EP1503742A2 - Matrix comprising a bioactive component containing phospholipid - Google Patents

Matrix comprising a bioactive component containing phospholipid

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Publication number
EP1503742A2
EP1503742A2 EP03722502A EP03722502A EP1503742A2 EP 1503742 A2 EP1503742 A2 EP 1503742A2 EP 03722502 A EP03722502 A EP 03722502A EP 03722502 A EP03722502 A EP 03722502A EP 1503742 A2 EP1503742 A2 EP 1503742A2
Authority
EP
European Patent Office
Prior art keywords
component
weight
matrix
matrix according
acid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP03722502A
Other languages
German (de)
French (fr)
Inventor
Dirk Cremer
Elisabeth Markl
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Cargill Texturizing Solutions Deutschland GmbH and Co KG
Original Assignee
Bioghurt Biogarde GmbH and Co KG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from DE10250727A external-priority patent/DE10250727B4/en
Application filed by Bioghurt Biogarde GmbH and Co KG filed Critical Bioghurt Biogarde GmbH and Co KG
Publication of EP1503742A2 publication Critical patent/EP1503742A2/en
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4858—Organic compounds
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to a matrix with a bioactive, phospholipid-containing component and the use thereof.
  • the substance class of the phospholipids are so-called complex lipids with amphiphilic, ie at the same time lipophilic and hydrophilic properties, which among other things enables them to form lipid bilayers in aqueous media.
  • phospholipids are phosphodiesters in which the phosphoric acid is esterified on the one hand with a sphingosine or glyceride residue and on the other hand with choline, ethanolamine, serine, inositol or glycerol.
  • Phosphatidylcholine is also known as lecithin and is also the eponym for a large group of special phospholipids, the lecithins.
  • Phosphatidylserine and phosphatidylethanolamine are also known as cephalins.
  • the lyso derivatives which also belong to this group, are formed by hydrolytic cleavage using specific phospholipases.
  • Capsules containing phospholipids are well known from the prior art and mostly contain phospholipids as the coating substance. If phospholipids are used in the filling, i.e. in the capsule core, they mostly act in small proportions there as formulation aids with mostly solubilizing properties.
  • the phospholipids Due to their amphiphilic properties, the phospholipids also serve as coating substances for the known liposomes and transferosomes. In In this context, they are used primarily because of their bioadhesive properties in the area of mucosal applications, with them being introduced in particular into the nasal and oral cavities.
  • phospholipids are also used as surface-active formulation aids (surfactants).
  • lysophospholipids are described as solubilizers for hydrophobic bioactive substances.
  • Lecithin as a bioactive ingredient contains soft gelatin capsules, which are commercially available as KAL S lecithin and which contain 1,200 mg soy lecithin. However, in order to be able to accommodate this amount of lecithin in a capsule, capsule sizes must be selected that approach the centimeter limit and thus limited compliance.
  • PS phosphatidylserine
  • the PS obtained in this way or corresponding PS products is embedded in a hard fat in aqueous Systems can be stabilized.
  • the suggestions made there are limited to soft gelatin capsules, which should have the special PS in the content.
  • the system described there stabilizes the known hydrolysis-unstable phosphatidylserine, but it has the disadvantage that this formulation cannot be encapsulated.
  • the encapsulation of phospholipids generally causes great problems, since, as described, they also act as emulsifiers and thus rapidly cause the as yet uncured (dried) casing to mix with the contents during the encapsulation process. As a result, the capsules leak in a relatively short time, they leak and are therefore no longer usable.
  • the object of the present invention was therefore to provide a matrix with a bioactive, phospholipid-containing component which does not have the disadvantages of the prior art described and which are formulated in an economically justifiable manner can.
  • the bioactive phospholipid components incorporated into the matrix should have sufficient stability for the most common uses, even in the encapsulated state.
  • the bioactive component being 5 to 98% by weight of phosphatidylserine (PS) and 1 to 90% by weight of phosphatidylcholine (PC) and moreover 1 to 94% by weight of at least one further component the range of fat components of vegetable and / or animal origin, wax component, polyalcohol component and other physiologically compatible additives.
  • PS phosphatidylserine
  • PC phosphatidylcholine
  • the phosphatidylserine or phosphatidylcholine portions contained therein are extremely stable with respect to the otherwise negative hydrolysis or the general breakdown of encapsulated lecithins. This is particularly pronounced with blends that are highly viscous and also have the property of thixotropy. Until now it was only known that highly viscous blends make lecithins more stable, however, these highly viscous mixtures could then no longer be encapsulated (see DE-OS 1 99 1 7 249). This is all the more surprising since phosphatidylserine in particular is known to be significantly less stable than other phospholipids.
  • the compounds each preferably contain a residue which is derived from a C 2 -C 30 carboxylic acid bonded to the hydroxyl groups of the glycerol, in particular a C 12 -C 28 carboxylic acid.
  • the acid residues can be linear or branched, saturated or mono- or polyunsaturated.
  • residues which, by binding acetic acid, butyric acid, caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, arachic acid, behenic acid, lignoceric acid, R-linolenic acid, eicosapentaenoic acid, erucic acid, Nervonic acid, - or R-Eleostearic acid or parinic acid are formed.
  • Residues which are formed by binding palmitic acid, stearic acid, oleic acid, linoleic acid, ⁇ -linolenic acid, arachidonic acid or docosahexaenoic acid are particularly preferred.
