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WO2024208506A1 - Combinaison de principes actifs oraux contenant de la l-arginine, de la l-citrulline, du sélénite et du bore soluble dans l'eau - Google Patents

Combinaison de principes actifs oraux contenant de la l-arginine, de la l-citrulline, du sélénite et du bore soluble dans l'eau Download PDF

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Publication number
WO2024208506A1
WO2024208506A1 PCT/EP2024/055572 EP2024055572W WO2024208506A1 WO 2024208506 A1 WO2024208506 A1 WO 2024208506A1 EP 2024055572 W EP2024055572 W EP 2024055572W WO 2024208506 A1 WO2024208506 A1 WO 2024208506A1
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Prior art keywords
arginine
active ingredient
citrulline
vitamin
ingredient combination
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German (de)
English (en)
Inventor
Wolfgang RÜDINGER
Rohan Charles Fernando
Kristian Becker
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Rfb Healthcare GmbH
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Rfb Healthcare GmbH
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Publication of WO2024208506A1 publication Critical patent/WO2024208506A1/fr
Anticipated expiration legal-status Critical
Pending legal-status Critical Current

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    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/095—Sulfur, selenium, or tellurium compounds, e.g. thiols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/04—Sulfur, selenium or tellurium; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/22—Boron compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • 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
    • 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
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
    • 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
    • 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
    • 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
    • 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
    • A61P9/12—Antihypertensives
    • 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
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate

Definitions

  • the present invention relates to an oral active ingredient combination as a medicament, nutritional supplement or as a food for special medical purposes with which the metabolic syndrome and general signs of aging or age-related diseases can be positively influenced. Furthermore, the oral active ingredient combination can be used as a nutritional additive in animal feed or as a veterinary drug.
  • metabolic syndrome is attributed to a variety of risk factors, in particular hypercaloric nutrition, lack of physical exercise, oxidative stress and smoking. This leads to obesity, which subsequently leads to insulin resistance.
  • the main influence on the development of metabolic syndrome is the Visceral fat. This tissue, rich in fat cells, is located between the organs of the abdominal cavity. The fat cells are hormonally active and promote insulin resistance, among other things.
  • a diet with high levels of cell-free flour, sugar, and other refined industrial foods, which could promote an inflammatory microbiome in the intestine, is considered to be a contributing cause.
  • metabolic syndrome is the price of little exercise, (too) much food, nicotine, stress, ... and other circumstances that determine the way of life in industrialized nations.
  • statins are used as standard therapy to lower cholesterol (LDL) and in particular triglycerides to reduce the risk of heart attacks and strokes.
  • LDL lower cholesterol
  • triglycerides to reduce the risk of heart attacks and strokes.
  • Long-term therapy with statins often results in clinically relevant side effects such as increased blood pressure, muscular complaints, cramps, weight gain, increased blood sugar and liver values, gastrointestinal complaints, chronic fatigue, itching or headaches.
  • These secondary diseases are often treated with other medications. This means that usually a large number of different medications are prescribed and taken.
  • the expected or necessary effect is not achieved in some cases. Even food supplements or foods for special medical purposes can occasionally have undesirable side effects. Often there is a lack of in these cases, there is a lack of sufficient effectiveness.
  • the problem therefore remains of finding effective agents that are as free from undesirable effects as possible for treating the signs of aging and metabolic syndrome.
  • the aim of the present invention was therefore to develop a product that is as free from side effects as possible for the treatment and/or support of the therapy of age- or lifestyle-related metabolic syndrome as part of diet management to regain and maintain vitality, strength and endurance.
  • an oral active ingredient combination comprising L-arginine, L-citrulline and a selenium compound, in particular selenite, as well as boron, all in water-soluble form, wherein L-arginine, L-citrulline and the selenium compound are dosed for absorption from food after ingestion at an interval of 2 to 4 hours after the boron.
  • the latter is achieved either by taking a separately packaged dose of the boron at a later time or by providing L-arginine, L-citrulline and the selenium compound in a sustained-release form with delayed release but rapid absorption in a mixture with non-sustained-release boron.
  • the oral active ingredient combination is used as a nutritional additive for animal feed (see EU Regulation No. 1831/2003) or as a veterinary medicinal product for mammals or as a medicinal product, as a food supplement or as a food for special medical purposes (see EU Regulation No. 609/2013) for humans.
  • the first component of the active ingredient combination according to the invention is L-arginine. This is a semi-essential amino acid that occurs in many proteins and is commercially available. L-arginine is used in water-soluble form. L-arginine is mainly produced by extraction from duck feathers. This results in an acidic L-arginine HCl that has reduced bioavailability and is not vegan.
  • vegan L-arginine is obtained by fermenting sugar cane or grain as an L-arginine base.
  • the disadvantage is the fishy taste of the L-arginine base.
  • vegan L-arginine alpha-ketoglutarate obtained by fermentation is used, which has high bioavailability and a neutral taste.
  • Other physiologically acceptable and water-soluble salts of L-arginine such as citrates or malates are also possible.
  • the active ingredient combination according to the invention comprises L-citrulline as a second component.
  • This amino acid is also well known and commercially available.
  • L-citrulline is also used in water-soluble form, preferably in the form of a water-soluble derivative, particularly preferably as malate.
  • Argilin retard www.argilin.de
  • Zestval Arginin 4.0 NEM www.zestonics.com
  • aminoplus Arginin + Citrulline www.kyberg-vital.de
  • the third component is a water-soluble selenium compound, in particular selenite, preferably an alkali salt of selenious acid.
  • selenite preferably an alkali salt of selenious acid.
  • Sodium selenite and selenomethionine as well as selenocysteine are particularly preferred.
  • Well-known dietary supplements that contain selenium as a compound together with L-arginine and/or L-citrulline and in some cases also other components are Dorecfil (www.exvital.de), Arteries-Blood Vessel Support (www.biotikon.de), Vitamaze L-Arginine plus (www.vitamaze.shop), Mascupro Testo & Energy/Mascupro Fertility (www.mascupro.de), and aminoplus mann (www.kyberg-vital.de). All of these products do not contain boron.
  • the active ingredient combination according to the invention comprises boron in water-soluble form, which is dosed before the components L-arginine, L-citrulline and selenium compound.
  • a water-soluble boron salt is used, particularly preferably an inorganic borate, in particular sodium tetraborate. Boric acid can also be used.
  • the staggered dosing can be achieved on the one hand by separate dosage forms, which can be the same or different. For example, capsules, dragees, tablets, juice, drops, syrup, powder or granules are suitable. It is expedient to provide one of the two doses to be taken at different times in one dosage form, preferably in one or more capsules, tablets, dragees or a sachet with powder and/or granules for stirring into liquid.
  • the boron salt is provided as a tablet, capsule or dragee and the components L-arginine, L-citrulline and selenium compound are provided as a powder or granules in a sachet, wherein the dosage form preferably contains a daily dose or half a daily dose or a quarter of a daily dose.
  • the components L-arginine, L-citrulline and selenium compound are provided together with the boron salt in a dosage form.
  • the components L-arginine, L-citrulline and selenium compound are used in sustained release form with delayed release of the active ingredient.
  • Galenic forms with delayed release of the active ingredient are known per se for pharmaceuticals. They are used to release an active ingredient at a later time after ingestion or over a longer period of time. According to the invention, delayed release is used, but not release over a longer period of time.
  • the selected, special sustained release form ensures a delayed release of the components L-arginine, L-citrulline and selenium compound only approx. 2 to 4 hours after ingestion.
