US20040157903A1 - Compositions based on amino acids for improving the myocardial ventricular function in patients suffering from diabetes - Google Patents
Compositions based on amino acids for improving the myocardial ventricular function in patients suffering from diabetes Download PDFInfo
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- US20040157903A1 US20040157903A1 US10/480,774 US48077403A US2004157903A1 US 20040157903 A1 US20040157903 A1 US 20040157903A1 US 48077403 A US48077403 A US 48077403A US 2004157903 A1 US2004157903 A1 US 2004157903A1
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- amino acids
- compositions
- threonine
- lysine
- active ingredients
- Prior art date
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
Definitions
- the present invention refers to compositions based on amino acids for improving the myocardial ventricular function in patients suffering from diabetes, in particular II type diabetes.
- the present invention has the aim of indicating an absolutely innovative therapeutic approach to the above mentioned problem.
- a first aim of the invention is that of indicating compositions capable of determining a noticeable improvement of the myocardial ventricular function in patients suffering from diabetes, particularly but not exclusively II type diabetes.
- a further aim of the invention is that of indicating compositions capable of determining, in patients of the above type, a noticeable increase of the ventricular ejection fraction, at rest and at peak of the isometric exercise.
- a further aim of the invention is that of indicating compositions capable of eliminating the reduction of the ventricular ejection fraction which, in patients suffering from diabetes, occurs during isometric strain.
- compositions being provided either for oral and parenteral use, are characterized by comprising, as main active ingredients, the branched chain amino acids leucine, isoleucine and valine, up to 75% of all the amino acids or active ingredients being present, by expressing the value in molecular weights.
- compositions according to the invention also comprise, as further active ingredients, threonine and/or lysine, where in particular threonine plus lysine are present up to 50% of all the amino acids or active ingredients being present, by expressing the value in molecular weights.
- compositions can provide for, as further active ingredients, other essential amino acids, in particular methionine and/or phenylalanine and/or histidine and/or tryphtophan, and non essential amino acids, in particular tyrosine and/or cyst(e)ine (i.e. cystine and cysteine).
- other essential amino acids in particular methionine and/or phenylalanine and/or histidine and/or tryphtophan
- non essential amino acids in particular tyrosine and/or cyst(e)ine (i.e. cystine and cysteine).
- the sum of the amounts expressed in molecular weights of threonine and lysine is greater than the sum of the single amounts of the other essential amino acids being provided, but in any case lower than the sum of the single amounts of the branched chain amino acids being provided.
- the amounts expressed in molecular weight of threonine and of lysine can be each greater than the single amounts of the other essential amino acids being provided, but in any case lower than the single quantities of the branched chain amino acids being provided.
- compositions according to the invention can also comprise one or more further amino acids, with respect to those as previously indicated, the sum of which, expressed in molecular weight, is preferably lower than 20% with respect to the active ingredients, and less than 10% for each single further amino acid.
- the pH of the solution of the mixture should be substantially neutral, in order to prevent urinary calcium losses
- the mixture should be safe, in respect to calcium balance (i.e.: with no urinary losses) and homocyst(e)ine production (i.e., preferably related to the amount of all amino acids, a strictly correct ratio of sulphur containing amino acids, with a ratio cyst(e)ine/methionine of at least 2:1 on a stoichiometric basis).
- homocyst(e)ine production i.e., preferably related to the amount of all amino acids, a strictly correct ratio of sulphur containing amino acids, with a ratio cyst(e)ine/methionine of at least 2:1 on a stoichiometric basis.
- the content of essential amino acids in the mixture should be preferably in an adequate ratio to fulfill real human nutritional needs (and this can be optimized by the co-operative adjunction of adequate and small ratios of some non essential amino acids).
- compositions according to the invention comprising essential amino acids (leucine, isoleucine, valine, threonine, lysine, methionine, phenylalanine, histidine, tryphtophan) and some non essential amino acids (tyrosine and cyst(e)ine), in different but fixed and co-operative molar ratios among them, is the following one:
- branched chain amino acids leucine 40-60% in molecular weight
- isoleucine 20-40% in molecular weight
- valine 20-40% in molecular weight
- threonine plus lysine preferably in a molar ratio with the said branched chain amino acids between 20 and 50%, preferably in a threonine to lysine ratio in which lysine is from 10 to 50% more represented than threonine;
- cyst(e)ine i.e., cystine and cysteine
- methionine up to 50% of histidine (the ratio between cyst(e)ine and methionine should be preferably of 50 to 200% greater for cyst(e)ine in molar ratio)
- phenylalanine and tyrosine in molar ratio up to 50% of histidine (in which tyrosine is preferably represented up to 50% of the molar weight of phenylalanine),
- tryphtophan up to 10% of the weight of all the other amino acids, on a molar weight basis.
