WO1994004158A1 - Use of ribose in the preparation of a drug for use in the treatment of decrease in body performance, in particular organ insufficiency - Google Patents
Use of ribose in the preparation of a drug for use in the treatment of decrease in body performance, in particular organ insufficiency Download PDFInfo
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- WO1994004158A1 WO1994004158A1 PCT/DE1993/000776 DE9300776W WO9404158A1 WO 1994004158 A1 WO1994004158 A1 WO 1994004158A1 DE 9300776 W DE9300776 W DE 9300776W WO 9404158 A1 WO9404158 A1 WO 9404158A1
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
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- ribose for the manufacture of a medicament for the treatment of poor performance of the body, in particular organ insufficiency
- the invention relates to the use of ribose for the manufacture of a medicament.
- Heart diseases in particular heart attacks, coronary heart diseases and heart failure, which, although all heart diseases are strictly differentiated in medical diagnosis, in their pathophysiological causes and thus also in their therapy , effective and easily accessible drugs.
- Heart failure is a clinically defined syndrome, which is characterized by the effects of an abnormal function of the heart chambers and neuro-humoral regulation, and leads to the fact that the body tissues do not meet any metabolic needs Amount of blood is available. Heart failure is furthermore decisively characterized in that it leads to reduced physical performance, salt-water retention and significantly reduced life expectancy. Heart failure can have a number of triggering causes, of which the most common are pulmonary embolism, infections, anemia, thyrotoxicosis and pregnancy, cardiac arrhythmias, myocarditis, endocarditis, increased salt intake, arterial hypertension and heart attack. On the other hand, there are also forms of heart failure in which the causes are unknown. In almost all cases, however, the disease leads in the long term to characteristic symptoms with typical changes in the salt-water balance, the lungs and breathing, and the liver, and to changes in the heart muscle which lead to a breakdown of the Cardiac output and thus leads to death.
- cardiac insufficiencies has hitherto been treated with digitalis preparations, such as digoxin or methyl digoxin, and with diuretics, such as chlorothiazide, triamterene or furose id.
- digitalis preparations such as digoxin or methyl digoxin
- diuretics such as chlorothiazide, triamterene or furose id.
- Catecholamines such as dobutamine or phosphodiesterase inhibitors such as Amniron and Enoxi on are used primarily for short-term treatment.
- Vasodilating substances such as hydralazine, prazosin or nitrates, such as isosorbitol dinitrate, have also been successfully used, in particular in congestive cardiomvopathy or in coronary heart disease.
- the treatment of heart failure with ⁇ -receptor blockers such as prazosin has also been described.
- drugs for the treatment of heart failure in particular chronic heart failure, which have an effect on the renin-angiotensin system
- these include in particular the active substances enalapril and captopril.
- therapy failures are found time and again, ie patients who do not respond to the medicines described so far or only inadequately. There is therefore a great need for further therapeutically active substances for the treatment of heart diseases.
- the aim of the invention is therefore to overcome the disadvantages mentioned above and to provide a further active ingredient for the treatment of poor performance.
- D-ribose for the manufacture of a medicament for the treatment of poor performance of the body, in particular organ deficiencies.
- Preferred indications for the medicament produced according to the invention are heart failure and in particular non-ischemic heart diseases.
- the medicament produced in accordance with the invention is suitable for both oral and parenteral, in particular intravenous or intraarterial administration.
- intravascular administration preferably at least 5 mg D-ribose / kg body weight / hour is administered. A minimum amount of at least 25 mg / kg body weight / hour is particularly preferred.
- the upper limit is usually parenteral, in particular intra-venous and intra-arterial administration per hour at a maximum of 100 mg ribose per kg body weight.
- Appropriate doses are 20 mg per hour Ribose per kg body weight.
- Daily doses of 10 to 120 g are expedient for oral use, 45 to 85 g being preferred.
- Doses of 50 to 70 g per day are particularly preferred.
- the minimum daily dose is expediently 70 mg per kg body weight, preferably 400 mg to 1700 mg, values of 600 to 1400 mg being particularly preferred.
- a further preferred application of the medicaments produced according to the invention is in the therapy of shock, a multi-organ failure of gradually different manifestation, which is caused either by an acute insufficient nutritional blood supply to vital organs as a result of endogenous or exogenous intoxications or by certain endocrine-metabolic crises.
- multi-organ failure can occur as a result of cardiogenic shock in the event of acute pump failure of the heart muscle, as a result of hypovolemia as a result of internal or external blood loss, as a result of fluid loss as a result of diarrhea, vomiting and as a result of trauma, but also as a result of sodium deficiency and in the case of immune-allergic mechanisms.
- a relative reduction in the circulating body fluids can also result from neurogenic reflex vasodilation in the case of blunt trauma.
- shock is a common disease that is usually treated with intensive medical measures, such as volume supply through crystalline or colloidal solutions or blood transfusions, oxygen supply and artificial respiration, catecholamines, corticosteroids, thrombolytics. Despite of these therapeutic measures, the morbidity and mortality of the shock is high.
