding 14%.
  • the compounds found in the oils and their extracts act synergistically to give the desired biochemical action in humans and animals for the treatment of a wide range of diseases and conditions.
  • the lipid substrate can be selected from animal or plant sources, of either terrestrial or marine origin, or the substrate can be constituted from lipids or their extracts impregnated onto artificial substrates supplemented with mineral and organic amendments (see Waller et al 2002, Plant Pathologists Pocketbook 3rd Edition, CABI, New York).
  • Sources of animal lipids include goanna, sheep, chicken, emu, ostrich, camel, duck, geese, pig, cattle, horse, mutton bird, fish and shellfish including mussels.
  • Sources of plant oils include seeds/nuts of Macadamia sp, Canarium spp, peanut, sunflower, safflower, linseed, soybean, wheat, oats, barley, almond, avocado, cashew, quandong, maize, wattle, olive, palm and rice.
  • Other vegetable/plant/seed sources include coconut, pili nut, ngali nut, neem seed, sesame and canola.
  • the fungi inoculated onto the lipid substrate will have been isolated from the substrate (ie is endogenous to the lipid substrate) and found to transform the specific or similar substrates.
  • Such fungi are typically found in the sexual and asexual states of the Phyla Zygomycotina, Ascomycotina and Basidiomycotina. This is therefore understood to cover the fungi Deuteromycetes which is the asexual state of the main phyla.
  • Fungi also typically found to transform lipid substrates include Phoma sp, Cladosporium sp, Rhodotorula mucilaginosa, Cryptococcus albidus, Trichosporon pullulans, Mucor spp, Epicoccom purpurescens, Rhizopus stolonifer, Penicillium chrysogenum, Nigrospora sphaerica, Chaetomium globosum . Fungi demonstrating the ability to transform or having this potential may be typically improved by either traditional or molecular genetic techniques to enhance enzyme formation and activity.
  • the substrate may also or instead be inoculated with enzymes derived from fungi.
  • additional enzymes are endogenous to the fungi, but can also be developed from alternative sources or genetically modified isolates.
  • Such enzymes may also be purified and their activity increased by alteration of their structure using physical, chemical or other techniques.
  • the lipid substrate is sterilised and then inoculated with one or more fungi or their enzymes as required.
  • the substrate may be sliced, minced, chopped or ground to enable it to be spread in a layer typically between 0.5 and 10 cm on a surface that may be a solid sheet, or perforated to allow oxygen to the lower surface and oil to drip from the substrate and be collected in a suitable container. Inoculation uses standard procedures (see Waller et al 2002) including spraying or painting the lipid surface with fungal spores suspended in sterile water.
  • the substrate is then typically incubated for a period between about 7 days and about 120 days, more typically between about 7 and 65 days, or about 7 and 56 days, or about 7 and 42 days, or about 7 and 35 days.
  • the substrate is incubated for a period between about 7 and 28 days or about 7 and 21 days and most typically between 14, 21, 28, 35, 42, 56, and 65 days.
  • the inoculated lipid substrate is incubated at a temperature between 4-35° C., typically around 15-20° C., and a relative humidity between 80-100%, typically 95%.
  • the animal lipid substrate containing the fungi is minced or ground and transferred to a stainless vessel prior to the rendering process.
  • This process typically involves rendering at a temperature between 40-80° C., typically around 70-75° C. with constant slow speed stirring until the lipid substrate has melted into oil.
  • This oil is then typically centrifuged and filtered and can be further extracted.
  • the filtrate which contains the biologically active oil is then typically further sterilised by heating for a period of between about 15 minutes and about 8 hours, more typically between about 1 hour and 6 hours, even more typically between about 1 hour and 4 hours.
  • the filtrate is heated to a temperature between about 100-160° C., more typically between about 110-150° C. and even more typically between about 120-140° C., most typically about 130-135° C.
  • the inoculated and incubated lipid substrate/s containing fungi may be minced or ground prior to cold pressing using a screw press, the oil from the screw press then being centrifuged and filtered.
  • This oil is then typically sterilised by heating for a period of between about 15 minutes and about 8 hours, more typically between about 1 hour and 6 hours, even more typically between about 1 hour and 4 hours.
  • the oil is heated to a temperature between about 100-160° C., more typically between about 110-150° C. and even more typically between about 120-140° C., most typically about 130-135° C.
  • the oil produced is then treated as for animal substrates.
  • the oil obtained from the above processes may then be subjected to solvent extraction which typically involves mixing the oil on a mass or volume basis in the ratio of 1/1 or 2/1 solvent to oil then cooling over a temperature range of 20° C. to ⁇ 40° C. for a time period from 30 minutes up to 24 hours.
  • the solvent is decanted or poured off, centrifuged if required containing, and evaporated dryness to obtain the extract.
  • the resulting residue contains the biologically-active chemical compounds.
  • oil or extracts from the above processes may also be subjected (including any derivatives obtained by chemical treatment of oils and their extracts) to the following processes in order to obtain specific fractions or chemical compounds,
  • a second aspect of the present invention provides a method for the treatment or prophylaxis of a wide range of diseases, disorders and conditions in humans and other animals by the administration of the fatty acid esters and/or amides of biologically-active oils and/or their extracts.
  • Esters include methyl, ethyl, propyl and isopropyl groups. Methyl and isopropyl esters of the extracts of these oils have been in-vivo tested successfully on rats for the treatment of arthritis with success.
  • a related aspect of the present invention provides the use of the fatty acid esters and/or amides of biologically-active oils produced according to the present invention, and/or their extracts, for the preparation of a medicament for the treatment or prophylaxis of a wide range of diseases, disorders and conditions in humans and other animals by the administration.
  • the biologically active oils produced can be used to treat and/or prevent a wide range of diseases, disorders or conditions in humans and other animals.
