AT18425U1 - COMBINATION PREPARATION FOR THE DIETARY TREATMENT OF STOMACH AND INTESTINAL COMPLAINT CAUSED BY HELICOBACTER PYLORI INFECTIONS - Google Patents

Abstract

The present invention comprises an enteric capsule containing at least sulforaphane and/or a precursor thereof, curcumin, piperine and a probiotic.

Description

Description

COMBINATION PREPARATION FOR THE DIETARY TREATMENT OF STOMACH AND INTESTINAL COMPLAINT CAUSED BY HELICOBACTER PYLORI INFECTIONS

FIELD OF THE INVENTION

[0001] The invention comprises a combination preparation for special medical purposes, preferably for the dietary treatment of gastric complaints caused by Helicobacter pylori infections. The invention relates to a capsule containing at least the active ingredients sulforaphane and/or a precursor thereof, curcumin, piperine, and a probiotic.

BACKGROUND OF THE INVENTION

[0002] With a prevalence of approximately 50% worldwide, Helicobacter pylori infection is one of the most common chronic bacterial infections.

[0003] Helicobacter pylori infections are thought to be responsible for a number of gastric diseases associated with increased gastric acid secretion. These include, for example, type B gastritis, gastric ulcers, and duodenal ulcers. Testing for Helicobacter pylori infection is therefore an essential part of diagnosing gastric diseases.

[0004] Chronic infection with Helicobacter pylori is a risk factor for the development of gastric cancer and MALT lymphoma. Furthermore, Helicobacter pylori has been associated with many other diseases, such as idiopathic chronic urticaria, chronic immune thrombocytopenia, etiologically unexplained iron deficiency anemia, and Parkinson's disease.

[0005] Eradication therapy for Helicobacter pylori usually consists of a combination of a proton pump inhibitor with at least two antibiotics, as antibiotic monotherapies are not sufficiently effective. However, eradication often fails due to reinfection via oral plaque. Antibiotic resistance may also be a possible cause of failure.

[0006] However, none of these therapeutic approaches has so far been able to achieve a significant and sustained improvement in Helicobacter pylori infection.

[0007] Accordingly, there is neither a general remedy nor preparations for long-term improvement of basic symptoms. SUMMARY OF THE INVENTION

[0008] The above-mentioned problem is solved by the combination preparation or capsule of the present invention.

[0009] In particular by a capsule containing at least the active ingredients i.. sulforaphane and/or a precursor thereof,

il. Curcumin,

ill. Piperine, and

iv. a probiotic.

[0010] Specifically, the capsule is characterized in that the sulforaphane and/or a precursor thereof is contained as broccoli extract, preferably as broccoli seed extract or as broccoli sprout extract.

[0011] Specifically, the capsule is characterized in that the broccoli extract contains at least 5% sulforaphane and/or a precursor thereof, preferably at least 10%.

[0012] Specifically, the capsule is characterized in that it contains sulforaphane and/or a precursor thereof in an amount of 10 - 30 mg, preferably in an amount of 30 mg.

[0013] The capsule is specifically characterized in that the precursor of sulforaphane is glucoraphanin.

[0014] The capsule is specifically characterized by the fact that it additionally contains the enzyme myrosinase.

[0015] Specifically, the capsule is characterized in that curcumin is an extract of Curcuma longa, preferably the extract of Curcuma longa contains at least 90% curcuminoids.

[0016] Specifically, the capsule is characterized in that it contains curcumin in an amount of 1,200 mg, preferably in an amount of 90 mg.

[0017] Specifically, the capsule is characterized in that piperine is contained in an amount of 0.10 2.50 mg, preferably in an amount of 1.3 mg.

[0018] Specifically, the capsule is characterized in that the probiotic is contained in an amount of at least 1x10° cfu, preferably in an amount of 13.2x10° cfu.

[0019] Specifically, the capsule is characterized in that the probiotic is contained in an amount of 5 - 150 mg, preferably in an amount of 132 mg.

[0020] Specifically, the capsule is characterized in that the probiotic is selected from the group consisting of Lactobacillus spp., preferably Lactobacillus acidophilus, Lactobacillus rhamnosus, and Lactobacillus casei; Lactococcus lactis; Bifidobacterium spp., preferably Bifidobacterium infantis, Bifidobacterium breve, and Bifidobacterium longum; Streptococcus spp., preferably Streptococcus thermophilus; Saccharomyces spp., preferably Saccharomyces boulardii; and a combination thereof.

[0021] Specifically, the capsule is characterized in that it is an immediate release capsule.

[0022] Specifically, the capsule is characterized in that it contains at least one pharmaceutically or dietary acceptable excipient and/or additive.