  • a suitable time-delayed release of active ingredients is achieved, for example, by coating the components with pH-activated substances that are insoluble at low pH and dissolve easily in the small intestine in a basic environment at a higher pH, typically > pH 7, and release the enclosed active ingredients. These conditions are met, for example, by shellac-coated microgranules and ethyl cellulose or alginate-based micro- or nanoparticles.
  • starch-coated microgranules or nanoparticles can be used, for example, which are released by alpha-amylase digestion after passage through the stomach in the duodenum/jejunum.
  • the effect of the uncoated active ingredients occurs through rapid absorption in the upper digestive tract, in particular during passage through the stomach, with rapid bioavailability of the boron and, if applicable, the other cofactors contained in water-soluble form.
  • the release and rapid absorption of the coated components in the small intestine then occurs approximately 2 to 4 hours later, e.g. through pH-activated or alpha-amylase-induced release.
  • the rapid bioavailability of the delayed-release, delayed-release components is preferably ensured by using appropriate, readily water-soluble derivatives such as inorganic or organic salts or e.g. as esters.
  • the active ingredient combination in a dosage form preferably comprises a water-soluble boron salt or boric acid as a powder, optionally with other easily water-soluble co-factors, and the components L-arginine, L-citrulline and selenium compound in water-soluble form as microgranules coated with shellac in a sachet. For ingestion, the sachet contents are stirred into water to produce a drinking solution.
  • a suitable daily dose is usually divided into 1 to 3 individual doses, preferably into 1 to 2 individual doses and particularly preferably as 1 individual dose taken in the morning.
  • a daily dose or sustained-release, time-delayed amount of the components L-arginine, L-citrulline and selenium compound in the active ingredient combination usually comprises, based on a person with a body weight of 80 kg, from 0.5 to 10.0 g L-arginine, from 1.0 to 10.0 g L-citrulline and from 10 to 150 pg selenium compound.
  • the amounts stated refer to the amounts calculated as free amino acid or selenium; the preferred compounds are used in correspondingly greater quantities. It is advantageous if the amount of L-citrulline is 1.5 to 3 times the amount of L-arginine.
  • the active ingredient combination comprises a separate or non-sustained-release daily dose of boron containing 1 to 9 mg, preferably 2 to 5 mg, particularly preferably around 3 mg of boron.
  • the daily dose calculated for a body weight of 80 kg can usually also be used for a lower or higher body weight, e.g. for a body weight of 60 to 100 kg or up to 120 kg. With a very high body weight, from around 110 kg or 120 kg, taking two doses calculated for a weight of 80 kg should be considered; from around 140 or 150 kg this is preferred.
  • the oral active ingredient combination according to the invention can contain further amino acids and/or further co-factors, ie minerals and/or vitamins and/or antioxidants.
  • the further amino acids or the co-factors can be combined with the boron compound be combined/mixed together in one dosage form or be present in whole or in part in another dosage form, for example in another capsule or tablet or another sachet.
  • the additional co-factor(s) is/are used in a form that is readily soluble in water.
  • a first preferred additional co-factor is magnesium.
  • a daily dose is generally from 100 or 200 to 800 or 1000 mg of magnesium, preferably from 120 to 150 mg.
  • the use of a water-soluble magnesium salt is advantageous, magnesium citrate, magnesium gluconate, magnesium L-threonate or magnesium bisglycinate are preferably used, magnesium bisglycinate is particularly preferred.
  • a second preferred additional co-factor is zinc. From 10 to 25 mg of zinc per daily dose is well suited, preferably about 15 mg. Zinc is often used as zinc oxide but preferably in the form of a readily water-soluble salt, in particular as zinc glycinate, zinc citrate, zinc gluconate and most preferably as zinc glycinate.
  • a third preferred additional co-factor is manganese.
  • a daily dose is usually from 0.5 to 5 mg manganese, preferably about 3 mg.
  • Manganese is preferably used in the form of a water-soluble salt, in particular as manganese glycinate or manganese gluconate.
  • a fourth preferred further co-factor is folic acid or folate.
  • folic acid or folate In particular, from 200 to 1000 pg of folic acid or folate, calculated as folic acid, preferably about 400 pg, are used per daily dose.
  • a preferably used water-soluble form is methyl tetrahydrofolate.
  • a fifth preferred further co-factor is vitamin C.
  • vitamin C Preferably, from 200 to 1000 mg of vitamin C, particularly preferably about 200 to 300 mg, are used per daily dose.
  • a preferred form is calcium ascorbate or Vitamin C ester or vitamin C complex consisting of calcium ascorbate and L-threonate.
  • a sixth preferred additional co-factor is vitamin B2.
  • 1 to 5 mg of vitamin B2 are used per daily dose, particularly preferably about 3 to 5 mg.
  • a seventh preferred additional co-factor is vitamin B6.
  • a daily dose of 1 to 20 mg of vitamin B6 is preferred, in particular about 5 mg.
  • An eighth preferred additional co-factor is vitamin B12.
  • the preferred additional co-factors are included in the oral active ingredient combination according to the invention, for example two, three or even more. Particularly preferably, all eight preferred additional co-factors are included. Also particularly preferably, vitamin C, folic acid, manganese, zinc and magnesium are included as additional co-factors, in particular in an intestinally compatible form with high bioavailability (e.g. as calcium ascorbate, methyl tetrahydrofolate and the minerals as glycinate or citrate). The preferred additional co-factor(s) are included in particular in the amounts mentioned and/or in the form of the compounds mentioned. According to the invention, the additional co-factors are preferably combined with boron in a dosage form.
  • the dosage form of the oral active ingredient combination is produced in a manner known per se. Excipients are often used for this purpose. These are normally inert and are used to improve shelf life, stability, for shaping, for adjusting the weight and consistency, for taste and appearance.
  • excipients can be important for promoting release, absorption and bioavailability, for adjusting the pH value and osmolarity, for protection and for the manufacturing process.
  • Typical excipients include antioxidants, flavorings, binders, fragrances, emulsifiers, colorants, film formers, fillers, gelling agents, taste correctors, complexing agents, preservatives, solvents, solubilizers, buffers, ointment bases, acidifiers, acidity regulators, acids and bases, lubricants, sweeteners, coating agents, thickeners and disintegrants.
  • the oral active ingredient combination supports the reduction of LDL cholesterol and especially triglycerides, and also improves blood pressure, testosterone levels and liver function or liver metabolism, expressed in an unexpectedly high reduction in the liver markers gamma-GT and GPT.
  • the treatment showed no side effects, and no additive oxidative stress (radical stress) occurred during the study period.
  • the areas of application also include use as a nutritional additive for animal feed and as a veterinary drug for mammals, particularly horses, dogs and cats.