  • Typical diseases, disorders or conditions which may be treated or prevented include: respiratory diseases or conditions such as asthma, bronchial disease and chronic obstructive pulmonary disease (COPD), vascular diseases or conditions such as atherosclerosis, coronary artery diseases, hypertension and sickle cell disease-associated vaso-occlusion, skin diseases or conditions such as various dermatitis, psoriasis and atopic eczema, all types of burns, gastrointestinal diseases or conditions such as ulcers, gastric reflux, inflammatory bowel disease, ulcerative colitis, Crohn's disease, pancreatitis and periodontal disease, cancers including bowel cancer and prostate cancer, sarcoidosis, septic shock, musculo-skeletal diseases or conditions such as arthritis including osteoarthritis and rheumatoid arthritis, chronic joint and ligament pain, leukemia, diabetes, allergy including o
  • the biologically active oils and their extracts appear to inhibit the synthesis of the C reactive protein ie they are C reactive protein inhibitors. (Refer to test results for patient 7 in the examples of therapeutic activity below). Hence these oils and their extracts may used to treat a wide range of human and animal diseases and conditions associated with the production of the C reactive protein.
  • C-Reactive Protein belongs to the pentraxin family of proteins, so-called because it has five identical subunits, encoded by a single gene on chromosome 1, which associate to form a stable disc-like pentameric structure. It was so named because it reacts with the somatic C polysaccharide of Streptococcus pneumoniae , and was first discovered in 1930 by Tillet and Frances. In the presence of calcium, CRP specifically binds to phosphocholine moieties.
  • CRP phosphocholine is found in microbial polysaccharides (where CRP-binding activates the classical complement pathway and opsonises ligands for phagocytosis), the pro-inflammatory platelet-activating factor (PAF) (which is neutralised), and polymorphs (which are down-regulated).
  • PAF platelet-activating factor
  • CRP chronic myeloma
  • the plasma level can double at least every 8 hours, reaching a peak after about 50 hours. After effective treatment or removal of the inflammatory stimulus, levels can fall almost as rapidly as the 5-7-hour plasma half-life of labelled exogenous CRP. The only condition that interferes with the “normal” CRP response is severe hepatocellular impairment.
  • the biologically active extracts appear to inhibit leukotriene synthesis ie they are 5-lipoxygenase inhibitors.
  • the biologically active oils produced have also been noted to synergistically enhance the efficacy of a variety of pharmaceuticals including dexamethasone and prednisone.
  • Such synergy is of great clinical benefit as raised levels of pro-inflammatory leukotrienes or 5-lipoxygenase are associated not only with asthma but also with rheumatoid arthritis, osteoarthritis, scleroderma and inflammatory bowel diseases such as Crohn's disease, and the administration of an active oil of the present invention allows lower doses of steroids to be used. (See FIG. 4 for the synergistic action of a lipoxygenase inhibitor plus a steroid.)
  • a third aspect of the present invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising a biologically active oil, or a fatty acid ester and/or amide of a biologically-active oil and/or an extract thereof, together with a pharmaceutically acceptable carrier, excipient or adjuvant.
  • the compositions can be in the form of immediate release, extended release, pulse release, variable release, controlled release, timed release, sustained release, delayed release, long acting, and combinations thereof.
  • FIG. 1 is a flow chart of the process for extraction of biologically active oils from the crude oil/filtrate.
  • FIG. 2 is a flow chart of the process for production of biologically active oils according to the present invention.
  • FIG. 3 is a summary of the enzymatic pathways acted upon by the biologically active oils to suppress pro-inflammatory leukotrienes
  • FIG. 4 Shows how steroids and the lipoxygenase inhibitor(s)(LI) from a biologically-active emu oil can act co-operatively to suppress pro-inflammatory leukotrienes.
  • this invention relates to the fungal metabolism/transformation of lipid substrates.
  • the fungi can be endogenous or exogenous to the lipid substrate.
  • only fungi with very specific capabilities will grow on lipid substrates. Not all have the potential to transform the lipid substrate from which they were isolated, or other lipid substrates.
  • the present invention can utilise all fungi which grow on and metabolise/transform lipid substrates to produce oils which contain biologically-active chemical compounds.
  • Fungi are isolated and cultured from lipids using standard methods (see Waller et al 2002 for some common methods). Fungi can be found growing on or near the surface of naturally colonised lipidic substrates. Typically, the fungi are isolated from lipidic substrates naturally colonised by the fungi onto various standard agar media using standard techniques. Typically, fungi growing on the surface of lipid substrates are obtained by removing fragments of fungus with a sterile probe and placing the fragment on media for subsequent growth and identification. Typically endogenous fungi are obtained following surface sterilisation of the lipid substrate with alcohol or hypochlorite. Fragments of the lipid substrate are then placed on media containing antibiotics to suppress bacterial growth.
  • Emerging fungi are sub-cultured to fresh sterile media for growth and subsequent identification.
  • Media typically include Potato Dextrose agar, Malt Extract agar, V8 juice agar, Cornmeal agar, Oatmeal agar.
  • the fungi can be subcultured from isolation plates on the same or other standard media.
  • Such fungi can undergo traditional or genetic techniques to enhance formation and activity of target compounds.
  • Fungi isolated from lipidic substrates can be tested for their transformation of lipid substrates. Those fungi found to transform most effectively can replace less effective isolates to increase production of biologically-active compounds. These processes are used widely to enhance production of biologically active compounds and were used, for instance, to enhance production of penicillin.
  • Enzymes can be isolated and purified from the fungi and their activity maximised using physical or chemical treatment techniques, according to R. K. Saxena, Anita Sheoran, Bhoopander Giri, W. Sheba Davidson, (2003) Review of Purification Strategies for Microbial Lipases, 52, 1-18 which is incorporated herein by reference. Enzymes are only isolated from fungi which are known to grow on and transform/metabolise lipid substrates to produce oil containing biologically-active chemical compounds.
