WO2010057804A1 - Fettemulsion zur künstlichen ernährung von schwerkranken intensivpatienten - Google Patents
Fettemulsion zur künstlichen ernährung von schwerkranken intensivpatienten Download PDFInfo
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- WO2010057804A1 WO2010057804A1 PCT/EP2009/064839 EP2009064839W WO2010057804A1 WO 2010057804 A1 WO2010057804 A1 WO 2010057804A1 EP 2009064839 W EP2009064839 W EP 2009064839W WO 2010057804 A1 WO2010057804 A1 WO 2010057804A1
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- Prior art keywords
- acid
- triglyceride
- fatty acids
- fat emulsion
- pharmaceutical preparation
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- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/225—Polycarboxylic acids
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- 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
- A23L33/115—Fatty acids or derivatives thereof; Fats or oils
- A23L33/12—Fatty acids or derivatives thereof
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- 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
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- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0029—Parenteral nutrition; Parenteral nutrition compositions as drug carriers
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A—HUMAN NECESSITIES
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- 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 a pharmaceutical preparation for the prophylaxis and treatment of Critical Illness Polyneuropathy (CIP) and Critical Illness Myopathy (CIM). Furthermore, the invention relates to an isotonic fat emulsion comprising at least one triglyceride having at least one fatty acid residue with an odd number of carbon atoms, wherein the fatty acid residue has a carbon chain having 5 to 15 carbon atoms.
- CIP Critical Illness Polyneuropathy
- CCM Critical Illness Myopathy
- the invention relates to the use of the isotonic fat emulsion as a dietetic and further the invention relates to the use of the pharmaceutical preparation / isotonic fat emulsion in parenteral nutrition or as part of a dietetic, in particular the use of a fat emulsion for the artificial nutrition of septic intensive care patients.
- CIP Critical Illness Polyneuropathy
- CIM Critical Illness Myopathy
- Another background of the present invention is in the field of artificial nutrition of intensive care patients by fat emulsions for intravenous use or lipid-containing diets.
- Fat emulsions for parenteral nutrition serve to deliver fats in an intravenously acceptable dosage form when normal oral nutrition is not possible or medically contraindicated.
- Common fat emulsions in the art are made from vegetable oils such as safflower oil or soybean oil, in some cases additionally containing triglycerides of medium-long fatty acids (so-called medium-chain triglycerides (MCT)) and / or oils of marine origin (fish oils mostly from cold-water fish).
- MCT medium-chain triglycerides
- DE-OS 37 21 137 describes lipid emulsions for parenteral nutrition comprising eicosapentaenoic acid triglyceride and / or docosahexaenoic acid triglyceride, or fish oils containing such triglycerides, as well as vegetable oils containing omega-6 fatty acids and MCT.
- EP 0 120 169 B1 discloses synthetic triglycerides which contain a polyunsaturated fatty acid (preferably eicosapentaenoic acid) at the central carbon atom of the glycerol molecule can carry.
- the glycerides prepared according to this specification can be used for nutrition, nutritional supplementation or therapeutic nutritional medicines.
- US-4,526,902 describes mixtures comprising 25-75% by weight of eicosapentaenoic acid and one omega-6 fatty acid, which are used enterally as a component of pharmaceuticals or fat-containing foods such as butter or the like.
- US 2008/0132571 A1 discloses preparations and methods for the treatment of catabolism effects in patients, wherein odd-numbered fatty acids and their glycerides are used to increase the intracellular ratio of AMP to ATP and to increase the activity of the AMP-activated protein kinase (AMPK) to be brought.
- AMPK AMP-activated protein kinase
- the object of the present invention was to provide a pharmaceutical preparation for accompanying nutritive treatment critically ill, z. B. septic intensive care patients and for the prophylaxis and treatment of subsequent complications of intensive care such as CIP and / or CIM to provide.
- An object of the present invention is thus a pharmaceutical preparation for the prophylaxis or treatment of CIP and / or CIM, comprising a fat emulsion with at least one triglyceride (A) of the formula (I),
- radicals R 1 , R 2 or R 3 are independently of one another.
- the triglyceride (A) of the fat emulsion to be used in the present invention consists of glycerol esterified with fatty acids, at least one of which has an odd number of carbon atoms of 5 to 15 carbon atoms.
