EP1450629A1 - Solid and stable creatine/citric acid composition(s) and compositions containing carbohydrate(s) or hydrates thereof, method for the production and use thereof - Google Patents
Solid and stable creatine/citric acid composition(s) and compositions containing carbohydrate(s) or hydrates thereof, method for the production and use thereofInfo
- Publication number
- EP1450629A1 EP1450629A1 EP02785417A EP02785417A EP1450629A1 EP 1450629 A1 EP1450629 A1 EP 1450629A1 EP 02785417 A EP02785417 A EP 02785417A EP 02785417 A EP02785417 A EP 02785417A EP 1450629 A1 EP1450629 A1 EP 1450629A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- creatine
- citric acid
- acid composition
- carbohydrate
- solid
- 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.)
- Ceased
Links
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Natural products OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 title claims abstract description 126
- CVSVTCORWBXHQV-UHFFFAOYSA-N creatine Chemical compound NC(=[NH2+])N(C)CC([O-])=O CVSVTCORWBXHQV-UHFFFAOYSA-N 0.000 title claims abstract description 126
- 239000000203 mixture Substances 0.000 title claims abstract description 87
- 229960003624 creatine Drugs 0.000 title claims abstract description 61
- 239000006046 creatine Substances 0.000 title claims abstract description 61
- 150000001720 carbohydrates Chemical class 0.000 title claims abstract description 48
- 239000007787 solid Substances 0.000 title claims abstract description 17
- 150000004677 hydrates Chemical class 0.000 title claims abstract description 6
- 238000000034 method Methods 0.000 title claims description 13
- 238000004519 manufacturing process Methods 0.000 title claims description 7
- PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 title abstract 4
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- DLNGCCQFGNSBOP-UHFFFAOYSA-N 2-[carbamimidoyl(methyl)amino]acetic acid;2-oxopropanoic acid Chemical compound CC(=O)C(O)=O.NC(=N)N(C)CC(O)=O DLNGCCQFGNSBOP-UHFFFAOYSA-N 0.000 claims description 6
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- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 4
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- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 4
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- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 2
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 claims description 2
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- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 2
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- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 claims description 2
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- 239000003163 gonadal steroid hormone Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 150000002584 ketoses Chemical class 0.000 description 1
- TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 1
- 235000015122 lemonade Nutrition 0.000 description 1
- AGBQKNBQESQNJD-UHFFFAOYSA-M lipoate Chemical compound [O-]C(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-M 0.000 description 1
- 235000019136 lipoic acid Nutrition 0.000 description 1
- VUZPPFZMUPKLLV-UHFFFAOYSA-N methane;hydrate Chemical compound C.O VUZPPFZMUPKLLV-UHFFFAOYSA-N 0.000 description 1
- 238000010327 methods by industry Methods 0.000 description 1
- 235000013379 molasses Nutrition 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000006069 physical mixture Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 239000011833 salt mixture Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229960002663 thioctic acid Drugs 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 230000004102 tricarboxylic acid cycle Effects 0.000 description 1
- 150000003628 tricarboxylic acids Chemical class 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- 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
- A23L33/17—Amino acids, peptides or proteins
- A23L33/175—Amino acids
-
- 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
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- 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
-
- 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
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- 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
- A61P25/06—Antimigraine agents
-
- 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
- A61P25/20—Hypnotics; Sedatives
-
- 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
- A61P25/22—Anxiolytics
-
- 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
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- 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
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- 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
- A61P9/12—Antihypertensives
-
- 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 a formulation which contains one or more solid and stable creatine / citric acid compounds and one or more carbohydrates or their hydrates, a process for their preparation and their use.
- Creatine salts are known in a wide variety of forms and contain the physiologically harmless creatine cation of the formula (I)
- Creatine is not only an endogenous substance and a valuable nutritional supplement, but also has valuable therapeutic properties. Creatine has been known as a muscle substance for over 100 years, and it serves as a source of energy for the muscle. A number of scientific studies have shown that taking creatine can lead to an increase in muscle mass and muscle performance. There is also scientific evidence that the pancreas releases more insulin under the influence of creatine. Insulin promotes the absorption of glucose and amino acids in the muscle cell and stimulates protein synthesis. Insulin also reduces the rate of protein breakdown. Citric acid is a tricarboxylic acid that is known to be common in the plant kingdom as well as in many animal tissues and body fluids. Citric acid is one of the series of prominent compounds that are involved in the physiological oxidation of fats, proteins and carbohydrates to carbon dioxide and water (see, inter alia, tricarboxylic acid cycle).
- Citric acid which was first isolated from lime juice by the Swedish chemist Karl Wilhelm Scheele in 1784, is currently produced biotechnologically by fermentation of cane sugar or molasses by the Aspergillus niger mold. Citric acid is used in its natural form or as a food additive E 330 in the packaging of food, but also in baking powders, lemonade and generally for acidification and as a flavoring. Citric acid is also used to increase the stability of foods or other organic substances.
- the pure, anhydrous citric acid mostly forms colorless, rhombic crystals with a slightly acidic taste.
- U.S. Patent 5,973,199 discloses, inter alia, Isolated, water-soluble salts of creatine and citric acid are known, which have a melting point of 1 1 2 to 1 1 4 ° C.
- This creatine citrate is produced by suspending citric acid monohydrate in ethyl acetate, then adding creatine monohydrate and then mixing the mixture for 4 hours at 25 ° C. This gives a product which contains about 90% of creatine citrate with a melting point between 11 and 14 ° C. and varying proportions of solvents.
- di- and tricreatine citrates (US Pat. No. 6,21,1407), the melting points of which should be 146 ° C. or 1,54 ° C. and which have a creatine content of 57.7 or 67.2% by weight. -% exhibit. Information about however, the structure of such salts cannot be found in this document.
- Effervescent formulations which contain creatine citrate as a 1: 1 salt or physical mixtures of creatine and citric acid are known from US Pat. No. 5,925,378.
- creatine salts such as The creatine pyruvates and ascorbates as well as the citrates have valuable physiological, therapeutic and dietary properties.
- Most of the known creatine salts are used, for example, to increase endurance and strength in sports, to reduce weight and body fat, and as a protective substance for body cells and tissues, in particular cardiovascular, hepatic, nephrotic, peritoneal and neuronal tissue, as a substance for inhibition radical formation and as a radical scavenger substance in body cells and tissues (also synovial tissue), furthermore in the health sector and as a food supplement.
- creatine pyruvates Typical of the physical properties of many creatine salts are the creatine pyruvates, which as stable substances are stable compounds at temperatures below 40 ° C. However, if creatine pyruvate is exposed to temperatures above 40 ° C or if formulations containing creatine pyruvate are produced with the addition of certain non-stabilizing substances, a rapid disintegration of the creatine pyruvate can be observed.
- the storage stability of the creatine pyruvates is usually not very pronounced, especially at higher temperatures, which is probably also due to the fact that, for example, the pyruvates are unstable 2-oxocarboxylic acid salts and more the most of decompose known salts of creatine easily to form creatinine. Since creatine is also present as an inner salt and is only a weak base, the storage stability is negatively influenced, especially over a longer period. In particular, combinations of creatine compounds, such as, for example, citrates with compounds that tend to be unstable, lead to quality losses for these reasons.
- WO 98/28263 discloses pyruvates in the form of storage-stable creatine compounds which, in addition to pharmaceutical formulation auxiliaries and others, are available in physiologically compatible compositions. can also be combined with carbohydrates such as glucose, dextrose and maltose.
- Formulations containing creatine consisting of a neurotransmitter, lipoic acid and optionally L-camitin, coenzyme Q and other physiologically active additives, such as e.g. Sugars, describes DE-OS 1 98 30 768, which formulations can contain, in particular, creatine pyruvate and, inter alia, should also be stable in storage.
- DE-OS 1 98 36 450 discloses stable pyruvic acid (salts) - containing formulations for animal nutrition which, in addition to three further component groups, also contain physiologically valuable additives, such as carbohydrates.
- Organic acids such as citric acid and aminocarboxylic acids such as creatine are proposed as further components.
- the preferred pyruvic acid salt is the creatine pyruvate.