  • Fungi are stored using standard techniques such as lyophilisation, storage at low temperatures, in sterile water, on nutrient agar under oil, or when desiccated (see Waller et al 2002 for some standards techniques of storing fungi).
  • Animal and plant lipid substrates are stored in enclosed containers. Animal lipids are stored at temperatures typically below ⁇ 18° C. Animal lipids may be freeze-dried and ground or minced prior to storage at low temperatures. Plant lipid substrates are stored under standard conditions of low humidity, typically below 9%. Temperature is maintained below 30° C.
  • the lipid substrate Prior to transformation, the lipid substrate is sterilised in order to remove endogenous microbes. Sterilisation may include washing in ethanol or hypochlorite solution, gamma irradiation or its equivalent, or heat treatment (see Waller et al 2002, Plant Pathologists Pocketbook 3 rd Edition, CABI, New York for examples of techniques in common use).
  • lipid substrate/s may be modified by addition of specific mineral and organic additives such as found in Czapek Dox agar (see Waller for a recipe for Czapek Dox, a commonly used mineral supplement).
  • the plant substrate is sterilised in order to remove endogenous microbes.
  • Sterilisation may include washing in ethanol or hypochlorite solution, gamma irradiation or its equivalent, or heat treatment (see Waller et al 2002, Plant Pathologists Pocketbook 3 rd Edition, CABI, New York for examples of techniques in common use).
  • lipid substrate/s may be modified by addition of specific mineral and organic additives such as those found in Czapek Dox agar (see Waller for a recipe for Czapek Dox).
  • the lipid substrate is inoculated with one or more fungi or their enzymes as required.
  • the substrate may be sliced, minced, chopped or ground to enable it to be spread in a layer typically between 0.5 and 10 cm on a surface that may be a solid sheet, or perforated to allow oxygen to the lower surface and oil to drip from the substrate and be collected in a suitable container. Inoculation uses standard procedures (see Waller et al 2002) including spraying or painting the lipid surface with fungal spores suspended in sterile water.
  • the inoculated lipid substrate is incubated at a temperature between 4-35° C. commonly around 15-20° C., and a relative humidity between 80-100%, typically 95%.
  • the substrate is then typically incubated for a period between 7 days and about 120 days, and typically between 7, 14, 28, 35, 42, 56, 65 days.
  • the lipid substrate used during fungal metabolism will determine the method used to extract the biologically active oil.
  • the three main methods that may be used are: temperature rendering, solvent extraction and cold pressing. The latter two methods are used only in respect of the production of plant oils.
  • the animal lipid substrate containing the fungi is minced or ground and transferred to a stainless vessel prior to the rendering process.
  • This process typically involves rendering at a temperature between 40-80° C., usual temperature set around 70-75° C. with constant slow speed stirring until the lipid substrate has melted into oil; heating may be electrical, or by steam or hot water.
  • the liquid in the vessel that contains the oil is then centrifuged, followed by filtration.
  • the residue that remains from the centrifuging step may then be subjected to further extractions, generally using standard procedures used in the plant-seed oil and pharmaceutical industries as well as in natural product isolations used in research.
  • the filtrate which contains the biologically active oil
  • the filtrate is then heated for a further period of between 15 minutes and about 8 hours at temperatures ranging from 100 to about 160° C. under inert gas atmosphere or at normal atmospheric conditions. Typical conditions that are commonly used are 135° C. for 2 hours under inert gas atmosphere such as nitrogen.
  • This step sterilises the oil, and in addition denatures any protein/s present.
  • After cooling to a suitable temperature using a heat exchanger the oil is then filtered again to remove any residual precipitated protein and/or fungi particulate which may be present.
  • the oil is packaged into 20 and or 200 litre pharmaceutical grade drums for storage. For extraction of biologically active compounds from oil refer to FIG. 1 .
  • the inoculated and incubated lipid substrate/s containing fungi may be minced or ground prior to cold pressing using a screw press, the oil from the screw press then being centrifuged and filtered.
  • This oil is heated for a further period of between 15 minutes and about 8 hours at temperatures ranging from 100 to about 160° C. under inert gas atmosphere or at normal atmospheric conditions. Typical conditions commonly used are 135° C. for 2 hours under inert gas atmosphere such as nitrogen.
  • This step sterilises the oil, and in addition denatures any protein/s that may be present.
  • the oil is filtered again to remove any residual precipitated protein and/or fungi particulate.
  • the oil is packaged into 20 and or 200 litre pharmaceutical grade drums for storage.
  • the cake from the press is solvent extracted using a range of common solvents selected from such as hexane, isohexane, petroleum spirits, methanol, isopropanol, propanol, ethanol and diethyl ether.
  • the solvent is then removed by evaporation and recovered for future use.
  • the techniques used are standard in plant oil industry.
  • the oil produced is then treated as described for animal substrates.
  • the oil obtained from the above processes may then be subjected to solvent extraction at various temperatures typically using one or more of the following solvents: methanol, ethanol, propanol, isopropanol, diethyl ether, light petroleum spirits, butanol, acetone and acetonitrile.
  • solvents typically using one or more of the following solvents: methanol, ethanol, propanol, isopropanol, diethyl ether, light petroleum spirits, butanol, acetone and acetonitrile.
  • This procedure involve mixing the oil on a mass or volume basis in the ratio of 1/1 or 2/1 solvent to oil then cooling over a temperature range of 20° C. to ⁇ 40° C. for a time period from 30 minutes up to 24 hours.
  • the solvent is decanted or poured off, centrifuged if required containing the biologically-active molecules and evaporated dryness to obtain the extract.
  • Typical conditions provide 100 gm of oil thoroughly mixed with 100 gm methanol and held at 0C for 16 hours, then centrifuged if required and solvent evaporated on laboratory scale using a rotary film evaporator. The resulting residue contains the biologically-active chemical compounds. Solvent should be recovered for recycling.