[0023] Specifically, the capsule is characterized in that the excipient and/or additive is selected from fillers, lubricants, preservatives, antioxidants, disintegrants, binders, thickeners, colorants, sweeteners, or flavorings.

[0024] Specifically, the capsule contains 30 mg sulforaphane, 90 mg curcumin, 1.3 mg piperine, and 132 mg Lactobaecillus acidophilus.

[0025] The capsule is specifically characterized by the fact that it additionally contains ascorbic acid.

[0026] Specifically, the capsule is characterized by containing ascorbic acid in an amount of 1-80 mg.

[0027] Specifically, the capsule is used to manufacture a medicament for the treatment of stomach and intestinal disorders.

[0028] Specifically, the capsule is used to manufacture a medicinal product for the treatment of symptoms caused by an infection with Helicobacter pylori.

[0029] Specifically, the capsule is used as a medicine, food supplement, or dietary food.

[0030] In particular, the capsule has the advantage that the active ingredients can develop their synergistic effect by taking them simultaneously in one capsule. Specifically, both sulforaphane and curcumin have germicidal effects on Helicobacter pylori, with curcumin additionally possessing anti-inflammatory and antioxidant properties. Sulforaphane also inhibits the bacterial enzyme urease, which is produced by Helicobacter pylori.

Lactobacillus acidophilus is produced to protect against the acidic environment of the stomach. Lactobacillus acidophilus is a beneficial bacterium naturally occurring in the stomach and intestines. It competes with Helicobacter pylori for colonization sites in the gastric mucosa and supports the microbiota, which is generally weakened by concurrent antibiotic use.

[0031] Specifically, one dose is one capsule. A daily dose comprises at least one dose, i.e., one capsule.

[0032] Specifically, the daily dose of the capsule comprises 1, 2, 3, 4, 5, 6, or more capsules. Preferably, 1 capsule is taken twice daily, unchewed, with plenty of water. Specifically, these capsules are taken before breakfast and before dinner.

DETAILED DESCRIPTION OF THE INVENTION

[0033] Specific terms as used in the description have the following meaning.

[0034] The term "immediate release" refers to a solid dosage form with immediate release of the active ingredient, consisting of a capsule shell and filling. An immediate release is therefore not enteric-coated.

[0035] "Sulforaphane" is also known by the chemical name 1-isothiocyanato-4-methylsulfinyl-butane and is an isothiocyanate. Sulforaphane is found primarily in broccoli, Brussels sprouts, and cauliflower. For several years, research has been conducted into its potential use in cancer therapy, arthritis, and respiratory diseases. A precursor to sulforaphane is glucoraphanin.

[0036] Glucoraphanin is a mustard oil glycoside (glucosinolate) found in various cruciferous plants, particularly in brassicas such as broccoli. Sulforaphane is formed during the enzymatic hydrolysis of glucoraphanin, for example, by the plant's own myrosinase.

[0037] In the capsule, the sulforaphane may also be present as a precursor of glucoraphanin or as a mixture of sulforaphane and glucoraphanin.

[0038] In one embodiment of the invention, a capsule comprises broccoli extract containing the sulforaphane and/or a precursor thereof.

[0039] In one embodiment of the invention, a capsule comprises broccoli seed extract containing the sulforaphane and/or a precursor thereof.

[0040] In one embodiment of the invention, a capsule comprises broccoli sprout extract containing the sulforaphane and/or a precursor thereof.

[0041] In one embodiment of the invention, the broccoli extract is a broccoli seed extract or a broccoli sprout extract.

[0042] In one embodiment of the invention, the broccoli extract contains sulforaphane and/or a precursor thereof in a range of 5-20%, 5-15%, 10-20%, or 10-15%. Preferably, the broccoli extract contains at least 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, or more of sulforaphane and/or a precursor thereof, preferably at least 10%.

[0043] In one embodiment of the invention, the capsule contains sulforaphane and/or a precursor thereof in an amount of 5-50, 5-45, 5-40, 5-35, 5-30, 5-25, 5-20, 5-15, 5-10, 10-50, 10-45, 10-35, 10-30, 10-25, 10-20, 10-15, 20-50, 20-45, 20-40, 20-35, 20-30, or 20-25 mg. Preferably, the capsule contains sulforaphane and/or a precursor thereof in an amount of 10-30 mg, preferably in an amount of 20 or 30 mg.

[0044] In one embodiment of the invention, the capsule contains sulforaphane and glucoraphanin.

[0045] In one embodiment of the invention, the capsule contains sulforaphane or

Glucoraphanin.

[0046] "Myrosinase" is an enzyme of plant origin that catalyzes the conversion of glucoraphanin to sulforaphane. Myrosinase is found primarily in cruciferous vegetables (Brassicaceae), such as mustard, Brussels sprouts, and radish, as well as in caper plants (Capparaceae), such as capers.

