DE19800812A1 - Effervescent oral composition containing L-arginine, as nutrient and for treating heart disease and hypercholesterolemia - Google Patents
Effervescent oral composition containing L-arginine, as nutrient and for treating heart disease and hypercholesterolemiaInfo
- Publication number
- DE19800812A1 DE19800812A1 DE1998100812 DE19800812A DE19800812A1 DE 19800812 A1 DE19800812 A1 DE 19800812A1 DE 1998100812 DE1998100812 DE 1998100812 DE 19800812 A DE19800812 A DE 19800812A DE 19800812 A1 DE19800812 A1 DE 19800812A1
- Authority
- DE
- Germany
- Prior art keywords
- arginine
- dosage form
- oral dosage
- effervescent
- hypercholesterolemia
- 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.)
- Granted
Links
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 title claims abstract description 18
- 229930064664 L-arginine Natural products 0.000 title claims abstract description 18
- 235000014852 L-arginine Nutrition 0.000 title claims abstract description 18
- 239000000203 mixture Substances 0.000 title claims description 21
- 208000035150 Hypercholesterolemia Diseases 0.000 title description 2
- 208000019622 heart disease Diseases 0.000 title 1
- 235000015097 nutrients Nutrition 0.000 title 1
- 239000002253 acid Substances 0.000 claims abstract description 7
- 239000006186 oral dosage form Substances 0.000 claims description 12
- KWTQSFXGGICVPE-WCCKRBBISA-N Arginine hydrochloride Chemical group Cl.OC(=O)[C@@H](N)CCCN=C(N)N KWTQSFXGGICVPE-WCCKRBBISA-N 0.000 claims description 7
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- 239000000843 powder Substances 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical group [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 4
- 238000012937 correction Methods 0.000 claims description 3
- 239000008187 granular material Substances 0.000 claims description 3
- 239000002552 dosage form Substances 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 150000001483 arginine derivatives Chemical class 0.000 claims 1
- 239000003826 tablet Substances 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 abstract description 4
- 239000008203 oral pharmaceutical composition Substances 0.000 abstract 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- 238000004090 dissolution Methods 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 235000019634 flavors Nutrition 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 3
- 239000008399 tap water Substances 0.000 description 3
- 235000020679 tap water Nutrition 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 235000015203 fruit juice Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000008092 positive effect Effects 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 206010007558 Cardiac failure chronic Diseases 0.000 description 1
- 208000032064 Chronic Limb-Threatening Ischemia Diseases 0.000 description 1
- 240000000902 Diospyros discolor Species 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 1
- 206010034576 Peripheral ischaemia Diseases 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 235000019568 aromas Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 229940109275 cyclamate Drugs 0.000 description 1
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000000260 hypercholesteremic effect Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0007—Effervescent
-
- 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]
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
Die Erfindung betrifft Brausemittel enthaltende orale Darreichungsformen von L-Arginin und seinen Derivaten mit hoher Patientencompliance.The invention relates to oral effervescent agents Dosage forms of L-arginine and its derivatives with high patient compliance.
L-Arginin ist eine semiessentielle Aminosäure und kann als Reinsubstanz, Salz oder Prodrug in parenteraler Form zur Behandlung von Störungen des Säure-Base-Haushalts eingesetzt werden. Als semiessentiell wird eine Aminosäure bezeichnet, die nur in bestimmten Lebenssituationen, z. B. während der Kindheit essentiell ist. Weiterhin hat L-Arginin nach parenteraler und oraler Gabe eine Reihe von vorteilhaften Wirkungen bei Patienten mit unterschiedlichen Krankheiten.L-arginine is a semi-essential amino acid and can be used as Pure substance, salt or prodrug in parenteral form Treatment of disorders of the acid-base balance used become. An amino acid is called semi-essential, that only in certain life situations, e.g. B. during the Childhood is essential. L-arginine also has after parenteral and oral administration a number of beneficial Effects in patients with different diseases.
In Bode-Böger, S. M., Böger, R. H., Alfke, H., Heinzel, D., Tsikas, D., Creutzig, A., Alexander, K., Frölich, J.C.: "L-arginine induces NO-dependent vasodilation in patients with critical limb ischemia - a randomized, controlled study", Circulation, 93: 85-90, 1996, wird die positive Wirkung von L-Arginin bei peripheren arteriellen Verschlußkrankheiten beschrieben. Die Verabreichung des L-Arginin erfolgt als intravenöse Infusion.In Bode-Böger, S. M., Böger, R. H., Alfke, H., Heinzel, D., Tsikas, D., Creutzig, A., Alexander, K., Frölich, J.C .: "L-arginine induces NO-dependent vasodilation in patients with critical limb ischemia - a randomized, controlled study ", Circulation, 93: 85-90, 1996, the positive effects of L-arginine in peripheral arterial occlusive diseases described. L-arginine is administered as intravenous infusion.
Wascher, T. C., Bahadori, B., Habersack-Wallner, S., Toplak, H.: "Oral L-arginine supplementation in chronic heart failure", Circulation 95(6): 1674, 1997, beschreiben den Zusammenhang von oral verabreichtem L-Arginin und dessen positiven Einfluß bei Herzversagen. Wascher, T.C., Bahadori, B., Habersack-Wallner, S., Toplak, H .: "Oral L-arginine supplementation in chronic heart failure ", Circulation 95 (6): 1674, 1997, describe the Relationship of orally administered L-arginine and its positive influence in heart failure.
In Clarkson, P., Adams, M.R., Powe, A. J. et al.: "Oral L-arginine improves endothelium-dependent dilation in hypercholesterolemic young adults", J. Clin. Invest., 97(8): 1989-1994, 1996, wird der positive Effekt von L-Arginin bei Hypercholesterinämie beschrieben.In Clarkson, P., Adams, M.R., Powe, A.J. et al .: "Oral L-arginine improves endothelium-dependent dilation in hypercholesterolemic young adults ", J. Clin. Invest., 97 (8): 1989-1994, 1996, the positive effect of L-arginine Hypercholesterolemia described.
Um eine nachweisbare Wirkung zu erzielen, müssen die Mengen an oral zu verabreichendem L-Arginin sehr groß sein (im Bereich von mehreren Gramm).To achieve a demonstrable effect, the quantities very large in oral L-arginine (im Range of several grams).
Allerdings zieht die Verwendung von sehr großen Mengen an L-Arginin
in den bisher üblichen Darreichungsformen, nämlich
Tabletten oder Pulver, das vor der Einnahme in einem
geeigneten Liquidum, wie z. B. Fruchtsaft, aufgelöst wird,
folgende Nachteile mit sich:
Wenn die Verabreichung in Form von Tabletten mit sehr großem
Umfang erfolgt, ist die orale Aufnahme durch verminderte
Schluckbarkeit stark beeinträchtigt. Wenn sie in Form von
Tabletten mit üblicher Größe erfolgt, führt das dazu, daß
der Patient zu überdurchschnittlich häufiger
Arzneimitteleinnahme gezwungen wird, um eine ausreichende
Wirkstoffmenge aufzunehmen. Die Patientencompliance ist
dementsprechend gering.However, the use of very large amounts of L-arginine in the usual forms of administration, namely tablets or powder, before being taken in a suitable liquid, such as. B. fruit juice, the following disadvantages:
If administered in the form of tablets on a very large scale, oral intake is severely impaired by reduced swallowing ability. If it is in the form of tablets of the usual size, the patient is forced to take medication more frequently than average in order to take up a sufficient amount of active ingredient. The patient compliance is accordingly low.
Die Verabreichung des Wirkstoffs in Form von Pulver, das zuvor in einem geeigneten Getränk aufgelöst wurde, wird ebenfalls sehr schlecht von Patienten angenommen, da der Geschmack dieser Lösung abstoßend ist und die Auflösungsgeschwindigkeit des Pulvers in der Flüssigkeit als zu langsam empfunden wird.The administration of the active substance in the form of powder, the has been previously dissolved in a suitable beverage also very poorly received by patients because the Taste of this solution is repulsive and the Dissolution rate of the powder in the liquid as is felt too slowly.
Der bisherige Versuch, eine Geschmackskorrektur durch Zugabe von Aromaträgern zu erreichen, erwies sich als unbefriedigend, sowohl in geschmacklicher Hinsicht, als auch mit Bezug auf die Auflösungsgeschwindigkeit.The previous attempt to correct the taste by adding reaching from aroma carriers proved to be unsatisfactory, both in terms of taste, as well with respect to the dissolution rate.
Der Erfindung liegt somit die Aufgabe zugrunde, eine orale Darreichungsform von L-Arginin und seinen Derivaten aufzufinden, die von Patienten insbesondere mit Hinblick auf ihren Geschmack und ihre Auflösungsgeschwindigkeit als gut eingestuft wird.The invention is therefore based on the object of an oral Dosage form of L-arginine and its derivatives locate that with regard to patients in particular their taste and their dissolution rate as well is classified.
Überraschenderweise wurde nun gefunden, daß die Auflösungsgeschwindigkeit der oralen Darreichungsform sowie deren geschmackliche Akzeptanz in Gegenwart von CO2, das aus einem Brausemittel mit einer Säure freigesetzt wird, deutlich erhöht ist. Auch der pH-Wert der Lösung ist von Bedeutung, da eine Verschiebung Richtung Neutralwert die geschmackliche Akzeptanz verbessert.Surprisingly, it has now been found that the dissolution rate of the oral dosage form and its taste acceptance in the presence of CO 2 , which is released from an effervescent with an acid, is significantly increased. The pH of the solution is also important because a shift towards the neutral value improves the taste acceptance.
Als Brausemittel können alle üblichen CO2-Entwickler eingesetzt werden, bevorzugt Hydrogencarbonat, Carbonat oder Gemische davon, besonders bevorzugt Natriumhydrogencarbonat, Calciumcarbonat oder Gemische davon.All customary CO 2 developers can be used as effervescent agents, preferably hydrogen carbonate, carbonate or mixtures thereof, particularly preferably sodium hydrogen carbonate, calcium carbonate or mixtures thereof.
Als Säuren eignen sich alle Säuren, die üblicherweise in Brausezubereitungen zur Erzeugung von CO2 aus einem Brausemittel eingesetzt werden. Bevorzugt verwendet werden Acidum tartaricum, Acidum citricum, Adipinsäure oder Gemische davon. Besonders bevorzugt verwendet werden Acidum tartaricum, Acidum citricum oder Gemische davon.Suitable acids are all acids which are usually used in effervescent preparations for the production of CO 2 from an effervescent. Acidum tartaricum, Acidum citricum, adipic acid or mixtures thereof are preferably used. Acidum tartaricum, Acidum citricum or mixtures thereof are particularly preferably used.
Neben den Brausemitteln und Säuren können die erfindungsgemäßen oralen Darreichungsformen weitere übliche Zusätze, wie Farbstoffe und Geschmackskorrigentia, enthalten.In addition to the effervescent agents and acids, the Oral dosage forms according to the invention are further conventional Additives such as colorants and flavor correctives, contain.
Als Geschmackskorrigenz kommen alle üblichen Aromastoffe und Süßungsmittel in Betracht. Bevorzugt werden Aroma citricum, Saccharin, Cyclamat oder Gemische davon eingesetzt. All the usual aromas and flavors come as a flavor correction Sweeteners into consideration. Aroma citricum are preferred, Saccharin, cyclamate or mixtures thereof are used.
Die erfindungsgemäße orale Darreichungsform wird vor der Verabreichung an den Patienten in einem geeigneten Liquidum aufgelöst. Beispielsweise seien Wasser, Fruchtsäfte oder Tees genannt.The oral dosage form according to the invention is before Administration to the patient in a suitable liquid dissolved. For example, water, fruit juices or Called teas.
In den folgenden Versuchen wurden Zubereitungen von L-Arginin mit verschiedenen Geschmackskorrigenzien hergestellt, sowie Verfahren zur schnellen und vollständigen Lösung erprobt. Die verschiedenen Zubereitungen wurden in einem doppel-blinden, randomisierten Verfahren an die Normalprobanden gegeben.In the following experiments, preparations of L-arginine with different taste corrections manufactured, as well as procedures for quick and complete Solution tested. The various preparations were made in a double-blind, randomized procedure to the Given normal subjects.
Unmittelbar nach Einnahme des Trunkes erhielt der Proband eine visuelle Analogskala (VAS) von 10 cm Länge, an deren linkem Ende ein Gesicht mit Negativausdruck und an der rechten Seite ein Gesicht mit Positivausdruck abgebildet war. Der Proband sollte nun durch einen senkrechten Strich andeuten, wie gut die Mischung geschmeckt hatte.The subject received immediately after taking the drink a visual analog scale (VAS) of 10 cm in length, on the on the left end a face with negative expression and on the a positive expression face is shown on the right was. The subject should now see a vertical line indicate how good the mixture had tasted.
Mischung A bestand aus 5 g L-Arginin-HCl, 0,02 g Natriumsaccharin und 0.02 g Aroma citricum. Diese Mischung wurde in 100 ml Leitungswasser bei 150 aufgelöst und getrunken.Mixture A consisted of 5 g L-arginine HCl, 0.02 g Sodium saccharin and 0.02 g aroma citricum. This mix was dissolved in 100 ml of tap water at 150 and drunk.
Mischung B bestand aus 5 g L-Arginin-HCl, 1,5 g Natriumhydrogencarbonat, 1,2 g Acidum citricum, 0,02 g Natriumsaccharin und 0,02 g Aroma citricum. Diese Mischung wurde ebenfalls in 100 ml Leitungswasser bei 150 augelöst und getrunken.Mixture B consisted of 5 g L-arginine HCl, 1.5 g Sodium bicarbonate, 1.2 g acidic citricum, 0.02 g Sodium saccharin and 0.02 g aroma citricum. This mix was also dissolved in 100 ml tap water at 150 and drunk.
Bei der geschmacklichen Akzeptanzprüfung zeigte Mischung A einen Wert von 0,71 ± 0,33 (Mittelwert ± Standardabweichung) auf der visuellen Analogskala. Mischung B zeigte den Wert 6.63 ± 3,0. Der Unterschied zwischen beiden Werten war mit einem p ≦ 0,001 hochsignifikant. p wurde nach dem student t-test, zweiseitig, bestimmt.In the taste acceptance test, mixture A showed a value of 0.71 ± 0.33 (mean ± standard deviation) on the visual analog scale. Mix B showed the value 6.63 ± 3.0. The difference between the two values was with a p ≦ 0.001 highly significant. p was after the student t test, two-sided, determined.
Es ist aus dieser Untersuchung zu erkennen, daß überraschenderweise die Gegenwart von CO2 aus Natriumhydrogencarbonat und Acidum citricum für die geschmackliche Akzeptanz von ganz entscheidender Bedeutung ist.It can be seen from this study that, surprisingly, the presence of CO 2 from sodium hydrogen carbonate and Acidum citricum is of crucial importance for the taste acceptance.
Im folgenden wurden weitere L-Arginin-HCl-Lösungen mit Hinblick, pH-Wert und Lösungsgeschwindigkeit und untersucht.In the following, other L-arginine-HCl solutions were used View, pH and dissolution rate and examined.
Untersucht wurden 14 verschiedene Mischungen, die jeweils
5 g L-ArgHCl/Dosis enthielten, aufgelöst in 100 ml
Leitungswasser (15°C)
14 different mixtures were investigated, each containing 5 g L-ArgHCl / dose, dissolved in 100 ml tap water (15 ° C)
Gemessen wurde mit der Glaselektrode (Eichung pH = 7.00).The measurement was carried out with the glass electrode (calibration pH = 7.00).
Der pH-Wert kann durch entsprechende Änderung des Verhältnisses zwischen Natriumhydrogencarbonat und Acidum citricum bzw. Acidum tartaricum eingestellt werden. Vergleicht man z. B. Mischung II mit Mischung V, so ist die Zusammensetzung in beiden Fällen identisch mit Ausnahme der Menge an Natriumhydrogencarbonat und Acidum citricum. Der pH-Wert der Mischung III beträgt 5.42, während der pH-Wert der Mischung V 7.73 beträgt.The pH can be adjusted by changing the Ratio between sodium bicarbonate and acidum citricum or Acidum tartaricum can be set. Comparing z. B. Mix II with mixture V, is that Composition in both cases identical with the exception of Amount of sodium hydrogen carbonate and Acidum citricum. Of the pH of mixture III is 5.42, while the pH the mixture is V 7.73.
Tests mit diesen Proben wurden doppelblind in Abständen von jeweils 1/2 Stunde durchgeführt.Tests with these samples were double blind at intervals of every 1/2 hour.
Weitere Proben, die nur L-Arginin-HCl und neutralisierende Zusätze, wie Na-Carbonat oder -hydrogen carbonat, enthielten, wurden von den Probanden so negativ bewertet, daß Geschmacksproben unterbleiben mußten.More samples that are only L-arginine-HCl and neutralizing Additives such as sodium carbonate or hydrogen carbonate, were so negatively evaluated by the test persons that tasting had to be avoided.
Die Tests zeigen, daß die orale Verabreichung von L-Arginin-HCl als Pulver oder Granulat positiv bewertet wurde, wenn sie als geschmacklich angenehm empfunden wurde und/oder sich das Pulver bzw. Granulat schnell löst. Dies war dann der Fall, wenn beim Auflösen der oralen Darreichungsform CO2 freigesetzt wurde.The tests show that the oral administration of L-arginine-HCl as powder or granules was rated positively if it was perceived as having a pleasant taste and / or if the powder or granules dissolved quickly. This was the case when CO 2 was released when the oral dosage form was dissolved.