- the medicament produced according to the invention By administering the medicament produced according to the invention, it is surprisingly possible to improve the heart rate, the systolic blood pressure and the oxygen partial pressure in the blood. Existing oliguria is also favorably influenced.
- the doses to be administered are comparable to those used to treat heart failure.
- a preferred use of the medicament produced according to the invention is in the therapy of the weakness in the performance of the peripheral muscles, which occurs most frequently with an atherosclerotic change in the blood vessels.
- Other causes of changes in blood vessels can include inflammation of the vessels, an evasive vasospasm, an embolism, or thrombosis.
- the disease manifests itself through pain and / or cramps in the affected muscles, and through a restriction of the muscular performance.
- the drug treatment of poorly-performing people caused in this way has so far been done with anticoagulant agents (e.g. acetylsalicylic acid, heparin), thrombolytics (e.g. streptokinase), hemodilution (e.g. dextran infusion) and blood flow-promoting agents (e.g. pentoxifylline) ) carried out.
- anticoagulant agents e.g. acetylsalicylic acid, heparin
- thrombolytics e.g. str
- ribose is preferably used with the usual, the expert known pharmaceutically acceptable carrier materials and excipients.
- ACE inhibitors angiotensin converting enzyme inhibitors
- a 46-year-old patient with hypovolemic shock received treatment with an intravenously infused 10% ribose solution.
- the dosage was 20 mg D-ribose / kg body weight / hour for 24 hours.
- improved measured values for heart rate, systolic blood pressure and oxygen partial pressure were found in the arterial blood.
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Abstract
Description
Verwendung von Ribose zur Herstellung eines Arzneimittels zur Behandlung von Leistungsschwächen des Körpers, insbesondere von OrganinsuffizienzenUse of ribose for the manufacture of a medicament for the treatment of poor performance of the body, in particular organ insufficiency
Beschreibungdescription
Die Erfindung betrifft die Verwendung von Ribose zur Herstellung eines Arzneimittels.The invention relates to the use of ribose for the manufacture of a medicament.
S. Segal et al. in Proc. Soc. Exp. Biol. Med. (1957) , 95, 55-555 beschreiben, d iß Ribose bei Gesunden und Diabeti¬ kern zu einer Senkung des Blutzuckerspiegels um 16% - 65% führt.S. Segal et al. in proc. Soc. Exp. Biol. Med. (1957), 95, 55-555 describe that ribose leads to a 16% -65% lowering of the blood sugar level in healthy people and diabetics.
Es ist außerdem bekannt, daß Ribose im Menschen die Konzentration von 2,3-Diphosphoglyceriden im Vergleich zu Inosin weniger stark erhöht (Christian Petrich et al, Blut 30., S. 175 - 182 (1975)) . Dabei wurde auch gefunden, daß bei Applikation von Ribose der Blutzuckerspiegel um ca. ein Viertel abnimmt und es dabei zu Hunger- und Schwächegefühlen der behandelten Personen kommt.It is also known that ribose in humans increases the concentration of 2,3-Diphosphoglyceriden compared to inosine less (Christian Petrich et al, Blood 30, pp 175 -. 182 (1975)). It was also found that when ribose was applied, the blood sugar level decreased by about a quarter and the people treated felt hungry and weak.
Aus B. M. Patten, Lancet (1982), i, 1071 ist bekannt, daß D-Ribose bei Patienten mit Myoadenylat-Deaminase-Mangel zu symptomatischer Verbesserung und zu einer Zunahme der durch die Erkrankung beeinträchtigten Muskelkraft führt. Des weiteren ist es aus US-A-4,719,201 bekannt, daß sich ischämisches Gewebe rascher erholt, wenn es mit einer Ribose enthaltenden physiologischen Salzlösung perfundiert wird. Derartig perfundierte Gewebe können in einer Ribose enthaltenden Lösung bei Organtransplan¬ tationen längere Zeit ohne Schaden gelagert und trans¬ portiert werden. Aus den US-A-4,605,644 und US- A-4, 871,718 sowie aus H.-G. Zimmer, J. Physiol., Paris (1980), 76, 769 - 775, H.-G. Zimmer, Pflügers Arch (1978) 376, 223-227 und H.-G. Zimmer, Science (1983) 220, 81-82 ist es auch bekannt, daß eine Perfusion des Herzmuskels mit Ribose die ATP-Spiegel in den Muskelzellen von Tieren erhöht und damit zur Bekämpfung der schädlichen bioche¬ mischen Wirkungen einer Hypoxie bzw. Ischämie eingesetzt werden kann.It is known from BM Patten, Lancet (1982), i, 1071 that D-ribose leads to symptomatic improvement in patients with myoadenylate deaminase deficiency and to an increase in the muscle strength impaired by the disease. It is further known from US-A-4,719,201 that ischemic tissue recovers more quickly when perfused with a physiological saline solution containing ribose. Such perfused tissues can be used in a solution containing ribose in organ transplants can be stored and transported for a long time without damage. From US-A-4,605,644 and US-A-4, 871,718 and from H.-G. Zimmer, J. Physiol., Paris (1980), 76, 769-775, H.-G. Zimmer, Pflügers Arch (1978) 376, 223-227 and H.-G. Zimmer, Science (1983) 220, 81-82, it is also known that perfusion of the heart muscle with ribose increases the ATP levels in the muscle cells of animals and is therefore used to combat the harmful biochemical effects of hypoxia or ischemia can.
Bei N. S. Perlmutter et al., J. Nucl. Med. (1991), 32, 193-200 wird von einer Verbesserung der diagnostischen Genauigkeit der Thallium-201 Myokardszintigraphie durch Infusion von Ribose berichtet.In N. S. Perlmutter et al., J. Nucl. Med. (1991), 32, 193-200 reported an improvement in the diagnostic accuracy of thallium-201 myocardial scintigraphy by infusion of ribose.
Bei W. Pliml et al (Lancet 1992, 340) wird beschrieben, Ribose zur Behandlung der koronaren Herzkrankheit einzu¬ setzen.W. Pliml et al (Lancet 1992, 340) describe using ribose for the treatment of coronary heart disease.
Für die Behandlung von Herzerkrankungen, insbesondere des Herzinfarktes, der koronaren Herzkrankheit sowie der Herzinsuffizienz, die, obwohl allesamt Herzerkrankungen, in der medizinischen Diagnostik, in ihren pathophysio- logischen Ursachen und damit auch in ihrer Therapie streng unterschieden werden, besteht ein großer Bedarf an effektiven, wirksamen und einfach zugänglichen Arznei¬ mitteln.There is a great need for effective treatment of heart diseases, in particular heart attacks, coronary heart diseases and heart failure, which, although all heart diseases are strictly differentiated in medical diagnosis, in their pathophysiological causes and thus also in their therapy , effective and easily accessible drugs.
Die Herzinsuffizienz ist ein klinisch definiertes Syn- dro , das durch die Auswirkungen einer abnormen Funktion von Herzkammern und neuro-humoraler Regulation gekenn¬ zeichnet ist, und dazu führt, daß den Körpergeweben keine, den metabolischen Bedürfnissen entsprechende Blutmenge zur Verfügung steht. Die Herzinsuffizienz ist weiters dadurch entscheidend charakterisiert, daß sie zu verminderter körperlicher Leistungsfähigkeit, Salz-Was¬ ser-Retention und deutlich verminderter Lebenserwartung führt. Die Herzinsuffizienz kann eine Reihe von auslö¬ senden Ursachen haben, von denen Lungenembolie, Infekti¬ onen, Anämie, Thyreotoxicose und Schwangerschaft, Herzrhythmusstörugnen, Myokarditis, Endokarditis, erhöhte Salzaufnahme, arterieller Bluthochdruck und Herzinfarkt zu den häufigsten gehören. Andererseits gibt es aber auch Formen der Herzinsuffizienz, bei denen die Ursachen unbekannt sind. In nahezu allen Fällen führt die Erkran¬ kung jedoch langfristig zu einer charakteristischen Symptomatik mit typischen Veränderungen des Salz-Was¬ ser-Haushalts, der Lungen und der Atmung, und der Leber, und zu Veränderungen am Herzmuskel, der zu einem Zusam¬ menbruch der Herzleistung und damit zum Tode führt.Heart failure is a clinically defined syndrome, which is characterized by the effects of an abnormal function of the heart chambers and neuro-humoral regulation, and leads to the fact that the body tissues do not meet any metabolic needs Amount of blood is available. Heart failure is furthermore decisively characterized in that it leads to reduced physical performance, salt-water retention and significantly reduced life expectancy. Heart failure can have a number of triggering causes, of which the most common are pulmonary embolism, infections, anemia, thyrotoxicosis and pregnancy, cardiac arrhythmias, myocarditis, endocarditis, increased salt intake, arterial hypertension and heart attack. On the other hand, there are also forms of heart failure in which the causes are unknown. In almost all cases, however, the disease leads in the long term to characteristic symptoms with typical changes in the salt-water balance, the lungs and breathing, and the liver, and to changes in the heart muscle which lead to a breakdown of the Cardiac output and thus leads to death.
Die Behandlung solcher Herzinsuffizienzen wurde bislang mit Digitalispräparaten, wie Digoxin oder Metyldigoxin sowie mit Diuretika, wie Chlorothiazid, Triamteren oder Furose id, behandelt. Vor allem für die kurzfristige Behandlung werden Katecholamine, wie Dobutamin oder Hemmstoffe der Phosphodiesterase, wie Amniron und Enoxi on eingesetzt. Ebenfalls wurden erfolgreich vasodilatierende Substanzen, wie Hydralazin, Prazosin oder auch Nitrate, wie Isosorbitdinitrat, und zwar hier wiederum insbesondere bei der kongestiven Kardiomvopathie bzw. bei koronarer Herzkrankheit eingesetzt. Auch die Behandlung der Herzinsuffizienz mit α-Rezeptorenblockern, wie Prazosin ist beschrieben worden. In letzter Zeit wurden auch verstärkt Arzneistoffe zur Behandlung der Herzinsuffizienz, und zwar insbesondere der chronischen Herzinsuffizienz, eingesetzt, die auf das Renin- Angiotensin-System einwirken. Hierzu zählen insbesondere die Wirkstoffe Enalapril und Captopril. Bei allen diesen Substanzen finden sich jedoch immer wieder Therapiever¬ sager, d. h. Patienten, die auf die bislang beschriebenen Medikamente nicht oder nur unzureichend ansprechen. Es besteht daher ein großer Bedarf nach weiteren therapeu¬ tisch wirksamen Substanzen zur Behandlung von Herzkrank¬ heiten.The treatment of such cardiac insufficiencies has hitherto been treated with digitalis preparations, such as digoxin or methyl digoxin, and with diuretics, such as chlorothiazide, triamterene or furose id. Catecholamines such as dobutamine or phosphodiesterase inhibitors such as Amniron and Enoxi on are used primarily for short-term treatment. Vasodilating substances, such as hydralazine, prazosin or nitrates, such as isosorbitol dinitrate, have also been successfully used, in particular in congestive cardiomvopathy or in coronary heart disease. The treatment of heart failure with α-receptor blockers such as prazosin has also been described. Recently, drugs for the treatment of heart failure, in particular chronic heart failure, which have an effect on the renin-angiotensin system, have also been increasingly used. These include in particular the active substances enalapril and captopril. With all these substances, however, therapy failures are found time and again, ie patients who do not respond to the medicines described so far or only inadequately. There is therefore a great need for further therapeutically active substances for the treatment of heart diseases.
Die Erfindung hat daher zum Ziel, die zuvor genannten Nachteile zu überwinden und einen weiteren Wirkstoff zur Behandlung von Leistungsschwächen bereitzustellen.The aim of the invention is therefore to overcome the disadvantages mentioned above and to provide a further active ingredient for the treatment of poor performance.
Es wurde nun gefunden, daß sich dieses Ziel überraschen¬ derweise durch die Verwendung von D-Ribose zur Herstel¬ lung eines Arzneimittels zur Behandlung von Leistungs¬ schwächen des Körpers, insbesondere von Organinsuffizi¬ enzen, erzielen läßt. Bevorzugte Indikationen für das erfindungsgemäß hergestellte Arzneimittel sind die Herzinsuffizienz und insbesondere die nicht-ischämischen Herzerkrankungen.It has now been found that this goal can surprisingly be achieved by using D-ribose for the manufacture of a medicament for the treatment of poor performance of the body, in particular organ deficiencies. Preferred indications for the medicament produced according to the invention are heart failure and in particular non-ischemic heart diseases.
Es wurde nun überraschenderweise gefunden, daß sich die Herzinsuffizienz besonders gut durch die Verabreichung von D-Ribose behandeln läßt. Das erfindungsgemäß herge¬ stellte Arzneimittel eignet sich sowohl zur oralen als auch zur parenteralen, insbesondere zur intravenösen oder intraarteriellen Verabreichung. Bei der intravasalen Verabreichung wird vorzugsweise mindestens 5 mg D-Ribose/kg Körpergewicht/Stunde verabreicht. Besonders bevorzugt ist eine Mindestmenge von mindestens 25 mg/kg Körpergewicht/Stunde. Die obere Grenze liegt üblicher¬ weise bei der parenteralen, insbesondere bei der intra¬ venösen und bei der intraarteriellen Verabreichung in der Stunde bei maximal 100 mg Ribose pro kg Körpergewicht. Zweckmäßige Dosen betragen hierbei in der Stunde 20 mg Ribose pro kg Körpergewicht. Bei der oralen Anwendung sind Tagesdosen von 10 bis 120 g zweckmäßig, wobei 45 bis 85 g bevorzugt sind. Besonders bevorzugt sind Dosen von 50 bis 70 g pro Tag. Bezogen auf das Körpergewicht beträgt zweckmäßigerweise die Mindesttagesdosis 70 mg pro kg Körpergewicht, vorzugsweise 400 mg bis 1700 mg, wobei Werte von 600 bis 1400 mg besonders bevorzugt sind.It has now surprisingly been found that heart failure can be treated particularly well by the administration of D-ribose. The medicament produced in accordance with the invention is suitable for both oral and parenteral, in particular intravenous or intraarterial administration. For intravascular administration, preferably at least 5 mg D-ribose / kg body weight / hour is administered. A minimum amount of at least 25 mg / kg body weight / hour is particularly preferred. The upper limit is usually parenteral, in particular intra-venous and intra-arterial administration per hour at a maximum of 100 mg ribose per kg body weight. Appropriate doses are 20 mg per hour Ribose per kg body weight. Daily doses of 10 to 120 g are expedient for oral use, 45 to 85 g being preferred. Doses of 50 to 70 g per day are particularly preferred. Based on the body weight, the minimum daily dose is expediently 70 mg per kg body weight, preferably 400 mg to 1700 mg, values of 600 to 1400 mg being particularly preferred.
