WO2023160841A1 - Gastro-resistant capsule and use thereof - Google Patents

Gastro-resistant capsule and use thereof Download PDF

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Publication number
WO2023160841A1
WO2023160841A1 PCT/EP2022/082190 EP2022082190W WO2023160841A1 WO 2023160841 A1 WO2023160841 A1 WO 2023160841A1 EP 2022082190 W EP2022082190 W EP 2022082190W WO 2023160841 A1 WO2023160841 A1 WO 2023160841A1
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weight
enteric
capsule
approx
capsule according
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PCT/EP2022/082190
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German (de)
French (fr)
Inventor
Stephan Hausmanns
Martin Junginger
Alexander Raab
Holger Becker
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Gelita Ag
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Publication of WO2023160841A1 publication Critical patent/WO2023160841A1/en

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    • 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
    • A61K9/4816—Wall or shell material
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/175—Amino acids
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/18—Peptides; Protein hydrolysates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/745—Bifidobacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/28—Insulins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/39—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
    • 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
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
    • A23P10/00—Shaping or working of foodstuffs characterised by the products
    • A23P10/30—Encapsulation of particles, e.g. foodstuff additives

Definitions

  • the present invention relates to an enteric-coated capsule.
  • the invention also relates to the use of this gastric juice-resistant capsule as a pharmaceutical or dietary supplement for enriching the intestinal flora with probiotic bacteria, or for the enteric administration of proteins and/or peptides which develop a physiological effect in the small intestine or are resorbed.
  • Probiotic bacteria which include in particular certain types of the species Lactobacillus and Bifidobacterium, develop their effect primarily in the small intestine by being part of the intestinal flora, among other things, by suppressing the growth of unwanted microorganisms and by producing short-chain fatty acids (e.g. propionic acid and butyric acid). Promote the functioning of the intestinal epithelial cells.
  • Lactobacillus and Bifidobacterium develop their effect primarily in the small intestine by being part of the intestinal flora, among other things, by suppressing the growth of unwanted microorganisms and by producing short-chain fatty acids (e.g. propionic acid and butyric acid). Promote the functioning of the intestinal epithelial cells.
  • short-chain fatty acids e.g. propionic acid and butyric acid
  • Probiotic bacteria can be present in or added to certain foods (probiotics) through fermentation processes. In this case, however, the passage through the stomach is problematic, so that it is usually unclear whether and to what extent the probiotic bacteria reach the small intestine in a form capable of reproduction. For this reason, probiotic bacteria are also offered as food supplements or pharmaceuticals in such dosage forms that are intended to enable the bacteria to be fully or partially released only in the intestine. For example, the bacteria are deliberately overdosed to compensate for losses in the stomach, or capsules with an enteric coating are used to enable release in the intestine (enteric administration). A similar problem also exists when administering acid-sensitive proteins and/or peptides, which can also lose some or all of their physiological activity as a result of contact with gastric acid.
  • the object of the present invention is to propose an enteric form of administration for probiotic bacteria or for acid-sensitive proteins and/or peptides.
  • an enteric-juice-resistant capsule which comprises a capsule material and a filling enclosed by the capsule material, the capsule material comprising gelatin and pectin, and the filling comprising (i) probiotic bacteria or (ii) acid-sensitive proteins and/or peptides .
  • capsules based on gelatine are known in various forms, with a particular distinction being made between hard capsules and soft capsules.
  • the capsule according to the invention is in particular a soft capsule in which, due to the properties of the capsule material and the manufacturing process, it is fundamentally possible to completely enclose the filling with the capsule material.
  • This complete and hermetic encapsulation with the capsule material is a significant advantage of soft capsules compared to hard capsules with regard to the protection of the bacteria, proteins and/or peptides to be administered, both against gastric acid and against external influences before administration.
  • Another advantage of softgels is the possibility of a liquid filling.
  • the capsule material comprises a proportion of pectin in addition to gelatin.
  • Pectin is a vegetable polysaccharide which, like gelatine, has the properties of a hydrocolloid and is capable of forming gels.
  • a capsule is referred to as gastro-resistant if it survives at least 1 hour in simulated gastric acid (pH 1.2 at 37° C.) according to the disintegration test (USP ⁇ 701>) defined in the US Pharmacopeia.
  • the capsule material desirably comprises gelatin and pectin in a weight ratio of from about 99:1 to about 70:30.
  • Particularly good gastric resistance can be achieved with a weight ratio of gelatin and pectin in the range from about 95:5 to about 80:20, more preferably from about 90:10 to about 85:15.
  • a particular advantage of the gastric juice-resistant capsule according to the invention can be seen in particular in the fact that, apart from the addition of pectin, no further measures are required, in particular no coating or other treatment of the capsule in a subsequent process step.
  • the capsule according to the invention can be produced relatively inexpensively.
  • the production can also be carried out by means of the known processes for the production of soft gelatine capsules, such as the rotary die process. A modification of the production equipment and process parameters compared to normal soft gelatine capsules that do not contain pectin is not necessary.
  • the pectin contained in the capsule material can in particular be a low-methylated pectin, an amidated low-methylated pectin (amidopectin) or a high-methylated pectin.
  • a pectin is described as low or high methylated if the degree of methylation is below or above 50%.
  • composition of the capsule material according to the invention also offers the advantageous possibility of sealing the capsule during the Manufacturing process, especially in the rotary die process, at relatively low temperatures, for example in the range of about 36 to 38 ° C to perform. Limiting the temperature during capsule manufacture is beneficial with regard to the stability of the filling, especially when it contains probiotic bacteria.
  • the capsule material is typically formed from a gel mass which still has a significantly higher water content than the capsule material in the finished capsule.
  • this gel mass comprises a total of approx. 30 to approx. 50% by weight of gelatin and pectin, preferably approx. 35 to approx. 45% by weight, more preferably approx about 42% by weight, the gel mass then being dried to a water content of the capsule material of about 5 to about 10% by weight, preferably from about 6 to about 8% by weight.
  • the proportions by weight of gelatin given in the context of the invention relate in each case to the weight of the gelatin including the proportion of water bound in the gelatin, which is typically in the range of about 10% by weight.
  • the water content of the gel mass from which the capsule material of the capsule according to the invention is formed is typically in the range from about 30 to about 50% by weight, preferably from about 35 to about 45% by weight, more preferably from about 38 up to approx. 42% by weight.
  • the water content of the capsule material is, as mentioned above, in the range from about 5 to about 10% by weight, preferably from about 6 to about 8% by weight.
  • the capsule material of the capsule according to the invention typically comprises a total of approx. 50 to approx. 75% by weight gelatin and pectin, preferably approx. 55 to approx. 70% by weight, more preferably approx. 60 to approx. 65% by weight .%.
  • various conventional types of gelatin can generally be used, which are also otherwise used in the production of soft gelatin capsules.
  • preference is given to a medium-bloom gelatin which preferably has a gel strength of 110 to 150 g bloom, more preferably 115 to 145 g bloom.
  • the gelatin used can be produced from animal raw materials containing collagen by means of acid extraction (type A gelatin) or by means of alkaline extraction (type B gelatin).
  • the gelatin is preferably a type B gelatin, in particular a type B gelatin produced from bovine bones.
  • the capsule material of the enteric-coated capsule according to the invention advantageously contains one or more plasticizers. These ensure sufficient flexibility of the capsule material during drying and later storage and use of the capsule.
  • the plasticizer(s) in the capsule material of the capsule according to the invention are preferably selected from sugar alcohols, in particular from glycerol, sorbitol, sorbitan, mannitol, maltitol and/or xylitol, or from propylene glycol, polypropylene glycol and polyethylene glycol.
  • the capsule material is formed from a gel mass comprising about 15% to about 25% by weight of sugar alcohols, preferably about 18% to about 22% by weight. Particularly advantageous mechanical properties of the capsule material or the capsule result from these proportions.
  • the capsule material is formed from a gel mass which comprises about 7 to about 8% by weight of glycerol and about 11 to about 13% by weight of sorbitol and/or sorbitan. Sorbitan is formed by the dehydration of sorbitol and can exist in different isomers. According to a particularly preferred embodiment of the capsule according to the invention, the capsule material is formed from a gel mass which comprises: approx. 34 to approx. 36% by weight gelatin, approx. 4 to approx. 6% by weight pectin, approx.
  • the capsule material of the capsule according to the invention preferably comprises: about 53 to about 57% by weight gelatin, about 7 to about 8% by weight pectin, about 11 to about 12% by weight glycerin, about 18 to about 20% by weight sorbitol and/or sorbitan, about 6 to about 8% by weight water.
  • the capsule according to the invention is produced starting from the gel mass and the filling according to a production process known per se for soft gelatine capsules, in particular by means of the rotary die process.
  • the filling is introduced between two strands of gel mass in a continuous process.
  • the strands are portioned using an appropriate mold and the gel mass is hermetically sealed around the filling.
  • the gel mass is then dried to form the capsule material with the above-mentioned residual water content.
  • the filling of the gastric juice-resistant capsule according to the invention comprises probiotic bacteria.
  • the selection and proportions of different probiotic bacteria can be adjusted and varied depending on the specific application of the capsule.