  • a dosage form containing boron salt and the other co-factors magnesium, manganese, zinc, folic acid, vitamin C, vitamin B2 and vitamin B12 was provided in the form of capsules and a second dosage form containing L-arginine, L-citrulline and selenium compound in the form of a powder for dissolving in sachets.
  • the 2 capsules as a daily dose for morning intake contained together:
  • vitamin C as calcium ascorbate
  • vitamin B12 as methylcobalamin
  • the powder for 2 to 4 hour delayed administration contained per sachet as a daily dose:
  • Group B received the oral active ingredient combination according to the invention with an intake of the co-factors in the morning and approximately 2 to 4 hours later the intake of the components L-arginine, L-citrulline and selenium compound.
  • group A took all components simultaneously in the morning.
  • weight and blood values were determined.
  • weight and blood values were determined again and the subjects were asked in a final interview about a range of conditions such as fatigue, physical fitness or mental stability/stress resistance.
  • group B 4 women and 6 men were recruited.
  • 1 subject in group A stopped participating; of the remaining subjects, 6 were men and 3 were women in group A.
  • the blood values determined were: HbA1 c, total bilirubin as well as indirect and direct, GPT, gamma GT, LDH, HDL, LDL, triglycerides, creatinine, urea, uric acid, iron, albumin, 17-beta-estradiol (in women, all of whom showed no stimulation of estradiol levels during menopause), testosterone (in men without medicinal testosterone substitution), SHBG, CRP, IL6, IP 10, Lp-PLA2, MDA-LDL, nitrotyrosine, AGE, Lp-PLA 2.
  • Significant differences between groups A and B were found for HbA1 c, LDL cholesterol, triglycerides, GPT, gamma GT, testosterone (men) and nitrotyrosine.
  • Example 1 Blood pressure
  • the oral active ingredient combination according to the invention is therefore very well suited to support high blood pressure therapy, so that if necessary, the dosage of the drugs can be reduced and/or in the case of several of the “blood pressure medication” can be omitted. If blood pressure values are in the upper normal range or if blood pressure is slightly elevated, taking the oral combination of active ingredients may be sufficient to prevent or delay the development of manifest high blood pressure.
  • nitrotyrosine indicates nitrosative stress. It is known that in the context of inflammatory diseases, especially those caused by bacteria, the eNOS enzyme system and thus the NO supply for vascular regulation can be destabilized. As a result, reactive oxygen radicals can intensify the inflammatory processes. Inflammatory vascular wall reactions are crucial for the development or intensification of atherosclerotic vascular changes and their secondary diseases. Therefore, sufficient stabilization and activation of the vascular wall-regulating enzyme eNOS is very important for sufficient and regulated NO supply over the course of the day.
  • Example 3 Diabetes, liver function, lipid metabolism, sex hormones
  • the blood value measurements for blood lipids, the "liver values", sugar and sex hormones are summarized in Table 2. In each case, the difference between the measured blood value at the end of the study minus the value at the beginning of the study before starting to take the test medication is given. [00045] Table 2
  • the value was reduced between -0.05 and -0.33 mg/dl in 5/10 (50%) of the subjects and between -0.02 and -0.29 mg/dl in 6/9 (67%) of the comparison group A.
  • the liver enzyme GPT improved significantly more in group B than in the comparison group A.
  • 8/10 (80%) of the subjects showed an improvement with a reduction between -1 and -39 U/l.
  • the comparison group A only 4/9 (44%) of the subjects showed a reduction between -2 and -7 U/l.
  • the liver enzyme gamma-GT showed an effect in more subjects, but on average it was less effective than in group B.
  • group B 5/10 (50%) showed an improvement of between -4 and -89 U/l.
  • group B there was an improvement of GPT into the normal range in 2 subjects (from 60 U/l to 21 U/l and from 53 U/l to 31 U/l), and of Gamma GT in one subject (108 U/l to 19 U/l).
  • no subject was able to achieve an improvement in the liver enzyme values into the normal range; on the contrary, in one subject the GPT value deteriorated beyond the normal range (from 21 U/l to 36 U/l).
  • Triglycerides were reduced between -25.60 mg/dl and -204.00 mg/dl in 8/10 (80%) of the subjects in group B, and between -0.70 mg/dl and -42.00 mg/dl in 5/9 (56%) of the subjects in the comparison group A.
  • group B 5 Subjects showed an improvement into the normal range (from 360 mg/dl to 156 mg/dl, from 214 mg/dl to 134 mg/dl, from 251 mg/dl to 136 mg/dl, from 206 mg/dl to 132 mg/dl, and from 150 mg/dl (normal limit) to 75.5 mg/dl).
  • Table 3 Number of patients with slight or significant improvement of the respective symptoms
  • the symptom "tiredness” was mentioned before the start of the study by 6 of the 10 subjects in group B and by 4 of the 9 subjects in comparison group A. Surprisingly, 4 of the 6 affected subjects in group B reported a significant improvement compared to only 2 of the 4 affected subjects in comparison group A. Other examples are “cramps” and “muscle tension”, which were significantly improved in the 2 and 3 affected subjects in group B, respectively, compared to only a slight improvement in the 3 subjects with cramps and 2 subjects with muscle tension in comparison group A. A similar picture can be seen with "joint pain” with a significant improvement in 3 of 4 subjects in group B, compared to only a slight improvement in the 3 subjects in comparison group A.
  • a surprising treatment success was seen in one subject in Group B had a "tinnitus” that disappeared completely during the 8-week study medication and, surprisingly, returned after the study medication had been stopped.
  • Arginine products are generally known to reduce systolic and diastolic peripheral blood pressure.
  • the TELCOR-Arginine plus study cited also explicitly refers to the reduction in blood pressure at night. The study results reported were that systolic blood pressure fell by 16.5% and diastolic by 14.7% the night before the start of the study. At the end of the 6-month study, the nighttime reduction in diastolic blood pressure increased by 2.9% to 17.9% and systolic by 3.2% to 19.4%. According to the German Hypertension League, these reductions are within the range of fluctuations in the circadian rhythm.
  • Another aspect to be taken into account when interpreting the study is that no study participants with existing drug therapy for hypertension were included in the TELCOR-Arginine plus study.
  • the surprisingly significant reduction in blood pressure after taking the active ingredient combination according to the invention was even achieved in the test subjects on top of the continuation of the respective medicinal anti-hypertensive therapy.
  • the oral active ingredient combination as a drug for the treatment of one or more of the diseases/symptoms of the metabolic syndrome - i.e. peripheral insulin resistance/diabetes type II, obesity, hypertension, lipid metabolism disorders as well as erectile dysfunction, libido disorders and menopausal complaints - promising.
  • Therapeutic use to improve liver dysfunction is also possible.
  • the combination of active ingredients is ideally suited to be used as a dietary supplement or food for special medical purposes for preventive purposes and as an adjunct to therapy from the age of 40.