Eine weitere bevorzugte Anwendung der erfindungsgemäß hergestellten Arzneimittel liegt in der Therapie des Schocks, einem Multiorganversagen graduell unterschied¬ licher Ausprägung, das entweder durch eine akute unzu¬ reichende nutritive Durchblutung lebenswichtiger Organe infolge endogener oder exogener Intoxikationen oder bestimmter endokrin-metabolischer Krisen verursacht ist. Im einzelnen kann sich das Multiorganversagen durch einen kardiogenen Schock bei akutem Pumpversagen des Herzmus¬ kels, durch Hypovolä ie infolge von innerem oder äußerem Blutverlust, durch Flüssigkeitsverluste infolge von Durchfall, Erbrechen sowie durch Traumen, aber auch durch Natriummangel und bei immunallergischen Mechanismen auftreten. Zu einer relativen Verminderung der zirkulie¬ renden Körperflüssigkeiten kann es auch durch neurogen- reflektorische Vasodilatation bei stumpfen Traumen kommen.A further preferred application of the medicaments produced according to the invention is in the therapy of shock, a multi-organ failure of gradually different manifestation, which is caused either by an acute insufficient nutritional blood supply to vital organs as a result of endogenous or exogenous intoxications or by certain endocrine-metabolic crises. In particular, multi-organ failure can occur as a result of cardiogenic shock in the event of acute pump failure of the heart muscle, as a result of hypovolemia as a result of internal or external blood loss, as a result of fluid loss as a result of diarrhea, vomiting and as a result of trauma, but also as a result of sodium deficiency and in the case of immune-allergic mechanisms. A relative reduction in the circulating body fluids can also result from neurogenic reflex vasodilation in the case of blunt trauma.
Auch beim Schock hat sich die Applikation des erfindungsgemäß hergestellten Arzneimittels als zweckmä¬ ßig erwiesen. Der Schock ist eine häufig auftretende Erkankung, die üblicherweise mit intensivmedizinischen Maßnahmen, wie Volumenzufuhr durch kristalline oder kolloidale Lösungen oder Bluttransfusionen, Sauerstoff¬ zufuhr und künstlicher Beatmung, Katecholaminen, Kortikosteroiden, Thrombolytika behandelt wird. Trotz dieser therapeutischen Maßnahmen ist ie Morbidität und Mortalii t des Schocks hoch.In the case of shock, too, the application of the medicament produced according to the invention has proven to be expedient. The shock is a common disease that is usually treated with intensive medical measures, such as volume supply through crystalline or colloidal solutions or blood transfusions, oxygen supply and artificial respiration, catecholamines, corticosteroids, thrombolytics. Despite of these therapeutic measures, the morbidity and mortality of the shock is high.
Durch die Verabreichung des erfindungsgemäß hergestellten Arzneimittels ist es überraschenderweise möglich, die Herzfrequenz, den systolischen Blutdruck sowie den Sauerstoffpartialdruck im Blut zu verbessern. Ebenfalls wird eine bestehende Oligurie günstig beeinflußt. Die hierbei zu verabreichenden Dosen sind mit denjenigen vergleichbar, die zur Behandlung der Herzinsuffizienz eingesetzt werden.By administering the medicament produced according to the invention, it is surprisingly possible to improve the heart rate, the systolic blood pressure and the oxygen partial pressure in the blood. Existing oliguria is also favorably influenced. The doses to be administered are comparable to those used to treat heart failure.
Eine bevorzugte Anwendung des erfindungsgemäß herge¬ stellten Arzneimittels liegt in der Therapie der Lei¬ stungsschwäche der peripheren Muskulatur, die am häufig¬ sten bei einer atherosklerotischen Veränderung der Blutgefäße auftritt. Andere Ursachen für Veränderungen der Blutgefäße können eine Entzündung der Gefäße, ein anfausweise auftretender Gefäßspasmus, eine Embolie oder eine Thrombose sein. Die Erkrankung äußert sich durch Schmerzen und/oder Krämpfe in der betroffenen Muskulatur, und durch eine Einschränkung der muskulären Leistungsfä¬ higkeit. Die medikamentöse Behandlung derart verursachter Leistungsschwachen wurde bislang mit blutgerinnungs- hemmenden Mitteln (z. B. Acetylsalicylsaure, Heparin) , Thrombolytika (z. B. Streptokinase) , Hämodilution (z. B. Dextran Infusion) und durchblutungsfordernden Mitteln (z. B. Pentoxifyllin) durchgeführt. Durch die Verabreichung des erfindungsgemäß hergestellten Arznei¬ mittels ist es überraschenderweise möglich, die Lei¬ stungsminderung der peripheren Muskulatur ganz oder zumindest teilweise zu beseitigen.A preferred use of the medicament produced according to the invention is in the therapy of the weakness in the performance of the peripheral muscles, which occurs most frequently with an atherosclerotic change in the blood vessels. Other causes of changes in blood vessels can include inflammation of the vessels, an evasive vasospasm, an embolism, or thrombosis. The disease manifests itself through pain and / or cramps in the affected muscles, and through a restriction of the muscular performance. The drug treatment of poorly-performing people caused in this way has so far been done with anticoagulant agents (e.g. acetylsalicylic acid, heparin), thrombolytics (e.g. streptokinase), hemodilution (e.g. dextran infusion) and blood flow-promoting agents (e.g. pentoxifylline) ) carried out. By administering the medicament produced according to the invention, it is surprisingly possible to completely or at least partially eliminate the reduction in performance of the peripheral muscles.
Bei der erfindungsgemäßen Herstellung des Arzneimittels wird Ribose vorzugsweise mit üblichen, dem Fachmann bekannten pharmazeutisch verträglichen Trägermaterialien und Exzipientien verwendet.In the preparation of the medicament according to the invention, ribose is preferably used with the usual, the expert known pharmaceutically acceptable carrier materials and excipients.
Die Erfindung soll durch die folgenden Beispiele näher erläutert werden.The invention is illustrated by the following examples.
Beispiel 1example 1
Anwendung bei der HerzinsuffizienzUse in heart failure
Ein 72-jähriger Patient mit Herzinsuffizienz Grad III nach NYHA (New York Heart Association) und entsprechender starker Einschränkung der körperlichen Leistungsfähigkeit zeigte relatives Wohlbefinden in Ruhe, jedoch traten schon bei geringer körperlicher Belastung Beschwerden auf. Die klinische Untersuchung ergab prätibiale Ödeme, Orthopnoe und Zeichen der oberen Einflußstauung. Der Patient war bereits mit Angiotensin Converting Enzym Hemmer (ACE-Hemmer) vorbehandelt.A 72-year-old patient with grade III heart failure according to NYHA (New York Heart Association) and correspondingly severe impairment of physical performance showed relative well-being at rest, but symptoms appeared even with low physical exertion. Clinical examination revealed pretibial edema, orthopnea, and signs of upper stasis. The patient had previously been treated with angiotensin converting enzyme inhibitors (ACE inhibitors).
Nach Einnahme von 60 g D-Ribose in vier Einzeldosen von 15 g pro Tag für einen Zeitraum von 3 Tagen, und unter Beibehaltung der oben beschriebenen Medikation, zeigt sich eine deutliche Verbesserung der Symptomatik. Die Herzinsuffizienz konnte nunmehr dem Grad II NYHA zuge¬ ordnet werden, d. h. Beschwerden traten erst bei stär¬ kerer Belastung auf. Die prätibialen Ödeme waren vermin¬ dert .After taking 60 g of D-ribose in four individual doses of 15 g per day for a period of 3 days, and while maintaining the medication described above, there is a significant improvement in the symptoms. The heart failure could now be assigned to grade II NYHA, i.e. H. Complaints only occurred when the load was higher. The pretibial edema was reduced.
Nach Behandlung mit Ribose wurde die eingetretene Ver¬ besserung mittels Ergometrie bestimmt. Vor Beginn der P.ibosebehandlung mußte di^ Ergometrie nach einer Bela- stυngszeit von 2 Minuten 1-3 Sekunden wegen Dyspnoe abge¬ brochen werden. Durch die Ribosebehandlung konnte die Be- lastunqszeit auf 4 Minuten 8 Sekunden qesteiqert werden. Beispiel 2After treatment with ribose, the improvement occurred was determined by means of ergometry. Before the treatment of P.ibose began, the ergometry had to be stopped after a loading time of 2 minutes 1-3 seconds due to dyspnea. The ribose treatment increased the exposure time to 4 minutes and 8 seconds. Example 2
Anwendung beim SchockUse in shock
Ein 46-jähriger Patient mit hypovolämischem Schock erhielt, neben der üblichen Behandlung mit Volumensub¬ stitution und assistierter Beatmung, eine Behandlung mit einer intravenös infundierten 10%igen Riboselösung. Die Dosierung betrug 20 mg D-Ribose/kg Körpergewicht/Stunde für 24 Stunden. Bereits nach dreistündiger Infusion fanden sich im Vergleich zur Ausgangssituation und gegenüber vergleichbaren Kontrollpatienten verbesserte Meßwerte für Herzfrequenz, systolischen Blutdruck und Sauerstoffpartialdruck im arteriellen Blut. Nach Ablauf der Behandlung war keine Oligurie mehr vorhanden, Atmung und die renale Ausscheidung hatten sich normalisiert.In addition to the usual treatment with volume substitution and assisted ventilation, a 46-year-old patient with hypovolemic shock received treatment with an intravenously infused 10% ribose solution. The dosage was 20 mg D-ribose / kg body weight / hour for 24 hours. Already after three hours of infusion, compared to the initial situation and compared to comparable control patients, improved measured values for heart rate, systolic blood pressure and oxygen partial pressure were found in the arterial blood. After the treatment, there was no oliguria, respiration and renal excretion normalized.
Beispiel 3Example 3
Ein 54-jähriger Patient mit arterieller Verschlußkrank¬ heit, der mit Acetylsalicylsäure vorbehandelt war, mußte beim Laufbandgehtest die Belastung nach einer Gehstrecke von 81 m wegen schwerer krampfartiger Schmerzen in beiden Unterschenkeln abbrechen. Nach zweitägiger oraler Ein¬ nahme von D-Ribose in einer Dosierung von 45 g pro Tag,~ und unter Beibehaltung der bisherigen Medikation, konnten bei einem erneuten Laufbandgehtest 309 m zurückgelegt werden, bis es zu ähnlichen Symptomen kam. Die Erho¬ lungszeit bis zum Verschwindung der Symptome war im Vergleich zum ersten Gehtest deutlich verkürzt. Beispiel 4A 54-year-old patient with arterial occlusive disease who had been pretreated with acetylsalicylic acid had to stop the exercise after walking for 81 m because of severe cramp-like pain in both lower legs. After two days of oral Ein¬ takeover of D-ribose in a dose of 45 g per day, ~ and while maintaining the previous medication, could be covered m with a renewed Laufbandgehtest 309, until it came to similar symptoms. The recovery time until the symptoms disappeared was significantly reduced compared to the first walking test. Example 4
Bei einem 69-jährigen Patienten, der über Schwindelan¬ fälle klagte, fanden sich im 24-Stunden Langzeitelektro¬ kardiogramm (LZ-EKG) gehäuft ventrikuläre Extrasystolen, teilweise in Salven auftretend. In einem Kontroll-LZ-EKG nach dreitägiger Einnahme von D-Ribose in einer Dosierung von 60 g pro Tag, war die Zahl der Extrasystolen um 63% vermindert und es traten keine Salven mehr auf. Der Patient hatte während der Behandlung keine Schwindelan¬ fälle mehr.In a 69-year-old patient who complained of dizziness, ventricular extrasystoles were found frequently in the 24-hour long-term electrocardiogram (LZ-EKG), sometimes occurring in salvos. In a control LZ ECG after three days of taking D-Ribose at a dose of 60 g per day, the number of extrasystoles was reduced by 63% and there were no more salvos. The patient no longer had dizziness during the treatment.
*** ***
Claims
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU49423/93A AU4942393A (en) | 1992-08-25 | 1993-08-25 | Use of ribose in the preparation of a drug for use in the treatment of decrease in body performance, in particular organ insufficiency |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP4228215.2 | 1992-08-25 | ||
| DE19924228215 DE4228215A1 (en) | 1992-08-25 | 1992-08-25 | Use of ribose for the manufacture of a medicament for the treatment of poor performance of the body, in particular organ deficiency |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1994004158A1 true WO1994004158A1 (en) | 1994-03-03 |
Family
ID=6466387
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/DE1993/000776 Ceased WO1994004158A1 (en) | 1992-08-25 | 1993-08-25 | Use of ribose in the preparation of a drug for use in the treatment of decrease in body performance, in particular organ insufficiency |
Country Status (3)
| Country | Link |
|---|---|
| AU (1) | AU4942393A (en) |
| DE (1) | DE4228215A1 (en) |
| WO (1) | WO1994004158A1 (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002518321A (en) * | 1998-06-19 | 2002-06-25 | バイオエナジー インコーポレイティド | Compositions for increasing energy in vivo |
| WO2008091618A1 (en) * | 2007-01-23 | 2008-07-31 | Bioenergy, Inc. | Use of d-ribose to treat cardiac arrhythmias |
| EP2247183A4 (en) * | 2008-01-25 | 2011-06-22 | John E Foker | Methods and compositions for inhibiting progression to chronic cardiac failure |
| US9572882B2 (en) | 2000-07-28 | 2017-02-21 | Ribocor, Inc. | Compositions and methods for improving cardiovascular function |
| US10821123B2 (en) | 2016-02-01 | 2020-11-03 | Bioenergy Life Science, Inc. | Use of ribose for treatment of subjects having congestive heart failure |
| CN114209709A (en) * | 2021-12-16 | 2022-03-22 | 海门品尚医药科技有限公司 | Application of D-ribose in the preparation of drugs or food for improving drug-induced cardiotoxicity |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5443628B1 (en) * | 1994-08-08 | 1998-06-09 | Videojet Systems Int | High temperature jet printing ink |
| US6218366B1 (en) * | 1998-06-19 | 2001-04-17 | Bioenergy, Inc. | Method for raising the hypoxic threshold |
| US6429198B1 (en) | 1999-04-12 | 2002-08-06 | Bioenergy Inc. | Compositions for increasing athletic performance in mammals |