- the odd-numbered alkanoyles have a chain length of 5 to 15 carbon atoms. It is preferably the alkanoyle which is selected from one or more of the following fatty acids selected from the group consisting of pentanoic acid (C5: 0, n-valeric acid), heptanoic acid (C7: 0, enanthic acid), nonanoic acid (C9: 0, pelargonic acid) , Undecanoic acid (Cl 1: 0, undecylic acid), tridecanoic acid (C13: 0, tridecylic acid) and pentadecanoic acid (C 15: 0, pentadecylic acid) are derived.
- pentanoic acid C5: 0, n-valeric acid
- heptanoic acid C7: 0, enanthic acid
- nonanoic acid C9: 0, pelargonic acid
- Undecanoic acid Cl 1: 0, undecylic acid
- tridecanoic acid C13
- At least one of the radicals R, R 2 or R in the triglyceride (A) has a chain length of 5 to 9 carbon atoms.
- At least one of the radicals R 1 , R 2 or R 3 in the triglyceride (A) -Heptanoyl ie a triglyceride consisting of an esterified glycerol, wherein at least one, preferably at least two hydroxyl groups Heptanoic acid are esterified.
- triglyceride (A) is triheptanoin, a glycerin in which the three hydroxy groups are esterified with n-heptanoic acid.
- the synthesis of the triglyceride (A) is familiar to the person skilled in the art.
- the required odd-numbered fatty acids (pentane, heptane, nonane, undecane, tridecane and pentadecanoic) are commercially available, for example from Sigma Chemicals Co ..
- triheptanoin can be obtained from Condea Chemie GmbH (Wirten, Germany) as special oil 107.
- Trinonanoin, Triundecanoin or Tripentadecanoin are z. B. by Chemos GmbH (Regenstauf, Germany) available.
- the triglyceride (A) may, in addition to the essential fatty acid radicals according to the invention having an odd number of carbon atoms between 5 and 15, also have further even-numbered fatty acid radicals.
- fat emulsions are preferred which have the triglyceride (A) in which at least one fatty acid residue is derived from omega-3 and / or omega-6 fatty acids.
- Omega-3 and omega-6 fatty acids are biologically important building blocks / nutrients that the human organism itself can not fully produce and that act as precursors to prostaglandins, eicosanoids and structural components of cell membranes.
- omega-6 fatty acids are various oils of vegetable origin, including soybean oil and safflower diuretic oil, the use of which is prior art for the preparation of intravenous fat emulsions.
- soybean oil oils of marine origin
- omega-3 fatty acids in intravenous fat emulsions
- EP-A-0298293 oils of marine origin
- highly purified fish oil concentrates derived from cold-water fish such as salmon, herring, Sardines or mackerel
- their content of omega-3 fatty acids is preferably 40% or more.
- Myristic acid C14 0, palmitic acid C 16: 0, stearic acid C 18: 0), monounsaturated fatty acids (palmitoleic acid C16: l, oleic acid C18: l), polyunsaturated fatty acids of the omega-3 and omega-6 type, eg eicosapentaenoic acid ( EPA, C20: 5 omega-3), docosahexaenoic acid (DHA, C22: 6 omega-3), linoleic acid (LA, C18: 2 omega-6) or gamma-linolenic acid (GLA, C18: 3 omega-6).
- the triglyceride (A) is present as a randomized structured lipid having a random distribution of the odd carbon number alkanoyl radicals and the alkanoyl radicals even carbon number at positions sn-1, sn-2 and sn-3 of the triglyceride molecule (A).
- the triglyceride (A) is present as a chemically defined structured lipid, that is, it has a chemically defined distribution of the odd number carbon number alkanoyl residues in positions sn-1 and sn-3 and the alkanoyl residues even carbon number at position sn-2 of the triglyceride molecule.
- the fat emulsions to be used according to the invention contain wholly or partially chemically defined or randomized structured lipids
- vegetable oils are preferably used as the source of omega-6 fatty acids or fish oil as the source of omega-3 fatty acids for the preparation of the structured lipids.
- Randomized structured triglycerides are obtainable, for example, by chemical transesterification of a mixture of a desired vegetable and / or fish oil with a triglyceride of odd-numbered fatty acids with a chain length of 5 to 15. In the case of chemically defined structured lipids, transesterification takes place enzymatically from the same basic materials.