  • the filling includes probiotic bacteria one or more genera selected from Lactobacillus, Bifidobacterium, Lactococcus, Pediococcus and Streptococcus. Bacteria of the species Lactobacillus lactis, Lactobacillus bulgaricus, Lactobacillus acidufilus and Bifidobacterium bifidum are preferred.
  • the filling preferably comprises a suspension of the probiotic bacteria in a hydrophobic medium.
  • the filling is essentially anhydrous or has a water activity a w of less than 0.4, preferably less than 0.3.
  • the absence of water in the filling significantly improves the stability and storage life of the probiotic bacteria, and on the other hand, an interaction with the capsule material can be avoided.
  • hydrophobic medium in which the probiotic bacteria are preferably suspended can also take into account the specific purpose of use of the capsule according to the invention.
  • a hydrophobic medium can be used with one or more components which in turn have a health-promoting effect.
  • the hydrophobic medium comprises one or more vegetable oils, animal oils and/or mixtures of triglycerides or fatty acids, which are preferably selected from rapeseed oil, borage oil, evening primrose oil, linseed oil, perilla oil, garlic oil, fish oil, krill oil, medium-chain triglycerides such as MCT oil, and omega-3 fatty acids such as DHA and EPA.
  • vegetable oils, animal oils and/or mixtures of triglycerides or fatty acids which are preferably selected from rapeseed oil, borage oil, evening primrose oil, linseed oil, perilla oil, garlic oil, fish oil, krill oil, medium-chain triglycerides such as MCT oil, and omega-3 fatty acids such as DHA and EPA.
  • the filling of the gastric juice-resistant capsule according to the invention comprises acid-sensitive proteins and/or peptides.
  • proteins/peptides which can advantageously be administered using the enteric-coated capsule according to the invention are undenatured type II collagen, proteohormones and peptide hormones such as insulin, and nutritionally active peptides such as collagen peptides, whey peptides, casein peptides and peptides from non-animal sources Sources.
  • the enteric-coated capsule according to the invention can have various sizes, which are generally known for soft gelatine capsules. In general, soft capsules with filling volumes in the range from approx. 100 pl to approx. 2,500 pl can be produced.
  • the capsule according to the invention therefore advantageously has a filling volume of approx. 300 to approx. 1000 pl, preferably from approx. 500 to approx. 750 pl. At the same time, these filling volumes are also sufficient for the administration of the planned amounts of probiotic bacteria, especially since an overdose is not necessary due to the gastric juice resistance of the capsule.
  • the capsule according to the invention can be designed as a round, oval or oblong capsule.
  • the thickness of the capsule material of the capsule according to the invention is typically in the range from about 250 to about 600 ⁇ m, preferably from about 400 to about 500 ⁇ m, for example about 450 ⁇ m. These values refer to the wall thickness of the finished capsule dried to the final water content. The thickness of the strands of gel mass during the manufacturing process is correspondingly greater, typically by a factor of about two.
  • the present invention further relates to the use of a gastric juice-resistant capsule according to the invention as a pharmaceutical or food supplement.
  • a first preferred embodiment relates to the use of a gastric juice-resistant capsule according to the invention for enriching the intestinal flora with probiotic bacteria.
  • This influencing of the intestinal flora, especially the small intestine has beneficial health effects, including the formation of short-chain fatty acids, especially propionic acid and Butyric acid, which reduces probiotic bacteria and suppresses the growth of harmful microorganisms.
  • the invention therefore relates in particular to the use of a gastric juice-resistant capsule according to the invention to improve intestinal health, in particular to prevent or treat irritable bowel syndrome, constipation, diarrhea, ulcerative colitis and Crohn's disease.
  • a second preferred embodiment relates to the use of a gastric juice-resistant capsule according to the invention as a pharmaceutical or food supplement for the enteric administration of proteins and/or peptides which have a physiological effect or are absorbed in the small intestine.
  • this includes, for example, undenatured type II collagen, proteohormones and peptide hormones such as insulin, and nutritionally active peptides such as collagen peptides, whey peptides, casein peptides and peptides from non-animal sources.
  • Type II undenatured collagen also known as UC-II
  • UC-II is used to relieve certain joint problems, including those caused by an autoimmune reaction against the body's own type II collagen in the joints.
  • UC-II exerts its physiological activity through an interaction with the Peyer's patches in the small intestine. In the process, immunological information is passed on, which should lead to suppression of the autoimmune reaction.
  • Enteral administration of UC-II by means of the capsule according to the invention can prevent partial degradation or inactivation during passage through the stomach and increase the effectiveness of the administered amount of UC-II.
  • a similar advantageous effect of the capsule according to the invention results from the administration of proteohormones or peptide hormones, which are generally resorbed in the small intestine in order to develop their physiological effect must.
  • Effective enteral administration of these acid-sensitive active substances would therefore be a conceivable alternative to subcutaneous administration, for example of insulin.
  • the capsule according to the invention can also be used advantageously for the administration of various nutritionally active peptides in order to protect them from a partial loss of effectiveness during passage through the stomach. It is known that such peptides with a molecular weight of up to 15 kDa can be resorbed in the small intestine.
  • collagen peptides which are obtained by enzymatic hydrolysis of collagen or gelatin, have various physiological activities and have positive effects on the health of bones, joints, muscles and skin, among other things.
  • Preferred collagen peptides within the scope of the invention are, for example, the products marketed by the applicant under the names VERISOL, FORTIGEL, FORTIBONE and CURADERM.
  • FIG. 1 schematic cross-sectional representation of a gastric juice-resistant capsule according to the invention.
  • FIG. 1 shows a schematic representation of a gastric juice-resistant capsule 10 according to the invention in cross section.
  • the capsule 10 comprises an encapsulating material 20 and a filling 30 , the filling 30 being completely enclosed by the encapsulating material 20 .
  • the encapsulating material 20 comprises gelatin and pectin. Preferred embodiments of the encapsulation material 20, in particular with regard to the qualitative and quantitative composition, have been described above.
  • the filling 30 includes probiotic bacteria.
  • the probiotic bacteria are preferably suspended in a hydrophobic medium.
  • Table 1 gives the percentage compositions (in % by weight), based on commercially available starting materials, for six exemplary embodiments of gel masses which can be used to produce gastric juice-resistant capsules according to the invention.
  • GELITA® EC is a mixture made by the applicant GELITA AG of approx. 88% by weight type B gelatine from bovine bones with a gel strength in the range from 115 to 145 g Bloom and approx. 12% by weight pectin.
  • Polysorb® 85/70/00 is a partially dehydrated sorbitol (ie sorbitol containing sorbitan) manufactured by Roquette with a solids content of approx. 85% by weight.
  • Neosorb® 70/70B is a sorbitol manufactured by Roquette with a solids content of approx. 70% by weight.
  • Sorbitol Special® is a mixture of sorbitol and sorbitan manufactured by SPI Pharma with a solids content of approx. 76% by weight.

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Abstract

The present invention relates to a gastro-resistant capsule. The capsule comprises a capsule material and a filling enclosed by the capsule material, wherein the capsule material comprises gelatin and pectin, and wherein the filling (i) has probiotic bacteria or (ii) acid-sensitive proteins and/or peptides.

Description

Magensaftresistente Kapsel und deren Verwendung Enteric-coated capsule and its use
Die vorliegende Erfindung betrifft eine magensaftresistente Kapsel. The present invention relates to an enteric-coated capsule.
Die Erfindung betrifft ferner die Verwendung dieser magensaftresistenten Kapsel als Pharmazeutikum oder Nahrungsergänzungsmittel zur Anreicherung der Darmflora mit probiotischen Bakterien, oder zur enterischen Verabreichung von Proteinen und/oder Peptiden, die im Dünndarm eine physiologische Wirkung entfalten oder resorbiert werden. The invention also relates to the use of this gastric juice-resistant capsule as a pharmaceutical or dietary supplement for enriching the intestinal flora with probiotic bacteria, or for the enteric administration of proteins and/or peptides which develop a physiological effect in the small intestine or are resorbed.
Die positiven Effekte von probiotischen Bakterien auf die Gesundheit sind seit längerem bekannt. Probiotische Bakterien, zu denen insbesondere bestimmte Arten der Spezies Lactobacillus und Bifidobacterium gehören, entfalten ihre Wirkung vornehmlich im Dünndarm, indem sie als Bestandteil der Darmflora u.a. das Wachstum von unerwünschten Mikroorganismen unterdrücken und durch die Produktion von kurzkettigen Fettsäuren (zum Beispiel Propionsäure und Buttersäure) die Funktionsfähigkeit der Darmepithelzellen fördern. The positive effects of probiotic bacteria on health have been known for a long time. Probiotic bacteria, which include in particular certain types of the species Lactobacillus and Bifidobacterium, develop their effect primarily in the small intestine by being part of the intestinal flora, among other things, by suppressing the growth of unwanted microorganisms and by producing short-chain fatty acids (e.g. propionic acid and butyric acid). Promote the functioning of the intestinal epithelial cells.
Probiotische Bakterien können in bestimmten Lebensmitteln (Probiotika) durch Fermentationsprozesse enthalten sein oder diesen zugesetzt werden. Problematisch ist in diesem Fall jedoch die Magenpassage, so dass meistens unklar ist, ob und in welchem Umfang die probiotischen Bakterien den Dünndarm in vermehrungsfähiger Form erreichen. Daher werden probiotische Bakterien auch als Nahrungsergänzungsmittel oder Pharmazeutika in solchen Darreichungsformen angeboten, die eine Freisetzung der Bakterien ganz oder teilweise erst im Darm ermöglichen sollen. Beispielsweise werden die Bakterien gezielt überdosiert, um Verluste im Magen zu kompensieren, oder es werden Kapseln mit einer magensaftresistenten Beschichtung eingesetzt, um die Freisetzung erst im Darm (enterische Verabreichung) zu ermöglichen. Eine ähnliche Problematik besteht auch bei der Verabreichung von säureempfindlichen Proteinen und/oder Peptiden, die ebenfalls durch einen Kontakt mit der Magensäure ihre physiologische Aktivität ganz oder teilweise einbüßen können. Probiotic bacteria can be present in or added to certain foods (probiotics) through fermentation processes. In this case, however, the passage through the stomach is problematic, so that it is usually unclear whether and to what extent the probiotic bacteria reach the small intestine in a form capable of reproduction. For this reason, probiotic bacteria are also offered as food supplements or pharmaceuticals in such dosage forms that are intended to enable the bacteria to be fully or partially released only in the intestine. For example, the bacteria are deliberately overdosed to compensate for losses in the stomach, or capsules with an enteric coating are used to enable release in the intestine (enteric administration). A similar problem also exists when administering acid-sensitive proteins and/or peptides, which can also lose some or all of their physiological activity as a result of contact with gastric acid.
Der vorliegenden Erfindung liegt die Aufgabe zugrunde, eine enterische Verabreichungsform für probiotische Bakterien oder für säureempfindliche Proteine und/oder Peptide vorzuschlagen. The object of the present invention is to propose an enteric form of administration for probiotic bacteria or for acid-sensitive proteins and/or peptides.
Diese Aufgabe wird erfindungsgemäß gelöst durch eine magensaftresistente Kapsel, die ein Kapselmaterial und eine von dem Kapselmaterial umschlossene Füllung umfasst, wobei das Kapselmaterial Gelatine und Pektin umfasst, und wobei die Füllung (i) probiotische Bakterien oder (ii) säureempfindliche Proteine und/oder Peptide umfasst. This object is achieved according to the invention by an enteric-juice-resistant capsule, which comprises a capsule material and a filling enclosed by the capsule material, the capsule material comprising gelatin and pectin, and the filling comprising (i) probiotic bacteria or (ii) acid-sensitive proteins and/or peptides .
Pharmazeutische Kapseln auf Basis von Gelatine sind in verschiedenen Formen bekannt, wobei insbesondere zwischen Hartkapseln und Weichkapseln unterschieden wird. Die erfindungsgemäße Kapsel ist insbesondere eine Weichkapsel, bei der es aufgrund der Eigenschaften des Kapselmaterials und des Herstellungsverfahrens grundsätzlich möglich ist, die Füllung vollständig mit dem Kapselmaterial zu umschließen. Diese vollständige und hermetische Umhüllung mit dem Kapselmaterial ist im Hinblick auf den Schutz der zu verabreichenden Bakterien, Proteine und/oder Peptide, sowohl gegen die Magensäure als auch gegen äußere Einflüsse vor der Verabreichung, ein wesentlicher Vorteil von Weichkapseln im Vergleich zu Hartkapseln. Ein weiterer Vorteil von Weichkapseln ist die Möglichkeit einer flüssigen Füllung. Pharmaceutical capsules based on gelatine are known in various forms, with a particular distinction being made between hard capsules and soft capsules. The capsule according to the invention is in particular a soft capsule in which, due to the properties of the capsule material and the manufacturing process, it is fundamentally possible to completely enclose the filling with the capsule material. This complete and hermetic encapsulation with the capsule material is a significant advantage of soft capsules compared to hard capsules with regard to the protection of the bacteria, proteins and/or peptides to be administered, both against gastric acid and against external influences before administration. Another advantage of softgels is the possibility of a liquid filling.
Bei der erfindungsgemäßen Kapsel wird deren Magensaftresistenz, d.h. die enterischen Eigenschaften des Kapselmaterials, dadurch erreicht, dass das Kapselmaterial neben Gelatine einen Anteil an Pektin umfasst. Es handelt sich bei Pektin um ein pflanzliches Polysaccharid, welches ähnlich wie Gelatine die Eigenschaften eines Hydrokolloids aufweist und zur Ausbildung von Gelen in der Lage ist. Überraschenderweise hat sich gezeigt, dass der Zusatz von Pektin zu Gelatine zu einem magensaftresistenten Kapselmaterial führt, so dass mit der erfindungsgemäßen Kapsel eine enterische Verabreichung der probiotischen Bakterien möglich ist. In the case of the capsule according to the invention, its resistance to gastric juice, ie the enteric properties of the capsule material, is achieved in that the capsule material comprises a proportion of pectin in addition to gelatin. Pectin is a vegetable polysaccharide which, like gelatine, has the properties of a hydrocolloid and is capable of forming gels. Surprisingly, it has been shown that the addition of pectin to Gelatin leads to a gastric juice-resistant capsule material, so that enteric administration of the probiotic bacteria is possible with the capsule according to the invention.
Eine Kapsel wird im Rahmen der vorliegenden Erfindung als magensaftresistent bezeichnet, wenn sie gemäß dem in der US-Pharmacopeia definierten Desintegrationstest (USP <701 >) mindestens 1 Stunde in simulierter Magensäure (pH 1,2 bei 37 °C) übersteht. In the context of the present invention, a capsule is referred to as gastro-resistant if it survives at least 1 hour in simulated gastric acid (pH 1.2 at 37° C.) according to the disintegration test (USP <701>) defined in the US Pharmacopeia.
Das Kapselmaterial umfasst im Rahmen der vorliegenden Erfindung günstigerweise Gelatine und Pektin in einem Gewichtsverhältnis von ca. 99: 1 bis ca. 70:30. Eine besonders gute Magensaftresistenz kann mit einem Gewichtsverhältnis von Gelatine und Pektin im Bereich von ca. 95:5 bis ca. 80:20 erreicht werden, weiter bevorzugt von ca. 90: 10 bis ca. 85: 15. In the context of the present invention, the capsule material desirably comprises gelatin and pectin in a weight ratio of from about 99:1 to about 70:30. Particularly good gastric resistance can be achieved with a weight ratio of gelatin and pectin in the range from about 95:5 to about 80:20, more preferably from about 90:10 to about 85:15.
Ein besonderer Vorteil der erfindungsgemäßen magensaftresistenten Kapsel ist insbesondere darin zu sehen, dass abgesehen von dem Zusatz von Pektin keine weiteren Maßnahmen erforderlich sind, insbesondere keine Beschichtung oder sonstige Behandlung der Kapsel in einem nachfolgenden Verfahrensschritt. Die erfindungsgemäße Kapsel kann dadurch relativ kostengünstig hergestellt werden. Die Herstellung kann ferner mittels der bekannten Verfahren für die Herstellung von Gelatineweichkapseln erfolgen, wie z.B. das Rotary- Die-Verfahren. Eine Modifizierung der Produktionsvorrichtungen und Prozessparameter gegenüber normalen Gelatineweichkapseln, die kein Pektin enthalten, ist nicht erforderlich. A particular advantage of the gastric juice-resistant capsule according to the invention can be seen in particular in the fact that, apart from the addition of pectin, no further measures are required, in particular no coating or other treatment of the capsule in a subsequent process step. As a result, the capsule according to the invention can be produced relatively inexpensively. The production can also be carried out by means of the known processes for the production of soft gelatine capsules, such as the rotary die process. A modification of the production equipment and process parameters compared to normal soft gelatine capsules that do not contain pectin is not necessary.
Das in dem Kapselmaterial enthaltene Pektin kann insbesondere ein niedrigmethyliertes Pektin, ein amidiertes niedrigmethyliertes Pektin (Amidopektin) oder ein hochmethyliertes Pektin sein. Ein Pektin wird als niedrig- bzw. hochmethyliert bezeichnet, wenn der Methylierungsgrad unter bzw. über 50% liegt. The pectin contained in the capsule material can in particular be a low-methylated pectin, an amidated low-methylated pectin (amidopectin) or a high-methylated pectin. A pectin is described as low or high methylated if the degree of methylation is below or above 50%.
Ferner bietet die erfindungsgemäße Zusammensetzung des Kapselmaterials auch die vorteilhafte Möglichkeit, die Versiegelung der Kapsel während des Herstellungsprozesses, insbesondere beim Rotary-Die-Verfahren, bei relativ niedrigen Temperaturen, z.B. im Bereich von ca. 36 bis 38 °C, durchzuführen. Die Begrenzung der Temperatur bei der Kapselherstellung ist günstig im Hinblick auf die Stabilität der Füllung, insbesondere wenn diese probiotische Bakterien umfasst. Furthermore, the composition of the capsule material according to the invention also offers the advantageous possibility of sealing the capsule during the Manufacturing process, especially in the rotary die process, at relatively low temperatures, for example in the range of about 36 to 38 ° C to perform. Limiting the temperature during capsule manufacture is beneficial with regard to the stability of the filling, especially when it contains probiotic bacteria.
Bei der Herstellung der erfindungsgemäßen Kapsel wird das Kapselmaterial typischerweise aus einer Gelmasse gebildet, die noch einen deutlich höheren Wassergehalt aufweist als das Kapselmaterial in der fertigen Kapsel. Hinsichtlich des Anteils an Hydrokolloiden in dem Kapselmaterial ist es günstig, wenn diese Gelmasse insgesamt ca. 30 bis ca. 50 Gew.% an Gelatine und Pektin umfasst, bevorzugt ca. 35 bis ca. 45 Gew.%, weiter bevorzugt ca. 38 bis ca. 42 Gew.%, wobei die Gelmasse anschließend bis zu einem Wassergehalt des Kapselmaterials von ca. 5 bis ca. 10 Gew.%, bevorzugt von ca. 6 bis ca.8 Gew.%, getrocknet wird. In the production of the capsule according to the invention, the capsule material is typically formed from a gel mass which still has a significantly higher water content than the capsule material in the finished capsule. With regard to the proportion of hydrocolloids in the capsule material, it is favorable if this gel mass comprises a total of approx. 30 to approx. 50% by weight of gelatin and pectin, preferably approx. 35 to approx. 45% by weight, more preferably approx about 42% by weight, the gel mass then being dried to a water content of the capsule material of about 5 to about 10% by weight, preferably from about 6 to about 8% by weight.
Die im Rahmen der Erfindung angegebenen Gewichtsanteile an Gelatine beziehen sich jeweils auf das Gewicht der Gelatine einschließlich des in der Gelatine gebundenen Wasseranteils, der typischerweise im Bereich von ca. 10 Gew.% liegt. The proportions by weight of gelatin given in the context of the invention relate in each case to the weight of the gelatin including the proportion of water bound in the gelatin, which is typically in the range of about 10% by weight.
Der Wassergehalt der Gelmasse, aus der das Kapselmaterial der erfindungsgemäßen Kapsel gebildet ist, liegt typischerweise im Bereich von ca. 30 bis ca. 50 Gew.%, bevorzugt von ca. 35 bis ca. 45 Gew.%, weiter bevorzugt von ca. 38 bis ca. 42 Gew.%. Nach der Trocknung der Gelmasse liegt der Wassergehalt des Kapselmaterials wie oben erwähnt im Bereich von ca. 5 bis ca. 10 Gew.%, bevorzugt von ca. 6 bis ca. 8 Gew.%. The water content of the gel mass from which the capsule material of the capsule according to the invention is formed is typically in the range from about 30 to about 50% by weight, preferably from about 35 to about 45% by weight, more preferably from about 38 up to approx. 42% by weight. After the gel mass has dried, the water content of the capsule material is, as mentioned above, in the range from about 5 to about 10% by weight, preferably from about 6 to about 8% by weight.
Hieraus resultiert für das Kapselmaterial der erfindungsgemäßen Kapsel, dass dieses typischerweise insgesamt ca. 50 bis ca. 75 Gew.% Gelatine und Pektin umfasst, bevorzugt ca. 55 bis ca. 70 Gew.%, weiter bevorzugt ca. 60 bis ca. 65 Gew.%. Für das Kapselmaterial der erfindungsgemäßen Kapsel können generell verschiedene herkömmliche Gelatinetypen eingesetzt werden, die auch sonst bei der Herstellung von Gelatineweichkapseln Anwendung finden. Bevorzugt ist im Rahmen der Erfindung eine mittelbloomige Gelatine, die bevorzugt eine Gelstärke von 110 bis 150 g Bloom aufweist, weiter bevorzugt von 115 bis 145 g Bloom. As a result, the capsule material of the capsule according to the invention typically comprises a total of approx. 50 to approx. 75% by weight gelatin and pectin, preferably approx. 55 to approx. 70% by weight, more preferably approx. 60 to approx. 65% by weight .%. For the capsule material of the capsule according to the invention, various conventional types of gelatin can generally be used, which are also otherwise used in the production of soft gelatin capsules. Within the scope of the invention, preference is given to a medium-bloom gelatin which preferably has a gel strength of 110 to 150 g bloom, more preferably 115 to 145 g bloom.
Die eingesetzte Gelatine kann aus kollagenhaltigen tierischen Rohmaterialien mittels saurer Extraktion (Typ-A-Gelatine) oder mittels alkalischer Extraktion (Typ-B-Gelatine) hergestellt sein. Bevorzugt ist die Gelatine im Rahmen der vorliegenden Erfindung eine Typ-B-Gelatine, insbesondere eine aus Rinderknochen hergestellte Typ-B-Gelatine. The gelatin used can be produced from animal raw materials containing collagen by means of acid extraction (type A gelatin) or by means of alkaline extraction (type B gelatin). In the context of the present invention, the gelatin is preferably a type B gelatin, in particular a type B gelatin produced from bovine bones.
Das Kapselmaterial der erfindungsgemäßen magensaftresistenten Kapsel enthält günstigerweise einen oder mehrere Weichmacher. Diese gewährleisten eine ausreichende Flexibilität des Kapselmaterials während der Trocknung und der späteren Lagerung und Anwendung der Kapsel. The capsule material of the enteric-coated capsule according to the invention advantageously contains one or more plasticizers. These ensure sufficient flexibility of the capsule material during drying and later storage and use of the capsule.
Der oder die Weichmacher in dem Kapselmaterial der erfindungsgemäßen Kapsel sind bevorzugt ausgewählt aus Zuckeralkoholen, insbesondere aus Glycerin, Sorbit, Sorbitan, Mannit, Maltit und/oder Xylit, oder aus Propylenglycol, Polypropylenglycol und Polyethylenglycol. The plasticizer(s) in the capsule material of the capsule according to the invention are preferably selected from sugar alcohols, in particular from glycerol, sorbitol, sorbitan, mannitol, maltitol and/or xylitol, or from propylene glycol, polypropylene glycol and polyethylene glycol.
Bei einer bevorzugten Ausführungsform ist das Kapselmaterial aus einer Gelmasse gebildet, die ca. 15 bis ca. 25 Gew.% an Zuckeralkoholen umfasst, bevorzugt ca. 18 bis ca. 22 Gew.%. Mit diesen Anteilen ergeben sich besonders vorteilhafte mechanische Eigenschaften des Kapselmaterials bzw. der Kapsel. In a preferred embodiment, the capsule material is formed from a gel mass comprising about 15% to about 25% by weight of sugar alcohols, preferably about 18% to about 22% by weight. Particularly advantageous mechanical properties of the capsule material or the capsule result from these proportions.
Besonders günstig ist es, wenn das Kapselmaterial aus einer Gelmasse gebildet ist, die ca. 7 bis ca. 8 Gew.% Glycerin und ca. 11 bis ca. 13 Gew.% Sorbit und/oder Sorbitan umfasst. Sorbitan entsteht durch die Dehydratisierung von Sorbit und kann in verschiedenen Isomeren vorliegen. Gemäß einer besonders bevorzugten Ausführungsform der erfindungsgemäßen Kapsel ist das Kapselmaterial gebildet aus einer Gelmasse, die umfasst: ca. 34 bis ca. 36 Gew.% Gelatine, ca. 4 bis ca. 6 Gew.% Pektin, ca. 7 bis ca. 8 Gew.% Glycerin, ca. 11 bis ca. 13 Gew.% Sorbit und/oder Sorbitan; und Wasser bis 100 Gew.%, und anschließender Trocknung der Gelmasse bis zu einem Wassergehalt des Kapselmaterials von ca. 6 bis ca. 8 Gew.%. It is particularly favorable if the capsule material is formed from a gel mass which comprises about 7 to about 8% by weight of glycerol and about 11 to about 13% by weight of sorbitol and/or sorbitan. Sorbitan is formed by the dehydration of sorbitol and can exist in different isomers. According to a particularly preferred embodiment of the capsule according to the invention, the capsule material is formed from a gel mass which comprises: approx. 34 to approx. 36% by weight gelatin, approx. 4 to approx. 6% by weight pectin, approx. 7 to approx wt% glycerin, about 11 to about 13 wt% sorbitol and/or sorbitan; and water up to 100% by weight, and subsequent drying of the gel mass until the water content of the capsule material is from about 6 to about 8% by weight.
Dementsprechend umfasst das Kapselmaterial der erfindungsgemäßen Kapsel bevorzugt: ca. 53 bis ca. 57 Gew.% Gelatine, ca. 7 bis ca. 8 Gew.% Pektin, ca. 11 bis ca. 12 Gew.% Glycerin, ca. 18 bis ca. 20 Gew.% Sorbit und/oder Sorbitan, ca. 6 bis ca. 8 Gew.% Wasser. Accordingly, the capsule material of the capsule according to the invention preferably comprises: about 53 to about 57% by weight gelatin, about 7 to about 8% by weight pectin, about 11 to about 12% by weight glycerin, about 18 to about 20% by weight sorbitol and/or sorbitan, about 6 to about 8% by weight water.
Die Herstellung der erfindungsgemäßen Kapsel erfolgt ausgehend von der Gelmasse und der Füllung nach einem an sich bekannten Herstellungsverfahren für Gelatineweichkapseln, insbesondere mittels des Rotary-Die-Verfahrens. Hierbei wird in einem kontinuierlichen Prozess die Füllung zwischen zwei Stränge der Gelmasse eingeführt. Die Stränge werden durch ein entsprechendes Formwerkzeug portioniert und die Gelmasse um die Füllung hermetisch versiegelt. Anschließend erfolgt die Trocknung der Gelmasse zu dem Kapselmaterial mit dem oben genannten Restwasseranteil. The capsule according to the invention is produced starting from the gel mass and the filling according to a production process known per se for soft gelatine capsules, in particular by means of the rotary die process. The filling is introduced between two strands of gel mass in a continuous process. The strands are portioned using an appropriate mold and the gel mass is hermetically sealed around the filling. The gel mass is then dried to form the capsule material with the above-mentioned residual water content.
Die Füllung der erfindungsgemäßen magensaftresistenten Kapsel umfasst bei einer ersten bevorzugten Ausführungsform probiotische Bakterien. Die Auswahl und die Anteile von verschiedenen probiotischen Bakterien können in Abhängigkeit vom konkreten Anwendungszweck der Kapsel angepasst und variiert werden. Typischerweise umfasst die Füllung probiotische Bakterien einer oder mehrerer Gattungen, die ausgewählt sind aus Lactobacillus, Bifidobacterium, Lactococcus, Pediococcus und Streptococcus. Bevorzugt sind Bakterien der Arten Lactobacillus lactis, Lactobacillus bulgaricus, Lactobacillus acidufilus und Bifidobacterium bifidum. In a first preferred embodiment, the filling of the gastric juice-resistant capsule according to the invention comprises probiotic bacteria. The selection and proportions of different probiotic bacteria can be adjusted and varied depending on the specific application of the capsule. Typically, the filling includes probiotic bacteria one or more genera selected from Lactobacillus, Bifidobacterium, Lactococcus, Pediococcus and Streptococcus. Bacteria of the species Lactobacillus lactis, Lactobacillus bulgaricus, Lactobacillus acidufilus and Bifidobacterium bifidum are preferred.
Bevorzugt umfasst die Füllung eine Suspension der probiotischen Bakterien in einem hydrophoben Medium. Insbesondere ist es günstig, wenn die Füllung im Wesentlichen wasserfrei ist oder eine Wasseraktivität aw von weniger als 0,4 aufweist, bevorzugt von weniger als 0,3. Die Abwesenheit von Wasser in der Füllung verbessert zum einen wesentlich die Stabilität und Lagerfähigkeit der probiotischen Bakterien, und zum anderen kann dadurch eine Wechselwirkung mit dem Kapselmaterial vermieden werden. The filling preferably comprises a suspension of the probiotic bacteria in a hydrophobic medium. In particular, it is favorable if the filling is essentially anhydrous or has a water activity a w of less than 0.4, preferably less than 0.3. On the one hand, the absence of water in the filling significantly improves the stability and storage life of the probiotic bacteria, and on the other hand, an interaction with the capsule material can be avoided.
Die Auswahl des hydrophoben Mediums, in dem die probiotischen Bakterien bevorzugt suspendiert sind, kann u.a. auch unter Berücksichtigung des konkreten Einsatzzwecks der erfindungsgemäßen Kapsel erfolgen. Insbesondere kann ein hydrophobes Medium eingesetzt werden mit einem oder mehreren Bestandteilen, die ihrerseits eine gesundheitsfördernde Wirkung aufweisen. The selection of the hydrophobic medium in which the probiotic bacteria are preferably suspended can also take into account the specific purpose of use of the capsule according to the invention. In particular, a hydrophobic medium can be used with one or more components which in turn have a health-promoting effect.
Günstig ist es, wenn das hydrophobe Medium ein oder mehrere pflanzliche Öle, tierische Öle und/oder Mischungen von Triglyceriden oder Fettsäuren umfasst, die bevorzugt ausgewählt sind aus Rapsöl, Borretschöl, Nachtkerzenöl, Leinsamenöl, Perillaöl, Knoblauchöl, Fischöl, Krillöl, mittel kettigen Trigylceriden wie MCT-ÖI, und Omega-3-Fettsäuren wie DHA und EPA. It is favorable if the hydrophobic medium comprises one or more vegetable oils, animal oils and/or mixtures of triglycerides or fatty acids, which are preferably selected from rapeseed oil, borage oil, evening primrose oil, linseed oil, perilla oil, garlic oil, fish oil, krill oil, medium-chain triglycerides such as MCT oil, and omega-3 fatty acids such as DHA and EPA.
Die Füllung der erfindungsgemäßen magensaftresistenten Kapsel umfasst bei einer zweiten bevorzugten Ausführungsform säureempfindliche Proteine und/ oder Peptide. Beispiele für solche Protei ne/Peptide, die vorteilhafterweise mittels der erfindungsgemäßen magensaftresistenten Kapsel verabreicht werden können, sind undenaturiertes Kollagen vom Typ II, Proteohormone und Peptidhormonen wie z.B. Insulin, und ernährungsphysiologisch wirksamen Peptiden wie z.B. Kollagenpeptiden, Molkepeptiden, Caseinpeptiden und Peptiden aus nicht-tierischen Quellen. Die erfindungsgemäße magensaftresistente Kapsel kann verschiedene Größen aufweisen, die bei Gelatineweichkapseln allgemein bekannt sind. Generell können Weichkapseln mit Füllvolumina im Bereich von ca. 100 pl bis ca. 2.500 pl hergestellt werden. Es hat sich im Rahmen der Erfindung jedoch gezeigt, dass tendenziell kleinere Kapseln bessere enterische Eigenschaften, d.h. eine höhere Magensaftresistenz, aufweisen als größere Kapseln. Die erfindungsgemäße Kapsel weist daher günstigerweise ein Füllvolumen von ca. 300 bis ca. 1.000 pl auf, bevorzugt von ca. 500 bis ca. 750 pl. Diese Füllvolumina sind gleichzeitig auch ausreichend für die Verabreichung der vorgesehenen Mengen an probiotischen Bakterien, zumal eine Überdosierung aufgrund der Magensaftresistenz der Kapsel nicht erforderlich ist. In a second preferred embodiment, the filling of the gastric juice-resistant capsule according to the invention comprises acid-sensitive proteins and/or peptides. Examples of such proteins/peptides which can advantageously be administered using the enteric-coated capsule according to the invention are undenatured type II collagen, proteohormones and peptide hormones such as insulin, and nutritionally active peptides such as collagen peptides, whey peptides, casein peptides and peptides from non-animal sources Sources. The enteric-coated capsule according to the invention can have various sizes, which are generally known for soft gelatine capsules. In general, soft capsules with filling volumes in the range from approx. 100 pl to approx. 2,500 pl can be produced. Within the scope of the invention, however, it has been shown that smaller capsules tend to have better enteric properties, ie higher resistance to gastric juice, than larger capsules. The capsule according to the invention therefore advantageously has a filling volume of approx. 300 to approx. 1000 pl, preferably from approx. 500 to approx. 750 pl. At the same time, these filling volumes are also sufficient for the administration of the planned amounts of probiotic bacteria, especially since an overdose is not necessary due to the gastric juice resistance of the capsule.
Die erfindungsgemäße Kapsel kann als runde, als ovale oder als oblonge Kapsel ausgeführt sein. The capsule according to the invention can be designed as a round, oval or oblong capsule.
Die Dicke des Kapselmaterials der erfindungsgemäßen Kapsel liegt typischerweise im Bereich von ca. 250 bis ca. 600 pm, bevorzugt von ca. 400 bis ca. 500 pm, beispielsweise bei ca. 450 pm. Diese Werte beziehen sich auf die Wandstärke der fertigen, auf den endgültigen Wassergehalt getrockneten Kapsel. Die Dicke der Gelmasse-Stränge beim Herstellungsprozess ist entsprechend größer, typischerweise um etwa den Faktor zwei. The thickness of the capsule material of the capsule according to the invention is typically in the range from about 250 to about 600 μm, preferably from about 400 to about 500 μm, for example about 450 μm. These values refer to the wall thickness of the finished capsule dried to the final water content. The thickness of the strands of gel mass during the manufacturing process is correspondingly greater, typically by a factor of about two.
Die vorliegende Erfindung betrifft ferner die Verwendung einer erfindungsgemäßen magensaftresistenten Kapsel als Pharmazeutikum oder Nahrungsergänzungsmittel. The present invention further relates to the use of a gastric juice-resistant capsule according to the invention as a pharmaceutical or food supplement.
Eine erste bevorzugte Ausführungsform betrifft die Verwendung einer erfindungsgemäßen magensaftresistenten Kapsel zur Anreicherung der Darmflora mit probiotischen Bakterien. Diese Beeinflussung der Darmflora, insbesondere des Dünndarms, hat vorteilhafte gesundheitliche Auswirkungen, die u.a. auf die Bildung von kurzkettigen Fettsäuren, insbesondere Propionsäure und Buttersäure, durch die probiotischen Bakterien zurückgehen, sowie auf die Unterdrückung des Wachstums von schädlichen Mikroorganismen. A first preferred embodiment relates to the use of a gastric juice-resistant capsule according to the invention for enriching the intestinal flora with probiotic bacteria. This influencing of the intestinal flora, especially the small intestine, has beneficial health effects, including the formation of short-chain fatty acids, especially propionic acid and Butyric acid, which reduces probiotic bacteria and suppresses the growth of harmful microorganisms.
Die Erfindung betrifft daher insbesondere auch die Verwendung einer erfindungsgemäßen magensaftresistenten Kapsel zur Verbesserung der Darmgesundheit, insbesondere zur Vorbeugung oder Behandlung des Reizdarmsyn- droms, von Verstopfung, von Diarrhö, von Colitis ulcerosa und von Morbus Crohn. The invention therefore relates in particular to the use of a gastric juice-resistant capsule according to the invention to improve intestinal health, in particular to prevent or treat irritable bowel syndrome, constipation, diarrhea, ulcerative colitis and Crohn's disease.
Eine zweite bevorzugte Ausführungsform betrifft die Verwendung einer erfindungsgemäßen magensaftresistenten Kapsel als Pharmazeutikum oder Nahrungsergänzungsmittel zur enterischen Verabreichung von Proteinen und/oder Peptiden, die im Dünndarm eine physiologische Wirkung entfalten oder resorbiert werden. Wie bereits oben erwähnt, fallen hierunter beispielsweise undenaturiertes Kollagen vom Typ II, Proteohormone und Peptidhormonen wie z.B. Insulin, und ernährungsphysiologisch wirksamen Peptiden wie z.B. Kollagenpeptiden, Molkepeptiden, Caseinpeptiden und Peptiden aus nicht-tierischen Quellen. A second preferred embodiment relates to the use of a gastric juice-resistant capsule according to the invention as a pharmaceutical or food supplement for the enteric administration of proteins and/or peptides which have a physiological effect or are absorbed in the small intestine. As already mentioned above, this includes, for example, undenatured type II collagen, proteohormones and peptide hormones such as insulin, and nutritionally active peptides such as collagen peptides, whey peptides, casein peptides and peptides from non-animal sources.
Undenaturiertes Kollagen vom Typ II, auch als UC-II bezeichnet, wird zur Linderungen von bestimmten Gelenkbeschwerden verabreicht, die u.a. durch eine Autoimmunreaktion gegen körpereigenes Typ-II-Kollagen in den Gelenken verursacht werden. Seine physiologische Aktivität entfaltet UC-II durch eine Interaktion mit den Peyer-Plaques im Dünndarm. Dabei werden immunologische Informationen weitergeleitet, die zu einer Unterdrückung der Autoimmunreaktion führen sollen. Durch eine enterale Verabreichung von UC-II mittels der erfindungsgemäßen Kaspel kann eine partielle Degradation oder Inaktivierung bei der Magenpassage verhindert und die Wirksamkeit der verabreichten Menge an UC-II erhöht werden. Type II undenatured collagen, also known as UC-II, is used to relieve certain joint problems, including those caused by an autoimmune reaction against the body's own type II collagen in the joints. UC-II exerts its physiological activity through an interaction with the Peyer's patches in the small intestine. In the process, immunological information is passed on, which should lead to suppression of the autoimmune reaction. Enteral administration of UC-II by means of the capsule according to the invention can prevent partial degradation or inactivation during passage through the stomach and increase the effectiveness of the administered amount of UC-II.
Eine ähnliche vorteilhafte Wirkung der erfindungsgemäßen Kaspel ergibt sich bei der Verabrechung von Proteohormonen oder Peptidhormonen, die zur Entfaltung ihrer physiologische Wirkung generell im Dünndarm resorbiert werden müssen. Eine effektive enterale Verabreichung dieser säureempfindlichen Wirkstoffe wäre insofern eine denkbare Alternative zu einer subkutanen Verabreichung, z.B. von Insulin. A similar advantageous effect of the capsule according to the invention results from the administration of proteohormones or peptide hormones, which are generally resorbed in the small intestine in order to develop their physiological effect must. Effective enteral administration of these acid-sensitive active substances would therefore be a conceivable alternative to subcutaneous administration, for example of insulin.
Schließlich kann die erfindungsgemäßen Kapsel auch vorteilhaft für die Verabreichung von verschiedenen ernährungsphysiologisch wirksamen Peptiden genutzt werden, um diese vor einem teilweisen Wirksamkeitsverlust bei der Magenpassage zu schützen. Es ist bekannt, dass solche Peptide mit einem Molekulargewicht von bis 15 kDa im Dünndarm resorbiert werden können. Insbesondere Kollagenpeptide, die durch enzymatische Hydrolyse von Kollagen oder Gelatine gewonnen werden, weisen diverse physiologische Aktivitäten auf und haben positive Effekte auf die Gesundheit u.a. der Knochen, Gelenke, Muskeln und Haut. Bevorzugte Kollagenpeptide im Rahmen der Erfindung sind beispielsweise die von der Anmelderin unter den Namen VERISOL, FORTIGEL, FORTIBONE und CURADERM vertriebenen Produkte. Finally, the capsule according to the invention can also be used advantageously for the administration of various nutritionally active peptides in order to protect them from a partial loss of effectiveness during passage through the stomach. It is known that such peptides with a molecular weight of up to 15 kDa can be resorbed in the small intestine. In particular, collagen peptides, which are obtained by enzymatic hydrolysis of collagen or gelatin, have various physiological activities and have positive effects on the health of bones, joints, muscles and skin, among other things. Preferred collagen peptides within the scope of the invention are, for example, the products marketed by the applicant under the names VERISOL, FORTIGEL, FORTIBONE and CURADERM.
Die nachfolgenden Ausführungsbeispiele dienen der näheren Erläuterung der Erfindung, ohne diese in irgendeiner Weise zu beschränken. The following exemplary embodiments serve to explain the invention in more detail without restricting it in any way.
Es zeigt: It shows:
Figur 1 : schematische Querschnittsdarstellung einer erfindungsgemäßen magensaftresistenten Kapsel. FIG. 1: schematic cross-sectional representation of a gastric juice-resistant capsule according to the invention.
In der Figur 1 ist eine schematische Darstellung einer erfindungsgemäßen magensaftresistenten Kapsel 10 im Querschnitt dargestellt. Die Kapsel 10 umfasst ein Kapselmaterial 20 und eine Füllung 30, wobei die Füllung 30 von dem Kapselmaterial 20 vollständig umschlossen wird. FIG. 1 shows a schematic representation of a gastric juice-resistant capsule 10 according to the invention in cross section. The capsule 10 comprises an encapsulating material 20 and a filling 30 , the filling 30 being completely enclosed by the encapsulating material 20 .
Das Kapselmaterial 20 umfasst Gelatine und Pektin. Bevorzugte Ausführungsformen des Kapselmaterials 20, insbesondere hinsichtlich der qualitativen und quantitativen Zusammensetzung, wurden oben beschrieben. Die Füllung 30 umfasst probiotische Bakterien. Bevorzugt sind die probiotischen Bakterien in einem hydrophoben Medium suspendiert. The encapsulating material 20 comprises gelatin and pectin. Preferred embodiments of the encapsulation material 20, in particular with regard to the qualitative and quantitative composition, have been described above. The filling 30 includes probiotic bacteria. The probiotic bacteria are preferably suspended in a hydrophobic medium.
Beispiele examples
In der nachfolgenden Tabelle 1 sind die prozentualen Zusammensetzungen (in Gew.%), ausgehend von kommerziell erhältlichen Ausgangsprodukten, für sechs Ausführungsbeispiele von Gelmassen angegeben, die zur Herstellung von erfindungsgemäßen magensaftresistenten Kapseln eingesetzt werden können. Table 1 below gives the percentage compositions (in % by weight), based on commercially available starting materials, for six exemplary embodiments of gel masses which can be used to produce gastric juice-resistant capsules according to the invention.
Tabelle 1
Figure imgf000013_0001
Table 1
Figure imgf000013_0001
GELITA® EC ist eine von der Anmelderin GELITA AG hergestellte Mischung aus ca. 88 Gew.% Typ-B-Gelatine aus Rinderknochen mit einer Gelstärke im Bereich von 115 bis 145 g Bloom und ca. 12 Gew.% Pektin. GELITA® EC is a mixture made by the applicant GELITA AG of approx. 88% by weight type B gelatine from bovine bones with a gel strength in the range from 115 to 145 g Bloom and approx. 12% by weight pectin.
Polysorb® 85/70/00 ist ein von der Fa. Roquette hergestelltes, partiell dehydratisiertes Sorbit (d.h. Sorbit mit Anteilen an Sorbitan) mit einem Feststoffgehalt von ca. 85 Gew.%. Neosorb® 70/70B ist ein von der Fa. Roquette hergestelltes Sorbit mit einem Feststoffgehalt von ca. 70 Gew.%. Polysorb® 85/70/00 is a partially dehydrated sorbitol (ie sorbitol containing sorbitan) manufactured by Roquette with a solids content of approx. 85% by weight. Neosorb® 70/70B is a sorbitol manufactured by Roquette with a solids content of approx. 70% by weight.
Sorbitol Special® ist ein von der Fa. SPI Pharma hergestelltes Gemisch aus Sorbit und Sorbitan mit einem Feststoffgehalt von ca. 76 Gew.%. Sorbitol Special® is a mixture of sorbitol and sorbitan manufactured by SPI Pharma with a solids content of approx. 76% by weight.
Für alle sechs Ausführungsbeispiele der Gelmasse ergeben sich daraus jeweils die Mengenanteile der einzelnen Komponenten gemäß der nachfolgenden Tabelle 2: For all six exemplary embodiments of the gel mass, this results in the proportions of the individual components according to Table 2 below:
Tabelle 2
Figure imgf000014_0001
Table 2
Figure imgf000014_0001
Im Rahmen des Herstellungsverfahrens der erfindungsgemäßen magenresistenten Kapseln, beispielsweise gemäß dem Rotary-Die-Verfahren, wird eine Füllung, die probiotische Bakterien umfasst, insbesondere in Form einer Suspension in einem hydrophoben Medium, von der Gelmasse umschlossen und letzere getrocknet, um das Kapselmaterial mit einem Restwassergehalt von vorzugsweise ca. 6 bis ca. 8 Gew.% zu erhalten. As part of the manufacturing process of the gastric-resistant capsules according to the invention, for example according to the rotary die process, a filling that includes probiotic bacteria, in particular in the form of a suspension in a hydrophobic medium, is enclosed by the gel mass and the latter is dried in order to fill the capsule material with a Residual water content of preferably about 6 to about 8% by weight.

Claims

P a t e n t a n s p r ü c h e Magensaftresistente Kapsel (10), umfassend ein Kapselmaterial (20) und eine von dem Kapselmaterial umschlossene Füllung (30), wobei das Kapselmaterial Gelatine und Pektin umfasst, und wobei die Füllung (i) probiotische Bakterien oder (ii) säureempfindliche Proteine und/oder Peptide umfasst. Magensaftresistente Kapsel nach Anspruch 1, wobei die Kapsel eine Weichkapsel ist. Magensaftresistente Kapsel nach Anspruch 1 oder 2, wobei das Kapselmaterial Gelatine und Pektin in einem Gewichtsverhältnis von ca. 99: 1 bis ca. 70:30 umfasst, bevorzugt von ca. 95:5 bis ca. 80:20, weiter bevorzugt von ca. 90: 10 bis ca. 85: 15. Magensaftresistente Kapsel nach einem der vorhergehenden Ansprüche, wobei das Kapselmaterial gebildet ist aus einer Gelmasse, die insgesamt ca. 30 bis ca. 50 Gew.% an Gelatine und Pektin umfasst, bevorzugt ca. P a t e n t claims Enteric-coated capsule (10) comprising a capsule material (20) and a filling (30) enclosed by the capsule material, wherein the capsule material comprises gelatin and pectin, and wherein the filling comprises (i) probiotic bacteria or (ii) acid-sensitive proteins and/or peptides. An enteric capsule according to claim 1, wherein the capsule is a soft capsule. Enteric-coated capsule according to claim 1 or 2, wherein the capsule material comprises gelatin and pectin in a weight ratio of from about 99: 1 to about 70:30, preferably from about 95:5 to about 80:20, more preferably from about 90: 10 to about 85: 15. Enteric juice-resistant capsule according to one of the preceding claims, wherein the capsule material is formed from a gel mass which comprises a total of about 30 to about 50% by weight of gelatin and pectin, preferably about
35 bis ca. 45 Gew.%, weiter bevorzugt ca. 38 bis ca. 42 Gew.%, und anschließender Trocknung der Gelmasse bis zu einem Wassergehalt des Kapselmaterials von ca. 5 bis ca. 10 Gew.%, bevorzugt von ca. 6 bis ca. 35 to about 45% by weight, more preferably about 38 to about 42% by weight, and subsequent drying of the gel mass to a water content of the capsule material of about 5 to about 10% by weight, preferably about 6 until about.
8 Gew.%. Magensaftresistente Kapsel nach einem der vorhergehenden Ansprüche, wobei das Kapselmaterial gebildet ist aus einer Gelmasse, die einen Wassergehalt von ca. 30 bis ca. 50 Gew.% aufweist, bevorzugt von ca. 8% by weight. Gastric juice-resistant capsule according to one of the preceding claims, wherein the capsule material is formed from a gel mass which has a water content of approx. 30 to approx. 50% by weight, preferably approx.
35 bis ca. 45 Gew.%, weiter bevorzugt von ca. 38 bis ca. 42 Gew.%, und anschließender Trocknung der Gelmasse bis zu einem Wassergehalt des Kapselmaterials von ca. 5 bis ca. 10 Gew.%, bevorzugt von ca. 6 bis ca. 8 Gew.%. Magensaftresistente Kapsel nach Anspruch 4 oder 5, wobei das Kapselmaterial insgesamt ca. 50 bis ca. 75 Gew.% Gelatine und Pektin umfasst, bevorzugt ca. 55 bis 70 Gew.%, weiter bevorzugt ca. 60 bis ca. 65 Gew.%. Magensaftresistente Kapsel nach einem der vorhergehenden Ansprüche, wobei die Gelatine eine Gelstärke von 110 bis 150 g Bloom aufweist, bevorzugt von 115 bis 145 g Bloom. Magensaftresistente Kapsel nach einem der vorhergehenden Ansprüche, wobei die Gelatine eine Typ-B-Gelatine ist, bevorzugt eine aus Rinderknochen hergestellte Typ-B-Gelatine. Magensaftresistente Kapsel nach einem der vorhergehenden Ansprüche, wobei das Kapselmaterial einen oder mehrere Weichmacher umfasst, die bevorzugt ausgewählt sind aus Zuckeralkoholen, insbesondere aus Glycerin, Sorbit, Sorbitan, Mannit, Maltit und/oder Xylit, oder aus Propylenglycol, Polypropylenglycol und Polyethylenglycol. Magensaftresistente Kapsel nach Anspruch 9, wobei das Kapselmaterial gebildet ist aus einer Gelmasse, die ca. 15 bis ca. 25 Gew.% an Zuckeralkoholen umfasst, bevorzugt ca. 18 bis ca. 22 Gew.%. Magensaftresistente Kapsel nach Anspruch 10, wobei das Kapselmaterial gebildet ist aus einer Gelmasse, die ca. 7 bis 8 Gew.% Glycerin und ca. 35 to approx. 45% by weight, more preferably from approx. 38 to approx. 42% by weight, and subsequent drying of the gel mass until the water content of the capsule material is from approx. 5 to approx. 10% by weight, preferably from approx. 6 to about 8% by weight. Enteric-coated capsule according to claim 4 or 5, wherein the capsule material comprises a total of about 50 to about 75% by weight gelatin and pectin, preferably about 55 to 70% by weight, more preferably about 60 to about 65% by weight. Enteric-juice-resistant capsule according to one of the preceding claims, wherein the gelatine has a gel strength of 110 to 150 g Bloom, preferably 115 to 145 g Bloom. An enteric capsule according to any one of the preceding claims, wherein the gelatin is a type B gelatin, preferably a type B gelatin made from bovine bones. Enteric juice-resistant capsule according to one of the preceding claims, wherein the capsule material comprises one or more plasticizers, which are preferably selected from sugar alcohols, in particular from glycerol, sorbitol, sorbitan, mannitol, maltitol and/or xylitol, or from propylene glycol, polypropylene glycol and polyethylene glycol. Enteric-coated capsule according to claim 9, wherein the capsule material is formed from a gel mass comprising about 15 to about 25% by weight of sugar alcohols, preferably about 18 to about 22% by weight. Enteric-coated capsule according to claim 10, wherein the capsule material is formed from a gel mass containing about 7 to 8% by weight glycerol and about
11 bis ca. 13 Gew.% Sorbit und/oder Sorbitan umfasst. Magensaftresistente Kapsel nach einem der vorhergehenden Ansprüche, wobei das Kapselmaterial gebildet ist aus einer Gelmasse, die umfasst:11 to about 13% by weight of sorbitol and/or sorbitan. Enteric-coated capsule according to one of the preceding claims, wherein the capsule material is formed from a gel mass comprising:
- ca. 34 bis ca. 36 Gew.% Gelatine, - about 34 to about 36% by weight gelatin,
- ca. 4 bis ca. 6 Gew.% Pektin, - approx. 4 to approx. 6% by weight pectin,
- ca. 7 bis ca. 8 Gew.% Glycerin, - ca. 11 bis ca. 13 Gew.% Sorbit und/oder Sorbitan; und - about 7 to about 8% by weight of glycerin, - from about 11 to about 13% by weight of sorbitol and/or sorbitan; and
- Wasser bis 100 Gew.%, und anschließender Trocknung der Gelmasse bis zu einem Wassergehalt des Kapselmaterials von ca. 6 bis ca. 8 Gew.%. Magensaftresistente Kapsel nach Anspruch 12, wobei das Kapselmaterial umfasst: - Water up to 100% by weight, and subsequent drying of the gel mass to a water content of the capsule material of about 6 to about 8% by weight. Enteric-coated capsule according to claim 12, wherein the capsule material comprises:
- ca. 53 bis ca. 57 Gew.% Gelatine, - about 53 to about 57% by weight gelatin,
- ca. 7 bis ca. 8 Gew.% Pektin, - approx. 7 to approx. 8% by weight pectin,
- ca. 11 bis ca. 12 Gew.% Glycerin, - about 11 to about 12% by weight of glycerin,
- ca. 18 bis ca. 20 Gew.% Sorbit und/oder Sorbitan; und - from about 18 to about 20% by weight of sorbitol and/or sorbitan; and
- ca. 6 bis ca. 8 Gew.% Wasser. Magensaftresistente Kapsel nach einem der vorhergehenden Ansprüche, wobei die Füllung probiotische Bakterien einer oder mehrerer Gattungen umfasst, die ausgewählt sind aus Lactobacillus, Bifidobacterium, Lacto- coccus, Pediococcus und Streptococcus, bevorzugt aus Bakterien der Arten Lactobacillus lactis, Lactobacillus bulgaricus, Lactobacillus acidophilus und Bifidobakterium bifidum. Magensaftresistente Kapsel nach einem der vorhergehenden Ansprüche, wobei die Füllung eine Suspension der probiotischen Bakterien in einem hydrophoben Medium umfasst. Magensaftresistente Kapsel nach einem der vorhergehenden Ansprüche, wobei die Füllung im Wesentlichen wasserfrei ist oder eine Wasseraktivität aw von weniger als 0,4 aufweist, bevorzugt von weniger als 0,3. Magensaftresistente Kapsel nach Anspruch 15 oder 16, wobei das hydrophobe Medium ein oder mehrere pflanzliche Öle, tierische Öle und/oder Mischungen von Triglyceriden und/oder Fettsäuren umfasst, die bevorzugt ausgewählt sind aus Rapsöl, Borretschöl, Nachtkerzenöl, Leinsamenöl, Perillaöl, Knoblauchöl, Fischöl, Krillöl, mittel kettigen Triglyceriden wie MCT-ÖI, und Omega-3-Fettsäuren wie DHA und EPA. Magensaftresistente Kapsel nach einem der Ansprüche 1 bis 13, wobei die Füllung säureempfindliche Proteine und/oder Peptide umfasst, die ausgewählt sind aus undenaturiertem Kollagen vom Typ II, Proteohormone und Peptidhormonen wie z.B. Insulin, und ernährungsphysiologisch wirksamen Peptiden wie z.B. Kollagenpeptiden, Molkepeptiden, Caseinpeptiden und Peptiden aus nicht-tierischen Quellen. Magensaftresistente Kapsel nach einem der vorhergehenden Ansprüche, wobei die magensaftresistente Kapsel ein Füllvolumen von ca. 300 bis ca. 1.000 pl aufweist, bevorzugt von ca. 500 bis ca. 750 pl. Magensaftresistente Kapsel nach einem der vorhergehenden Ansprüche, wobei das Kapselmaterial eine Dicke im Bereich von ca. 250 bis ca. 600 pm aufweist, bevorzugt von ca. 400 bis ca. 500 pm. Verwendung einer magensaftresistente Kapsel nach einem der vorhergehenden Ansprüche als Pharmazeutikum oder Nahrungsergänzungsmittel zur Anreicherung der Darmflora mit probiotischen Bakterien. Verwendung einer magensaftresistente Kapsel nach Anspruch 21 zur Verbesserung der Darmgesundheit, insbesondere zur Vorbeugung und/oder Behandlung des Reizdarmsyndroms, von Verstopfung, von Diarrhö, von Colitis ulcerosa und von Morbus Crohn. Verwendung einer magensaftresistente Kapsel nach einem der Ansprüche 1 bis 20 als Pharmazeutikum oder Nahrungsergänzungsmittel zur enterischen Verabreichung von Proteinen und/oder Peptiden, die im Dünndarm eine physiologische Wirkung entfalten oder resorbiert werden. - about 6 to about 8% by weight of water. Enteric juice-resistant capsule according to one of the preceding claims, wherein the filling comprises probiotic bacteria of one or more genera selected from Lactobacillus, Bifidobacterium, Lactococcus, Pediococcus and Streptococcus, preferably from bacteria of the species Lactobacillus lactis, Lactobacillus bulgaricus, Lactobacillus acidophilus and Bifidobacterium bifidum. Enteric-coated capsule according to any one of the preceding claims, wherein the filling comprises a suspension of the probiotic bacteria in a hydrophobic medium. Enteric-coated capsule according to any one of the preceding claims, wherein the filling is substantially anhydrous or has a water activity a w of less than 0.4, preferably less than 0.3. Enteric-coated capsule according to claim 15 or 16, wherein the hydrophobic medium comprises one or more vegetable oils, animal oils and/or mixtures of triglycerides and/or fatty acids, which are preferably selected from rapeseed oil, borage oil, evening primrose oil, Flaxseed oil, perilla oil, garlic oil, fish oil, krill oil, medium chain triglycerides like MCT oil, and omega-3 fatty acids like DHA and EPA. Enteric-coated capsule according to one of claims 1 to 13, wherein the filling comprises acid-sensitive proteins and/or peptides selected from undenatured type II collagen, proteohormones and peptide hormones such as insulin, and nutritionally active peptides such as collagen peptides, whey peptides, casein peptides and Peptides from non-animal sources. Enteric-coated capsule according to one of the preceding claims, wherein the enteric-coated capsule has a filling volume of about 300 to about 1000 pl, preferably from about 500 to about 750 pl. Enteric-coated capsule according to one of the preceding claims, wherein the capsule material has a thickness in the range from about 250 to about 600 μm, preferably from about 400 to about 500 μm. Use of a gastric juice-resistant capsule according to one of the preceding claims as a pharmaceutical or food supplement for enriching the intestinal flora with probiotic bacteria. Use of an enteric-coated capsule according to claim 21 for improving intestinal health, in particular for the prevention and/or treatment of irritable bowel syndrome, constipation, diarrhea, ulcerative colitis and Crohn's disease. Use of a gastric juice-resistant capsule according to any one of claims 1 to 20 as a pharmaceutical or food supplement for the enteric administration of proteins and/or peptides which have a physiological effect or are absorbed in the small intestine.
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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1973533A2 (en) * 2005-12-22 2008-10-01 Banner Pharmacaps Inc. Gastric reflux resistant dosage forms
CN106727725A (en) * 2016-12-13 2017-05-31 合肥赛为智慧医疗有限公司 A kind of probiotics capsulae enterosolubilis and its utricule for treating enteric flora disturbance
EP3205339A1 (en) * 2014-10-06 2017-08-16 Fuji Capsule Co., Ltd. Method of producing enteric-coated seamless soft capsule
US20200236984A1 (en) * 2017-12-08 2020-07-30 Morishita Jintan Co., Ltd. Three-layered capsule constructed with non-hydrogenated oil and production thereof
WO2020247352A1 (en) * 2019-06-03 2020-12-10 R.P. Scherer Technologies, Llc Delayed release softgel capsules
DE102020210725A1 (en) * 2019-10-31 2021-05-06 Gelita Ag Nutritionally optimized collagen peptide
WO2022104338A1 (en) * 2020-11-11 2022-05-19 R.P. Scherer Technologies, Llc Delayed release softgel capsules

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102813275B (en) 2011-06-10 2015-09-30 杭州养生堂保健品有限公司 A kind of masticatory pattern soft capsule skin and masticatory pattern soft capsule
DE102015121923A1 (en) 2015-12-16 2017-06-22 Gelita Ag Casting compound and process for the production of gelatine products
DE102017107845A1 (en) 2017-04-11 2018-10-11 Gelita Ag Gelatin product with a core component and process for its preparation

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1973533A2 (en) * 2005-12-22 2008-10-01 Banner Pharmacaps Inc. Gastric reflux resistant dosage forms
EP3205339A1 (en) * 2014-10-06 2017-08-16 Fuji Capsule Co., Ltd. Method of producing enteric-coated seamless soft capsule
CN106727725A (en) * 2016-12-13 2017-05-31 合肥赛为智慧医疗有限公司 A kind of probiotics capsulae enterosolubilis and its utricule for treating enteric flora disturbance
US20200236984A1 (en) * 2017-12-08 2020-07-30 Morishita Jintan Co., Ltd. Three-layered capsule constructed with non-hydrogenated oil and production thereof
WO2020247352A1 (en) * 2019-06-03 2020-12-10 R.P. Scherer Technologies, Llc Delayed release softgel capsules
DE102020210725A1 (en) * 2019-10-31 2021-05-06 Gelita Ag Nutritionally optimized collagen peptide
WO2022104338A1 (en) * 2020-11-11 2022-05-19 R.P. Scherer Technologies, Llc Delayed release softgel capsules

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