[0047] In one embodiment of the invention, the capsule contains myrosinase from broccoli extract, mustard powder, or nasturtium.

[0048] In one embodiment of the invention, the capsule contains broccoli extract, mustard powder, or nasturtium which contain myrosinase.

[0049] In one embodiment of the invention, the capsule contains myrosinase in an amount of 1-20, 1-15, 1-10, 5-20, 5-15, 5-10, 5-9, 5-8, 6-20, 6-15, 6-10, 6-9, or 6-8 mg. Preferably, the capsule contains myrosinase in an amount of 5-10 mg, preferably in an amount of at least 7 mg.

[0050] In a specific embodiment, the capsule contains 7.8 mg myrosinase.

[0051] In one embodiment of the invention, the capsule contains broccoli extract, wherein the broccoli extract contains myrosinase in a concentration of 4% by weight.

[0052] "Curcumin" is the main component of turmeric, Curcuma longa L., a member of the ginger family, which is native to India and Southeast Asia and has been traditionally used for thousands of years, primarily as a digestive aid and for bile duct disorders. It is also used for food preservation and as a yellow dye for textiles. Ground turmeric is a main component of curry powder. Key components of turmeric are the curcuminoids, which, in addition to curcumin, also include demethoxycurcumin, bisdemethoxycurcumin, and cyclocurcumin (Curcumin | to IV).

[0053] The various effects of curcumin and curcuminoids have been intensively researched for several years. To date, anti-inflammatory, immune-modulating, antioxidant, antiseptic, analgesic, antiproliferative, cytotoxic, and antitumor properties have been demonstrated, among others. Pharmacokinetic studies on the properties of curcumin show that it is poorly absorbed after oral administration, and only traces of the compound are found in the blood, while the majority is excreted in the feces. Therefore, curcumin is found only in low concentrations in the blood.

[0054] In one embodiment of the invention, the capsule contains an extract of Curcuma longa containing curcumin. In a preferred embodiment, the extract of Curcuma longa contains at least 90% curcuminoids.

[0055] In one embodiment of the invention, the capsule contains curcumin in an amount of 1-200, 10-200, 20-200, 30-200, 40-200, 50-200, 60-200, 1-250, 10-250, 20-250, 30-250, 40-250, 50-250, or 60-250 mg.

[0056] In one embodiment of the invention, the capsule contains at least 1, 5, 10, 50, 100, 150, 200, or 250 mg of curcumin. Preferably, one capsule contains 60, 70, 80, or 90 mg of curcumin. Specifically, one capsule contains 60 or 90 mg of curcumin.

[0057] Piperine is the main alkaloid of black pepper (Piper nigrum) and is responsible for the spice's pungent taste. Piperine can be synthetically produced from piperidine and piperic acid, but can also be extracted from black pepper with ethanol and then crystallized. Like all pungent substances, piperine stimulates metabolism and secretion (saliva, digestive juices) and has an antimicrobial effect. Furthermore, piperine increases the bioavailability of various substances after oral administration by inhibiting first-pass metabolism through the liver and leading to increased absorption. Specifically, piperine increases the bioavailability of drugs by inhibiting glucuronidation in the liver and small intestine. Piperine is known to increase serum concentration, the extent of

It can increase the absorption and bioavailability of curcumin by up to 20-fold in both rats and humans. Piperine is therefore administered together with curcumin to increase the concentration of curcumin in the blood.

[0058] A capsule of the present invention preferably contains Bioperine® black pepper extract 95% piperine.

[0059] In one embodiment of the invention, the capsule contains piperine in an amount of 0.05-3.0, 0.10-2.50, 0.10-2.00, 0.10-1.50, 0.10-1.00, 0.20-3.00, 0.20-2.50, 0.20-2.00, 0.20-1.50, 0.20-1.00, 0.30-3.00, 0.30-2.50, 0.30-2.00, 0.30-1.50, 0.30-1.00, 0.40-3.00, 0.40-2.50, 0.40-2.00, 0.40-1.50, 0.40-1.00, 0.50-3.00, 0.50-2.50, 0.50-2.00, 0.50-1.50, 0.50-1.00, 0.60-3.00, 0.60-2.50, 0.60-2.00, 0.60-1.50, 0.60-1.00, 0.70-3.00, 0.70-2.50, 0.70-2.00, 0.70-1.50, 0.70-1.00, 0.80-3.00, 0.80-2.50, 0.80-2.00, 0.80-1.50, or 0.80-1.00 mg.