- the pharmaceutical preparation of the invention comprises a fat emulsion comprising at least one additional triglyceride (B) other than (A).
- the triglyceride (B) comprises triglycerides of marine or plant origin. Since the recovery of pure omega-3 or omega-6 fatty acids from fish oil or vegetable oils or the chemical synthesis of these fatty acids on the one hand consuming and costly, while on the other hand, the said oils of marine or vegetable origin have a high content of the corresponding fatty acids, it is accordingly
- the present invention does not require the isolation of omega-3 or omega-6 fatty acids or omega-3 or omega-6 fatty acids containing triglycerides from these oils, but the oils can be used as such for the preparation of the fat emulsions erf ⁇ ndungsloom to be used.
- long-chain saturated fatty acids are automatically provided as their above-mentioned representatives myristic, palmitic and stearic, as well as the monounsaturated oleic acid, which is contained both in marine oils and - in a particularly high concentration - in olive oil.
- Medium-chain fatty acids or triglycerides are contained in semi-synthetic MCT oil (miglyol oil) and more than 90% (based on the total fatty acid content) as caprylic and capric acid. In this form they are particularly suitable to be used as triglyceride (B) in the fat emulsion to be used according to the invention.
- the amount of triglyceride (A) is from 50 to 80% by weight, more preferably from 60 to 70% by weight, based on the total weight of all triglycerides in the emulsion.
- the pharmaceutical preparation according to the invention triglycerides in an amount of 5 to 30 wt.%, More preferably from 10 to 20 wt .-%, based on the total pharmaceutical preparation on.
- the fat emulsion of the pharmaceutical preparation according to the invention contains, in addition to the triglyceride (A) and optionally other triglycerides / lipids, advantageously water for injection as well as other auxiliaries and additives corresponding to the prior art in the preparation of intravenous fat emulsions, e.g. Emulsifiers, co-emulsifiers, stabilizers and suitable substances for the adjustment of isotonicity.
- triglyceride (A) and optionally other triglycerides / lipids advantageously water for injection as well as other auxiliaries and additives corresponding to the prior art in the preparation of intravenous fat emulsions, e.g. Emulsifiers, co-emulsifiers, stabilizers and suitable substances for the adjustment of isotonicity.
- emulsifiers physiologically well-tolerated emulsifiers are used, such as.
- the phospholipid content in the emulsion to be used according to the invention is preferably 0.4 to 2.0% by weight, preferably 0.6% to 1.5% by weight, in each case based on the total weight of the emulsion.
- co-emulsifiers can be used, for.
- the alkali salts of long chain fatty acids such as sodium stearate, sodium oleate, etc.
- cholesterol or cholesterol esters eg, cholesterol acetate
- their concentration as in the case of using cholesterol or cholesterol esters alone or in combination with other co-emulsifiers, is 0.01% by weight to 0.1% by weight, preferably 0.02% 0.04 wt .-%, each based on the total weight of the emulsion.
- the fat emulsion of the pharmaceutical preparation according to the invention may be enriched with antioxidants which protect against the formation of undesired peroxides.
- Suitable antioxidants are, in particular, vitamin E (alpha-, beta- or gamma-tocopherol) and vitamin C (for example as ascorbyl palmitate), vitamins E and C or their isomers or derivatives being present either alone or in combination can.
- weight fraction is between 0.002 and 0.03% (alpha tocopherol) or 0.001 and 0.015% (ascorbyl palmitate), based in each case on the total weight of the emulsion to be used according to the invention.
- the fat emulsion to be used according to the invention in the pharmaceutical preparation according to the invention also contains L-carnitine in an amount of preferably 0.01 to 0.1% by weight, in each case based on the total weight of the emulsion.
- the preparation according to the invention may additionally contain the vitamins biotin and / or cobalamin: their concentrations are 1-10 mg biotin or 0.1-1 mg cobalamin per 100 g lipid content of the preparation.
- the isotonization of the fat emulsion is preferably carried out with the aid of polyols such as glycerol, xylitol or sorbitol, which are used in an amount of preferably 2 to 3 wt .-% each based on the total weight of the emulsion.