  • the acid residues bound to the two OH groups of the glycerol still available can be the same or different.
  • Phosphatidylserine and phosphatidylcholine represent the bioactive part in the total matrix according to the invention; the other components give the overall matrix its advantageous properties due to their proportions.
  • bioactive is understood to mean the action of phosphatidylserine and phosphatidylcholine in such a way that they develop a biological effect in the resorption area, on the transport route or at the destination in the living organism during or after their release from the total matrix , which usually applies to corresponding preparations in the human or veterinary field.
  • This bioactive effect is of course not limited to the two phospholipids mentioned, but can also be developed by the other components involved in the overall matrix. However, their bioactive effect is not in the foreground for the matrix according to the invention.
  • a matrix has been shown to be particularly suitable, the bioactive component of which contains 10 to 40% by weight and particularly preferably 15 to 30% by weight of phosphatidylserine. Also particularly suitable is a matrix whose bioactive component contains 2.0 to 20% by weight of phosphatidylcholine.
  • compositionsen which consists of 10 to 70 wt .-% and particularly preferably 20 to 50 wt .-% of the fat component and / or 3 to 30 wt .-% and particularly preferably 5 to 20 wt .-% of the wax component, 1 to 30 wt .-% and particularly preferably 1 to 20 wt .-% of the polyalcohol component and / or 1, 0 to 5 wt .-% of other physiologically compatible additives.
  • the matrix as a fat component can preferably be refined, hydrogenated and / or fractionated fats and in particular those which are rich in omega-3 and / or omega-6 fatty acids, such as docosahexaenoic acid, arachidonic acid, Eicosapentaenoic acid and conjugated linolenic acid, free fatty acids, especially omega-3 and omega-6 fatty acids, as a wax component preferably beeswax, candellila wax, shellack, paraffin, mono- or diglycerides, and also as a polyalcohol combination, preferably with a po contain ethyl en g ly kol, polysorbate, polyglycerol esters, sugar esters or sorbitan esters.
  • omega-3 and / or omega-6 fatty acids such as docosahexaenoic acid, arachidonic acid, Eicosapentaenoic acid and conjugated linolenic acid, free fatty acids, especially omega-3 and omega-6
  • the matrix can also advantageously tocopherols and their derivatives, tocotrienols and their derivatives, polycosanols and their derivatives, vitamins such as vitamins C and E, also in derivatized form, amino acids, in particular the essential, branched and non-proteinogenic such as theanine, amino acid derivatives such as Creatine, taurine, carnitine, phytosterols and their derivatives, (poly) -phenolic compounds and their derivatives such as catechol, phenolic acids such as gallic acid, hydroxycinnamic acids, coumarins, (iso-) flavonoids such as quercetin or genistein, lignans and lignins as well as tannin, saponins, mono -, Sesqui- and di-terpenes, carotenoids such as beta-carotene, lutein or lycopene, glucosinolates, fiber such as non-starch polysaccharides, extracts of plant and /
  • the stabilization of phosphatidylserine and phosphatidylcholine according to the invention is effected in particular by further matrix components which are selected such that the total matrix (ie consisting of PS / PC and the other components) is solid at room temperature, to an extent that in the case of Use of fats (triglycerides) is the solid fraction of the triglyceride that can be determined by DSC> 80% at 23 ° C.
  • the components are advantageously chosen so that the overall matrix exhibits the property of shear thinning, which can be achieved, for example, by the preferred use of a combination of fat and wax (eg beeswax) in connection with PC / PS in the matrix if the triglyceride contains one sufficiently high proportion of fixed, ie contains unmelted triglycerides.
  • preferred matrix components have a saturated fatty acid content of over 50% and advantageously no more than four main triglyceride species are present.
  • palm kernel oil in conjunction with beeswax has proven particularly advantageous here.
  • the person skilled in the art can thus readily select matrices suitable according to the invention on the basis of criteria 1) the solid fraction of the triglyceride which can be determined by DSC is> 80% at 23 ° C., and 2) the fraction of saturated fatty acids is above 50%.
  • the phosphatidylserine and phosphatidylcholine are stabilized by using a matrix which contains a polyalcohol component.
  • this matrix can be somewhat more liquid, in particular glycerol being added as the polyalcohol component.
  • the disadvantages of conventional lecithin matrices can be overcome.
  • Lecithin matrices the water content is always low due to the strongly lipophilic properties of the matrix and the water present does not move freely in the matrix, but is bound to the polar head groups and hydrates them or hydrolyzes the head group. This causes the instability of the phospholipid (i.e. PC or PS) in conventional matrices.
  • a polyalcohol component according to the invention for example glycerol as the polar substance, displaces the water from the head group and thereby prevents or at least delays the hydrolysis of the phospholipid.
  • the matrix therefore preferably contains at least one fat component in addition to PS and PC, even more preferably a fat component and wax component, and in a further embodiment preferably at least one polyalcohol component.
  • particularly suitable as matrix materials are substances which enable complete encapsulation to be achieved, and substances which provide a matrix with high stability and low shear stress.
  • the claimed matrix has a water-containing covering, which can also be permanently elastic.
  • the coating which preferably also consists of gelatin, glycerol, sugar (alcohols), starch, polysaccharides and mixtures thereof, should have a water content of 1.0 to 10.0% by weight, based on the total coating. Sorbitol is particularly preferred as sugar alcohols for the coating and carrageenans, alginates and / or pectins as polysaccharide components.
  • the coating of the matrix contains, as further additives, silicon dioxide, calcium carbonate, food-grade dyes, color pigments and / or talc.
  • weight ratios of the coating to the bioactive component which are between 1: 0.25 to 10.0 and particularly preferably 1: 1 to 5.0, have been found to be particularly suitable.
  • the total diameter of the matrix is, of course, also dependent on the respective intended use, and should in particular be between 0.3 and 20 mm according to the present invention.
  • the present invention also claims its use, with the components contained in it in particular strengthening the mental and / or physical endurance and performance, preventing elevated serum cholesterol levels, promoting or / and maintaining health, and in general the focus is on improving well-being.
  • the matrix according to the invention With the matrix according to the invention, a formulation of phosphatidylserine and phosphatidylcholine was thus found which can be prepared in an economically justifiable manner and which, in contrast to the known other formulations, has a pronounced oxidative and hydrolytic stability.
  • the matrix according to the invention thus combines two features that were previously incompatible, namely being encapsulable and at the same time having sufficient stability. This combination is particularly pronounced for matrices with thixotropic or shear-thinning properties. But it also occurs in matrix forms that are pasty and behave in a Newtonian way.
  • the following examples illustrate these advantages of the matrix with a bioactive, phospholipid-containing component according to the invention.
  • the hard matrix contained 20% by weight of phosphatidylserine and 15% by weight of phosphatidylcholine as the bioactive component. Further constituents were in each case 3% by weight of phosphatidylinositol and 2% by weight of phosphatidylethanolamine, 38% by weight of a mixture of refined soybean oils, two partially hydrogenated soybean oils of different melting points and 3% by weight of a beeswax, 2% by weight % of a mixture consisting of vitamins E and D, tocotrieole and R-carotene. The remaining 100% by weight consisted of the typical lecithin accompanying substances such as glycolipids, phytosterols and oligosugars.
  • the two bioactive components were homogeneously distributed in the matrix, which was in the form of pellets with a diameter of 3 to 8 mm.
  • the hard matrix contained 20% by weight of phosphatidylserine, 5% by weight of phosphatidylcholine and 4% by weight of phosphatidylinositol as the bioactive component. Further constituents were in each case 6% by weight of phosphatidylethanolamine and 2% by weight of phosphatidic acid, 45% by weight of palm kernel oil and 5% by weight of a beeswax and 0.2% of vitamin E. The rest of 100% by weight consisted of the typical lecithin accompanying substances such as glycolipids, phytosterols and oligosugars.
  • Example 3 Example 3:
  • the hard matrix contained 30% by weight of phosphatidylserine, 4% by weight of phosphatidylcholine and 2% by weight of phosphatidylinositol as the bioactive component. Further constituents were in each case 4% by weight of phosphatidylethanolamine and 1% by weight of phosphatidic acid, 45% by weight of palm kernel oil and 5% by weight of a beeswax and 0.2% of vitamin E. The rest consisted of 100% by weight from the typical lecithin accompanying substances such as glycolipids, phytosterols and oligosugars.
  • Table 1 shows that, for example, the very hydrolysis-sensitive phosphatidylserine (PS) encapsulated in a soft gelatin capsule, that embedding the phospholipids in the matrix according to the invention effects, among other things, a stabilizing effect against hydrolysis.
  • PS very hydrolysis-sensitive phosphatidylserine
  • Examples 1 to 3 are the three described examples of the invention; Examples 4 to 6 are comparative examples. Table 1

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Abstract

The invention relates to a matrix comprising a bioactive component containing phospholipid made of 5 - 98 wt.- % phosphatidylserine and 1 - 90 wt.- % phosphatidylcholine. Additionally, 1 - 94 wt.- % of a vegetal and/or animal fat component, a wax component, a polyalcohol-component and/or additional physiologically compatible additives can be contained. Preferably, the matrix has a permanently elastic aqueous covering and an overall diameter of between 0.3 - 20 mm. Said matrix can be used especially for increasing physical and mental productive capacity and endurance,.

Description

Matrix mit einer bioaktiven Phospholipid-haltigen KomponenteMatrix with a bioactive phospholipid-containing component
Beschreibungdescription
Gegenstand der vorliegenden Erfindung ist eine Matrix mit einer bioaktiven, Phospholipid-haltigen Komponente sowie deren Verwendung.The present invention relates to a matrix with a bioactive, phospholipid-containing component and the use thereof.
Bei der Substanzklasse der Phospholipide handelt es sich um sogenannte komplexe Lipide mit amphiphilen, also gleichzeitig lipophilen und hydrophilen Eigenschaften, was sie unter anderem zur Ausbildung von Lipid-Doppel- schichten in wässrigen Medien befähigt.The substance class of the phospholipids are so-called complex lipids with amphiphilic, ie at the same time lipophilic and hydrophilic properties, which among other things enables them to form lipid bilayers in aqueous media.
Phospholipide (auch Phosphatide genannt) sind chemisch betrachtet Phos- phodiester, bei denen die Phosphorsäure einerseits mit einem Sphingosin- oder Glyceridrest und andererseits mit Cholin, Ethanolamin, Serin, Inosit oder Glycerin verestert ist. Das Phosphatidylcholin ist auch als Lecithin bekannt und ist zugleich Namensgeber für eine große Gruppe spezieller Phospholipide, die Lecithine. Phosphatidylserin und Phosphatidylethanol- amin werden auch als Kephaline bezeichnet.From a chemical point of view, phospholipids (also called phosphatides) are phosphodiesters in which the phosphoric acid is esterified on the one hand with a sphingosine or glyceride residue and on the other hand with choline, ethanolamine, serine, inositol or glycerol. Phosphatidylcholine is also known as lecithin and is also the eponym for a large group of special phospholipids, the lecithins. Phosphatidylserine and phosphatidylethanolamine are also known as cephalins.
Die ebenfalls zu dieser Gruppe gehörenden Lyso-Derivate entstehen durch hydrolytische Spaltung mittels spezifischer Phospholipasen.The lyso derivatives, which also belong to this group, are formed by hydrolytic cleavage using specific phospholipases.
Phospholipid-haltige Kapseln sind aus dem Stand der Technik hinlänglich bekannt und enthalten Phospholipide zumeist als Hüllsubstanz. Werden Phospholipide in der Füllung, also im Kapselkern eingesetzt, so fungieren sie dort zumeist in geringen Anteilen als Formulierungs-Hilfsmittel mit meist lösungsvermittelnden Eigenschaften.Capsules containing phospholipids are well known from the prior art and mostly contain phospholipids as the coating substance. If phospholipids are used in the filling, i.e. in the capsule core, they mostly act in small proportions there as formulation aids with mostly solubilizing properties.
Aufgrund ihrer amphiphilen Eigenschaften dienen die Phospholipide auch als Hüllsubstanzen der bekannten Liposomen und Transferosomen. In diesem Zusammenhang werden sie vor allem aufgrund ihrer bioadhesiven Merkmale im Bereich der Schleimhautapplikationen eingesetzt, wobei sie insbesondere in die Nasen- und Mundhöhlen eingebracht werden.Due to their amphiphilic properties, the phospholipids also serve as coating substances for the known liposomes and transferosomes. In In this context, they are used primarily because of their bioadhesive properties in the area of mucosal applications, with them being introduced in particular into the nasal and oral cavities.
In chemisch modifizierter Form werden Phospholipide aber auch als oberflächenaktive Formulierungshilfsmittel (Surfactants) verwendet.In chemically modified form, however, phospholipids are also used as surface-active formulation aids (surfactants).
Bekannt ist es auch, mittels Ultraschall Visikel herzustellen, die Phospholipide als Umhüllung tragen.It is also known to use ultrasound to produce visicles which carry phospholipids as a covering.
Spezielle Granulate mit Lecithinhüllen sind aus der japanischen Anmeldung JP 91 47 043 bekannt, sowie aus EP-A 493 441 . Diese Granulate, die unter anderem Steroide als bioaktive Substanzen enthalten, werden als Futtermittel-Additive eingesetzt.Special granules with lecithin casings are known from Japanese application JP 91 47 043 and from EP-A 493 441. These granules, which contain steroids as bioactive substances, are used as feed additives.
Lyso-Phospholipide werden gemäß WO 87/04347 als Lösungsvermittler für hydrophobe bioaktive Substanzen beschrieben.According to WO 87/04347, lysophospholipids are described as solubilizers for hydrophobic bioactive substances.
In den internationalen Anmeldungen WO 99/1 641 9 und 99/1 6421 sind lungengängige Darreichungsformen beschrieben, die als Träger für das Phosphatidylcholin organische Halogenverbindungen einsetzen.International applications WO 99/1 641 9 and 99/1 6421 describe respirable dosage forms which use organic halogen compounds as carriers for the phosphatidylcholine.
Lecithin als bioaktiven Inhaltsstoff enthalten Weichgelatinekapseln, die sich als KALS Lecithin im Handel befinden und die 1 200 mg Sojalecithin enthal- ten. Um diese Menge Lecithin allerdings in einer Kapsel unterbringen zu können, müssen Kapselgrößen gewählt werden, die sich der Zentimetergrenze nähern und somit eine eingeschränkte Compliance bedingen.Lecithin as a bioactive ingredient contains soft gelatin capsules, which are commercially available as KAL S lecithin and which contain 1,200 mg soy lecithin. However, in order to be able to accommodate this amount of lecithin in a capsule, capsule sizes must be selected that approach the centimeter limit and thus limited compliance.
Aus dem deutschen Patent DE 1 99 1 7 249 ist ein Verfahren zur Herstel- lung von Phosphatidylserin (PS), also einem Phospholipid, bekannt. In diesem Zusammenhang ist angegeben, dass das so erhaltene PS oder entsprechende PS-Produkte durch Einbetten in einem Hartfett in wässrigen Systemen stabilisiert werden können. Die dort gemachten Vorschläge beschränken sich allerdings auf Weichgelatinekapseln, die das spezielle PS im Inhalt aufweisen sollen. Das dort beschriebene System stabilisiert zwar das bekanntermaßen hydrolyseinstabile Phosphatidylserin, es weist aber den Nachteil auf, dass diese Formulierung nicht verkapselbar ist.A method for producing phosphatidylserine (PS), that is to say a phospholipid, is known from German patent DE 1 99 1 7 249. In this connection it is stated that the PS obtained in this way or corresponding PS products is embedded in a hard fat in aqueous Systems can be stabilized. However, the suggestions made there are limited to soft gelatin capsules, which should have the special PS in the content. The system described there stabilizes the known hydrolysis-unstable phosphatidylserine, but it has the disadvantage that this formulation cannot be encapsulated.
Formulierungen von Phosphatidylserin und Phosphatidylcholin, insbesondere im Gemisch mit anderen Lecithinen und/oder Ölen, haben sich in Weichkapseln als nicht ausreichend stabil erwiesen. Auch sind aufgrund der technologischen Anforderungen, die eine Verkapselung mit sich bringt, welche typischerweise nach dem sogenannten Rotary-Die erfolgt, dem Mischen ("Blenden") enge Grenzen bezüglich des Schmelzpunktes und Fließverhaltens des Kapselinhaltes gesetzt. Auch die beim Verkapselungs- prozess vorherrschenden Verarbeitungstemperaturen wirken sich meist negativ auf die Eigenschaften der Kapselumhüllung bzw. der Kapselinhalte aus.Formulations of phosphatidylserine and phosphatidylcholine, in particular in a mixture with other lecithins and / or oils, have not proven to be sufficiently stable in soft capsules. Also, due to the technological requirements that an encapsulation entails, which typically takes place according to the so-called rotary die, the mixing ("blending") is subject to narrow limits with regard to the melting point and flow behavior of the capsule contents. The processing temperatures prevailing in the encapsulation process also usually have a negative effect on the properties of the capsule casing or the capsule contents.
Eine Folge dieser beschriebenen Instabilität der Lecithine als Kapselinhalte ist, dass statt einer gewünschten flüssigen Formulierung bestenfalls mäßig pastöse Blends verkapselt werden können.One consequence of this instability of the lecithins as capsule contents is that instead of a desired liquid formulation, at best moderately pasty blends can be encapsulated.
Hinzu kommt, dass die Verkapselung von Phospholipiden allgemein große Probleme bereitet, da diese, wie beschrieben, auch als Emulgatoren wirken und damit während des Verkapselungsprozesses rasch eine Vermischung der noch nicht ausgehärteten (getrockneten) Hülle mit dem Inhalt bewirken. Dadurch werden die Kapseln in relativ kurzer Zeit undicht, sie lecken und sind damit nicht mehr verwendbar.In addition, the encapsulation of phospholipids generally causes great problems, since, as described, they also act as emulsifiers and thus rapidly cause the as yet uncured (dried) casing to mix with the contents during the encapsulation process. As a result, the capsules leak in a relatively short time, they leak and are therefore no longer usable.
Für die vorliegende Erfindung hat sich deshalb die Aufgabe gestellt, eine Matrix mit einer bioaktiven, Phospholipid-haltigen Komponente bereit zu stellen, die die Nachteile des beschriebenen Standes der Technik nicht aufweist und die in wirtschaftlich vertretbarer Weise formuliert werden kann. Zudem sollten die in die Matrix eingebrachten bioaktiven Phospho- lipid-Komponenten eine für die häufigsten Anwendungszwecke ausreichende Stabilität selbst im verkapselten Zustand aufweisen.The object of the present invention was therefore to provide a matrix with a bioactive, phospholipid-containing component which does not have the disadvantages of the prior art described and which are formulated in an economically justifiable manner can. In addition, the bioactive phospholipid components incorporated into the matrix should have sufficient stability for the most common uses, even in the encapsulated state.
Gelöst wurde diese Aufgabe mit einer entsprechenden Matrix, die als bioaktive Komponente 5 bis 98 Gew.-% Phosphatidylserin (PS) und 1 bis 90 Gew.-% Phosphatidylcholin (PC) und darüber hinaus 1 bis 94 Gew.-% mindestens einer weiteren Komponente der Reihe Fett-Komponente pflanzlichen und/oder tierischen Ursprungs, Wachs-Komponente, Polyalkohol- Komponente und weitere physiologisch verträgliche Zusätze enthält.This problem was solved with a corresponding matrix, the bioactive component being 5 to 98% by weight of phosphatidylserine (PS) and 1 to 90% by weight of phosphatidylcholine (PC) and moreover 1 to 94% by weight of at least one further component the range of fat components of vegetable and / or animal origin, wax component, polyalcohol component and other physiologically compatible additives.
Überraschend hat sich mit der erfindungsgemäßen Matrix herausgestellt, dass die darin enthaltenen Phosphatidylserin- bzw. Phosphatidylcholin- Anteile gegenüber der sonst negativen Hydrolyse bzw. dem allgemeinen Abbau verkapselter Lecithine äußerst stabil sind. Dies ist insbesondere bei Blends stark ausgeprägt, die hochviskos sind und zusätzlich die Eigenschaft der Thixotropie aufweisen. Bislang war nur bekannt, dass hochviskose Blends zwar Lecithine stabiler machen, diese hochviskosen Mischungen waren dann allerdings nicht mehr verkapselbar (siehe DE-OS 1 99 1 7 249) . Dies ist umso überraschender als insbesondere von Phosphatidylserin bekannt ist, dass es signifikant weniger stabil als andere Phospholipide ist.It has surprisingly been found with the matrix according to the invention that the phosphatidylserine or phosphatidylcholine portions contained therein are extremely stable with respect to the otherwise negative hydrolysis or the general breakdown of encapsulated lecithins. This is particularly pronounced with blends that are highly viscous and also have the property of thixotropy. Until now it was only known that highly viscous blends make lecithins more stable, however, these highly viscous mixtures could then no longer be encapsulated (see DE-OS 1 99 1 7 249). This is all the more surprising since phosphatidylserine in particular is known to be significantly less stable than other phospholipids.
Die Verbindungen enthalten neben der Kopfgruppe (also Serin bzw. Cholin) an den Positionen sn-1 bzw. sn-2 vorzugsweise jeweils einen Rest, der von einer an die Hydroxylgruppen des Glycerins gebundenen C2-C30- Carbonsäure, insbesondere einer C12-C28-Carbonsäure stammt. Die Säurereste können linear oder verzweigt, gesättigt oder ein- oder mehrfach ungesättigt sein. Besonders bevorzugte Reste sind Reste, die durch die Bindung von Essigsäure, Buttersäure, Capronsäure, Caprylsäure, Caprinsäure, Laurinsäure, Myristinsäure, Arachinsäure, Behensäure, Lignocerinsäure, R-Linolensäure, Eicosapentaensäure, Erucasäure, Nervonsäure, - oderR-Eleostearinsäure oder Parinarsäure gebildet werden. Besonders bevorzugt sind Reste, die durch Bindung von Palmitinsäure, Stearinsäure, Ölsäure, Linolsäure, α-Linolensäure, Arachidonsäure oder Docosahexaensäure gebildet werden. Die an die beiden noch verfügbaren OH-Gruppen des Glycerins gebundenen Säurereste können dabei gleich oder unterschiedlich sein.In addition to the head group (i.e. serine or choline) at the positions sn-1 or sn-2, the compounds each preferably contain a residue which is derived from a C 2 -C 30 carboxylic acid bonded to the hydroxyl groups of the glycerol, in particular a C 12 -C 28 carboxylic acid. The acid residues can be linear or branched, saturated or mono- or polyunsaturated. Particularly preferred residues are residues which, by binding acetic acid, butyric acid, caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, arachic acid, behenic acid, lignoceric acid, R-linolenic acid, eicosapentaenoic acid, erucic acid, Nervonic acid, - or R-Eleostearic acid or parinic acid are formed. Residues which are formed by binding palmitic acid, stearic acid, oleic acid, linoleic acid, α-linolenic acid, arachidonic acid or docosahexaenoic acid are particularly preferred. The acid residues bound to the two OH groups of the glycerol still available can be the same or different.
Phosphatidylserin und Phosphatidylcholin repräsentieren in der erfindungsgemäßen Gesamtmatrix den bioaktiven Teil; die anderen Komponenten verleihen der Gesamtmatrix aufgrund ihrer Anteile ihre vorteilhaften Eigenschaften.Phosphatidylserine and phosphatidylcholine represent the bioactive part in the total matrix according to the invention; the other components give the overall matrix its advantageous properties due to their proportions.
Unter dem Begriff "bioaktiv" wird im Zusammenhang mit der vorliegenden Erfindung die Wirkung von Phosphatidylserin und Phosphatidylcholin in der Art verstanden, dass sie im lebenden Organismus während oder nach ihrer Freisetzung aus der Gesamtmatrix im Resorptionsbereich, auf dem Transportweg oder am Zielort eine biologische Wirkung entfalten, was üblicherweise auf entsprechende Präparate im Human- oder Veterinärbereich zutrifft. Dabei ist diese bioaktive Wirkung selbstverständlich nicht auf die beiden genannten Phospholipide beschränkt, sondern kann auch durch die anderen an der Gesamtmatrix beteiligten Komponenten entfaltet werden. Deren bioaktive Wirkung steht allerdings für die erfindungsgemäße Matrix nicht im Vordergrund.In connection with the present invention, the term “bioactive” is understood to mean the action of phosphatidylserine and phosphatidylcholine in such a way that they develop a biological effect in the resorption area, on the transport route or at the destination in the living organism during or after their release from the total matrix , which usually applies to corresponding preparations in the human or veterinary field. This bioactive effect is of course not limited to the two phospholipids mentioned, but can also be developed by the other components involved in the overall matrix. However, their bioactive effect is not in the foreground for the matrix according to the invention.
Im vorliegenden Zusammenhang hat sich insbesondere eine Matrix als besonders geeignet gezeigt, deren bioaktive Komponente 1 0 bis 40 Gew.-% und besonders bevorzugt 1 5 bis 30 Gew.-% an Phosphatidylserin enthält. Ebenfalls besonders geeignet ist eine Matrix, deren bioaktive Komponente 2,0 bis 20 Gew.-% an Phosphatidylcholin enthält.In the present context, a matrix has been shown to be particularly suitable, the bioactive component of which contains 10 to 40% by weight and particularly preferably 15 to 30% by weight of phosphatidylserine. Also particularly suitable is a matrix whose bioactive component contains 2.0 to 20% by weight of phosphatidylcholine.
Aus dem relativ breiten Spektrum möglicher Zusammensetzungen hat sich für die beanspruchte Matrix eine Zusammensetzung als vorteilhaft erwie- sen, die aus 10 bis 70 Gew.-% und besonders bevorzugt 20 bis 50 Gew.- % der Fett-Komponente und/oder 3 bis 30 Gew.-% und besonders bevorzugt 5 bis 20 Gew.-% der Wachs-Komponente, 1 bis 30 Gew.-% und besonders bevorzugt 1 bis 20 Gew.-% der Polyalkohol-Komponente und/oder 1 ,0 bis 5 Gew.-% an weiteren physiologisch verträglichen Zusätzen besteht.From the relatively broad spectrum of possible compositions, one composition has proven to be advantageous for the claimed matrix. sen, which consists of 10 to 70 wt .-% and particularly preferably 20 to 50 wt .-% of the fat component and / or 3 to 30 wt .-% and particularly preferably 5 to 20 wt .-% of the wax component, 1 to 30 wt .-% and particularly preferably 1 to 20 wt .-% of the polyalcohol component and / or 1, 0 to 5 wt .-% of other physiologically compatible additives.
Neben den erfindungswesentlichen bioaktiven Komponenten Phosphatidylserin und Phosphatidylcholin kann die Matrix als Fett-Komponente vorzugs- weise raffinierte, hydrierte und/oder fraktionierte Fette und insbesondere solche, die reich sind an Omega-3 und/oder Omega-6 Fettsäuren, wie Docosahexaensäure, Arachidonsäure, Eicosapentaensäure und konjugierte Linolenensäure, freie Fettsäuren, insbesondere Omega-3 und Omega-6 Fettsäuren, als Wachskomponente vorzugsweise Bienenwachs, Candellila- wachs, Shellack, Paraffin, Mono- oder Diglyceride, sowie als Polyalkohol- Ko mp o n e nte vo rzu g swei se Po lyethyl en g ly ko l , Po lysorbat, Polyglycerinester, Zuckerester oder Sorbitanester enthalten. Die Matrix kann auch vorteilhafterweise Tocopherole und deren Derivate, Tocotrienole und deren Derivate, Polycosanole und deren Derivate, Vitamine wie Vitamin C und E, auch in derivatisierter Form, Aminosäuren, insbesondere die essenziellen, verzweigten und nicht proteinogenen wie z.B. Theanin, Aminosäuren-Derivate wie Kreatin, Taurin, Karnitin, Phytosterine und deren Derivate, (poly)-phenolische Verbindungen und deren Derivate wie Catechol, Phenolsäuren wie Gallussäure, Hydroxyzimtsäuren, Kumarine, (Iso-)Flavonoide wie Quercetin oder Genistein, Lignane und Lignine sowie Tannin, Saponine, Mono-, Sesqui- und Di-Terpene, Carotinoide wie beta- Carotin, Lutein oder Lykopin, Glucosinolate, Ballaststoffe wie Nicht-Stärke- Polysaccaride, Extrakte pflanzlichen und/oder tierischen Ursprungs, physiologisch aktive Proteine wie Lactoferrin und Glycomakropeptid, Phospho- und Glycolipide wie z.B. Sphingosin oder (Phyto-) Sphingomyelin, und/oder mineralische Bestandteile, aber auch andere geeignete bioaktive Bestandteile enthalten, was die vorliegende Erfindung ebenfalls berücksichtigt.In addition to the bioactive components phosphatidylserine and phosphatidylcholine, which are essential to the invention, the matrix as a fat component can preferably be refined, hydrogenated and / or fractionated fats and in particular those which are rich in omega-3 and / or omega-6 fatty acids, such as docosahexaenoic acid, arachidonic acid, Eicosapentaenoic acid and conjugated linolenic acid, free fatty acids, especially omega-3 and omega-6 fatty acids, as a wax component preferably beeswax, candellila wax, shellack, paraffin, mono- or diglycerides, and also as a polyalcohol combination, preferably with a po contain ethyl en g ly kol, polysorbate, polyglycerol esters, sugar esters or sorbitan esters. The matrix can also advantageously tocopherols and their derivatives, tocotrienols and their derivatives, polycosanols and their derivatives, vitamins such as vitamins C and E, also in derivatized form, amino acids, in particular the essential, branched and non-proteinogenic such as theanine, amino acid derivatives such as Creatine, taurine, carnitine, phytosterols and their derivatives, (poly) -phenolic compounds and their derivatives such as catechol, phenolic acids such as gallic acid, hydroxycinnamic acids, coumarins, (iso-) flavonoids such as quercetin or genistein, lignans and lignins as well as tannin, saponins, mono -, Sesqui- and di-terpenes, carotenoids such as beta-carotene, lutein or lycopene, glucosinolates, fiber such as non-starch polysaccharides, extracts of plant and / or animal origin, physiologically active proteins such as lactoferrin and glycomacropeptide, phospho- and glycolipids such as eg sphingosine or (phyto-) sphingomyelin, and / or mineral components, but also other suitable ones bioactive Contain components, which also takes into account the present invention.