  • the dosage form to combine various forms of release, which include without limitation, immediate release, extended release, pulse release, variable release, controlled release, timed release, sustained release, delayed release, long acting, and combinations thereof.
  • immediate release, extended release, pulse release, variable release, controlled release, timed release, sustained release, delayed release, long acting characteristics and combinations thereof is performed using well known procedures and techniques available to the ordinary artisan. Each of these specific techniques or procedures for obtaining the release characteristics is well known to those persons skilled in the art.
  • a “controlled release form” means any form having at least one component formulated for controlled release.
  • immediate release form means any form having at least some of its pharmaceutically active components formulated for immediate release.
  • any mode of administration is acceptable and include oral, rectal, topical, nasal, transdermal or parenteral (eg subcutaneous, intramuscular and intravenous) routes.
  • any biologically-acceptable dosage form, and combinations thereof, are contemplated by the inventive subject matter.
  • dosage forms include, without limitation, chewable tablets, quick dissolve tablets, effervescent tablets, reconstitutable powders, elixirs, liquids, solutions, suspensions, emulsions, tablets, multi-layer tablets, bi-layer tablets, capsules, soft gelatin capsules, lard gelatin capsules, caplets, lozenges, chewable lozenges, beads, powders, granules, particles, microparticles, dispersible granules, cachets, douches, suppositories, creams, lotions, topicals, inhalants, aerosol inhalants, patches, particle inhalants, implants, depot implants, ingestibles, injectables, infusions, functional foods and combinations thereof.
  • the preparation of the above dosage is well known to those persons skilled in the art. Generally, each would contain a predetermined amount of the active component in association with a carrier which constitutes one
  • compositions suitable for parenteral administration conveniently comprise a sterile aqueous preparation of the active component which is formulated according to known methods using suitable dispersing and suspending agents.
  • a sterile injectable preparation may be formulated as a solution or suspension in a non-toxic parenterally acceptable diluent or solvent (eg water, isotonic sodium chloride solution).
  • a non-toxic parenterally acceptable diluent or solvent eg water, isotonic sodium chloride solution.
  • Sterile fixed oils can also be employed as a solvent or suspending medium.
  • Typical dosages extracts from 0.01 mg to 1000 mg per kilogram, several doses may be necessary throughout the day, oil from 5 mL to 20 mL per day in 5 mL doses. Initial daily doses of 30 or 40 ml of pure oil is also typical. Multiple doses per day are contemplated to achieve appropriate systemic levels of the active component.
  • the formulation of therapeutic compositions is well known to persons skilled in this field. Suitable pharmaceutically acceptable carriers and/or diluents include any and all conventional solvents, dispersion media, fillers, solid carriers, aqueous solutions, coatings, isotonic and absorption delaying agents and the like. Such formulations and formulating is described in Remingtons's Pharmaceutical Sciences (18 th Edn), Mack Publishing CO, Pennsylvania, USA.
  • Examples of creams for topical application were prepared according to the following protocols: Formulation 1 COMPO- SITION DESCRIPTION (% w/w) PHASE A Water Water 52.475 Glycerol Glycerol 3.000 Disodium EDTA Disodium EDTA 0.100 Stabileze QM TM Poly(methyl vinyl ether/maleic 0.350 anhydride) decadiene crosspolymer PHASE B Oil Biologically-active oil 30.000 Prolipid 141 TM Emulsifier blend of stearic acid, behenyl 5.000 alcohol, glycerol-monostearate, lecithin, C12-C16 alcohols and palmitic acid Cerasynt 840 TM PEG-20 stearate 1.000 Ceraphyl 230 TM Di-isopropyl adipate 4.000 Vitamin E acetate Vitamin E acetate 0.200 PHASE C 10% w/v NaOH Sodium hydroxide 0.875 Water Water 2.000 PHASE D Liquapar Optima TM Ph
  • Stabileze QM, Ceraphyl 230, Prolipid 141 and Liquapar Optima are trade marks of International Specialty Products, Inc. 1361 Alps Road Wayne N.J. 07470 FORMULATION 7 COMPO- SITION DESCRIPTION (% w/w) PHASE A Water Water 53.525 Glycerol Glycerol 3.000 Disodium EDTA Disodium EDTA 0.100 Stabileze QM TM Poly(methyl vinyl ether/maleic 0.350 anhydride) decadiene crosspolymer PHASE B Oil Biologically-active oil 20.000 Neem seed oil Neem seed oil 4.000 Tea tree oil Tea tree oil 1.000 Prolipid 141 TM Emulsifier blend of stearic acid, behenyl 6.250 alcohol, glycerol-monostearate, lecithin, C12-C16 alcohols and palmitic acid Ceraphyl 140A TM Isodecyl Oleate 7.5 Vitamin E acetate Vitamin E acetate 0.
  • Stabileze QM Stabileze QM
  • Ceraphyl 140A Stabileze QM
  • Prolipid 141 and Liquapar Optima are trade marks of International Specialty Products, Inc. 1361 Alps Road Wayne N.J. 07470 FORMULATION 8 COMPO- SITION DESCRIPTION (% w/w) PHASE A Water Water 53.525 Glycerol Glycerol 3.000 Disodium EDTA Disodium EDTA 0.100 Stabileze QM TM Poly(methyl vinyl ether/maleic 0.350 anhydride) decadiene crosspolymer PHASE B Oil Biologically-active oil 25.000 Prolipid 141 TM Emulsifier blend of stearic acid, behenyl 6.250 alcohol, glycerol-monostearate, lecithin, C12-C16 alcohols and palmitic acid Ceraphyl 140 TM Isodecyl Oleate 5.000 Vitamin E acetate Vitamin E acetate 0.200 PHASE C 10% w/v Na
  • Stabileze QM, Ceraphyl 140A, Prolipid 141 and Liquapar Optima are trade marks of International Specialty Products, Inc. 1361 Alps Road Wayne N.J. 07470 FORMULATION 9 COMPO- SITION DESCRIPTION (% w/w) PHASE A Water Water 51.475 Glycerol Glycerol 3.000 Disodium EDTA Disodium EDTA 0.100 Stabileze QM TM Poly(methyl vinyl ether/maleic 0.400 anhydride) decadiene crosspolymer PHASE B Oil Biologically-active oil 20.000 Prolipid 141 TM Emulsifier blend of stearic acid, behenyl 5.000 alcohol, glycerol-monostearate, lecithin, C12-C16 alcohols and palmitic acid Ceraphyl 140A TM Isodecyl Oleate 5.000 Vitamin E acetate Vitamin E acetate 0.200 PHASE C 10% w/v NaOH Sodium hydroxide 1.000 Water
  • Stabileze QM, Ceraphyl 140A, Prolipid 141 and Liquapar Optima are trade marks of International Specialty Products, Inc. 1361 Alps Road Wayne N.J. 07470 FORMULATION 10 COMPO- SITION DESCRIPTION (% w/w) PHASE A Water Water 67.950 Glycerol Glycerol 3.000 Disodium EDTA Disodium EDTA 0.100 Stabileze QM TM Poly(methyl vinyl ether/maleic 0.500 anhydride) decadiene crosspolymer PHASE B Oil Biologically-active oil 10.000 Vitamin E Vitamin E 2.000 Vitamin C Palmitate Vitamin C Palmitate 3.000 Prolipid 141 TM Emulsifier blend of stearic acid, behenyl 4.000 alcohol, glycerol-monostearate, lecithin, C12-C16 alcohols and palmitic acid Ceraphyl 140A TM Isodecyl Oleate 5.000 Vitamin E acetate Vitamin E acetate 0.200 PH