- the preferred isotonizing agent is glycerol.
- the pharmaceutical agent according to the present invention is administered in a pharmaceutically effective amount.
- the pharmaceutically effective dose i. the amount of triglyceride (A) to be supplied with the pharmaceutical preparation according to the invention to reduce the complications of severe, e.g. As septic diseases and their intensive care treatment to reduce their intensity and shorten duration, at 1 to 2 g per kg of body weight and day.
- the supply preferably takes place continuously over 24 hours / day, but can also be divided into several portions, wherein an infusion rate of 0.25 g fat per kg body weight and hour should not be exceeded. In general, a multi-day medium to long-term administration is required to achieve the erfmdungswashe effect.
- the application of the pharmaceutical preparation according to the invention is carried out as part of a completely parenteral or combined parenteral / enteral nutrition, as in seriously ill z.
- the high energy content of the emulsion according to the invention should be taken into account in the total calorie intake with the parenteral or combined enteral / parenteral nutrition.
- essential fatty acids omega-3 or omega-6
- the latter need not be additionally substituted.
- the particularly preferred presence of omega-3 fatty acid residues in the emulsion and their anti-inflammatory properties can be synergistic effects and additionally promote the healing process.
- a further subject of the present invention is an isotonic fat emulsion comprising a triglyceride (A) of the formula (I)
- R, R or R is an alkanoyl radical having an odd number of 5 to 15 carbon atoms and which comprises at least one additional triglyceride (B) other than (A) and having at least one fatty acid residue is selected from the group consisting of medium chain fatty acids comprising caprylic acid, capric acid or lauric acid; long-chain saturated fatty acids, including myristic acid, palmitic acid or stearic acid; monounsaturated fatty acids comprising palmitoleic or oleic acid; and omega-3 and omega-6 type polyunsaturated fatty acids comprising eicosapentaenoic acid, docosahexaenoic acid, linoleic acid and gamma-linolenic acid.
- isotonic fat emulsion according to the invention correspond to the fat emulsion which is to be used according to the invention in the pharmaceutical preparation according to the invention.
- Another object of the present invention is the use of the isotonic fat emulsion according to the invention as a dietetic.
- the isotonic fat emulsion is preferably used for enteral nutrition.
- Another object of the present invention is a dietetic, comprising at least one triglyceride (A) of the formula (I).
- the dietetic preferably comprises the isotonic fat emulsion according to the invention.
- Another object of the present invention is the use of the isotonic fat emulsion according to the invention or a fat emulsion with at least one triglyceride (A) of the formula (I) or the pharmaceutical preparation according to the invention for the artificial nutrition of septic intensive care patients and / or for parenteral nutrition.
- a further object is a medicament comprising at least one triglyceride (A) of the formula (I),
- the medicament preferably comprises the isotonic fat emulsion according to the invention.
- the lipophilic components 1-9 listed in the table below are roughly mixed and dispersed with the aid of an Ultra-Turrax homogenizer. Thereafter, the hydrophilic components 10-13 are added using sodium oleate or stearate and NaOH as aqueous solutions and adjusting the pH of the batch mixture to 8.0-9.0 using the latter components. The actual homogenization of the batch is then carried out in a high-pressure homogenizer at pressures of about 400 kg / cm.
- the finished emulsion is filled into suitable glass or plastic containers and heat sterilized according to the usual procedures for parenteralia. This results in a sterile, pyrogen-free and stable fat emulsion having an average droplet size of less than 0.5 microns and has a shelf life of at least 24 months at room temperature.
- triglyceride (A) consisting of glycerin, which with heptanoic acid in the positions sn-1 and sn-3 and eicosapentaenoic acid: the at position sn-2 ((EPA), C2O 5 omega-3) Triglycerides esterified is used.
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Priority Applications (10)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
RU2011124887/15A RU2528108C2 (ru) | 2008-11-18 | 2009-11-09 | Жировая эмульсия для искусственного питания тяжелобольных, нуждающихся в интенсивной терапии |
BRPI0921917A BRPI0921917B8 (pt) | 2008-11-18 | 2009-11-09 | formulação farmacêutica. |
CN200980145702.6A CN102215839B (zh) | 2008-11-18 | 2009-11-09 | 用于人工喂养重病的重症特护患者的脂肪乳剂 |
ES09760502.6T ES2561207T3 (es) | 2008-11-18 | 2009-11-09 | Emulsión grasa para alimentar artificialmente a pacientes gravemente enfermos de cuidados intensivos |
EP09760502.6A EP2355813B1 (de) | 2008-11-18 | 2009-11-09 | Fettemulsion zur künstlichen ernährung von schwerkranken intensivpatienten |
CA2739390A CA2739390C (en) | 2008-11-18 | 2009-11-09 | Fat emulsion for artificially feeding seriously ill intensive care patients |
JP2011536823A JP2012509292A (ja) | 2008-11-18 | 2009-11-09 | 重症の集中治療患者への人工栄養のための脂肪乳剤 |
US13/126,245 US20110207819A1 (en) | 2008-11-18 | 2009-11-09 | Fat Emulsion for Artificially Feeding Seriously Ill Intensive Care Patients |
MX2011005201A MX338223B (es) | 2008-11-18 | 2009-11-09 | Emulsion de grasas para alimentar artificialmente a pacientes seriamente enfermos en cuidados intensivos. |
US14/930,723 US20160051506A1 (en) | 2008-11-18 | 2015-11-03 | Fat Emulsion for Artificially Feeding Seriously Ill Intensive Care Patients |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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DE102008057867.3 | 2008-11-18 | ||
DE102008057867A DE102008057867A1 (de) | 2008-11-18 | 2008-11-18 | Fettemulsion zur künstlichen Ernährung von schwerkranken Intensivpatienten |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US13/126,245 A-371-Of-International US20110207819A1 (en) | 2008-11-18 | 2009-11-09 | Fat Emulsion for Artificially Feeding Seriously Ill Intensive Care Patients |
US14/930,723 Continuation US20160051506A1 (en) | 2008-11-18 | 2015-11-03 | Fat Emulsion for Artificially Feeding Seriously Ill Intensive Care Patients |
Publications (1)
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WO2010057804A1 true WO2010057804A1 (de) | 2010-05-27 |
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PCT/EP2009/064839 WO2010057804A1 (de) | 2008-11-18 | 2009-11-09 | Fettemulsion zur künstlichen ernährung von schwerkranken intensivpatienten |
Country Status (12)
Country | Link |
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US (2) | US20110207819A1 (ja) |
EP (1) | EP2355813B1 (ja) |
JP (1) | JP2012509292A (ja) |
KR (1) | KR20110084513A (ja) |
CN (1) | CN102215839B (ja) |
BR (1) | BRPI0921917B8 (ja) |
CA (1) | CA2739390C (ja) |
DE (1) | DE102008057867A1 (ja) |
ES (1) | ES2561207T3 (ja) |
MX (1) | MX338223B (ja) |
RU (1) | RU2528108C2 (ja) |
WO (1) | WO2010057804A1 (ja) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8168611B1 (en) | 2011-09-29 | 2012-05-01 | Chemo S.A. France | Compositions, kits and methods for nutrition supplementation |
US8183227B1 (en) | 2011-07-07 | 2012-05-22 | Chemo S. A. France | Compositions, kits and methods for nutrition supplementation |
US11406616B2 (en) | 2016-06-08 | 2022-08-09 | Sunregen Healthcare Ag | Lipids with odd number of carbon atoms and their use as pharmaceutical composition or nutritional supplement |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE102009013914B4 (de) * | 2009-03-19 | 2011-05-05 | Bruker Daltonik Gmbh | Kalibriersubstanzen für Atmosphärendruck-Ionenquellen |
EP2671578A4 (en) * | 2011-01-31 | 2014-04-02 | Nippon Zoki Pharmaceutical Co | PROPHYLACTIC OR THERAPEUTIC MEDICINE FOR PERIPHERAL NEUROPATHY CAUSED BY AN ANTICANCER AGENT |
CN106900888B (zh) * | 2015-12-23 | 2021-12-24 | 丰益(上海)生物技术研发中心有限公司 | 含有奇数碳脂肪酸结构脂的油脂组合物及其应用 |
CN109602704A (zh) * | 2019-01-23 | 2019-04-12 | 广东嘉博制药有限公司 | 丁酸氯维地平脂肪乳注射液及其制备工艺 |
CN110326789A (zh) * | 2019-06-11 | 2019-10-15 | 上海互众药业有限公司 | 一种脂肪乳食品补充液及其制备方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20030162833A1 (en) * | 2001-08-01 | 2003-08-28 | Roe Charles R. | Fatty acid treatment for cardiac patients |
US6740679B1 (en) * | 1999-02-05 | 2004-05-25 | Baylor University Medical Center | Nutritional supplement or pharmaceutical preparation comprising triglycerides with seven-carbon fatty acid |
WO2004103307A2 (en) * | 2003-05-20 | 2004-12-02 | Baylor Research Institute | Method of use of five and fifteen carbon fatty acids |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2515174A1 (fr) | 1981-10-23 | 1983-04-29 | Roussel Uclaf | Nouveaux triglycerides, procede de preparation et d'applications en dietetique et en therapeutique |
US4526902A (en) | 1983-10-24 | 1985-07-02 | Century Laboratories, Inc. | Combined fatty acid composition for treatment or prophylaxis of thrombo-embolic conditions |
DE3721137A1 (de) | 1987-06-26 | 1989-01-05 | Dietl Hans | Fettemulsion zur intravenoesen anwendung |
DE3722540A1 (de) | 1987-07-08 | 1989-01-19 | Fresenius Ag | Fettemulsion, verfahren zu ihrer herstellung und ihre verwendung |
DE3734147C2 (de) * | 1987-10-09 | 1998-10-29 | Braun Melsungen Ag | Isotone omega-3-fettsäurenhaltige Fettemulsion und ihre Verwendung |
AU682894B2 (en) * | 1993-10-28 | 1997-10-23 | Institut National De La Recherche Agronomique | Composition based on amino acids intended for the treatment of sepsis or of an attack bringing about an inflammatory reaction, in animals and man |
RU2155612C2 (ru) * | 1997-01-30 | 2000-09-10 | Скрипченко Наталия Викторовна | Способ лечения острых инфекционных заболеваний периферической нервной системы |
CA2361070C (en) * | 1999-02-05 | 2012-04-17 | Baylor University Medical Center | Nutritional supplement or pharmaceutical preparation comprising triglycerides with seven-carbon fatty acid |
CA2463020A1 (en) * | 2001-10-11 | 2003-04-24 | Applied Research Systems Ars Holding N.V. | Use of gp130 activators in diabetic neuropathy |
CA2784420C (en) * | 2004-07-02 | 2020-11-10 | Baylor Research Institute | Glycogen or polysaccharide storage disease treatment method |
EP1723944B1 (de) * | 2005-02-16 | 2007-04-04 | Dr. Streatmans Chemische Produktion GmbH | Kosmetische und dermatologische Lichtschutzformulierungen mit einem Gehalt an chemischen UV-Filtern und Triheptanonin |
KR20090074221A (ko) | 2006-09-26 | 2009-07-06 | 베일러 리서치 인스티튜트 | 영양물 센서 |
-
2008
- 2008-11-18 DE DE102008057867A patent/DE102008057867A1/de not_active Withdrawn
-
2009
- 2009-11-09 CN CN200980145702.6A patent/CN102215839B/zh not_active Ceased
- 2009-11-09 BR BRPI0921917A patent/BRPI0921917B8/pt active IP Right Grant
- 2009-11-09 ES ES09760502.6T patent/ES2561207T3/es active Active
- 2009-11-09 CA CA2739390A patent/CA2739390C/en active Active
- 2009-11-09 JP JP2011536823A patent/JP2012509292A/ja active Pending
- 2009-11-09 EP EP09760502.6A patent/EP2355813B1/de active Active
- 2009-11-09 MX MX2011005201A patent/MX338223B/es active IP Right Grant
- 2009-11-09 US US13/126,245 patent/US20110207819A1/en not_active Abandoned
- 2009-11-09 KR KR1020117010418A patent/KR20110084513A/ko not_active Application Discontinuation