[0060] In one embodiment of the invention, the capsule contains at least 0.05, 0.10, 0.20, 0.30, 0.40, 0.50, 0.60, 0.70, 0.80, 0.90, 1.00, 1.50, 2.00, 2.50 or 3.00 mg of piperine. Preferably, a capsule contains 0.70, 0.80, 0.81, 0.82, 0.83, 0.84, 0.85, 0.86, 0.87, 0.88, 0.89, 0.9, 1.0, 1.1, 1.2, 1.3, or 1.4 mg of piperine. Specifically, a capsule contains 0.87 or 1.3 mg of piperine.

[0061] The term "probiotic" refers to living microorganisms that, when applied in sufficient numbers, can exert a health-promoting effect on the host. Probiotic microorganisms primarily include representatives of the lactobacilli, bifidobacteria, and yeasts such as Saccharomyces boulardii. A probiotic can be propagated in pure culture in a fermenter/bioreactor and subsequently processed by freeze-drying.

[0062] Preferably, a capsule contains at least 1x10®, 1x10%, 4.4x10°%, 8.8x10°%, 13.2x10°®, 1x107%, 1x10'', or 1x10’? colony forming units (cfu) per capsule of the probiotic, preferably in an amount of at least 4.4x10°, 8.8x10°%, or 13.2x10° cfu. Specifically, the capsule contains 8.8x10° cfu of the probiotic. Specifically, the capsule contains 13.2x10° cfu of the probiotic. Accordingly, one capsule contains at least 50, 100, 150, 200, 250, 300, 350, 400, 450, 500, or more mg of the probiotic, preferably 88 or 132 mg.

[0063] In one embodiment, the capsule contains at least 1, 2, 3, 4, or 5 probiotics selected from the group consisting of Lactobacillus spp., Lactococcus lactis, Bifidobacterium spp., Streptococcus spp., and Saccharomyces spp..

[0064] In one embodiment, the capsule contains at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 probiotics selected from the group consisting of Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus casei, Lactococcus lactis, Bifidobacterium infantis, Bifidobacterium breve, Bifidobacterium longum, Streptococcus thermophilus, and Saccharomyces boulardii.

[0065] The term "Lactobacillus spp." refers to the bacterial genus Lactobacillus from the Lactobacillaceae family. Representatives of the genus Lactobacillus are gram-positive bacteria; they do not form survival forms such as endospores and are incapable of active movement. Lactobacillus species are predominantly rod-shaped, with cells occurring singly or in chains. However, cocci-shaped variants can also occur.

[0066] "Lactobacillus acidophilus," or also called "L. acidophilus," refers to a bacterial species of the genus Lactobacillus. Lactobacillus acidophilus is a facultative anaerobic, Gram-positive rod that homofermentatively ferments glucose to lactic acid without producing any gases. It grows up to 45 °C (some strains up to 48 °C), and has diverse nutrient requirements for the culture medium.

[0067] “Lactobacillus rhamnosus,” or also called “L. rhamnosus,” refers to a bacterial species of the genus Lactobacillus. Lactobacillus rhamnosus is a Gram-positive, medium-length, rod-shaped bacterium. A single cell is 2.0-4.0 μm long and 0.8-1.0 μm wide. In the light microscopic image, individual cells as well as cell chains are seen. The bacterium does not possess flagella for active movement and cannot develop persistence forms such as endospores.

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form.

[0068] "Lactobacillus casei," or also called "L. casei," refers to a bacterial species of the genus Lactobacillus. Lactobacillus casei is a rod-shaped, Gram-positive bacterium. It belongs to the smaller Lactobacillus species and grows in the form of shorter or longer rods with mostly rounded corners and an average size of 0.9 μm in diameter and 2 μm in length. They are usually found singly or in pairs, less frequently in short chains.

[0069] "Lactococcus lactis," or also called "L. lactis," refers to a species of bacteria in the genus Lactococcus. Lactococcus lactis is a Gram-positive bacterium used in the production of buttermilk, curds, kefir, and cheese. The cells of Lactococcus lactis are cocci that form pairs or short chains and, depending on the growth conditions, appear oval with a length of 0.5 to 1.5 μm. They do not form survival forms such as endospores and are non-motile.

[0070] The term "Bifidobacterium spp." refers to the bacterial genus Bifidobacteria. Bifidobacteria, identical to the bacterial genus Bifidobacterium, belong to the family Bifidobacteriaceae, which are Gram-positive, non-motile, non-spore-forming, predominantly anaerobic rod-shaped bacteria and are often club-shaped ("coryneform").