- Combinations of creatine salts with carbohydrates are now known from the last four documents, and formulations are also described which may contain creatine, citric acid and carbohydrates. However, there is no indication that compositions consisting of creatine and citric acid can improve storage stability and other properties.
- compositions (s) in an easily metered form in which the disadvantages of the prior art are at least partially eliminated.
- creatine / citric acid composition when formulated with carbohydrates, become extremely temperature- and storage-stable even when other unstable and / or unstabilizing compounds are added.
- This increased storage stability even at elevated temperatures of e.g. 30 ° C and in particular> 35 ° C even for a long period of time is shown by a reduced formation of creatinine as a degradation product.
- the formulations according to the invention preferably have a creatinine content of 500 500 ppm, particularly preferably of ⁇ 350 ppm.
- the formulation according to the invention thus enables the compositions in question, consisting of creatine and citric acid, to be stored for a significantly longer time, as well as an increased resilience with regard to temperature and duration, both during processing and storage, which makes them accessible, for example, to new production and / or formulation processes.
- such formulations have proven to be particularly suitable, the components of which are creatine / citric acid composition (s) and carbohydrate (s) in a weight ratio of 1: 0.01 to 0.5 and very particularly preferably in a weight ratio of about 1: 0 , 1 are present.
- Preferred embodiments of the claimed formulations have a water content of up to 30% by weight.
- Creatine components which have proven particularly suitable are those which, as creatine / citric acid composition (s), contain physiologically tolerable salts, deposits and complexes in a molar ratio of creatine to citric acid of 1.0 to 3.0: 1.0.
- creatine / citric acid compounds that are unstable to external influences.
- their combinations with stable creatine / citric acid compositions are also encompassed by the invention.
- any carbohydrates for example all polyhydroxy aldehydes (aldoses) and polyhydroxy ketones (ketoses) and their derivatives, can be used to stabilize the formulations.
- aldo- and ketohexoses and the oligo- or polysaccharides derived therefrom and their O-glycosidic derivatives have proven particularly useful.
- monosaccharides such as glucose, fructose, ribose and sorbitol, and / or cyclic and open-chain oligohexoses with 2 to 10 monomer units, such as sucrose, lactose and maltose, but also polysaccharides with 1 1 to 10 6 monomer units, such as.
- B. inulin, arabino-galactan, maltodextrins, starch, chitosan and glycogen are preferred. It is important that any mixture of carbohydrates can be used.
- the present invention also takes into account formulations which, in addition to the components essential to the invention, additionally contain other creatine-containing compositions, in particular creatine salts, such as creatine pyruvates and ascorbates.
- creatine salts such as creatine pyruvates and ascorbates.
- proteins e.g. Collagen or whey powder
- suitable acids such as, for example, ascorbic acid
- the carbohydrate (s) are in the form of solutions, suspensions or as a solid substance with the creatine / citric acid composition in the temperature range from -20 to 120 ° C. and preferably implemented between 10 and 90 ° C., whereupon the solution obtained is optionally finally freed from the liquid phase, which is preferably carried out by solid / liquid separation, distillation, evaporation and / or concentration in each case in vacuo, spray drying or freeze drying or by any other suitable separation method.
- a mixture consisting of the acidic creatine / citric acid component or its solution and the solid carbohydrate component is subjected to a thermal treatment, a treatment with ultrasound and / or a microwave in the temperature range from -20 to 120 ° C. which can also be done in a vacuum and leads to the formation of homogeneous formulations. All of these reactions can be carried out in the presence of a solvent or diluent or also solvent-free. All common solvents, such as water, alcohols, ethers, ketones, esters, organic acids, aliphatic and aromatic hydrocarbons, have proven to be suitable solvents or diluents for the production of the aggregates claimed.
- the desired formulations can also be obtained simply by mixing the components dry.
- the carbohydrate component can be used to form the formulation in anhydrous form, as a hydrate or as a moist product.
- the acidic creatine salt component can also be used in anhydrous form, in aqueous solution or dissolved in one of the alcoholic or organic solvents or diluents already mentioned. All of the claimed implementation variants can be carried out in the known process engineering apparatuses, such as in kneaders, mixers, paddle dryers, stirred tanks and spray dryers.
- the creatine / citric acid composition (s) and carbohydrate-containing formulations according to the invention are thus obtained in high yield and purity without further necessary cleaning steps.
- the present invention thus provides that either both starting components are used in solid or in liquid form or that one component is solid and the other is liquid. It should only be noted that for the formulations according to the invention the creatine / citric acid component and the carbohydrate component are always used within the claimed weight ratios.
- the formulations according to the invention are used for pharmaceutical purposes or in Food industry, e.g. for increasing endurance and strength in sports, for reducing weight and body fat as well as a protective substance for body cells and tissues, especially cardiovascular, hepatic, ophthalmic, nephrotic and neuronal and transplant tissues, and as a substance for inhibiting radical formation and as Radical scavenger substance in body cells and tissues (also synovial tissue), in the health sector, in particular in the treatment of obesity and obesity, in the case of skin disorders, for wound healing and for lowering blood pressure, as well as in mental disorders in women, which are mainly caused by changes in the female sex hormone balance, such as Symptoms of premenstrual syndrome (PMS), dysmenorrhea, menopause, weather sensitivity, migraines, tension headache, insomnia and disturbed mood, and as a nutritional supplement.
- PMS Symptoms of premenstrual syndrome
- dysmenorrhea menopause
- weather sensitivity migraines
- migraines tension headache
- formulations according to the invention can be administered in the form of tablets, powders, dragees, capsules, drinks and jellies and in particular as effervescent tablets and effervescent powder, this series being able to be extended as desired.
- the present invention thus represents an important advance in the use of creatine / citric acid compositions in the therapeutic and dietetic field and in sports medicine. Because of the prior art, it was not to be expected that solid and storage-stable creatine / citric acid composition (s ) and carbohydrate-containing formulations are accessible with simple methods and lead to easy-to-dose products. In addition, it has been shown that the creatine / citric acid compositions do not undergo any condensation and decomposition reactions, but at most only very slight, when preparing the formulations. Of Furthermore, the claimed creatine / citric acid composition (s) and carbohydrate-containing formulations can be produced without subsequent work-up. Aqueous solutions containing the creatine component or solvent can also be used, in which case formulations with defined crystal water contents are obtained.
- the present invention in particular with the production variants also claimed, does not include mere mixtures of the components of the invention, creatine / citric acid composition (s) and carbohydrate (s), as are already well known from the prior art, but that it is the formulations claimed are actual physical or chemical reaction products.
- a creatine-citric acid compound (3: 1) (KC) as pure substance and mixtures of this compound (3: 1) with 1, 5 and 10 wt .-% addition of a carbohydrate (KH) were stored at 60 ° C for 28 days and then the contents of the creatine decomposition product creatinine determined.
- the starting data for the reference substance KC which is stable when cooled to room temperature (RT), with a creatine content of 67.1% by weight and a creatinine content of ⁇ 67 ppm (detection limit) serve as a comparison.
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Abstract
The invention relates to solid and stable creatine/citric acid composition(s) and formulations containing carbohydrate(s) or the hydrates thereof, whereby the weight ratio between the components creatine/citric acid composition(s) and the carbohydrate(s) ranges from 1:0.01 to 1.0. Any polyhydroxy aldehyde or polyhydroxy ketone can be used as a carbohydrate component in an anhydrous form, as hydrate, or as a moist product. The creatine component is preferably used in an anhydrous form or in an aqueous, alcoholic, or organic solution. The formulations are preferably produced by converting the carbohydrates in the form of solutions, suspensions, or as a solid substance with the cratine/carbohydrate composition or the solution thereof at a temperature of -20 to 120 DEG C, and by optionally isolating the liquid phase. Alternatively, the formulations are produced by thermal conditioning, ultrasound or microwave conditioning of mixtures containing the creatine component and solid carbohydrates, preferably in a vacuum. The resulting creatine/citric acid compositions and formulations containing carbohydrate can be used for endurance enhancement and strength enhancement in sports, for reducing weight and body fat, in the health sector, for women when feeling sick, or as a supplement in animal foods.