  • Stabileze QM Stabileze QM
  • Ceraphyl 140A Prolipid 141 and Liquapar Optima are trade marks of International Specialty Products, Inc. 1361 Alps Road Wayne N.J. 07470 FORMULATION 11 COMPOSITION DESCRIPTION (% w/w) PHASE A Water Water 57.300 Glycerol Glycerol 3.000 Disodium EDTA Disodium EDTA 0.100 Stabileze QM TM Poly(methyl vinyl ether/ 0.400 maleic anhydride) decadiene crosspolymer PHASE B Oil Biologically-active oil 20.000 Prolipid 141 TM Emulsifier blend of stearic 5.000 acid, behenyl alcohol, glycerol-monostearate, lecithin, C12-C16 alcohols and palmitic acid Methyl Salicylate Methyl Salicylate 10.000 Vitamin E acetate Vitamin E acetate 0.200 PHASE C 10% w/v NaOH Sodium hydroxide 1.000 Water Water
  • Emu-Kalaya Chrom. 3 0.08 +21 0.7+ Emu-Type 2 Chrom. 4 0.20 +12 0.5+ Jojoba Bean 1.24 +02 2.8+ with extr.
  • Emu-A 5 mg/rat) 0.23 +11 0.7+ with extr.
  • Emu-C 5 mg/rat) 0.92 +07 1.5+ with extr.
  • Emu-Ka 5 mg/rat) 0.08 +11 0.3+ with extr.
  • Arachidonic acid is converted into eicosanoids (or prostanoids) by two major pathways—the 5-lipoxygenase pathway, which leads to the formation of leukotrienes, and the cyclo-oxygenase pathway which leads to the formation of prostaglandins and thromboxanes.
  • Some, but not all, of the products of both of these pathways have potent pro-inflammatory properties.
  • LTB 4 is a very potent chemotactic agent, and its peptido-metabolites, LTC 4 , LTD 4 and LTE 4 , which were originally known as “slow reacting substance of anaphylaxis” or SRS-A, are potent bronchoconstrictor agents.
  • NASH non-steroidal anti-inflammatory drugs
  • NSAIDS non-steroidal anti-inflammatory drugs
  • FIG. 3 The principal steps of the 5-lipoxygenase pathway of these cells is shown in FIG. 3 .
  • arachidonic acid AA
  • PKA 2 phospholipase A 2
  • This AA is then substrate for the first enzyme in the pathway—5 lipoxygenase, which converts it to 5-hydroperoxyeicosatetraenoic acid (5-HPETE).
  • 5-HPETE is then converted enzymatically to either 5-hydroxyeicosa-tetraenoic acid (5-HETE) by glutathione peroxidase, or to leukotriene A 4 (LTA 4 ) by LTA 4 synthase.
  • LTA 4 is then converted either non-enzymatically to the all trans isomers of LTB 4 , or hydrolysed by LTA 4 hydrolase to leukotriene B 4 (LTB 4 ).
  • LTB 4 leukotriene B 4
  • Human PMN do not significantly metabolise LTB 4 any further, although other cells, such as eosinophils convert it to the potent vasoconstrictor peptido-leukotrienes, SRS-A.
  • the HPLC assay readily quantifies 5-HETE, 12-HETE, LTB 4 , and the two all trans-isomers of LTB- 4 , and thus gives quantitative data on the relative activities of the enzymes in the 5-lipoxygenase of neutrophils, as well as data on the 12-lipoxygenase pathway of platelets. Thus it is an ideal system to test potential inhibitors of these pathways.
  • inhibitory compounds may be tested on isolated human PMN and platelets, in which the pathways are activated by treating the PMN or platelets with arachidonic acid and the calcium ionophore A 23187 .
  • arachidonic acid eliminates the PLA- 2 step, and provides high levels of substrate for the pathway.
  • activation is known to maximally drive the pathway to produce the greatest synthesis of all the metabolites, and thus is also the least sensitive to inhibition.
  • compounds that do inhibit the pathway activated in this fashion are potentially potent inhibitors.
  • the PMN pellet was vigorously mixed with 1 mL of Hank's buffer by rapid aspiration/deaspiration into a 1 mL plastic disposable pipette, and then finally suspended in Hank's buffer at 2.4 ⁇ 10 6 PMN/ml (as measured using a Coulter counter), in preparation for the leukotriene assay.
  • the samples were reconstituted in 100 ⁇ L of the LTB 4 mobile phase, vortexed and transferred to Waters low volume inserts for injection (usually ⁇ 25 ⁇ l).
  • the HPLC was setup for the LTB 4 conditions, and all the samples assayed for LTB 4 and the all trans isomers of LTB 4 .
  • Emu-Type-B Chrom. 4 10 ⁇ g/mL 78 ⁇ 6 76 ⁇ 7 80 ⁇ 4 78 ⁇ 7 Emu-Type 2* Chrom. 4 5 ⁇ g/mL 95 ⁇ 9 96 ⁇ 8 88 ⁇ 2 90 ⁇ 7 Emu-Type-B Chrom. 24 50 ⁇ g/mL 0 0 0 4 ⁇ 2 Emu-Type-B Chrom. 24 10 ⁇ g/mL 82 ⁇ 14 86 ⁇ 14 88 ⁇ 9 66 ⁇ 9 Emu-Type-B Chrom.
  • the data shows that all three samples in table were potent inhibitors of the 5-LOZ pathway.
  • the data are compared to 12-methyl tetradecanoic acid which showed 100% inhibition as low as 20 ⁇ g/mL.
  • FAME sample was the least effective, where as Emu oil-WB and Ostrich oil samples are approximately the same as the three samples in Table 7. This confirms that the process for the production of biologically-active oils may be reproduced using different lipid substrates etc.
  • Patient is a 54 year old Caucasian male with a 10 year history of mild to moderate asthma, which was controlled with 400 ug twice daily of beclomethasone and either salbutamol or turbutamine bronchodilator inhalers where needed. This was inadequate to control viral induced asthma following winter infections where oral prednisone at 5 mg/day was required to reduce chronic wheezing and coughing to an acceptable level.
  • the patient was administered 8 g/day of fungi-derived biologically-active emu oil in divided doses-4 g morning and night. Within 3 weeks all asthma symptoms reduced, and improvement continued following cessation of aerosol steroids. After 2 months on the oil, the patient controlled all symptoms of asthma with 4 g/day of the oil and no other medication. In addition, the administration of the oil has reduced the need for LOSEC to be taken for the patient's gastric reflux.
  • Patient is a 62 year old female with a 51 year history of chronic asthma (Classified as chronic airways limited), which was controlled by 10-50 mg/day of oral prednisone, 900 mg/day of neulin, plus frequent use of ventolin/atrovent puffers and nebules was required to control chronic wheezing and coughing to an acceptable level.
  • the patient was administered 6ml of fungi-derived biologically-active emu oil in divided doses, 3 mL morning and night. The patient has been on this dose of oil for 11 months and this has virtually eliminated the wheezing noise, reduced the level of coughing, plus the level of prednisone has been reduced to 5 mg/day. Also use of puffers and nebules has been reduced.
  • Patient is an eurasian Male patient 23 years of age, diagnosed by colonoscopy, and is prescribed 40 mg prednisone daily reduced 5 mg every two weeks, 2 grams of mesalamine daily. 6 weeks later after blood results received, the patient is hospitalised and administered 7 days of hydrocortisone IV, lost 4 kg in weight, heads of hip bones began to die off as a resulting side effect of the medication.
  • the patient is prescribed post-hospital medication of:

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Wood Science & Technology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • General Health & Medical Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Microbiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Zoology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biochemistry (AREA)
  • Mycology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Pulmonology (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Rheumatology (AREA)
  • Cell Biology (AREA)
  • Medical Informatics (AREA)
  • Botany (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Cardiology (AREA)
  • Endocrinology (AREA)
  • Emergency Medicine (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Dermatology (AREA)
  • Vascular Medicine (AREA)
US10/559,599 2003-06-04 2004-06-04 Biologically active oils Abandoned US20060183799A1 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
US12/125,024 US8039512B2 (en) 2003-06-04 2008-05-21 Biologically active oils
US13/232,408 US8329748B2 (en) 2003-06-04 2011-09-14 Biologically active oils
US13/671,401 US8629181B2 (en) 2003-06-04 2012-11-07 Biologically active oils

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
AU2003902823 2003-06-04
AU2003902823A AU2003902823A0 (en) 2003-06-04 2003-06-04 Biologically active oils
PCT/AU2004/000745 WO2004108941A1 (en) 2003-06-04 2004-06-04 Biologically active oils

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US12/125,024 Continuation US8039512B2 (en) 2003-06-04 2008-05-21 Biologically active oils

Publications (1)

Publication Number Publication Date
US20060183799A1 true US20060183799A1 (en) 2006-08-17