[0071] "Bifidobacterium infantis", or also called "B. infantis", refers to a subspecies of Bifidobacterium longum. B. infantis, along with other bifidobacteria, is one of the first natural inhabitants of the large intestine and is among the most common representatives of the intestinal flora in breastfed newborns. B. infantis is marketed worldwide as a dietary supplement in a wide variety of products. B. infantis adheres firmly to the intestinal mucosa and multiplies rapidly there. B. infantis produces lactic and acetic acid when converting sugar, thereby lowering the pH value in its environment. This prevents pathogens from establishing themselves and multiplying, or only to a very limited extent. B. infantis also produces B vitamins, such as folic acid, thiamine (vitamin B1), pyridoxine (vitamin B6), biotin (vitamin B7), and niacin. The normal, non-pathogenic bacterial culture of the gastrointestinal tract, appendix and vagina includes, among others, B. bifidum, B. adolescentis, B. breve, B. longum and B. infantis.

[0072] "Bifidobacterium breve" refers to a species of bacteria of the genus Bifidobacterium. [0073] "Bifidobacterium longum" refers to a species of bacteria of the genus Bifidobacterium.

[0074] The term "Streptococcus spp." refers to the bacterial genus Streptococci. Streptococci are bacteria of the genus Streptococcus in the family Streptococcaceae, coccal (approximately spherical), preferentially arranged in chains, Gram-positive, and aerotolerant.

[0075] “Streptococcus thermophilus”, or also called “S. thermophilus”, refers to a subspecies of Streptococcus salivarius and is a Gram-positive, facultatively anaerobic, and spherical lactic acid bacterium.

[0076] The term “Saccharomyces spp.” refers to a yeast species of the family Saccharomycetaceae and forms a genus in the division of Ascomycetes.

[0077] "Saccharomyces boulardii," or also called "S. boulardii," refers to a yeast species of the genus Saccharomyces. Saccharomyces boulardii is also considered a subspecies or variety of Saccharomyces cerevisiae (Saccharomyces cerevisiae var. boulardii).

[0078] In a preferred embodiment, the capsule contains Lactobacillus acidophilus.

[0079] In a preferred embodiment, the capsule contains sulforaphane, curcumin, piperine, and Lactobacillus acidophilus. The sulforaphane may also be present as a precursor, glucoraphanin, or as a mixture of sulforaphane and glucoraphanin.

[0080] In another embodiment, the capsule contains sulforaphane, curcumin, piperine, Lactobacillus acidophilus, and myrosinase. The sulforaphane may also be present as a precursor, glucoraphanin, or as a mixture of sulforaphane and glucoraphanin.

[0081] “Ascorbic acid” is also known as vitamin C. In the invention, the term “ascorbic acid” also includes the salt of ascorbic acid ascorbate.

[0082] One capsule contains ascorbic acid in an amount of 1-80, 10-80, 20-80, 30-80, 40-80, 50-80, 60-80, 70-80, 1-70, 1-60, 1-50, 1-40, 1-30, 1-20, 1-10, 10-80, 10-70, 10-60, 10-50, 10-40, 10-30, 10-20, 20-80, 20-70, 20-60, 20-50, 20-40, 20-30, 30-80, 30-70, 30-60, 30-50, 30-40, 4080, 40-70, 40-60, 40-50, 50-80, 50-70, 50-60, 60-80, 60-70, or 70-80 mg.

[0083] In one embodiment of the invention, the capsule contains 1, 5, 10, 20, 30, 40, 50, 60, 70, or 80 mg of ascorbic acid.

[0084] In one embodiment of the invention, the capsule contains myrosinase and vitamin C. Vitamin C acts as a catalyst in the enzymatic conversion of glucoraphanin to sulforaphane by myrosinase.

[0085] In one embodiment, the capsule contains sulforaphane, curcumin, piperine, Lactobacillus acidophilus, myrosinase, and ascorbic acid. The sulforaphane may also be present as a precursor, glucoraphanin, or as a mixture of sulforaphane and glucoraphanin.

[0086] In one embodiment, the daily dose comprises 1, 2, 3, 4, 5, 6, or more capsules. Preferably, 1 capsule is taken twice daily, unchewed, with plenty of water. Specifically, these are taken before breakfast and before dinner.

[0087] Depending on the concentration of active ingredient in a capsule, the number of capsules per daily dose may vary.

[0088] In one embodiment, the preferred daily dose of sulforaphane comprises 60 mg per day. Specifically, the daily dose comprises 2 capsules, each capsule containing 30 mg of sulforaphane. Alternatively, the daily dose comprises 3 capsules, each capsule containing 20 mg of sulforaphane.

[0089] In one embodiment, the preferred daily dose of curcumin comprises 180 mg per day. Specifically, the daily dose comprises 2 capsules, each capsule containing 90 mg of curcumin. Alternatively, the daily dose comprises 3 capsules, each capsule containing 60 mg of curcumin.

[0090] In one embodiment, the preferred daily dose of piperine comprises 2.6 mg per day. Specifically, the daily dose comprises 2 capsules, each capsule containing 1.3 mg of piperine. Alternatively, the daily dose comprises 3 capsules, each capsule containing 0.87 mg of piperine.