Description
Feste und stabile Kreatin/Citronensäure-Zusammensetzung(en) und Kohlenhydrat(e) bzw. deren Hydrate enthaltende Formulierung, Verfahren zu ihrer Herstellung und deren VerwendungSolid and stable creatine / citric acid composition (s) and carbohydrate (s) or their formulation containing hydrates, process for their preparation and their use
Beschreibungdescription
Gegenstand der vorliegenden Erfindung ist eine Formulierung, die eine oder mehrere feste und stabile Kreatin/Citronensäure-Verbindungen und ein oder mehrere Kohlenhydrate bzw. deren Hydrate enthält, ein Verfahren zu ihrer Herstellung und deren Verwendung.The present invention relates to a formulation which contains one or more solid and stable creatine / citric acid compounds and one or more carbohydrates or their hydrates, a process for their preparation and their use.
Kreatin-Salze sind in den unterschiedlichsten Formen bekannt und enthalten das physiologisch unbedenkliche Kreatin-Kation der Formel (I)Creatine salts are known in a wide variety of forms and contain the physiologically harmless creatine cation of the formula (I)
Kreatin ist nicht nur eine körpereigene Substanz und ein wertvolles Nahrungsergänzungsmittel, sondern besitzt auch wertvolle therapeutische Eigenschaften. Kreatin ist seit über 100 Jahren als Muskelsubstanz bekannt, wobei es dem Muskel als Energiequelle dient. In einer Reihe von wissenschaftlichen Arbeiten wurde gezeigt, dass die Einnahme von Kreatin zu einer Steigerung der Muskelmasse und Muskelleistung führen kann. Es gibt auch wissenschaftliche Erkenntnisse, dass die Bauchspeicheldrüse unter dem Einfluss von Kreatin vermehrt Insulin freisetzt. Insulin fördert die Aufnahme von Glukose und Aminosäuren in die Muskelzelle und regt die Proteinsynthese an. Außerdem vermindert Insulin die Proteinabbaurate.
Bei der Citronensäure handelt es sich um eine Tricarbonsäure, die bekanntermaßen im Pflanzenreich sowie in vielen tierischen Geweben und Körperflüssigkeiten verbreitet ist. Citronensäure zählt u.a. zur Reihe der prominenten Verbindungen, die bei der physiologischen Oxidation von Fetten, Eiweißen und Kohlenhydraten zu Kohlendioxid und Wasser mitwirken (vgl. u.a. Tricarbonsäure-Zyclus).Creatine is not only an endogenous substance and a valuable nutritional supplement, but also has valuable therapeutic properties. Creatine has been known as a muscle substance for over 100 years, and it serves as a source of energy for the muscle. A number of scientific studies have shown that taking creatine can lead to an increase in muscle mass and muscle performance. There is also scientific evidence that the pancreas releases more insulin under the influence of creatine. Insulin promotes the absorption of glucose and amino acids in the muscle cell and stimulates protein synthesis. Insulin also reduces the rate of protein breakdown. Citric acid is a tricarboxylic acid that is known to be common in the plant kingdom as well as in many animal tissues and body fluids. Citric acid is one of the series of prominent compounds that are involved in the physiological oxidation of fats, proteins and carbohydrates to carbon dioxide and water (see, inter alia, tricarboxylic acid cycle).
Citronensäure, die erstmals durch den schwedischen Chemiker Karl Wilhelm Scheele im Jahr 1784 aus Limonensaft isoliert worden ist, wird aktuell durch Fermentation von Rohrzucker oder Molasse durch den Schimmelpilz Aspergillus niger biotechnologisch hergestellt. Citronensäure wird in ihrer natürlichen Form oder als Lebensmittelzusatzstoff E 330 bei der Konfektionierung von Lebensmitteln, aber auch in Backpulvern, Brauselimonaden und allgemein zur Ansäuerung sowie als Geschmacksstoff eingesetzt. Ferner dient Citronensäure zur Erhöhung der Stabilität von Lebensmitteln oder anderen organischen Substanzen.Citric acid, which was first isolated from lime juice by the Swedish chemist Karl Wilhelm Scheele in 1784, is currently produced biotechnologically by fermentation of cane sugar or molasses by the Aspergillus niger mold. Citric acid is used in its natural form or as a food additive E 330 in the packaging of food, but also in baking powders, lemonade and generally for acidification and as a flavoring. Citric acid is also used to increase the stability of foods or other organic substances.
Die reine, wasserfreie Citronensäure bildet zumeist farblose, rhombische Kristalle mit leicht saurem Geschmack.The pure, anhydrous citric acid mostly forms colorless, rhombic crystals with a slightly acidic taste.
Aus dem US-Patent 5,973, 199 sind u.a. isolierte, wasserlösliche Salze von Kreatin und Citronensäure bekannt, die einen Schmelzpunkt von 1 1 2 bis 1 1 4 °C aufweisen. Hergestellt wird dieses Kreatin-Citrat, indem Citronensäure-monohydrat in Ethylacetat suspendiert, dann Kreatin- monohydrat hinzugefügt und anschließend die Mischung für 4 Stunden bei 25 °C gemischt wird. Man erhält dadurch ein Produkt, das ca. 90 % an Kreatin-Citrat mit einem Schmelzpunkt zwischen 1 1 2 und 1 14 °C und variierende Lösemittelanteile enthält.U.S. Patent 5,973,199 discloses, inter alia, Isolated, water-soluble salts of creatine and citric acid are known, which have a melting point of 1 1 2 to 1 1 4 ° C. This creatine citrate is produced by suspending citric acid monohydrate in ethyl acetate, then adding creatine monohydrate and then mixing the mixture for 4 hours at 25 ° C. This gives a product which contains about 90% of creatine citrate with a melting point between 11 and 14 ° C. and varying proportions of solvents.
Vorbeschrieben sind ebenfalls Di- und Trikreatin-Citrate (US 6,21 1 ,407), deren Schmelzpunkte bei 146 °C bzw. 1 54 °C liegen sollen und die einen Gehalt an Kreatin von 57,7 bzw. 67,2 Gew.-% aufweisen. Angaben über
die Struktur derartiger Salze sind diesem Dokument aber nicht zu entnehmen.Also described above are di- and tricreatine citrates (US Pat. No. 6,21,1407), the melting points of which should be 146 ° C. or 1,54 ° C. and which have a creatine content of 57.7 or 67.2% by weight. -% exhibit. Information about however, the structure of such salts cannot be found in this document.
Brauseformulierungen, die Kreatincitrat als 1 : 1 -Salz oder physikalische Mischungen aus Kreatin und Citronensäure enthalten, sind aus der Patentschrift US 5,925,378 bekannt.Effervescent formulations which contain creatine citrate as a 1: 1 salt or physical mixtures of creatine and citric acid are known from US Pat. No. 5,925,378.
Viele Kreatin-Salze, wie u.a. die Kreatin-pyruvate, -ascorbate aber auch die - citrate, besitzen wertvolle physiologische, therapeutische und diätetische Eigenschaften. Die meisten der bekannten Kreatin-Salze finden beispielsweise Anwendung zur Steigerung der Ausdauer und Kraft im Sportbereich, zur Gewichts- und Körperfettreduzierung sowie als Schutzsubstanz für Körperzellen und -gewebe, insbesondere des kardiovaskulären, hepatischen, nephrotischen, peritonealen und neuronalen Gewebes, als Substanz zur Inhibition der Radikalbildung sowie als Radikalfängersubstanz in Körperzellen und -geweben (auch Synovialgewebe), des Weiteren im Gesundheitsbereich und als Nahrungsergänzungsmittel.Many creatine salts, such as The creatine pyruvates and ascorbates as well as the citrates have valuable physiological, therapeutic and dietary properties. Most of the known creatine salts are used, for example, to increase endurance and strength in sports, to reduce weight and body fat, and as a protective substance for body cells and tissues, in particular cardiovascular, hepatic, nephrotic, peritoneal and neuronal tissue, as a substance for inhibition radical formation and as a radical scavenger substance in body cells and tissues (also synovial tissue), furthermore in the health sector and as a food supplement.