- any other amino acid can be added to the above formulation, without altering the expected effects, provided that the sum of the additional amino acids is in a percentage lower than 20% with respect to the other active ingredients (less that 10% for each single amino acid).
- a significant characteristic of the above said formulation is that of having a pH in water solution comprised between 6.5 and 8.5, and therefore suitable for a safe oral or parenteral use, in humans or animals, according to needs. This feature prevents the excessive calcium urinary losses induced by protein sources of amino acids.
- the analyzed main metabolic parameters were: glycaemia, insulinemia, C-peptide, free fatty acids (FFA), total and fractioned cholesterol, triglycerids and fibrinogen.
- the left ventricular function was evaluated by means of 2D echocardiography, using a Hewlett-Packard Sonon 5500 system, with dedicated program for the execution of echo-stress methodologies and the quantification of ventricular images.
- the echocardiographic studies were encoded and blind analyzed, by two independent observers, without knowing the identity of the patient and the experimental condition.
- the echocardiographic analysis was carried out using a digital cine-loop method (Prevue System, Nova Microsonics Inc.).
- HbA1c (SD) (%) 8.7 ⁇ 1.7 8.6 ⁇ 1.6 n.s.
- Insulinemia ( ⁇ m/ml) 14 ⁇ 8 20 ⁇ 15 n.s.
- Cholesterolemia (mg/dl) 225 ⁇ 27 214 ⁇ 24 n.s.
- HDL cholesterol (SD) (mg/dl) 47 ⁇ 13 46 ⁇ 15 n.s.
- Triglyceridemia (SD) (mg/dl) 165 ⁇ 91 115 ⁇ 66 n.s.
- Free fatty acids (SD) ( ⁇ mol/l) 699 ⁇ 395 656 ⁇ 370 n.s.
- the isometric strain causes an extension of the regional contractile dysfunction independently of the type of treatment, but the extension of the contractile dysfunction at the strain peak is smaller during the treatment with the amino acids mixture according to the invention (1.49 ⁇ 0.45 vs. 1.29 ⁇ 0.41, p ⁇ 0.05).
- Said administration has in fact positively influenced the left ventricular myocardial function, both at rest and during isometric strain.
- the fact is particularly interesting that said administration prevents the depression of the function caused by isometric strain which characterizes diabetes patients.
- the administration of the amino acids mixture according to the invention reduces the further extension of the contractile dysfunction induced by acute ischemia during isometric strain.
- the oral administration of the described mixture of amino acids positively influences the myocardial ventricular function of patients suffering from diabetes, in particular II type diabetes.
- the positive influence is evident either at rest and during the acute overload imposed by an isometric strain during hand-grip, and also on the parietal contractile function, by means of a reduction of the extension of myocardial hibernation phenomena and of the extension of the contractile dysfunction induced by acute ischemia during isometric strain.