[0091] In one embodiment, the preferred daily dose of probiotic comprises 264 mg per day. Specifically, the daily dose comprises 2 capsules, with one capsule containing 132 mg or 13.2 x 10° cfu of probiotic. Specifically, a daily dose comprises 3 capsules, with one capsule containing 88 mg or 8.8 x 10° cfu of probiotic.

[0092] In one embodiment, the preferred daily dose of probiotic comprises 132 mg per day, with one capsule containing 264 mg of probiotic for stability reasons. Specifically, the daily dose comprises 2 capsules, with one capsule containing 132 mg or 13.2 x 10° cfu of probiotic. Specifically, a daily dose comprises 3 capsules, with one capsule containing 88 mg or 8.8 x 10° cfu of probiotic.

[0093] The term "combination preparation" refers to a preparation containing at least the active ingredients sulforaphane and/or a precursor thereof, curcumin, piperine, and a probiotic. The sulforaphane may also be present as a precursor glucoraphanin or as a mixture of sulforaphane and glucoraphanin. In addition, other pharmaceutically or dietary-compatible excipients and/or additives may be included in the preparation. The combination preparation may be a capsule.

[0094] The term "pharmaceutically or dietary acceptable adjuvants and/or additives" refers to substances (excipients) useful in the manufacture of a pharmaceutical composition or formulation, which are generally safe, non-toxic, and neither biologically nor otherwise undesirable, and which can be used for both veterinary use and human pharmaceutical products. According to the IPEC definition, an excipient is any component of a medicinal product which is not an active ingredient and is deliberately included in the

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pharmaceutical compound has been incorporated. Pharmaceutical compositions of the subject invention contain as active ingredients the components mentioned herein: sulforaphane and/or a precursor thereof, curcumin, piperine, and a probiotic. These components may be associated with one or more pharmaceutically acceptable carriers or excipients. The excipient used is typically one suitable for administration to human subjects or other mammals. In preparing the compositions, the active ingredient is usually mixed with an excipient and enclosed in a carrier, which may be in the form of a capsule. When the excipient serves as a diluent, it may be a solid, semi-solid, or liquid material that acts as a vehicle, carrier, or medium for the active ingredient. Thus, the combination preparation may be in one of the following forms: soft or hard gelatin capsule, pill, powder, sachet, or sterile-packaged powder.

[0095] Some examples of suitable excipients include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia, calcium phosphate, alginates, tragacanth, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, sterile water, syrup, and methylcellulose. The formulation may additionally include: lubricants such as talc, magnesium stearate, and mineral oil; wetting agents; emulsifying and suspending agents; preservatives such as methyl and propyl hydroxybenzoates; sweetening agents; and flavoring agents. The compositions of the invention may be formulated to provide rapid, sustained, or delayed release of the active ingredient after administration to the patient by employing methods known in the art. The amount of carriers, excipients, and/or additives in the pharmaceutical composition may be varied or widely adjusted depending on the particular application, the potency of the particular compound, and the desired concentration.

[0096] The pharmaceutically or dietary-compatible excipient and/or additive may be a "filler." Fillers primarily serve to achieve a target weight during weight-based production, depending on the number and size of the capsules and the quantity/weight of the active ingredient. Examples of fillers include lactose, cellulose, cellulose powder, starch, sucrose, polyethylene glycols (macrogols, PEG), and polyethylene oxides (PEO).

[0097] The pharmaceutically or dietary-acceptable excipient and/or additive may be a "lubricating agent." This excipient is often also called a lubricant and can be used, among other things, to facilitate swallowing the capsule. Examples of lubricants include polyethylene glycols (PEG, macrogols), polyethylene oxides (PEO), talc, or magnesium stearate.

[0098] The pharmaceutically or dietary-acceptable excipient and/or additive may be a "preservative." Preservatives are used to extend the shelf life of the pharmaceutical compound. Examples of preservatives include PHB esters, benzalkonium chloride, benzyl alcohol, or thimerosal.

[0099] Pharmaceutically or dietary-compatible excipients and/or additives can be "antioxidants." Oxidation-sensitive substances decompose during storage as a result of what is known as autoxidation. This reaction is triggered by atmospheric oxygen and catalyzed by UV light and heavy metals. Heat and free radicals also promote autoxidation. Even small amounts of antioxidants can reduce or even prevent autoxidation. These are substances that are more easily oxidized than the active ingredients and excipients to be protected. For this reason, they react in their place but are consumed over time. Oxidation-sensitive active ingredients can therefore be protected with the help of antioxidants. Examples of antioxidants include butylhydroxytoluene, all-rac-x-tocopherol, and EDTA.