Typisch für die physikalischen Eigenschaften vieler Kreatin-Salze sind die Kreatin-pyruvate, die als Reinsubstanz bei Temperaturen unter 40 °C stabile Verbindungen darstellen. Setzt man Kreatin-pyruvate jedoch Temperaturen oberhalb 40 °C aus oder stellt man Kreatin-pyruvate enthaltende Formulierungen unter Zusatz bestimmter nicht-stabilisierend wirkender Substanzen her, so ist ein rascher Zerfall der Kreatin-pyruvate zu beobachten.Typical of the physical properties of many creatine salts are the creatine pyruvates, which as stable substances are stable compounds at temperatures below 40 ° C. However, if creatine pyruvate is exposed to temperatures above 40 ° C or if formulations containing creatine pyruvate are produced with the addition of certain non-stabilizing substances, a rapid disintegration of the creatine pyruvate can be observed.
Somit ist die Lagerstabilität der Kreatin-pyruvate wie auch anderer Salze von Kreatin mit insbesondere organischen Säuren vor allem bei höheren Temperaturen meist nicht sehr ausgeprägt, was wohl auch darauf zurückzuführen ist, dass beispielsweise die Pyruvate instabile 2-Oxocarbonsäure-Salze darstellen und sich darüber hinaus die meisten der
bekannten Salze des Kreatins leicht unter Bildung von Kreatinin zersetzen. Da Kreatin zudem als inneres Salz vorliegt und nur eine schwache Base darstellt, wird die Lagerstabilität vor allem über einen längeren Zeitraum negativ beeinflusst. Insbesondere Kombinationen von Kreatin- Verbindungen, wie beispielsweise den Citraten mit zu Instabilität neigenden Verbindungen, führen aus diesen Gründen zu Qualitätseinbußen.The storage stability of the creatine pyruvates, like other salts of creatine with organic acids in particular, is usually not very pronounced, especially at higher temperatures, which is probably also due to the fact that, for example, the pyruvates are unstable 2-oxocarboxylic acid salts and more the most of decompose known salts of creatine easily to form creatinine. Since creatine is also present as an inner salt and is only a weak base, the storage stability is negatively influenced, especially over a longer period. In particular, combinations of creatine compounds, such as, for example, citrates with compounds that tend to be unstable, lead to quality losses for these reasons.
Aus WO 98/28263 sind Pyruvate in Form von lagerstabilen Kreatin- Verbindungen bekannt, die in physiologisch verträglichen Zusammensetzungen neben pharmazeutischen Formulierungshilfsmitteln u.a. auch mit Kohlenhydraten, wie Glucose, Dextrose und Maltose, kombiniert sein können.WO 98/28263 discloses pyruvates in the form of storage-stable creatine compounds which, in addition to pharmaceutical formulation auxiliaries and others, are available in physiologically compatible compositions. can also be combined with carbohydrates such as glucose, dextrose and maltose.
Kombinationen von u.a. Kreatin-pyruvaten mit Kohlenhydraten, wie Saccharose, Fructose, Glucose und Aspartam, die als Süßungsmittel fungieren, sind aus US 5,886,040 bekannt.Combinations of Creatine pyruvates with carbohydrates, such as sucrose, fructose, glucose and aspartame, which act as sweeteners, are known from US 5,886,040.
Kreatin enthaltende Formulierungen, bestehend aus einem Neurotransmitter, -Liponsäure und gegebenenfalls L-Camitin, Coenzym Q und weiteren physiologisch aktiven Zusätzen, wie z.B. Zuckern, beschreibt DE-OS 1 98 30 768, wobei diese Formulierungen insbesondere Kreatin- pyruvat enthalten können und u.a. auch lagerstabil sein sollen.Formulations containing creatine, consisting of a neurotransmitter, lipoic acid and optionally L-camitin, coenzyme Q and other physiologically active additives, such as e.g. Sugars, describes DE-OS 1 98 30 768, which formulations can contain, in particular, creatine pyruvate and, inter alia, should also be stable in storage.
Schließlich offenbart DE-OS 1 98 36 450 stabile Brenztraubensäure(-Salze)- enthaltende Formulierungen für die Tierernährung, die neben drei weiteren Komponenten-Gruppen auch physiologisch wertvolle Zusatzstoffe, wie Kohlenhydrate, enthalten. Als weitere Komponenten werden organische Säuren, wie z.B. Citronensäure, und Aminocarbonsäuren, wie z.B. das Kreatin, vorgeschlagen. Bevorzugtes Brenztraubensäure-Salz ist das Kreatin-pyruvat.
Aus den vier letztgenannten Dokumenten sind nun zwar Kombinationen von Kreatin-Salzen mit Kohlenhydraten bekannt und es sind auch Formulierungen beschrieben, die u.a. Kreatin, Citronensäure sowie Kohlenhydrate enthalten können. Es findet sich jedoch kein Hinweis darauf, dass durch Zusammensetzungen, bestehend aus Kreatin und Citronensäure, die Lagerstabilität und weitere Eigenschaften verbessert werden können.Finally, DE-OS 1 98 36 450 discloses stable pyruvic acid (salts) - containing formulations for animal nutrition which, in addition to three further component groups, also contain physiologically valuable additives, such as carbohydrates. Organic acids such as citric acid and aminocarboxylic acids such as creatine are proposed as further components. The preferred pyruvic acid salt is the creatine pyruvate. Combinations of creatine salts with carbohydrates are now known from the last four documents, and formulations are also described which may contain creatine, citric acid and carbohydrates. However, there is no indication that compositions consisting of creatine and citric acid can improve storage stability and other properties.
Es bestand daher die Aufgabe, Zusammensetzungen(en) in leicht dosierbarer Form zu entwickeln, bei denen die Nachteile des Standes der Technik zumindest teilweise beseitigt sind.The object was therefore to develop compositions (s) in an easily metered form in which the disadvantages of the prior art are at least partially eliminated.
Gelöst wurde diese Aufgabe durch eine feste und stabile Kreatin/ Citronensäure-Zusammensetzung(en) und Kohlenhydrat(e) bzw. deren Hydrate enthaltende Formulierung mit einem Gewichtsverhältnis der Bestandteile Kreatin/Citronensäure-Zusammensetzung(en) und Kohlenhydrat(e) von 1 :0,01 bis 1 ,0.This problem was solved by a solid and stable creatine / citric acid composition (s) and carbohydrate (s) or a formulation containing their hydrates with a weight ratio of the components creatine / citric acid composition (s) and carbohydrate (s) of 1: 0 , 01 to 1, 0.
Es wurde nun überraschenderweise gefunden, dass Kreatin/Citronensäure- Zusammensetzung(en), wenn sie mit Kohlenhydraten formuliert werden, sogar bei Zusatz von instabilen und/oder instabilisierend wirkenden weiteren Verbindungen extrem temperatur- und lagerstabil werden. Diese erhöhte Lagerstabilität auch bei erhöhten Temperaturen von z.B. 30 °C und insbesondere > 35 °C auch für eine lange Zeitdauer zeigt sich durch eine verringerte Bildung von Kreatinin als Abbauprodukt. Vorzugsweise besitzen die erfindungsgemäßen Formulierungen nach Lagerung bei 40 °C für 28 d einen Kreatinin-Gehalt von ≤500 ppm, besonders bevorzugt von <350 ppm.It has now surprisingly been found that creatine / citric acid composition (s), when formulated with carbohydrates, become extremely temperature- and storage-stable even when other unstable and / or unstabilizing compounds are added. This increased storage stability even at elevated temperatures of e.g. 30 ° C and in particular> 35 ° C even for a long period of time is shown by a reduced formation of creatinine as a degradation product. After storage at 40 ° C. for 28 days, the formulations according to the invention preferably have a creatinine content of 500 500 ppm, particularly preferably of <350 ppm.
Die erfindungsgemäße Formulierung ermöglicht somit eine wesentlich längere Lagerfähigkeit der in Frage kommenden Zusammensetzungen, bestehend aus Kreatin und Citronensäure, sowie eine erhöhte Belastbarkeit
hinsichtlich Temperatur und Dauer sowohl bei der Verarbeitung als auch der Lagerung, was sie u.a. beispielsweise neuen Herstellungs- und/oder Formulierungs-Verfahren zugänglich macht.The formulation according to the invention thus enables the compositions in question, consisting of creatine and citric acid, to be stored for a significantly longer time, as well as an increased resilience with regard to temperature and duration, both during processing and storage, which makes them accessible, for example, to new production and / or formulation processes.
Da diese Kreatin/Citronensäure-Zusammensetzung(en) enthaltenden Formulierungen aufgrund ihrer Stabilität einen erheblich verringerten Anteil an unerwünschten Abbau- und Nebenprodukten und physiologisch ungeeigneten Bestandteilen haben, können sie sehr gut dosiert werden und besitzen eine hohe Verträglichkeit.Since these formulations containing creatine / citric acid composition (s) have a considerably reduced proportion of undesirable degradation and by-products and physiologically unsuitable constituents due to their stability, they can be dosed very well and are highly tolerated.
In der Praxis haben sich insbesondere solche Formulierungen als sehr geeignet erwiesen, deren Bestandteile Kreatin/ Citronensäure- Zusammensetzung(en) und Kohlenhydrat(e) im Gewichtsverhältnis 1 :0,01 bis 0,5 und ganz besonders bevorzugt im Gewichtsverhältnis von etwa 1 :0,1 vorliegen. Bevorzugte Ausführungsformen der beanspruchten Formulierungen weisen einen Wassergehalt bis 30 Gew.-% auf.In practice, such formulations have proven to be particularly suitable, the components of which are creatine / citric acid composition (s) and carbohydrate (s) in a weight ratio of 1: 0.01 to 0.5 and very particularly preferably in a weight ratio of about 1: 0 , 1 are present. Preferred embodiments of the claimed formulations have a water content of up to 30% by weight.
Als besonders geeignete Kreatin-Komponenten haben sich solche bewährt, die als Kreatin/Citronensäure-Zusammensetzung(en) physiologisch verträgliche Salze, Anlagerungen und Komplexe im Molverhältnis Kreatin zu Citronensäure von 1 ,0 bis 3,0: 1 ,0 enthalten. Es kommen dabei u.a. auch Kreatin/Citronensäure-Verbindungen in Frage, die labil auf äußere Einflüsse reagieren. Aber auch deren Kombinationen mit stabilen Kreatin/ Citronensäure-Zusammensetzungen sind von der Erfindung umfasst.Creatine components which have proven particularly suitable are those which, as creatine / citric acid composition (s), contain physiologically tolerable salts, deposits and complexes in a molar ratio of creatine to citric acid of 1.0 to 3.0: 1.0. Among other things, also creatine / citric acid compounds that are unstable to external influences. However, their combinations with stable creatine / citric acid compositions are also encompassed by the invention.
Zur Stabilisierung der Formulierungen können prinzipiell beliebige Kohlenhydrate, z.B. alle Polyhydroxyaldehyde (Aldosen) und Polyhydroxyketone (Ketosen) sowie deren Derivate, herangezogen werden. Gemäß vorliegender Erfindung haben sich aber besonders die Aldo- und Ketohexosen sowie die davon abgeleiteten Oligo- oder Polysaccharide und deren O-glykosidischen Derivate bewährt. Insbesondere Monosaccharide, wie beispielsweise Glucose, Fructose, Ribose und Sorbit, und/oder
cyclische und offenkettige Oligohexosen mit 2 bis 10 Monomeren- Einheiten, wie die Saccharose, Lactose und Maltose, aber auch Polysaccharide mit 1 1 bis 106 Monomeren-Einheiten, wie z. B. Inulin, Arabino-galactan, Maltodextrine, Stärke, Chitosan und Glycogen, sind bevorzugt. Wichtig ist, dass auch beliebige Mischungen von Kohlenhydraten eingesetzt werden können.In principle, any carbohydrates, for example all polyhydroxy aldehydes (aldoses) and polyhydroxy ketones (ketoses) and their derivatives, can be used to stabilize the formulations. According to the present invention, however, the aldo- and ketohexoses and the oligo- or polysaccharides derived therefrom and their O-glycosidic derivatives have proven particularly useful. In particular monosaccharides, such as glucose, fructose, ribose and sorbitol, and / or cyclic and open-chain oligohexoses with 2 to 10 monomer units, such as sucrose, lactose and maltose, but also polysaccharides with 1 1 to 10 6 monomer units, such as. B. inulin, arabino-galactan, maltodextrins, starch, chitosan and glycogen are preferred. It is important that any mixture of carbohydrates can be used.
Die vorliegende Erfindung berücksichtigt aber auch Formulierungen, die neben den erfindungswesentlichen Komponenten zusätzlich weitere Kreatin enthaltende Zusammensetzungen, insbesondere Kreatin-Salze, wie Kreatin-pyruvate und - ascorbate, enthalten. Aber auch Proteine, wie z.B. Kollagen oder Molkepulver, und geeignete Säuren, wie beispielsweise die Ascorbinsäure, können die stabilisierende Wirkung der Kohlenhydrat- Komponente unterstützen.However, the present invention also takes into account formulations which, in addition to the components essential to the invention, additionally contain other creatine-containing compositions, in particular creatine salts, such as creatine pyruvates and ascorbates. But also proteins, e.g. Collagen or whey powder, and suitable acids, such as, for example, ascorbic acid, can support the stabilizing effect of the carbohydrate component.
Als besonders geeignet haben sich Formulierungen erwiesen, die nach folgenden Verfahren hergestellt werden: Gemäß einer ersten Ausführungsform werden die Kohlenhydrat(e) in Form von Lösungen, Suspensionen oder als Festsubstanz mit der Kreatin/Citronensäure- Zusammensetzung im Temperaturbereich von -20 bis 120 °C und bevorzugt zwischen 10 und 90 °C umgesetzt, worauf die erhaltene Lösung gegebenenfalls abschließend von der flüssigen Phase befreit wird, was vorzugsweise durch Fest-/Flüssig-Trennung, Destillation, Eindampfen und/oder Einengen jeweils im Vakuum, Sprühtrocknung oder Gefriertrocknung erfolgt oder durch jede andere geeignete Trennmethode. Gemäß einer zweiten Ausführungsform wird ein Gemenge, bestehend aus der sauren Kreatin/Citronensäure-Komponente oder deren Lösung und der festen Kohlenhydrat-Komponente, im Temperaturbereich von -20 bis 120 °C einer thermischen Behandlung, einer Behandlung mit Ultraschall und/oder Mikrowelle unterzogen, was auch im Vakuum erfolgen kann, und zur Bildung homogener Formulierungen führt.
Alle diese Umsetzungen können in Gegenwart eines Löse- oder Verdünnungsmittels durchgeführt werden oder auch lösemittelfrei. Als geeignete Löse- oder Verdünnungsmittel haben sich für die Herstellung der beanspruchten Aggregate alle gängigen Lösemittel erwiesen, wie Wasser, Alkohole, Ether, Ketone, Ester, organische Säuren, aliphatische und aromatische Kohlenwasserstoffe.Formulations which have been found to be particularly suitable have been prepared by the following processes: According to a first embodiment, the carbohydrate (s) are in the form of solutions, suspensions or as a solid substance with the creatine / citric acid composition in the temperature range from -20 to 120 ° C. and preferably implemented between 10 and 90 ° C., whereupon the solution obtained is optionally finally freed from the liquid phase, which is preferably carried out by solid / liquid separation, distillation, evaporation and / or concentration in each case in vacuo, spray drying or freeze drying or by any other suitable separation method. According to a second embodiment, a mixture consisting of the acidic creatine / citric acid component or its solution and the solid carbohydrate component is subjected to a thermal treatment, a treatment with ultrasound and / or a microwave in the temperature range from -20 to 120 ° C. which can also be done in a vacuum and leads to the formation of homogeneous formulations. All of these reactions can be carried out in the presence of a solvent or diluent or also solvent-free. All common solvents, such as water, alcohols, ethers, ketones, esters, organic acids, aliphatic and aromatic hydrocarbons, have proven to be suitable solvents or diluents for the production of the aggregates claimed.
Selbstverständlich können die gewünschten Formulierungen auch durch das bloße trockene Abmischen der Komponenten erhalten werden.Of course, the desired formulations can also be obtained simply by mixing the components dry.