Family

ID=31953864

Family Applications (4)

Application Number Title Priority Date Filing Date
US10/559,599 Abandoned US20060183799A1 (en) 2003-06-04 2004-06-04 Biologically active oils
US12/125,024 Expired - Fee Related US8039512B2 (en) 2003-06-04 2008-05-21 Biologically active oils
US13/232,408 Expired - Fee Related US8329748B2 (en) 2003-06-04 2011-09-14 Biologically active oils
US13/671,401 Expired - Fee Related US8629181B2 (en) 2003-06-04 2012-11-07 Biologically active oils

Family Applications After (3)

Application Number Title Priority Date Filing Date
US12/125,024 Expired - Fee Related US8039512B2 (en) 2003-06-04 2008-05-21 Biologically active oils
US13/232,408 Expired - Fee Related US8329748B2 (en) 2003-06-04 2011-09-14 Biologically active oils
US13/671,401 Expired - Fee Related US8629181B2 (en) 2003-06-04 2012-11-07 Biologically active oils

Country Status (9)

Country Link
US (4) US20060183799A1 (de)
EP (1) EP1654375B1 (de)
JP (2) JP2006526392A (de)
AT (1) ATE553207T1 (de)
AU (2) AU2003902823A0 (de)
CA (1) CA2527967A1 (de)
NO (1) NO20055497L (de)
WO (1) WO2004108941A1 (de)
ZA (1) ZA200509540B (de)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104745288A (zh) * 2015-03-23 2015-07-01 中南林业科技大学 一种红茶油的提取工艺
CN113440618A (zh) * 2021-07-06 2021-09-28 朱景平 一种透皮基质及其制备方法

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8298548B2 (en) 2007-07-18 2012-10-30 Solazyme, Inc. Compositions for improving the health and appearance of skin
US8277849B2 (en) * 2006-01-19 2012-10-02 Solazyme, Inc. Microalgae-derived compositions for improving the health and appearance of skin
US8927522B2 (en) 2008-10-14 2015-01-06 Solazyme, Inc. Microalgal polysaccharide compositions
US8557249B2 (en) 2008-11-07 2013-10-15 Solazyme, Inc. Cosmetic compositions comprising microalgal components
BR112015028457A8 (pt) 2013-05-15 2017-10-03 Solazyme Inc Composições cosméticas compreendendo óleo de microalgas
JP6167267B2 (ja) * 2015-09-18 2017-07-26 株式会社保健科学研究所 皮膚や大腸粘膜の改善剤
WO2017156164A1 (en) 2016-03-09 2017-09-14 Board Of Regents, The University Of Texas System 20-hete receptor (gpr75) antagonists and methods of use
CL2019001240A1 (es) 2019-05-06 2020-03-20 Naturalis S A 90% Proceso para la obtención de composiciones biológicamente activas a partir de aceite de emú, composición farmacéutica antiinflamatoria y anti-irritante, y composición farmacéutica regenerativa de la piel
CN110882572B (zh) * 2019-12-08 2021-11-23 怀化盛源油脂有限公司 一种食用油榨油过滤设备
US20240026394A1 (en) * 2020-12-04 2024-01-25 Evonik Operations Gmbh Enzyme based production of specialized pro-resolving mediators (spms) via docosahexaenoic acid (dha) and eicosapentaenoic acid (epa)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4485173A (en) * 1981-01-19 1984-11-27 Cpc International Inc. Preparation of fats and oils
US5431924A (en) * 1990-11-14 1995-07-11 Emu Products Western Australia Pty. Ltd. Anti-inflammatory composition derived from emu oil