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- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Organic Chemistry (AREA)
- Heart & Thoracic Surgery (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Hospice & Palliative Care (AREA)
- Endocrinology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12/104,722 US8653136B2 (en) | 2001-06-15 | 2008-04-17 | Compositions based on amino acids for improving the myocardial ventricular function in patients suffering from diabetes |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITT02001A000580 | 2001-06-15 | ||
| IT2001TO000580A ITTO20010580A1 (it) | 2001-06-15 | 2001-06-15 | Composizioni a base di aminoacidi per il miglioramento della funzioneventricolare miocardica in pazienti affetti da diabete. |
| PCT/IB2002/002149 WO2002102360A2 (en) | 2001-06-15 | 2002-06-10 | Compositions based on branched chain amino acids for improving the myocardial ventricular function in patients suffering from diabetes |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US12/104,722 Division US8653136B2 (en) | 2001-06-15 | 2008-04-17 | Compositions based on amino acids for improving the myocardial ventricular function in patients suffering from diabetes |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US20040157903A1 true US20040157903A1 (en) | 2004-08-12 |
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US10/480,774 Abandoned US20040157903A1 (en) | 2001-06-15 | 2002-06-10 | Compositions based on amino acids for improving the myocardial ventricular function in patients suffering from diabetes |
| US12/104,722 Expired - Fee Related US8653136B2 (en) | 2001-06-15 | 2008-04-17 | Compositions based on amino acids for improving the myocardial ventricular function in patients suffering from diabetes |
Family Applications After (1)
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| US12/104,722 Expired - Fee Related US8653136B2 (en) | 2001-06-15 | 2008-04-17 | Compositions based on amino acids for improving the myocardial ventricular function in patients suffering from diabetes |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070010437A1 (en) * | 2003-10-07 | 2007-01-11 | Dioguardi Francesco S | Amino acid based compositions for the treatment of pathological conditions distinguised by insufficient mitochondrial function |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1537864A1 (de) * | 2003-12-03 | 2005-06-08 | Franz-Peter Dr. Liebel | Verwendung von Aminosäuren und schwefeltragenden Verbindungen zur Prophylaxe und Therapie des UDP-Glucuronosyltransferase1-defizitären Diabetes mellitus Typ II |
| EP1537865A1 (de) * | 2003-12-03 | 2005-06-08 | Franz-Peter Dr. Liebel | Verwendung von schwefelhaltigen Verbindungen und proteolytischen Enzymen zur Prophylaxe und Therapie des UDP-Glucuronosyl-transferase 1-defizitären Diabetes mellitus Typ II |
| WO2005077400A1 (en) * | 2004-02-12 | 2005-08-25 | Campina Nederland Holding B.V. | Cysteine rich peptides for improving thiol homeostasis |
| JP2008056566A (ja) * | 2004-12-28 | 2008-03-13 | Toudai Tlo Ltd | 低酸素応答促進剤 |
| EP1983849B1 (en) * | 2006-01-20 | 2013-04-03 | Innova Food AB | A food composition comprising amino acids |
| US8633192B2 (en) | 2006-12-15 | 2014-01-21 | Tima Foundation | Compositions and uses thereof |
| EA016926B1 (ru) * | 2006-12-15 | 2012-08-30 | Тима Фаундейшн | Композиции для профилактики и лечения гипергликемии |
| US8795973B2 (en) * | 2010-11-29 | 2014-08-05 | University of Leceister | Methods for identifying inhibitors of mannan-binding lectin associated serine protease (MASP) proteins and uses thereof |
| JOP20190146A1 (ar) | 2016-12-19 | 2019-06-18 | Axcella Health Inc | تركيبات حمض أميني وطرق لمعالجة أمراض الكبد |
| IT201700087359A1 (it) * | 2017-07-28 | 2019-01-28 | Professional Dietetics Spa | Composizioni comprendenti amino acidi per l'uso nel trattamento di malattie associate a disfunzione mitocondriale |
| JP7266581B2 (ja) | 2017-08-14 | 2023-04-28 | アクセラ・ヘルス・インコーポレイテッド | 肝疾患の治療のためのアミノ酸組成物 |
| CN112839643A (zh) | 2018-06-20 | 2021-05-25 | 胺细拉健康公司 | 用于治疗肌肉中脂肪浸润的组合物及方法 |
Citations (1)
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| US4053589A (en) * | 1975-11-24 | 1977-10-11 | Control Drug Inc. | Method of treating nutritional deficiency during cardiac cachexia, diabetes, hypoglycemia, gastroenterology, lipid, cell glycogen and keratin-related skin conditions and alcoholism |