Erfindungsgemäß kann die Kohlenhydrat-Komponente zur Bildung der Formulierung in wasserfreier Form, als Hydrat oder als feuchtes Produkt eingesetzt werden. Die saure Kreatin-Salz-Komponente kann ebenfalls in wasserfreier Form, in wässriger Lösung oder gelöst in einem der bereits genannten alkoholischen oder organischen Löse- oder Verdünnungsmittel eingesetzt werden. Alle beanspruchten Umsetzungsvarianten können in den bekannten verfahrenstechnischen Apparaten, wie in Knetern, Mischern, Schaufeltrocknern, Rührbehältern sowie Sprühtrocknern, erfolgen.According to the invention, the carbohydrate component can be used to form the formulation in anhydrous form, as a hydrate or as a moist product. The acidic creatine salt component can also be used in anhydrous form, in aqueous solution or dissolved in one of the alcoholic or organic solvents or diluents already mentioned. All of the claimed implementation variants can be carried out in the known process engineering apparatuses, such as in kneaders, mixers, paddle dryers, stirred tanks and spray dryers.
Die erfindungsgemäßen Kreatin/Citronensäure-Zusammensetzung(en) und Kohlenhydrat enthaltende Formulierungen werden so ohne weitere notwendige Reinigungsschritte in hoher Ausbeute und Reinheit erhalten.The creatine / citric acid composition (s) and carbohydrate-containing formulations according to the invention are thus obtained in high yield and purity without further necessary cleaning steps.
Die vorliegende Erfindung sieht somit vor, dass entweder beide Ausgangskomponenten in fester oder in flüssiger Form eingesetzt werden oder dass eine Komponente fest und die andere flüssig ist. Zu beachten ist lediglich, dass für die erfindungsgemäßen Formulierungen die Kreatin/ Citronensäure-Komponente und die Kohlenhydrat-Komponente stets im Rahmen der beanspruchten Gewichtsverhältnisse eingesetzt werden.The present invention thus provides that either both starting components are used in solid or in liquid form or that one component is solid and the other is liquid. It should only be noted that for the formulations according to the invention the creatine / citric acid component and the carbohydrate component are always used within the claimed weight ratios.
Aufgrund ihrer vorzüglichen Eigenschaften finden die erfindungsgemäßen Formulierungen Verwendung für pharmazeutische Zwecke oder in der
Nahrungsmittelindustrie, z.B. zur Steigerung der Ausdauer und Kraft im Sportbereich, zur Gewichts- und Körperfettreduzierung sowie als Schutzsubstanz für Körperzellen und -gewebe, besonders kardiovaskuläre, hepatische, ophthalmische, nephrotische und neuronale sowie Transplantat-Gewebe, und als Substanz zur Inhibition der Radikalbildung sowie als Radikalfängersubstanz in Körperzellen und -geweben (auch Synovialgewebe), im Gesundheitsbereich, insbesondere bei der Behandlung von Fettsucht und Übergewicht, bei Hautstörungen, zur Wundheilung und zur Blutdruckabsenkung sowie bei Befindlichkeitsstörungen bei Frauen, die vor allem durch Veränderungen des weiblichen Sexualhormonhaushaltes verursacht werden, wie z.B. Erscheinungsformen des prämenstruellen Syndroms (PMS), der Dysmenorrhoe, des Klimakteriums, bei Wetterfühligkeit, Migräne, Spannungskopfschmerz, Schlaflosigkeit und gestörten Gemütszuständen, und als Nahrungsergänzungszusatz. Auch die Verwendung der Aggregate in der Tierernährung ist gemäß Erfindung vorgesehen.Because of their excellent properties, the formulations according to the invention are used for pharmaceutical purposes or in Food industry, e.g. for increasing endurance and strength in sports, for reducing weight and body fat as well as a protective substance for body cells and tissues, especially cardiovascular, hepatic, ophthalmic, nephrotic and neuronal and transplant tissues, and as a substance for inhibiting radical formation and as Radical scavenger substance in body cells and tissues (also synovial tissue), in the health sector, in particular in the treatment of obesity and obesity, in the case of skin disorders, for wound healing and for lowering blood pressure, as well as in mental disorders in women, which are mainly caused by changes in the female sex hormone balance, such as Symptoms of premenstrual syndrome (PMS), dysmenorrhea, menopause, weather sensitivity, migraines, tension headache, insomnia and disturbed mood, and as a nutritional supplement. The use of the aggregates in animal nutrition is also provided according to the invention.
Die erfindungsgemäßen Formulierungen können in Form von Tabletten, Pulvern, Dragees, Kapseln, Getränken und Gelees und insbesondere als Brausetabletten und Brausepulver verabreicht werden, wobei diese Reihe beliebig verlängert werden kann.The formulations according to the invention can be administered in the form of tablets, powders, dragees, capsules, drinks and jellies and in particular as effervescent tablets and effervescent powder, this series being able to be extended as desired.
Die vorliegende Erfindung stellt somit einen wichtigen Fortschritt in der Anwendung von Kreatin/Citronensäure-Zusammensetzungen im therapeutischen und diätetischen Bereich sowie in der Sportmedizin dar. Aufgrund des Standes der Technik konnte nämlich nicht erwartet werden, dass feste und lagerstabile Kreatin/Citronensäure-Zusammensetzung(en) und Kohlenhydrat enthaltende Formulierungen mit einfachen Methoden zugänglich sind und zu leicht dosierbaren Produkten führen. Darüber hinaus hat sich gezeigt, dass die Kreatin/Citronensäure-Zusammensetzungen bei der Bereitung der Formulierungen keine, höchstens aber nur sehr geringfügige Kondensations- und Zersetzungsreaktionen eingehen. Des
Weiteren gelingt die Herstellung der beanspruchten Kreatin/Citronensäure- Zusammensetzung(en) und Kohlenhydrat enthaltende Formulierungen ohne eine anschließend notwendige Aufarbeitung. Auch können wässrige Lösungen, enthaltend die Kreatin-Komponente oder Lösemittel, eingesetzt werden, wobei dann Formulierungen mit definierten Kristallwassergehalten erhalten werden.The present invention thus represents an important advance in the use of creatine / citric acid compositions in the therapeutic and dietetic field and in sports medicine. Because of the prior art, it was not to be expected that solid and storage-stable creatine / citric acid composition (s ) and carbohydrate-containing formulations are accessible with simple methods and lead to easy-to-dose products. In addition, it has been shown that the creatine / citric acid compositions do not undergo any condensation and decomposition reactions, but at most only very slight, when preparing the formulations. Of Furthermore, the claimed creatine / citric acid composition (s) and carbohydrate-containing formulations can be produced without subsequent work-up. Aqueous solutions containing the creatine component or solvent can also be used, in which case formulations with defined crystal water contents are obtained.
Festzuhalten bleibt, dass die vorliegende Erfindung insbesondere mit den ebenfalls beanspruchten Herstellungsvarianten keine bloßen Abmischungen der erfindungswesentlichen Komponenten Kreatin/Citronensäure- Zusammensetzung(en) und Kohlenhydrat(e) umfasst, wie sie bereits aus dem Stand der Technik hinlänglich bekannt sind, sondern dass es sich bei den beanspruchten Formulierungen um tatsächliche physikalische oder chemische Reaktionsprodukte handelt.It should be noted that the present invention, in particular with the production variants also claimed, does not include mere mixtures of the components of the invention, creatine / citric acid composition (s) and carbohydrate (s), as are already well known from the prior art, but that it is the formulations claimed are actual physical or chemical reaction products.
Die nachfolgenden Beispiele verdeutlichen die Vorteile der vorliegenden Erfindung.The following examples illustrate the advantages of the present invention.
BeispieleExamples
Eine Kreatin-Citronensäure- Verbindung (3: 1 ) (KC) als Reinsubstanz und Mischungen dieser Verbindung (3: 1 ) mit 1 , 5 und 10 Gew.-% Zusatz eines Kohlenhydrats (KH) wurden 28 Tage bei 60 °C gelagert und anschließend die Gehalte des Kreatinzersetzungsprodukts Kreatinin bestimmt. Als Vergleich dienen die Ausgangsdaten der bei Kühlung bis Raumtemperatur (RT) stabilen Referenzsubstanz KC mit einem Kreatin-Gehalt von 67, 1 Gew.-% und einem Kreatinin-Gehalt von < 67 ppm (Nachweisgrenze) .