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS59141515A (ja) * 1983-02-02 1984-08-14 Suntory Ltd 発酵養毛化粧料の製造方法
JPS6451091A (en) * 1987-08-20 1989-02-27 Nippon Oils & Fats Co Ltd Production of diacylglycerol rich in polyfunctional unsaturated fatty acid
JPH03206891A (ja) * 1990-01-05 1991-09-10 Nippon Oil & Fats Co Ltd 高度不飽和脂肪酸の分取方法
WO1992012711A1 (en) * 1991-01-24 1992-08-06 Martek Corporation Microbial oil mixtures and uses thereof
JP3280457B2 (ja) * 1993-03-04 2002-05-13 太陽化学株式会社 卵黄油モノグリセリドの製造方法
GB2293547A (en) 1994-09-27 1996-04-03 Joan Louise Hibberd Compositions containing tea tree oil
JP3689443B2 (ja) * 1994-12-16 2005-08-31 大阪市 高度不飽和脂肪酸含有グリセリドの製造方法
US5744128A (en) * 1995-05-03 1998-04-28 Holick; Michael F. Use of emu oil for stimulating skin and hair growth
US5834027A (en) * 1996-04-03 1998-11-10 Cardinale Fezler; Donna L. Injection of rhea and ostrich oils in animals
CN1191828C (zh) * 1997-03-27 2005-03-09 布里斯托尔-迈尔斯斯奎布公司 二十二碳六烯酸和花生四烯酸促进不足月婴儿生长的用途
JPH11113536A (ja) * 1997-10-13 1999-04-27 Seiji Toyama 殻付き加工卵及びその製造方法
JPH11221049A (ja) * 1998-02-06 1999-08-17 Asahi Denka Kogyo Kk 酵素処理卵黄の製造方法
AUPS082102A0 (en) * 2002-03-01 2002-03-21 Women's And Children's Hospital Therapeutic properties of oils

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4485173A (en) * 1981-01-19 1984-11-27 Cpc International Inc. Preparation of fats and oils
US5431924A (en) * 1990-11-14 1995-07-11 Emu Products Western Australia Pty. Ltd. Anti-inflammatory composition derived from emu oil

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104745288A (zh) * 2015-03-23 2015-07-01 中南林业科技大学 一种红茶油的提取工艺
CN113440618A (zh) * 2021-07-06 2021-09-28 朱景平 一种透皮基质及其制备方法

Also Published As

Publication number Publication date
AU2003902823A0 (en) 2003-06-26
ATE553207T1 (de) 2012-04-15
EP1654375A1 (de) 2006-05-10
US8039512B2 (en) 2011-10-18
EP1654375B1 (de) 2012-04-11
AU2004245575A1 (en) 2004-12-16
JP2011067213A (ja) 2011-04-07
NO20055497D0 (no) 2005-11-21
NO20055497L (no) 2005-12-27
US20120238625A1 (en) 2012-09-20
US8629181B2 (en) 2014-01-14
US8329748B2 (en) 2012-12-11
US20130064808A1 (en) 2013-03-14
WO2004108941A1 (en) 2004-12-16
WO2004108941A8 (en) 2005-01-27
JP2006526392A (ja) 2006-11-24
ZA200509540B (en) 2006-12-27
CA2527967A1 (en) 2004-12-16
US20090048338A1 (en) 2009-02-19
EP1654375A4 (de) 2008-11-12

Similar Documents

Publication Publication Date Title
US8039512B2 (en) Biologically active oils
AU737567B2 (en) Sea cucumber carotenoid lipid fraction products and methods of use
US6399105B1 (en) Sea cucumber carotenoid lipid fraction products and methods of use
CN114438142B (zh) 含有二高-γ-亚麻酸的微生物油和含有二高-γ-亚麻酸的微生物生物质
AU3138199A (en) Novel synergistic compositions containing aromatic compounds and terpenoids present in alpinia galanga
Badejogbin et al. Sodium butyrate recovers high-fat diet-fed female Wistar rats from glucose dysmetabolism and uric acid-associated cardiac tissue damage
CN109072173A (zh) 克里斯坦森氏菌(Christensenella intestinihominis)及其应用
JPH06505759A (ja) エミュー油から誘導した抗炎性混合物
US20120309699A1 (en) Compounds having anti-inflammatory activity
JP2008533131A (ja) イソオリエンチンを含むヒスタミン抑制用組成物
JP2001525364A (ja) 糖尿病を治療する方法及び組成物
JP2969234B2 (ja) Ａｃａｔ阻害剤
Kiani et al. Evaluating the inhibitory effects of probiotic bacteria and propolis extracts on the growth and histopathological changes in gastric tissues of Helicobacter pylori challenged Wistar rats
Bemmo et al. Viability and in vivo hypocholesterolemic effect of Lactobacillus plantarum 29V in local honey
AU2010257352B2 (en) Biologically active oils
WO2024075835A1 (ja) ナンノクロロプシス（Ｎａｎｎｏｃｈｌｏｒｏｐｓｉｓ）属藻類の水抽出物による体重増加の抑制作用
FR2481927A1 (fr) Composition anti-allergique et son procede de preparation a partir d'une bacterie lactique du genre streptococcus
Yang et al. Evaluation of lipid-lowering and immunomodulatory activities of extract oil of Tartary buckwheat fermented by Monascus purpureus in mice
RU2767908C1 (ru) Липидкоррегирующее средство из морских водорослей
JP2917037B2 (ja) Ａｃａｔ阻害剤
CA2123587A1 (fr) Produit bactericide, composition pharmaceutique le contenant et additif alimentaire
Kavitha et al. Antirheumatic potential of justicia gendarussa root extract on chronic arthritic models
Yu et al. Radical Scavenging and Hypolipidemic Activity of Aqueous Extracts from Labadou (A Traditional Fermented Soybean Food of Southern China)
JPH0253726A (ja) コレステロール低下剤および新規リン脂質
MXPA00007136A (en) Sea cucumber carotenoid lipid fraction products and methods of use

Legal Events

Date Code Title Description
STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION