US20050118232A1 - N-acyl-phosphatidyl-ethanolamines and/or mixtures of n-acyl-ethanolamines with phosphatidic acids or lysophosphatidic acids - Google Patents

N-acyl-phosphatidyl-ethanolamines and/or mixtures of n-acyl-ethanolamines with phosphatidic acids or lysophosphatidic acids Download PDF

Info

Publication number
US20050118232A1
US20050118232A1 US10/504,124 US50412405A US2005118232A1 US 20050118232 A1 US20050118232 A1 US 20050118232A1 US 50412405 A US50412405 A US 50412405A US 2005118232 A1 US2005118232 A1 US 2005118232A1
Authority
US
United States
Prior art keywords
acyl
ethanolamines
phosphatidyl
acids
compositions
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
US10/504,124
Other languages
English (en)
Inventor
Elvira Pistolesi
Benvenuto Cestaro
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.)
Hunza Di Pistolesi Elvira & C Sas
Original Assignee
Hunza Di Pistolesi Elvira & C Sas
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=27736279&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=US20050118232(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority claimed from IT2002MI000270A external-priority patent/ITMI20020270A1/it
Priority claimed from ITMI20022512 external-priority patent/ITMI20022512A1/it
Application filed by Hunza Di Pistolesi Elvira & C Sas filed Critical Hunza Di Pistolesi Elvira & C Sas
Assigned to HUNZA DI PISTOLESI ELVIRA & C. S.A.S. reassignment HUNZA DI PISTOLESI ELVIRA & C. S.A.S. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: CESTARO, BENVENUTO, PISTOLESI, ELVIRA
Publication of US20050118232A1 publication Critical patent/US20050118232A1/en
Priority to US11/858,059 priority Critical patent/US9789127B2/en
Abandoned legal-status Critical Current

Links

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
    • A61K31/66—Phosphorus compounds
    • A61K31/661—Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23J—PROTEIN COMPOSITIONS FOR FOODSTUFFS; WORKING-UP PROTEINS FOR FOODSTUFFS; PHOSPHATIDE COMPOSITIONS FOR FOODSTUFFS
    • A23J7/00—Phosphatide compositions for foodstuffs, e.g. lecithin
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/164—Amides, e.g. hydroxamic acids of a carboxylic acid with an aminoalcohol, e.g. ceramides
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/55—Phosphorus compounds
    • A61K8/553—Phospholipids, e.g. lecithin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
    • 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
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia
    • 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
    • A61P17/16—Emollients or protectives, e.g. against radiation
    • 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
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • 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
    • A61P3/04—Anorexiants; Antiobesity agents
    • 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
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/06—Preparations for care of the skin for countering cellulitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention relates to pharmaceutical, cosmetic and dietetic compositions and functional foods, constituted by:
  • N-Acyl-ethanolamines and N-acyl-phosphatidyl-ethanolamines (NAPEs) are known to be present in many foods of animal and vegetable origin (H. H. Schmid et al., 1990, Prog. Lipid Res., 29, 1-43), and are particularly abundant in foods such as soy, eggs and chocolate (K. D. Chapman et al., 1993, Arch. Biochem. Biophys, 301, 21-23; E. Di Tomaso et al., 1996, Nature, 382, 677-678).
  • NAEs are formed in vivo by hydrolysis of a NAPE molecule that gives rise to a mixture of NAE and a molecule of phosphatidic acid (PA) which, in turn, can be hydrolysed to lysophosphatidic acid (LPA) in accordance with the following scheme 1.
  • PA phosphatidic acid
  • LPA lysophosphatidic acid
  • GB 2051069 discloses the anti-lipemic and anti-atherosclerotic activity of N-Oleoyl-phosphatidylethanolamine (NOPE) and excludes any significant activity of other N-acyl-derivatives.
  • NOPE N-Oleoyl-phosphatidylethanolamine
  • NAEs have also been known for some time for their interesting pharmacological properties: N-arachidonoyl-ethanolamine has been demonstrated in vitro to be a cannabinoid receptor agonist (L. Hanus, 1993, J. Med. Chem., 36, 3032-3034); N-palmitoyl-ethanolamine, when administered intraperitoneally to rats, possesses anti-inflammatory and anti-anaphylactic activity (L. Facci et al., 1995, Proc. Natl. Acad. Sci.
  • N-palmitoyl-ethanolamine and N-stearoyl-ethanolamine have proved useful in the pharmacological treatment of inflammatory disorders resulting from degranulation of the mast cells (EP-A-0550006); they also inhibit peroxidation of the mitochondrial membranes in vitro (N. M. Gulaya et al., 1998, Chem. Phys. Lipids, 97, 49-54); N-oleoyl-ethanolamine (NOE) has a significant anorexic effect in the rat, when administered by the intraperitoneal route (F. Rodriguez de Fonseca et al., 2001, Nature, 414, 209-212). Since it is well known that NAEs are easily hydrolised to free fatty acids and ethanolamine in the gastrointestinal tract, its activity by the oral route is not expected.
  • the present invention relates to pharmaceutical and dietetic compositions and functional foods, constituted by:
  • N-acyl-phosphatidyl-ethanolamines do not include N-oleoyl-phosphathidyl-ethanolamine.
  • R 1 , R 2 and R 4 are acyl residues of long-chain fatty acids, in particular residues of palmitic, stearic, oleic, linoleic, conjugated linoleic, linolenic, gamma-linolenic, eicosapentaenoic and docosahexanoic acids, etc.
  • the phospholipid mixtures may be present in the compositions of the invention in the form of their complexes with bioflavonoids.
  • Said complexes hereinafter called “phosphobioflavonic complexes”, are a further object of the invention.
  • Said complexes constituted by aggregation of the phospholipid active components (NAPE and/or NAE plus PA and/or NAE plus LPA) with one or more types of bioflavonoids, can be obtained by suspending a dry phospholipid residue under strong stirring for a few minutes at a temperature preferably between 40° C. and 65° C. in a hydroalcoholic solution (alcohol preferably between 70 and 90%), buffered to an acid pH (pH preferably between 3 and 5), containing a fraction of one or more types of bioflavonoids, preferably in a percentage of between 0.5 and 15% by weight of the hydroalcoholic solution.
  • a hydroalcoholic solution alcohol preferably between 70 and 90%
  • an acid pH pH
  • ethanol is partially evaporated from the resulting emulsion under vacuum and then dehydrated by spray drying, to produce a dry granular residue of phosphobioflavonic complexes.
  • bioflavonoids which can be used to produce these phosphobioflavonic complexes include:
  • NAPE, NAE, PA and LPA are naturally present in the lipid fractions of many foodstuffs normally used in the human diet (soy lecithins, eggs, cocoa, meat, oily extracts of various seeds, etc.), and can easily be extracted and isolated to various degrees of purity in accordance with conventional methods.
  • the NAPE and NAE molecules can be obtained by synthesis according to chemical processes which have been known for some time.
  • NAE can prepared from ethanolamine and the corresponding fatty acid, for example in accordance with the methods described in:
  • NAPE can prepared from phosphatidylethanolamine and the corresponding fatty acid chloride or anhydride, in accordance with the methods described in:
  • R 1 , R 2 and R 4 represent the alkyl chain of saturated, mono- or polyunsaturated fatty acids with 12-22 C atoms;
  • R 3 represents a residue of choline, ethanolamine, inositol, glycerol, serine.
  • the therapeutically effective doses of preparations based on NAPE and/or NAE plus PA and/or LPA vary:
  • compositions of the invention may also contain other nutritional components which further implement the therapeutic properties and benefits of NAPE and/or the mixtures of NAE+PA and/or LPA. Examples of these components are:
  • the active components stored as dehydrated granulates or powders, can be used as such or in the form of aqueous or oily solutions to make various galenical preparations such as gelatin capsules, tablets, dragees, sachets, effervescent and non-effervescent cachets, chewing gum, etc.
  • Said active components in the form of dehydrated granulates or powders can also be used to make various functional foods:
  • compositions of the invention have proved surprisingly active in:
  • the preparations of the invention can therefore be used as adjuvants in the treatment of aging and many metabolic disorders connected with it (obesity and excess weight; diabetes; cerebro-degenerative disorders such as Alzheimer's disease, Parkinson's disease and senile dementia; stress, depression; tumours; menopausal syndromes; osteoporosis; prostate hypertrophy; skin aging; panniculopathy (cellulitis); and alopecia), possibly in combination with known drugs or diet supplements.
  • metabolic disorders connected with it include diabetes; cerebro-degenerative disorders such as Alzheimer's disease, Parkinson's disease and senile dementia; stress, depression; tumours; menopausal syndromes; osteoporosis; prostate hypertrophy; skin aging; panniculopathy (cellulitis); and alopecia
  • the invention therefore also concerns the use of phospholipid mixtures containing
  • the various compounds are dissolved and mixed in 10 volumes of chloroform: methanol (2:1, vol/vol).
  • the solvent is evaporated under vacuum, and the resulting dry residue is re-suspended in an aqueous solution buffered to physiological pH to form an aqueous mixture of a phospholipid emulsion containing the active component (N-linoleoyl-phosphatidylethanolamine).
  • the aqueous mixture can be frozen and dehydrated to obtain a dry residue of the phospholipid active component.
  • the various compounds are dissolved in chloroform-methanol and treated as described in example 1 to obtain an aqueous mixture of a phospholipid emulsion containing the active components (N-eicosapentaenoyl-ethanolamine and phosphatidic acid).
  • the aqueous mixture can be frozen and dehydrated to obtain a dry phospholipid residue of the active components as described in example 1.
  • the various compounds are dissolved in chloroform-methanol and treated as described in example 1 to obtain an aqueous mixture of a phospholipid emulsion containing the active components (N-linolenoyl-ethanolamine and phosphatidic acid).
  • the aqueous mixture can be frozen and dehydrated to obtain a dry phospholipid residue of the active components as described in example 1.
  • the various compounds are dissolved in chlotoform-methanol and treated as described in example 1 to obtain an aqueous mixture of a phospholipid emulsion containing the active constituent (N-gamma-linolenoyl-phosphatidylethanolamine).
  • the aqueous mixture can be frozen and dehydrated to obtain a dry phospholipid residue of the active constituent as described in example 1.
  • a dry phospholipid residue obtained as described in examples 1-4 above 20 g of a dry phospholipid residue obtained as described in examples 1-4 above+200 g of an oily solution (olive oil, soy, corn, sunflower, borage, blackcurrant, fish or seaweed oils, or mixtures thereof).
  • an oily solution oil, soy, corn, sunflower, borage, blackcurrant, fish or seaweed oils, or mixtures thereof.
  • the resulting emulsion is then cooled to room temperature and dehydrated by spray drying to form a dry granular residue of phosphobioflavonic complexes of N-docosahexanoyl-phosphatidylethanolamine and green tea catechins.
  • N-linolenoyl-ethanolamine and 50 g of lysophosphatidic acid (CLPA) are slowly added under strong stirring at 60° C. and emulsified for 10 minutes in 900 ml of a hydroalcoholic solution (85% alcohol) buffered to pH 4.0, containing 10% by weight of a mixture of catechins, epicatechins and proanthocyanidins extracted from grape seeds.
  • a hydroalcoholic solution 85% alcohol
  • the resulting emulsion is cooled to room temperature and dehydrated by spray drying to form a dry granular residue of phosphobioflavonic complexes of N-linolenoyl-ethanolamine and grape-seed bioflavonoids.
  • the rats were given a high-calorie, high-triglyceride, high-cholesterol diet.
  • mice 80 Male rats weighing 150-200 g each were used. The animals were divided into 8 groups of 10 animals:
  • Membrane fluidity Membrane fluidity (ghost erythrocytes) (plasma platelets) 1A) Control rats at time 0 100% 100% 1B) Control rats after 72% 69% a 20-day diet 2) Treated rats (NOE) 72% 70% 3) Treated rats (NOPE) 84% 81% 4) Treated rats (NOE + 86% 81% PA) 5) Treated rats (NOE + 83% 80% LPA) 6) Treated rats (NOPE + 91% 92% B.F.) 7) Treated rats (B.F.) 73% 70%
  • TMA-DPH in accordance with the method described by Caimi F. et al., 1999, Thromb. Hoemost., 82 pp. 149, is used as the fluorescent probe.
  • NAPE NAE+PA
  • NAE+LPA NAPE+B.F.
  • NAE plus PA and/or LPA+B.F. always provided highly significant results and advantages, both in preventing biological signs of aging (improvement in mitochondrial activity, better membrane fluidity, improvement in plasma antioxidant defences, and limited weight increase) and improving the clinical parameters tested in relation to prevention of aging, and many of the metabolic disorders associated therewith. It is noteworthy that also in humans no significant benefit can be obtained by administering equivalent oral doses of N-oleoyl-ethanolamine as such.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Polymers & Plastics (AREA)
  • Food Science & Technology (AREA)
  • Diabetes (AREA)
  • Endocrinology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Mycology (AREA)
  • Gerontology & Geriatric Medicine (AREA)
  • Birds (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Nutrition Science (AREA)
  • Biochemistry (AREA)
  • Obesity (AREA)
  • Psychiatry (AREA)
  • Rheumatology (AREA)
  • Hematology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Psychology (AREA)
  • Reproductive Health (AREA)
  • Urology & Nephrology (AREA)
US10/504,124 2002-02-12 2003-02-07 N-acyl-phosphatidyl-ethanolamines and/or mixtures of n-acyl-ethanolamines with phosphatidic acids or lysophosphatidic acids Abandoned US20050118232A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US11/858,059 US9789127B2 (en) 2002-02-12 2007-09-19 N-acyl-phosphatidyl-ethanolamines and/or mixtures of N-acyl-ethanolamines with phosphatidic acids or lysophosphatidic acids

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
IT2002MI000270A ITMI20020270A1 (it) 2002-02-12 2002-02-12 Preparazione nutrizionali e terapeutiche a base di n-acil-fosfatidil-etanolamine e/o miscele di n-acil-etanolamine con acidi fosfatidici o a
ITMI2002A00270 2002-02-13
ITMI20022512 ITMI20022512A1 (it) 2002-11-26 2002-11-26 Preparati a base di n-acil-fosfatidil-etanolamine e/o miscele di n-acil-etanolamine con acidi fosfatidici o acidi liso-fosfatidici.
ITMI2002A002512 2002-11-26
PCT/EP2003/001233 WO2003068210A1 (en) 2002-02-12 2003-02-07 N-acyl-phosphatidyl-ethanolamines and/or mixtures of n-acyl-ethanolamines with phosphatidic acids or lysophosphatidic acids

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US11/858,059 Continuation US9789127B2 (en) 2002-02-12 2007-09-19 N-acyl-phosphatidyl-ethanolamines and/or mixtures of N-acyl-ethanolamines with phosphatidic acids or lysophosphatidic acids

Publications (1)

Publication Number Publication Date
US20050118232A1 true US20050118232A1 (en) 2005-06-02

Family

ID=27736279

Family Applications (2)

Application Number Title Priority Date Filing Date
US10/504,124 Abandoned US20050118232A1 (en) 2002-02-12 2003-02-07 N-acyl-phosphatidyl-ethanolamines and/or mixtures of n-acyl-ethanolamines with phosphatidic acids or lysophosphatidic acids
US11/858,059 Active 2027-05-02 US9789127B2 (en) 2002-02-12 2007-09-19 N-acyl-phosphatidyl-ethanolamines and/or mixtures of N-acyl-ethanolamines with phosphatidic acids or lysophosphatidic acids

Family Applications After (1)

Application Number Title Priority Date Filing Date
US11/858,059 Active 2027-05-02 US9789127B2 (en) 2002-02-12 2007-09-19 N-acyl-phosphatidyl-ethanolamines and/or mixtures of N-acyl-ethanolamines with phosphatidic acids or lysophosphatidic acids

Country Status (8)

Country Link
US (2) US20050118232A1 (de)
EP (1) EP1482920B2 (de)
JP (1) JP4634040B2 (de)
AU (1) AU2003226974A1 (de)
CA (1) CA2475630C (de)
DE (1) DE60317639T3 (de)
ES (1) ES2297176T5 (de)
WO (1) WO2003068210A1 (de)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100068316A1 (en) * 2006-04-13 2010-03-18 Andrea Giori Phospholipid complexes of olive fruits or leaves extracts having improved bioavailability
CN111496823A (zh) * 2019-01-30 2020-08-07 精工爱普生株式会社 机器人、机器人系统和机器人控制装置

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITMI20021280A1 (it) * 2002-06-11 2003-12-11 Carlo Ghisalberti Metodo di trattamento anticellulite
ITMI20041280A1 (it) * 2004-06-24 2004-09-24 Hunza Di Pistolesi Elvira & C Preparazione farmaceutiche dietetiche e-o cosmetiche per il trattamento dell'obesita' dell'alopecia della cellulite e dell'invecchiamento cutaneo
DE102004052697A1 (de) * 2004-10-29 2006-05-04 Haehner, Thomas, Dr. Pharmazeutische Zubereitungen zur Behandlung von Folgen des Alkoholmissbrauchs, Hepatitis, Pankreatitis, Alzheimererkrankung, Morbus Parkinson, Diabetes, toxischen Nierenerkrankungen, Reperfusionsschäden, der Arteriosklerose sowie als Antidote gegen Umweltgifte und Medikamentenintoxikation
JP2007314427A (ja) * 2006-05-23 2007-12-06 Nippon Fine Chem Co Ltd リポ酸含有複合体
JP5259601B2 (ja) * 2007-08-28 2013-08-07 ユニチカ株式会社 コラーゲン産生促進剤
EP2107097B1 (de) 2008-04-02 2011-06-15 Nestec S.A. Funktionelle Mesophasen auf Oleylethanolamidbasis
KR20110033118A (ko) * 2008-07-08 2011-03-30 케미 에스.피.에이. Ｎ-아실-포스파티딜-에탄올아민의 생산 방법
JP2010189315A (ja) * 2009-02-18 2010-09-02 Unitika Ltd 関節軟骨損傷治癒促進剤及びそれを含有する飲食品
JP2010195752A (ja) * 2009-02-27 2010-09-09 Unitika Ltd 骨形成促進剤
WO2012143860A1 (en) * 2011-04-18 2012-10-26 Jian Guan Ameliorating cognitive decline
US20150218221A1 (en) * 2012-09-24 2015-08-06 Dsm Sinochem Pharmaceuticals Netherlands B.V. Method for producing a cyclic peptide
EP3174544B1 (de) * 2014-07-31 2020-12-09 Universita' Degli Studi Di Cagliari Ester eines phospholipids mit konjugierter linolsäure zur behandlung von psychiatrischen störungen mit neuroinflammatorischer und neurodegenerativer basis
JP6953811B2 (ja) * 2017-06-12 2021-10-27 ライオン株式会社 口腔用組成物及び口腔内常在菌の生育促進剤
EP3707513B1 (de) 2017-11-07 2024-02-07 Fondazione Istituto Italiano di Tecnologia Verfahren zur feststellung des vorliegens und fortschreitens einer neurodegenerativen erkrankung
IT202100018455A1 (it) 2021-07-13 2023-01-13 Fondazione St Italiano Tecnologia Biomarcatori della malattia di alzheimer

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4254115A (en) * 1979-06-18 1981-03-03 A. Nattermann & Cie. Gmbh Phospholipid derivative with an antilipemic and antiarteriosclerotic effect
US4963527A (en) * 1987-01-14 1990-10-16 Indena S.P.A. Phospholipid complexes of extracts of vitis vinifera, their preparation process and pharmaceutical and cosmetic compositions containing them
US6162637A (en) * 1994-09-13 2000-12-19 Institut National De La Recherche Agronomique - I.N.R.A. Aspergillus niger which produces vanillic acid from ferulic acid
US6294191B1 (en) * 1996-10-15 2001-09-25 The Liposome Company, Inc. N-acyl phosphatidylethanolamine-mediated liposomal drug delivery
US20010055627A1 (en) * 1997-09-26 2001-12-27 Najla Guthrie Compositions And Methods For Regulating Lipoproteins And Hypercholesterolemia With Limonoids, Flavonoids And Tocotrienols
US6429202B1 (en) * 1998-12-18 2002-08-06 Indena S.P.A. Phospholipid complexes of proanthocyanidin A2 as antiatherosclerotic agents
US6479054B1 (en) * 1998-09-21 2002-11-12 Showa Sangyo Co., Ltd. Process for obtaining genistin-rich isoflavone composition
US6576660B1 (en) * 1997-10-31 2003-06-10 Arch Development Corporation Methods and compositions for regulation of 5-α-reductase activity

Family Cites Families (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR972927A (fr) 1947-05-14 1951-02-05 Brillantine aux phosphatides (lécithines et céphalines) du soja
GB2051069B (en) * 1979-06-18 1983-08-24 Nattermann A & Cie Phospholipid derivatives useful in therapy as antilepaemics and antiarteriosclerotics and compositions containing them
DE3109420A1 (de) * 1981-03-12 1982-09-23 Kastell, Wolfgang, 2000 Hamburg Mittel zum anhalten des haarausfalls und zum foerdern des haarwuchses
DE3476770D1 (en) 1983-04-11 1989-03-23 Meito Sangyo Kk Production of primary or secondary alcohol derivatives of phospholipids by the enzymatic technique
IT1201149B (it) * 1987-01-14 1989-01-27 Indena Spa Complessi di bioflavonoidi con fosfolipidi,loro preparazione,uso e composizioni farmaceutici e cosmetiche
US5741513A (en) * 1990-02-08 1998-04-21 A. Natterman & Cie. Gmbh Alcoholic aqueous gel-like phospholipid composition, its use and topical preparations containing it
EP0604806A3 (de) * 1992-12-18 2000-07-19 Rhone-Poulenc Rorer Gmbh Phospholipidische Zusammensetzung
EP0620000A3 (de) 1992-12-18 1994-11-02 Rhone-Poulenc Rorer Gmbh Kosmetische und/oder pharmazeutische Verwendung von N-Acylalkanolaminen
JPH1084880A (ja) * 1996-09-13 1998-04-07 Takeda Shokuhin Kogyo Kk 脂質代謝促進作用を有するリン脂質含有組成物
US6454871B1 (en) * 1997-06-23 2002-09-24 Princeton Trade & Technology, Inc. Method of cleaning passageways using a mixed phase flow of gas and a liquid
JP3153505B2 (ja) * 1997-11-07 2001-04-09 矢橋工業株式会社 水酸アパタイトファイバーの製造方法
JP2000219880A (ja) * 1999-01-29 2000-08-08 Taiyo Kagaku Co Ltd 抗酸化剤
US6610749B2 (en) * 2000-02-18 2003-08-26 Arch Development Corporation Polyhydroxylated benzene-containing compounds
AU2002338329B2 (en) † 2001-03-27 2006-09-07 The Regents Of The University Of California Methods, compounds, and compositions for reducing body fat and modulating fatty acid metabolism
MY135783A (en) 2001-09-07 2008-06-30 Meiji Dairies Corp Nutritional composition for controlling blood sugar level
DE102007049867A1 (de) 2007-10-18 2009-04-30 Abb Ag Paramagnetischer Gassensor sowie Verfahren zum Betrieb desselben
US8232418B1 (en) * 2008-08-01 2012-07-31 Corn Products International, Inc. Method for the preparation of lecithin
CA2752908A1 (en) * 2009-04-01 2010-10-07 Genentech, Inc. Treatment of insulin-resistant disorders
WO2011091160A1 (en) * 2010-01-20 2011-07-28 Henry Wu Custom-formulated phospholipid microbubbles and methods and uses thereof

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4254115A (en) * 1979-06-18 1981-03-03 A. Nattermann & Cie. Gmbh Phospholipid derivative with an antilipemic and antiarteriosclerotic effect
US4963527A (en) * 1987-01-14 1990-10-16 Indena S.P.A. Phospholipid complexes of extracts of vitis vinifera, their preparation process and pharmaceutical and cosmetic compositions containing them
US6162637A (en) * 1994-09-13 2000-12-19 Institut National De La Recherche Agronomique - I.N.R.A. Aspergillus niger which produces vanillic acid from ferulic acid
US6294191B1 (en) * 1996-10-15 2001-09-25 The Liposome Company, Inc. N-acyl phosphatidylethanolamine-mediated liposomal drug delivery
US20010055627A1 (en) * 1997-09-26 2001-12-27 Najla Guthrie Compositions And Methods For Regulating Lipoproteins And Hypercholesterolemia With Limonoids, Flavonoids And Tocotrienols
US6576660B1 (en) * 1997-10-31 2003-06-10 Arch Development Corporation Methods and compositions for regulation of 5-α-reductase activity
US6479054B1 (en) * 1998-09-21 2002-11-12 Showa Sangyo Co., Ltd. Process for obtaining genistin-rich isoflavone composition
US6429202B1 (en) * 1998-12-18 2002-08-06 Indena S.P.A. Phospholipid complexes of proanthocyanidin A2 as antiatherosclerotic agents

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100068316A1 (en) * 2006-04-13 2010-03-18 Andrea Giori Phospholipid complexes of olive fruits or leaves extracts having improved bioavailability
US8084067B2 (en) * 2006-04-13 2011-12-27 Indena S.P.A. Phospholipid complexes of olive fruits extracts having improved bioavailability
CN111496823A (zh) * 2019-01-30 2020-08-07 精工爱普生株式会社 机器人、机器人系统和机器人控制装置

Also Published As

Publication number Publication date
DE60317639D1 (de) 2008-01-03
EP1482920B2 (de) 2011-07-20
US9789127B2 (en) 2017-10-17
JP4634040B2 (ja) 2011-02-16
DE60317639T3 (de) 2012-01-12
ES2297176T5 (es) 2011-12-07
WO2003068210A1 (en) 2003-08-21
ES2297176T3 (es) 2008-05-01
CA2475630A1 (en) 2003-08-21
JP2005525335A (ja) 2005-08-25
DE60317639T2 (de) 2008-10-30
EP1482920B1 (de) 2007-11-21
CA2475630C (en) 2011-01-18
US20100179107A1 (en) 2010-07-15
EP1482920A1 (de) 2004-12-08
AU2003226974A1 (en) 2003-09-04

Similar Documents

Publication Publication Date Title
US9789127B2 (en) N-acyl-phosphatidyl-ethanolamines and/or mixtures of N-acyl-ethanolamines with phosphatidic acids or lysophosphatidic acids
JP6995620B2 (ja) マルチサプリメント組成物
AU2011289846B2 (en) Lipid supplements for maintaining health and the treatment of acute and chronic disorders
JP4850986B2 (ja) カルノシンあるいはその誘導体および分枝アミノ酸を含む抗酸化活性を有する医薬組成物および／または栄養組成物
CN105079009B (zh) 预防和/或治疗心脑血管疾病的组合物
EP1583433B1 (de) Zubereitungen enthaltend mehrfach ungesättigte phospholipide, monoterpene und tryptophan und/oder phytol-derivate
US20090175968A1 (en) Dietary compositions for promoting brain health
EP3135281B1 (de) Zusammensetzung zur prävention oder verbesserung von peripherer neuropathie
WO2009062662A1 (en) Pharmaceutical and nutraceutical compositions based on menaquinols
KR20130046451A (ko) 심혈관 질환의 치료를 위한 폴리메톡시플라본 및 토코트리에놀의 생체이용율을 개선시키기 위한 조성물
Khan et al. Phospholipids: a novel adjuvant in herbal drug delivery systems
ITRM980706A1 (it) Composizione ad attivita' antiossidante e preventiva di alterazioni trombotiche e aterosclerotiche comprendente una carnitina ed un flavonoide.
US7033612B2 (en) Composition and method for treating age-related disorders
JP5635932B2 (ja) プロセシンググルコシダーゼ阻害剤
EA032717B1 (ru) Гомогенная композиция для перорального введения, содержащая омега-3 полиненасыщенные жирные кислоты и ресвератрол
Sapna Malviya et al. Phytosomes: a potential herbophospholipid complex for drug delivery.
ITMI951210A1 (it) Nuovi derivati dell'alfa-tocoferolo e composizioni farmaceutiche che li contengono quali principi attivi

Legal Events

Date Code Title Description
AS Assignment

Owner name: HUNZA DI PISTOLESI ELVIRA & C. S.A.S., ITALY

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:PISTOLESI, ELVIRA;CESTARO, BENVENUTO;REEL/FRAME:015699/0782

Effective date: 20040824

STCB Information on status: application discontinuation

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