| US6534480B2 (en) | 1999-06-17 | 2003-03-18 | Bioenergy Inc. | Compositions for increasing energy in vivo |
| US6339716B1 (en) | 1999-09-24 | 2002-01-15 | Bioenergy Inc. | Method for determining viability of a myocardial segment |
| US6159943A (en) * | 1999-09-24 | 2000-12-12 | Bioenergy, Inc. | Use of ribose to prevent cramping and soreness in muscles |
| WO2010021713A1 (en) * | 2008-08-20 | 2010-02-25 | Bioenergy, Inc. | Use of d-ribose for fatigued subjects |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4719201A (en) * | 1985-02-07 | 1988-01-12 | Regents Of The University Of Minnesota | Method for stimulating recovery from ischemia |
-
1992
- 1992-08-25 DE DE19924228215 patent/DE4228215A1/en not_active Withdrawn
-
1993
- 1993-08-25 AU AU49423/93A patent/AU4942393A/en not_active Abandoned
- 1993-08-25 WO PCT/DE1993/000776 patent/WO1994004158A1/en not_active Ceased
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4719201A (en) * | 1985-02-07 | 1988-01-12 | Regents Of The University Of Minnesota | Method for stimulating recovery from ischemia |
Non-Patent Citations (10)
| Title |
|---|
| B.M.PATTEN: "BEBEFICIAL EFFECT OF D-RIBOSE IN PATIENT WITH MYOADENYLATE DEAMINASE DEFICIENCY", LANCET, vol. 1982(I), no. 8280, 8 May 1982 (1982-05-08), pages 1071, XP001050584, DOI: doi:10.1016/S0140-6736(82)92124-9 * |
| H.-G. ZIMMER ET AL.: "Combination of Ribose with Calcium Antagonist and beta-Blocker Treatment in Closed-chest Rats", J.MOL.CELL CARDIOL., vol. 19, no. 7, July 1987 (1987-07-01), pages 635 - 639 * |
| H.-G. ZIMMER ET AL.: "Effects of ribose on cardiac metabolism and function in isoproterenol-treated rats", AM.J.PHYSIOL., vol. 245, no. 5PT1, November 1983 (1983-11-01), pages H880 - H886 * |
| H.-G.ZIMMER: "Restitution of myocardial adenine nucleotides : acceleration by administration of ribose", J.PHYSIOL.(PARIS), vol. 76, no. 7, 1980, pages 769 - 775 * |
| H.-G-ZIMMER ET AL.: "Ribose Accelerates the Repletion of the ATP Pool During Recovery from Reversible Ischemia of the Rat Myocardium", J.MOL.CELL.CARDIOL., vol. 16, no. 9, September 1984 (1984-09-01), pages 863 - 866, XP000856788 * |
| J.A.ST. CYR ET AL.: "Enhanced High Energy Phosphate Recovery with Ribose Infusion after Global Myocardial Ischemia in a Canine Model", J.SURG.RES., vol. 46, no. 2, February 1989 (1989-02-01), pages 157 - 162, XP023023557, DOI: doi:10.1016/0022-4804(89)90220-5 * |
| M.A.CLAY ET AL.: "CHRONIC ALCOHOLIC CARDIOMYOPATHY / PROTECTION OF THE ISOLATED ISCHAEMIC WORKING HEART BY RIBOSE", BIOCHEM.INT., vol. 17, no. 5, November 1988 (1988-11-01), pages 791 - 800 * |
| M.F.MCCARTY: "MANAGEMENT OF ACUTE MYOCARDIAL INFARCTION WITH NATURAL PHYSIOLOGICAL AGENTS", MED.HYPOTHESES, vol. 11, no. 4, August 1983 (1983-08-01), pages 449 - 465, XP023026028, DOI: doi:10.1016/0306-9877(83)90090-7 * |
| M.K.PASQUE ET AL.: "Ribose-enhanced myocardial recovery following ischemia in the isolated working rat heart", J.THORAC CARDIOVASC. SURG., vol. 83, no. 3, March 1982 (1982-03-01), pages 390 - 398 * |
| W.PLIML ET AL.: "Effects of ribose on exercise-induced ischaemia in stable coronary artery disease", LANCET, vol. 340, no. 8818, 29 August 1992 (1992-08-29), pages 507 - 510, XP000857272, DOI: doi:10.1016/0140-6736(92)91709-H * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002518321A (en) * | 1998-06-19 | 2002-06-25 | バイオエナジー インコーポレイティド | Compositions for increasing energy in vivo |
| US9572882B2 (en) | 2000-07-28 | 2017-02-21 | Ribocor, Inc. | Compositions and methods for improving cardiovascular function |
| WO2008091618A1 (en) * | 2007-01-23 | 2008-07-31 | Bioenergy, Inc. | Use of d-ribose to treat cardiac arrhythmias |
| US8101581B2 (en) | 2007-01-23 | 2012-01-24 | Bioenergy, Inc. | Use of D-ribose to treat cardiac arrhythmias |
| EP2247183A4 (en) * | 2008-01-25 | 2011-06-22 | John E Foker | Methods and compositions for inhibiting progression to chronic cardiac failure |
| US10821123B2 (en) | 2016-02-01 | 2020-11-03 | Bioenergy Life Science, Inc. | Use of ribose for treatment of subjects having congestive heart failure |
| CN114209709A (en) * | 2021-12-16 | 2022-03-22 | 海门品尚医药科技有限公司 | Application of D-ribose in the preparation of drugs or food for improving drug-induced cardiotoxicity |
Also Published As
| Publication number | Publication date |
|---|---|
| AU4942393A (en) | 1994-03-15 |
| DE4228215A1 (en) | 1994-03-03 |
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