[00100] The pharmaceutically or dietary-compatible excipients and/or additives can be "disintegrants." Disintegrants serve, for example, to direct moisture into the tablet core and, through their swelling, accelerate the disintegration of the tablet. They are therefore often referred to as disintegration accelerators. Examples of disintegrants include modified

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Starches such as carboxymethyl starch, croscarmellose or sodium bicarbonate.

[00101] The pharmaceutically or dietary-compatible excipients and/or additives can be "binders." Binders particularly help to enlarge the particles in a pharmaceutical compound, can reduce the dust content in the mass to be processed, and in the case of further processing into tablets or capsules, they can improve plastic formability. The choice of binder can influence the porosity, disintegration time, and solubility of a pharmaceutical compound. Examples of binders include starches, guar gum, xanthan gum, alginate, carrageenan, pectin, tragacanth, polyacrylic acids, polyvinylpyrrolidone, highly dispersed silicon dioxide, or substituted cellulose ethers such as methylcellulose, ethylcellulose, hydroxypropylcellulose,

[00102] Hydroxypropylmethylcellulose or carboxymethylcellulose.

[00103] Pharmaceutically or dietary-compatible excipients and/or additives may be "thickeners." Thickeners are substances that, even when added in small amounts, cause a very significant increase in the viscosity of liquids. Their effect is based on swelling (e.g., gelatin in gels) or the formation of associative bonds. Examples of thickeners include cellulose, such as cellulose powder, microcrystalline cellulose, and cellulose derivatives such as hydroxypropylmethylcellulose and ethylcellulose, pectins, guar, karaya, locust bean gum, carrageenan, polyethylene glycol, and polyacrylic acid (Carbopol 7M).

[00104] The pharmaceutically or dietary-acceptable excipients and/or additives may be "sweeteners." Sweeteners are often used in pharmaceutical compounds, for example, to reduce any bitterness and to make oral administration easier and more pleasant. Examples of sweeteners include sucrose, sorbitol, and sweeteners such as saccharin sodium and cyclamate.

[00105] The pharmaceutically or dietary-compatible excipients and/or additives may be "flavoring agents." Flavoring agents are often used in pharmaceutical compositions to adjust the taste and make oral administration easier and more pleasant. Various flavors are often used for taste correction.

[00106] The term "powder" refers to loose pharmaceutical powders, which are mixtures of finely divided medicinal products in dry form, which are ultimately processed into capsules, film-coated tablets, creams, or other medicinal forms. The powders contain one or more active ingredients with or without excipients. A distinction is made between divided (= single-dose) powders and multi-dose powders.

[00107] The term "granules" refers to grain-like structures consisting of coarsely ground solid substances. Granules consist of powder particles cemented together by a binding agent. They often have better water solubility than powder and are usually taken with plenty of liquid.

[00108] The term "dietetic food" generally refers to a food for special medical purposes that meets the specific nutritional requirements of persons suffering from, or who are malnourished as a result of, certain diseases, disorders or conditions. "Food for special medical purposes" is a category of foods for a particular diet that are specially processed or formulated and intended for the dietary treatment of patients and to be used under medical supervision. Their purpose is the exclusive or partial nutrition of patients with a limited, impaired or disturbed ability to ingest, digest, absorb, metabolise or excrete ordinary foods or certain nutrients contained therein or their metabolites, or of patients with other medically determined nutritional needs for whose dietary treatment modification of the normal diet, other foods for a particular diet or a combination of both is not sufficient.

[00109] Use of the present combination preparation as a dietary

Food is primarily used for the dietary treatment of stomach and intestinal complaints, especially stomach and intestinal complaints caused by an infection with Helicobacter pylori.

[00110] The term ‘food supplement’ refers to foodstuffs intended to supplement, but not replace, the normal diet and which consist of single or multiple concentrates of nutrients or other substances with a nutritional or physiological effect and which are marketed in dosed form, i.e. in the form of, for example, capsules, lozenges, tablets, pills and other similar presentations, powder sachets, liquid ampoules, bottles with dropper inserts and similar presentations of liquids and powders for ingestion in measured small quantities.

[00111] Helicobacter pylori (H. pylori) infection is a common bacterial infection that can cause gastritis, peptic ulcers, and certain types of stomach cancer. Symptoms of Helicobacter pylori infection include indigestion and upper abdominal pain or discomfort.

[00112] Numerous case reports and individual clinical studies demonstrate the antibacterial effect of broccoli on Helicobacter pylori. The natural content of sulforaphane, the antibacterial component of broccoli, is approximately 1 mg/20 g of raw broccoli, which, at a therapeutically effective daily dose of 60 mg of sulforaphane, corresponds to approximately 1 kg of raw broccoli. In cooked or otherwise thermally prepared broccoli, the sulforaphane levels are correspondingly lower.