- 2009-11-09 RU RU2011124887/15A patent/RU2528108C2/ru active
- 2009-11-09 WO PCT/EP2009/064839 patent/WO2010057804A1/de active Application Filing
-
2015
- 2015-11-03 US US14/930,723 patent/US20160051506A1/en not_active Abandoned
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6740679B1 (en) * | 1999-02-05 | 2004-05-25 | Baylor University Medical Center | Nutritional supplement or pharmaceutical preparation comprising triglycerides with seven-carbon fatty acid |
US20030162833A1 (en) * | 2001-08-01 | 2003-08-28 | Roe Charles R. | Fatty acid treatment for cardiac patients |
WO2004103307A2 (en) * | 2003-05-20 | 2004-12-02 | Baylor Research Institute | Method of use of five and fifteen carbon fatty acids |
Non-Patent Citations (6)
Title |
---|
AI-NASIRY S; GEUSENS N; HANSSENS M; LUYTEN C; PIJNENBORG R.: "The use of Alamar Blue assay for quantitative analysis of viability, migration and invasion of choriocarcinoma cells", HUMAN REPRODUCTION, vol. 22, no. 5, 2007, pages 1304 - 1309 |
HAMID R; ROTSHTEYN Y; RABADI L; PARIKH R; BULLOCK P.: "Comparison of alamarBlue and MTT assays for high through-put screening", TOXICOL IN VITRO, vol. 18, 2004, pages 703 - 10 |
NOCIARI MM; SHALEV A; BENIAS P; RUSSO C.: "A novel one-step, highly sensitive fluorometric assay to evaluate cell-mediated cytotoxicity", J IMMUNOL METH., vol. 213, 1998, pages 157 - 167 |
ROE C R ET AL: "Treatment of cardiomyopathy and rhabdomyolysis in long-chain fat oxidation disorders using an anaplerotic odd-chain triglyceride", JOURNAL OF CLINICAL INVESTIGATION, AMERICAN SOCIETY FOR CLINICAL INVESTIGATION, US, vol. 110, no. 2, 1 July 2002 (2002-07-01), pages 259 - 269, XP002995380, ISSN: 0021-9738 * |
SYKES ML; AVERY VM.: "Development of an Alamar Blue viability assay in 384-well format for high throughput whole cell screening of Trypanosoma brucei brucei bloodstream form strain 427", AM J TROP MED HYG., vol. 81, no. 4, 2009, pages 665 - 74 |
VAN DER HARST MR; BULL S; LAFFONT CM; KLEIN WR.: "Gentamicin neprotoxicyty-a comparison of in vitro finding with in vivo experiments in equines", VET RES COMMUN., vol. 29, no. 3, 2005, pages 247 - 61 |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8183227B1 (en) | 2011-07-07 | 2012-05-22 | Chemo S. A. France | Compositions, kits and methods for nutrition supplementation |
US8168611B1 (en) | 2011-09-29 | 2012-05-01 | Chemo S.A. France | Compositions, kits and methods for nutrition supplementation |
US8545896B2 (en) | 2011-09-29 | 2013-10-01 | Chemo S. A. France | Compositions, kits and methods for nutrition supplementation |
US11406616B2 (en) | 2016-06-08 | 2022-08-09 | Sunregen Healthcare Ag | Lipids with odd number of carbon atoms and their use as pharmaceutical composition or nutritional supplement |
Also Published As
Publication number | Publication date |
---|---|
MX2011005201A (es) | 2011-06-01 |
RU2011124887A (ru) | 2012-12-27 |
KR20110084513A (ko) | 2011-07-25 |
DE102008057867A1 (de) | 2010-05-20 |
BRPI0921917B8 (pt) | 2021-05-25 |
BRPI0921917A2 (pt) | 2015-12-29 |
EP2355813B1 (de) | 2015-11-04 |
CN102215839A (zh) | 2011-10-12 |
CA2739390A1 (en) | 2010-05-27 |
MX338223B (es) | 2016-04-08 |
US20110207819A1 (en) | 2011-08-25 |
BRPI0921917B1 (pt) | 2020-08-25 |
EP2355813A1 (de) | 2011-08-17 |
JP2012509292A (ja) | 2012-04-19 |
US20160051506A1 (en) | 2016-02-25 |
ES2561207T3 (es) | 2016-02-25 |
RU2528108C2 (ru) | 2014-09-10 |
CN102215839B (zh) | 2016-08-24 |
CA2739390C (en) | 2016-05-03 |
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