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Abstract

L'invention se rapporte à une combinaison de principes actifs oraux qui comprend de la L-arginine, de la L-citrulline et un composé de sélénium, et également du bore soluble dans l'eau. La L-arginine, la L-citrulline et le composé de sélénium sont formulés pour une ingestion à un intervalle de 2 à 4 heures après le bore, pour l'alimentation animale, des médicaments, des compléments alimentaires ou des aliments à des fins médicales particulières ou en tant que médicaments ou médicaments pour animaux permettant de traiter une ou plusieurs des pathologies suivantes : le diabète de type II, le surpoids, l'hypertension, les troubles du métabolisme des lipides, la dysfonction hépatique, la dysfonction érectile et les troubles de la libido.
PCT/EP2024/055572 2023-04-06 2024-03-04 Combinaison de principes actifs oraux contenant de la l-arginine, de la l-citrulline, du sélénite et du bore soluble dans l'eau Pending WO2024208506A1 (fr)

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AU2024253060A AU2024253060A1 (en) 2023-04-06 2024-03-04 Oral active ingredient combination containing l-arginine, l-citrulline, selenite and water-soluble boron

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EP23167108 2023-04-06
EP23167108.2 2023-04-06

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080268066A1 (en) * 2005-03-30 2008-10-30 Pficker Pharmaceuticals Ltd. Synergistic Formulation for Preventing and/or Treating Diabetes

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080268066A1 (en) * 2005-03-30 2008-10-30 Pficker Pharmaceuticals Ltd. Synergistic Formulation for Preventing and/or Treating Diabetes

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