[00113] The curcumin content of dried turmeric, Curcuma longa, is approximately 3%, while curry or other turmeric-containing spices contain significantly less (approximately 0.3%). A therapeutically effective daily dose of 180 mg of curcumin would correspond to the intake of 6 g of turmeric powder (or 60 g of curry).

[00114] The advantages of the capsule according to the invention lie, on the one hand, in the simplified, concentrated and tasteless intake of the ingredients sulforaphane and curcumin, and, on the other hand, in the combined administration of both ingredients in one capsule.

EXAMPLES

1. Composition of the product “CoCurmin Broccoli”: Ingredients per daily dose of active ingredient, for example per 2 or 3 capsules

Broccoli seed extract 585 mg

Contains Sulforaphane 58.5 mg Turmeric root extract (Curcuma longa) 257.1 mg

contains total curcuminoids 244.3 mg

of which curcumin 180 mg

Lactobacillus acidophilus* 132 mg (13.2 x 10% CFU) Black pepper extract 2.7 mg

contains piperine 2.6 mg

Ingredients: Broccoli seed extract, capsule shell hydroxypropylmethylcellulose, bulking agent microcrystalline cellulose, turmeric root extract, Lactobacillus acidophilus, medium-chain triglycerides from coconut, color chlorophyllin copper complex, black pepper extract.

*Bacterial culture overdosed by 100% for stability reasons (264 mg bacterial culture included)

Claims (18)

Claims 1. Capsule containing at least i. sulforaphane and/or the precursor glucoraphanin thereof, il. curcumin, ill. piperine, and iv. a probiotic. 2. Capsule according to claim 1, characterized in that the sulforaphane glucoraphanin and/or glucoraphanin is contained as broccoli extract, preferably as broccoli seed extract or as broccoli sprout extract. 3. Capsule according to claim 2, characterized in that the broccoli extract contains at least 5% sulforaphane and/or glucoraphanin, preferably at least 10%. 4. Capsule according to one of claims 1 to 3, characterized in that it contains sulforaphane and/or glucoraphanin in an amount of 10 - 30 mg, preferably in an amount of 30 mg. 5. Capsule according to one of claims 1 to 4, characterized in that it additionally contains the enzyme myrosinase. 6. Capsule according to one of claims 1 to 5, characterized in that curcumin is an extract from Curcuma longa, preferably the extract from Curcuma longa contains at least 90% curcuminoids. 7. Capsule according to one of claims 1 to 6, characterized in that curcumin is contained in an amount of 1 - 200 mg, preferably in an amount of 90 mg. 8. Capsule according to one of claims 1 to 7, characterized in that piperine is contained in an amount of 0.10 - 2.50 mg, preferably in an amount of 1.3 mg. 9. Capsule according to one of claims 1 to 8, characterized in that the probiotic is contained in an amount of at least 1x10® cfu, preferably in an amount of 13.2 x 10° cfu. 10. Capsule according to one of claims 1 to 9, characterized in that the probiotic is contained in an amount of 5-150 mg, preferably in an amount of 132 mg. 11. Capsule according to one of claims 1 to 10, characterized in that the probiotic is selected from the group consisting of Lactobacillus spp., preferably Lactobacillus acidophilus, Lactobacillus rhamnosus, and Lactobacillus casei; Lactococcus lactis; Bifidobacterium spp., preferably Bifidobacterium infantis, Bifidobacterium breve, and Bifidobacterium longum; Streptococcus spp., preferably Streptococcus thermophilus; Saccharomyces spp., preferably Saccharomyces boulardii; and a combination thereof. 12. Capsule according to one of claims 1 to 11, characterized in that it is an immediate release capsule. 13. Capsule according to one of claims 1 to 12, characterized in that it contains at least one pharmaceutically or dietary acceptable excipient and/or additive, preferably selected from fillers, lubricants, preservatives, antioxidants, disintegrants, binders, thickeners, colorants, sweeteners, or flavorings. 14. Capsule according to one of claims 1 to 13, containing 30 mg sulforaphane, 90 mg curcumin, 1.3 mg piperine, and 132 mg Lactobaecillus acidophilus. 15. Capsule according to one of claims 1 to 14, characterized in that it additionally contains ascorbic acid, preferably in an amount of 1 - 80 mg. 16. Use of the capsule according to any one of claims 1 to 15 for the manufacture of a medicament for the treatment of complaints caused by an infection with Helicobacter pylori, selected from the group consisting of indigestion, pain, and upper abdominal discomfort. 17. A food supplement containing the capsule according to any one of claims 1 to 15. 18. Dietary food containing the capsule according to any one of claims 1 to 15. No drawings for this