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| JPS60255722A (ja) | 1984-05-30 | 1985-12-17 | Otsuka Pharmaceut Factory Inc | 糖尿病用アミノ酸輸液 |
| US5032608A (en) * | 1986-09-10 | 1991-07-16 | Dudrick Stanley J | Method and substrate composition for treating atherosclerosis |
| US5132113A (en) * | 1990-10-26 | 1992-07-21 | Maurizio Luca | Nutritional composition containing essential amino acids |
| AU655780B2 (en) * | 1990-10-30 | 1995-01-12 | Clintec Nutrition Company | A method and composition for the protection of a metabolic recovery of ischemic cardiac tissue |
| US5276018A (en) * | 1992-07-17 | 1994-01-04 | Brigham And Women's Hospital | Composition comprising amino acids and methods for decreasing muscle breakdown |
| LU88369A1 (fr) * | 1993-07-12 | 1994-04-01 | Michel Urso Prof Medecin Et Ch | Acides aminés à chaînes ramifiées |
| IT1289754B1 (it) | 1996-12-16 | 1998-10-16 | Professional Dietetics Srl | Composizioni a base di aminoacidi |
| IT1320783B1 (it) * | 2000-07-04 | 2003-12-10 | Professional Dietetics Srl | Composizioni a base di aminoacidi, atte al miglioramento delleprestazioni muscolari. |
| IT1320782B1 (it) * | 2000-07-04 | 2003-12-10 | Professional Dietetics Srl | Composizioni a base di aminoacidi, atte al trattamentodell'insufficienza cardiaca. |
-
2001
- 2001-06-15 IT IT2001TO000580A patent/ITTO20010580A1/it unknown
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2002
- 2002-06-10 KR KR1020037016184A patent/KR100894365B1/ko not_active Expired - Fee Related
- 2002-06-10 DK DK02735773.0T patent/DK1399139T3/en active
- 2002-06-10 CA CA2448745A patent/CA2448745C/en not_active Expired - Fee Related
- 2002-06-10 WO PCT/IB2002/002149 patent/WO2002102360A2/en active Application Filing
- 2002-06-10 PT PT2735773T patent/PT1399139E/pt unknown
- 2002-06-10 ES ES02735773.0T patent/ES2527527T3/es not_active Expired - Lifetime
- 2002-06-10 EP EP02735773.0A patent/EP1399139B1/en not_active Expired - Lifetime
- 2002-06-10 JP JP2003504947A patent/JP4364632B2/ja not_active Expired - Fee Related
- 2002-06-10 US US10/480,774 patent/US20040157903A1/en not_active Abandoned
- 2002-06-10 AU AU2002309122A patent/AU2002309122A1/en not_active Abandoned
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2008
- 2008-04-17 US US12/104,722 patent/US8653136B2/en not_active Expired - Fee Related
-
2015
- 2015-01-12 CY CY20151100027T patent/CY1115918T1/el unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4053589A (en) * | 1975-11-24 | 1977-10-11 | Control Drug Inc. | Method of treating nutritional deficiency during cardiac cachexia, diabetes, hypoglycemia, gastroenterology, lipid, cell glycogen and keratin-related skin conditions and alcoholism |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070010437A1 (en) * | 2003-10-07 | 2007-01-11 | Dioguardi Francesco S | Amino acid based compositions for the treatment of pathological conditions distinguised by insufficient mitochondrial function |
| US7973077B2 (en) * | 2003-10-07 | 2011-07-05 | Professional Dietetics S.R.L. | Amino acid based compositions for the treatment of pathological conditions distinguised by insufficient mitochondrial function |
| US8211944B2 (en) | 2003-10-07 | 2012-07-03 | Professional Dietetics S.R.L. | Amino acid based compositions for the treatment of pathological conditions distinguished by insufficient mitochondrial function |
| US8324278B2 (en) | 2003-10-07 | 2012-12-04 | Determinants Of Metabolism Research Laboratory S.R.L. | Amino acid based compositions for the treatment of pathological conditions distinguished by insufficient mitochondrial function |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1399139A2 (en) | 2004-03-24 |
| US20080194665A1 (en) | 2008-08-14 |
| PT1399139E (pt) | 2015-01-14 |
| AU2002309122A1 (en) | 2003-01-02 |
| US8653136B2 (en) | 2014-02-18 |
| CY1115918T1 (el) | 2017-01-25 |
| WO2002102360A2 (en) | 2002-12-27 |
| KR20040008217A (ko) | 2004-01-28 |
| CA2448745C (en) | 2012-09-04 |
| ITTO20010580A1 (it) | 2002-12-15 |
| EP1399139B1 (en) | 2014-10-15 |
| KR100894365B1 (ko) | 2009-04-22 |
| JP2004534073A (ja) | 2004-11-11 |
| WO2002102360A3 (en) | 2003-05-30 |
| CA2448745A1 (en) | 2002-12-27 |
| JP4364632B2 (ja) | 2009-11-18 |
| ES2527527T3 (es) | 2015-01-26 |
| DK1399139T3 (en) | 2015-01-12 |
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