Gut aromatisierte und gesüßte Lösungen zeigen ebenfalls eine gute Akzeptanz. Bevorzugt werden Mischungen wenn zusätzlich der pH-Wert der Lösung zwischen 5 und 8 liegt, besonders bevorzugt wenn der pH-Wert zwischen 5 und 6 liegt.Well flavored and sweetened solutions also show one good acceptance. Mixtures are preferred if additionally the pH of the solution is between 5 and 8, especially preferred if the pH is between 5 and 6.
Die Mischungen III und IV und VIII und IX wurden als angenehm bewertet und sind zudem leicht und preiswert herzustellen.Mixtures III and IV and VIII and IX were called pleasantly rated and are also light and inexpensive to manufacture.
Claims (7)
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001055098A1 (en) * | 2000-01-28 | 2001-08-02 | The Procter & Gamble Company | Palatable arginine compounds and uses thereof for cardiovascular health |
| WO2001097635A3 (en) * | 2000-06-20 | 2002-04-11 | Coraltis Ltd | Microcapsules containing arginine and the different uses thereof |
| WO2001054686A3 (en) * | 2000-01-28 | 2002-05-02 | Procter & Gamble | L-arginine in combination with other compounds for treating cardiovascular diseases |
| DE10128934A1 (en) * | 2001-06-18 | 2003-02-06 | Bernhard Sibbe | Well tolerated, natural product-based composition for prophylaxis of angina pectoris, containing specific aminoacids, vitamins and/or peptides, preferably L-arginine, L-carnitine, L-lysine and vitamin C |
| EP1310174A1 (en) * | 2001-11-07 | 2003-05-14 | Hikari Seika Co., Ltd. | Taste-improving agent |
| EP2249776A4 (en) * | 2008-02-08 | 2014-01-08 | Colgate Palmolive Co | EFFERVESCENT COMPOSITIONS |
| EP2247278A4 (en) * | 2008-02-08 | 2014-02-19 | Colgate Palmolive Co | Cleaning compositions and methods |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0567433A1 (en) * | 1992-04-23 | 1993-10-27 | Sandoz Nutrition Ltd. | Orally-ingestible nutrition compositions having improved palatability |
| DE3725176C2 (en) * | 1986-08-01 | 1995-06-14 | Zambon Spa | Pharmaceutical composition with analgesic activity |
| DE3638414C2 (en) * | 1985-11-12 | 1996-03-28 | Zambon Spa | Pharmaceutical composition with analgesic effect |
-
1998
- 1998-01-12 DE DE1998100812 patent/DE19800812C2/en not_active Expired - Lifetime
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3638414C2 (en) * | 1985-11-12 | 1996-03-28 | Zambon Spa | Pharmaceutical composition with analgesic effect |
| DE3725176C2 (en) * | 1986-08-01 | 1995-06-14 | Zambon Spa | Pharmaceutical composition with analgesic activity |
| EP0567433A1 (en) * | 1992-04-23 | 1993-10-27 | Sandoz Nutrition Ltd. | Orally-ingestible nutrition compositions having improved palatability |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001055098A1 (en) * | 2000-01-28 | 2001-08-02 | The Procter & Gamble Company | Palatable arginine compounds and uses thereof for cardiovascular health |
| WO2001054686A3 (en) * | 2000-01-28 | 2002-05-02 | Procter & Gamble | L-arginine in combination with other compounds for treating cardiovascular diseases |
| US6794375B2 (en) | 2000-01-28 | 2004-09-21 | The Procter & Gamble Co. | Palatable arginine compounds and uses thereof for cardiovascular health |
| WO2001097635A3 (en) * | 2000-06-20 | 2002-04-11 | Coraltis Ltd | Microcapsules containing arginine and the different uses thereof |
| DE10128934A1 (en) * | 2001-06-18 | 2003-02-06 | Bernhard Sibbe | Well tolerated, natural product-based composition for prophylaxis of angina pectoris, containing specific aminoacids, vitamins and/or peptides, preferably L-arginine, L-carnitine, L-lysine and vitamin C |
| EP1310174A1 (en) * | 2001-11-07 | 2003-05-14 | Hikari Seika Co., Ltd. | Taste-improving agent |
| EP2249776A4 (en) * | 2008-02-08 | 2014-01-08 | Colgate Palmolive Co | EFFERVESCENT COMPOSITIONS |
| EP2247278A4 (en) * | 2008-02-08 | 2014-02-19 | Colgate Palmolive Co | Cleaning compositions and methods |
| US10959967B2 (en) | 2008-02-08 | 2021-03-30 | Colgate-Palmolive Company | Effervescent compositions |
Also Published As
| Publication number | Publication date |
|---|---|
| DE19800812C2 (en) | 2000-05-11 |
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