A creatine-citric acid compound (3: 1) (KC) as pure substance and mixtures of this compound (3: 1) with 1, 5 and 10 wt .-% addition of a carbohydrate (KH) were stored at 60 ° C for 28 days and then the contents of the creatine decomposition product creatinine determined. The starting data for the reference substance KC, which is stable when cooled to room temperature (RT), with a creatine content of 67.1% by weight and a creatinine content of <67 ppm (detection limit) serve as a comparison.
Claims
1 . Formulierung, die als Bestandteile eine feste und stabile Kreatin/ Citronensäure-Zusammensetzung und eine Kohlenhydrat- Komponente bzw. deren Hydrate enthält, dadurch gekennzeichnet, dass das Gewichtsverhältnis der Bestandteile Kreatin/ Citronensäure- Zusammensetzung und Kohlenhydrat von 1 :0,01 bis 1 ,0 ist.1 . Formulation which contains as components a solid and stable creatine / citric acid composition and a carbohydrate component or their hydrates, characterized in that the weight ratio of the components creatine / citric acid composition and carbohydrate of 1: 0.01 to 1.0 is.
2. Formulierung nach Anspruch 1 , dadurch gekennzeichnet, dass die Kreatin/Citronensäure-Zusammensetzung und die Kohlenhydrat-Komponente im Gewichtsverhältnis 1 :0,01 bis 0,5, vorzugsweise im Gewichtsverhältnis 1 :0, 1 vorliegen.2. Formulation according to claim 1, characterized in that the creatine / citric acid composition and the carbohydrate component are present in a weight ratio of 1: 0.01 to 0.5, preferably in a weight ratio of 1: 0.1.
3. Formulierung nach Anspruch 1 oder 2, dadurch gekennzeichnet, dass sie bis 30 Gew.-% Wasser enthält.3. Formulation according to claim 1 or 2, characterized in that it contains up to 30 wt .-% water.
4. Formulierung nach einem der Ansprüche 1 bis 3, dadurch gekennzeichnet, dass sie als Kreatin/Citronensäure-Zusammensetzung physiologisch verträgliche Salze, Anlagerungen und Komplexe im Molverhältnis Kreatin zu Citronensäure von 1 ,0 bis 3,0: 1 ,0 enthält.4. Formulation according to one of claims 1 to 3, characterized in that it contains, as creatine / citric acid composition, physiologically compatible salts, additions and complexes in a molar ratio of creatine to citric acid of 1.0 to 3.0: 1.0.
5. Formulierung nach einem der Ansprüche 1 bis 4, dadurch gekennzeichnet, dass sie als Kohlenhydrat-Komponente Polyhydroxyaldehyde und/oder Polyhydroxyketone enthält. 5. Formulation according to one of claims 1 to 4, characterized in that it contains as the carbohydrate component polyhydroxy aldehydes and / or polyhydroxy ketones.
6. Formulierung nach einem der Ansprüche 1 bis 5, dadurch gekennzeichnet, dass sie als Kohlenhydratkomponente Aldohexosen und/oder Ketohexosen, insbesondere deren Oligosaccharide, Polysaccharide und/oder O-glykosidische Derivate enthält.6. Formulation according to one of claims 1 to 5, characterized in that it contains aldohexoses and / or ketohexoses, in particular their oligosaccharides, polysaccharides and / or O-glycosidic derivatives as carbohydrate component.
7. Formulierung nach einem der Ansprüche 1 bis 6, dadurch gekennzeichnet, dass sie als Kohlenhydrat-Komponente Monosaccharide, wie beispielsweise Glucose, Fructose, Ribose und Sorbit, und/oder cyclische und offenkettige Oligohexosen mit 2 bis 10 Monomeren-Einheiten, wie beispielsweise Saccharose, Lactose und Maltose, und/oder Polysaccharide mit 1 1 bis 106 Monomeren- Einheiten, wie z.B. Inulin, Arabino-galactan, Maltodextrine, Stärke, Chitosan oder Glykogen, enthält.7. Formulation according to one of claims 1 to 6, characterized in that it contains, as carbohydrate component, monosaccharides, such as, for example, glucose, fructose, ribose and sorbitol, and / or cyclic and open-chain oligohexoses with 2 to 10 monomer units, such as, for example, sucrose , Lactose and maltose, and / or polysaccharides with 1 1 to 10 6 monomer units, such as inulin, arabinogalactan, maltodextrins, starch, chitosan or glycogen, contains.
8. Formulierung nach den Ansprüchen 1 bis 7, dadurch gekennzeichnet, dass sie zusätzlich weitere Kreatin-Zusammensetzungen, besonders bevorzugt Kreatin-Salze, wie Kreatin-pyruvate und - ascorbate, und/oder eine Protein- und/oder eine Säure-Komponente, wie Kollagen oder Ascorbinsäure, enthält.8. Formulation according to claims 1 to 7, characterized in that it additionally other creatine compositions, particularly preferably creatine salts, such as creatine pyruvate and - ascorbate, and / or a protein and / or an acid component, such as Contains collagen or ascorbic acid.
9. Verfahren zur Herstellung einer Formulierung nach einem der Ansprüche 1 bis 8, dadurch gekennzeichnet, dass die Kohlenhydrat-Komponente in Form einer Lösung oder Suspension oder als Festsubstanz mit der Kreatin/Citronensäure- Zusammensetzung im Temperaturbereich von -20 bis 1 20 °C, vorzugsweise zwischen 10 und 90 °C, umgesetzt wird und abschließend die flüssige Phase entfernt wird. 9. A method for producing a formulation according to one of claims 1 to 8, characterized in that the carbohydrate component in the form of a solution or suspension or as a solid substance with the creatine / citric acid composition in the temperature range from -20 to 1 20 ° C, preferably between 10 and 90 ° C, and finally the liquid phase is removed.
10. Verfahren nach Anspruch 9, dadurch gekennzeichnet, dass die flüssige Phase durch Fest-/Flüssig-Trennung, Destillation, Eindampfen und/oder Einengen jeweils im Vakuum, Sprühtrocknung oder Gefriertrocknung entfernt wird.10. The method according to claim 9, characterized in that the liquid phase is removed by solid / liquid separation, distillation, evaporation and / or concentration in each case in vacuo, spray drying or freeze drying.
1 1 . Verfahren zur Herstellung einer Formulierung nach einem der Ansprüche 1 bis 8 durch thermische Behandlung, Behandlung mit Ultraschall oder Mikrowelle von Gemengen, bestehend aus der Kreatin/Citronensäure-Zusammensetzung oder deren Lösung und der festen Kohlenhydrat-Komponente im Temperaturbereich von -20 bis 1 20 °C.1 1. Process for the preparation of a formulation according to any one of claims 1 to 8 by thermal treatment, treatment with ultrasound or microwave of mixtures consisting of the creatine / citric acid composition or its solution and the solid carbohydrate component in the temperature range from -20 to 1 20 ° C.
1 2. Verfahren nach Anspruch 1 1 , dadurch gekennzeichnet, dass die Behandlung unter Vakuum erfolgt.1 2. The method according to claim 1 1, characterized in that the treatment is carried out under vacuum.
13. Verfahren nach einem der Ansprüche 8 bis 12, dadurch gekennzeichnet, dass die Kohlenhydrat-Komponente in wasserfreier Form, als13. The method according to any one of claims 8 to 12, characterized in that the carbohydrate component in anhydrous form, as
Hydrat(e) oder feuchte(s) Produkt(e) eingesetzt wird.Hydrate (s) or moist (s) product (s) is used.
14. Verfahren nach einem der Ansprüche 8 bis 1 3, dadurch gekennzeichnet, dass die Kreatin/Citronensäure-Zusammensetzung in wasserfreier14. The method according to any one of claims 8 to 1 3, characterized in that the creatine / citric acid composition in anhydrous
Form oder in wässriger, alkoholischer oder organischer Lösung eingesetzt wird. Form or used in aqueous, alcoholic or organic solution.
1 5. Verfahren nach einem der Ansprüche 8 bis 14, dadurch gekennzeichnet, dass als Lösemittel Wasser, Alkohole, Ether, Ketone, Ester, organische Säuren und aliphatische oder aromatische Kohlenwasserstoffe sowie Mischungen daraus eingesetzt werden.1 5. The method according to any one of claims 8 to 14, characterized in that water, alcohols, ethers, ketones, esters, organic acids and aliphatic or aromatic hydrocarbons and mixtures thereof are used as solvents.
1 6. Verfahren nach einem der Ansprüche 9 bis 1 5, dadurch gekennzeichnet, dass die Herstellung in Knetern, Mischern, Schaufeltrocknern, Rührbehältern oder Sprühtrocknern durchgeführt wird.1 6. The method according to any one of claims 9 to 1 5, characterized in that the production is carried out in kneaders, mixers, paddle dryers, stirred tanks or spray dryers.
1 7. Verwendung der Formulierung nach einem der Ansprüche 1 bis 8 zur Herstellung eines Präparates zur pharmazeutischen Anwendung oder als Nahrungsergänzungszusatz.1 7. Use of the formulation according to any one of claims 1 to 8 for the manufacture of a preparation for pharmaceutical use or as a nutritional supplement.
18. Verwendung nach Anspruch 1 7 zur Steigerung der Ausdauer und Kraft im Sportbereich, zur Gewichts- und Körperfettreduzierung sowie als Schutzsubstanz für Körperzellen und -gewebe, besonders kardiovaskuläre, hepatische, ophthalmische, nephrotische und neuronale sowie Transplantat-Gewebe, und als Substanz zur18. Use according to claim 1 7 to increase endurance and strength in sports, for weight and body fat reduction and as a protective substance for body cells and tissues, especially cardiovascular, hepatic, ophthalmic, nephrotic and neuronal and graft tissue, and as a substance for
Inhibition der Radikalbildung sowie als Radikalfängersubstanz in Körperzellen und -geweben (auch Synovialgewebe), im Gesundheitsbereich, insbesondere bei der Behandlung von Fettsucht und Übergewicht, bei Hautstörungen, zur Wundheilung und zur Blutdruckabsenkung sowie bei Befindlichkeitsstörungen bei Frauen, wie z.B. Erscheinungsformen des prämenstruellen Syndroms (PMS), der Dysmenorrhoe, des Klimakteriums, bei Wetterfühligkeit, Migräne, Spannungskopfschmerz, Schlaflosigkeit und gestörten Gemütszuständen, als Nahrungsergänzungszusatz sowie in der Tierernährung. Inhibition of radical formation and as a radical scavenger substance in body cells and tissues (also synovial tissue), in the health sector, in particular in the treatment of obesity and obesity, in skin disorders, for wound healing and for lowering blood pressure, as well as in mental disorders in women, such as manifestations of premenstrual syndrome (PMS ), dysmenorrhea, menopause, weather sensitivity, migraines, tension headaches, insomnia and disturbed moods, as a nutritional supplement and in animal nutrition.
9. Verwendung nach Anspruch 17 oder 18 in Form von Tabletten, Pulvern, Dragees, Kapseln, Getränken und Gelees, insbesondere als Brausetabletten und Brausepulver. 9. Use according to claim 17 or 18 in the form of tablets, powders, dragees, capsules, drinks and jellies, in particular as effervescent tablets and effervescent powder.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10159244 | 2001-12-03 | ||
| DE10159244A DE10159244A1 (en) | 2001-12-03 | 2001-12-03 | Solid and stable creatine / citric acid composition (s) and carbohydrate (s) or their formulation containing hydrates, process for their preparation and their use |
| PCT/EP2002/013518 WO2003047367A1 (en) | 2001-12-03 | 2002-11-29 | Solid and stable creatine/citric acid composition(s) and compositions containing carbohydrate(s) or hydrates thereof, method for the production and use thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP1450629A1 true EP1450629A1 (en) | 2004-09-01 |
Family
ID=7707821
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP02785417A Ceased EP1450629A1 (en) | 2001-12-03 | 2002-11-29 | Solid and stable creatine/citric acid composition(s) and compositions containing carbohydrate(s) or hydrates thereof, method for the production and use thereof |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US20050037069A1 (en) |
| EP (1) | EP1450629A1 (en) |
| JP (1) | JP2005510579A (en) |
| AU (1) | AU2002350718A1 (en) |
| DE (1) | DE10159244A1 (en) |
| WO (1) | WO2003047367A1 (en) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007133731A2 (en) * | 2006-05-11 | 2007-11-22 | Avicena Group, Inc. | Creatine-ligand compounds and methods of use thereof |
| US20080197213A1 (en) * | 2007-02-20 | 2008-08-21 | Flashinski Stanley J | Active material diffuser and method of providing and using same |
| US20110123654A1 (en) * | 2008-06-06 | 2011-05-26 | Ralf Jaeger | Synergistic enhancement of cellular ergogenic nutrient uptake, like creatine or carnitine, with tarragon |
| DE102010045366A1 (en) * | 2010-09-14 | 2012-03-15 | Ozren König | Treating and preventing migraine and migraine/cluster-like headaches, comprises administering creatine derivatives |
| GB201107308D0 (en) * | 2011-05-03 | 2011-06-15 | Gorman Edward O | Oral rehydration products comprising creatine |
| US9233099B2 (en) | 2012-01-11 | 2016-01-12 | University Of Cincinnati | Methods of treating cognitive dysfunction by modulating brain energy metabolism |
| EP2918177B1 (en) * | 2014-03-11 | 2019-02-27 | Third of Life GmbH | Food supplement for sleep optimisation |
| ES2633360T3 (en) * | 2014-04-02 | 2017-09-20 | Alzchem Ag | Creatine and protein matrix as well as procedure for the production of this matrix |
| DE102022114966A1 (en) * | 2022-06-14 | 2023-12-14 | Alzchem Trostberg Gmbh | Water-soluble creatine agglomerate |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9611356D0 (en) * | 1996-05-31 | 1996-08-07 | Howard Alan N | Improvements in or relating to compositions containing Creatine, and other ergogenic compounds |
| US6274161B1 (en) * | 1996-05-31 | 2001-08-14 | The Howard Foundation | Compositions containing creatine in suspension |
| US5925378A (en) * | 1997-03-31 | 1999-07-20 | Fortress Systems, L.L.C. | Method for enhancing delivery and uniformity of concentration of cellular creatine |
| DE19836450A1 (en) * | 1998-08-12 | 2000-02-17 | Sueddeutsche Kalkstickstoff | Stable animal feed formulation containing pyruvic acid, e.g. supplement for horse, dog and cat, also contains aminoacid, other organic acid and/or physiologically valuable additive |
| US6242491B1 (en) * | 1999-06-25 | 2001-06-05 | Rima Kaddurah-Daouk | Use of creatine or creatine compounds for skin preservation |
| DE10017102A1 (en) * | 2000-04-06 | 2001-10-11 | Basf Ag | Process for the manufacture of solid creatine dosage forms and dosage forms obtainable thereby |
| US6211407B1 (en) * | 2000-05-03 | 2001-04-03 | Pfanstiehl Laboratories, Inc. | Dicreatine citrate and tricreatine citrate and method of making same |
| DE10065478C1 (en) * | 2000-12-28 | 2002-08-29 | Sueddeutsche Kalkstickstoff | Creatine / citric acid compound, process for its preparation and use |
-
2001
- 2001-12-03 DE DE10159244A patent/DE10159244A1/en not_active Withdrawn
-
2002
- 2002-11-29 US US10/495,827 patent/US20050037069A1/en not_active Abandoned
- 2002-11-29 JP JP2003548639A patent/JP2005510579A/en not_active Withdrawn
- 2002-11-29 EP EP02785417A patent/EP1450629A1/en not_active Ceased
- 2002-11-29 WO PCT/EP2002/013518 patent/WO2003047367A1/en not_active Application Discontinuation
- 2002-11-29 AU AU2002350718A patent/AU2002350718A1/en not_active Abandoned
Non-Patent Citations (1)
| Title |
|---|
| See references of WO03047367A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| DE10159244A1 (en) | 2003-06-18 |
| AU2002350718A1 (en) | 2003-06-17 |
| JP2005510579A (en) | 2005-04-21 |
| US20050037069A1 (en) | 2005-02-17 |
| WO2003047367A1 (en) | 2003-06-12 |
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