Die erfindungsgemäße Stabilisierung des Phosphatidylserins und Phos- phatidylcholins wird insbesondere durch weitere Matrixkomponenten bewirkt, die so ausgewählt sind, dass die Gesamtmatrix (also bestehend aus PS/PC sowie den weiteren Komponenten) bei Raumtemperatur fest ist und zwar in einem Ausmaß, dass im Fall der Verwendung von Fetten (Triglyce- riden) der über DSC bestimmbare feste Anteil des Triglycerids > 80 % bei 23 °C ist. Weiterhin werden die Komponente vorteilhafterweise so gewählt, dass die Gesamtmatrix die Eigenschaft der Scherverdünnung zeigt, was beispielsweise durch die bevorzugte Verwendung einer Kombination aus Fett und Wachs (z.B. Bienenwachs) in Verbindung mit PC/PS in der Matrix erreicht werden kann, wenn das Triglycerid einen genügend hohen Anteil an festen, d.h. nicht geschmolzenen Triglyceriden enthält. In diesem Fall weisen bevorzugte Matrixkomponenten einen Anteil an gesättigten Fettsäuren von über 50 % auf und es sind vorteilhafterweise nicht mehr als vier hauptsächlich vorkommende Triglyceridspezies vorhanden. Besonders vorteilhaft hat sich hier die Verwendung von Palmkernöl in Verbindung mit Bienenwachs herausgestellt.The stabilization of phosphatidylserine and phosphatidylcholine according to the invention is effected in particular by further matrix components which are selected such that the total matrix (ie consisting of PS / PC and the other components) is solid at room temperature, to an extent that in the case of Use of fats (triglycerides) is the solid fraction of the triglyceride that can be determined by DSC> 80% at 23 ° C. Furthermore, the components are advantageously chosen so that the overall matrix exhibits the property of shear thinning, which can be achieved, for example, by the preferred use of a combination of fat and wax (eg beeswax) in connection with PC / PS in the matrix if the triglyceride contains one sufficiently high proportion of fixed, ie contains unmelted triglycerides. In this case, preferred matrix components have a saturated fatty acid content of over 50% and advantageously no more than four main triglyceride species are present. The use of palm kernel oil in conjunction with beeswax has proven particularly advantageous here.
Der Fachmann kann somit erfindungsgemäß geeignete Matrizen ohne weiteres anhand der Kriterien 1 ) der über DSC bestimmbare feste Anteil des Triglycerids ist > 80 % bei 23 °C, und 2) der Anteil an gesättigten Fettsäuren liegt über 50 % auswählen.The person skilled in the art can thus readily select matrices suitable according to the invention on the basis of criteria 1) the solid fraction of the triglyceride which can be determined by DSC is> 80% at 23 ° C., and 2) the fraction of saturated fatty acids is above 50%.
In einer weiteren Ausführungsform der Erfindung erfolgt die Stabilisierung des Phosphatidylserins und Phosphatidylcholins durch Verwendung einer Matrix, welche eine Polyalkoholkomponente enthält. Diese Matrix kann insgesamt etwas flüssiger sein, wobei insbesondere Glycerin als Polyalkohol-Komponente zugesetzt ist. In dieser Ausführungsform können die Nachteile von herkömmlichen Lecithin-Matrizes überwunden werden. In Lecithin-Matrizes ist der Wassergehalt wegen der stark lipophilen Eigenschaften der Matrix stets gering und das vorhandene Wasser bewegt sich nicht frei in der Matrix, sondern es ist an die polaren Kopfgruppen gebunden und hydratisiert diese bzw. hydrolysiert die Kopfgruppe. Dadurch wird die Instabilität des Phospholipids (also PC bzw. PS) in herkömmlichen Matrizes bedingt. Durch die erfindungsgemäße Zugabe einer Polyalkohol- komponente, beispielsweise Glycerin als polaren Stoff, wird das Wasser von der Kopfgruppe verdrängt und dadurch die Hydrolyse des Phospholipids verhindert oder zumindest verzögert.In a further embodiment of the invention, the phosphatidylserine and phosphatidylcholine are stabilized by using a matrix which contains a polyalcohol component. Overall, this matrix can be somewhat more liquid, in particular glycerol being added as the polyalcohol component. In this embodiment, the disadvantages of conventional lecithin matrices can be overcome. In Lecithin matrices the water content is always low due to the strongly lipophilic properties of the matrix and the water present does not move freely in the matrix, but is bound to the polar head groups and hydrates them or hydrolyzes the head group. This causes the instability of the phospholipid (i.e. PC or PS) in conventional matrices. The addition of a polyalcohol component according to the invention, for example glycerol as the polar substance, displaces the water from the head group and thereby prevents or at least delays the hydrolysis of the phospholipid.
Erfindungsgemäß bevorzugt enthält die Matrix neben PS und PC deshalb weiterhin wenigstes eine Fett-Komponente, noch mehr bevorzugt eine Fett- Komponente und Wachskomponente und in einer weiteren Ausführungsform bevorzugt wenigstens eine Polyalkohol-Komponente.According to the invention, the matrix therefore preferably contains at least one fat component in addition to PS and PC, even more preferably a fat component and wax component, and in a further embodiment preferably at least one polyalcohol component.
Besonders geeignet als Matrixmaterialien sind erfindungsgemäß Stoffe, welche die Ausprägung einer vollständigen Verkapselung ermöglichen sowie Stoffe, welche eine Matrix mit hoher Stabilität und niedriger Scherbeanspruchung bereitstellen.According to the invention, particularly suitable as matrix materials are substances which enable complete encapsulation to be achieved, and substances which provide a matrix with high stability and low shear stress.
In einer bevorzugten Ausführungsform weist die beanspruchte Matrix eine wasserhaltige Umhüllung auf, die auch dauerelastisch sein kann.In a preferred embodiment, the claimed matrix has a water-containing covering, which can also be permanently elastic.
Dabei sollte die Umhüllung, die vorzugsweise auch aus Gelatine, Glycerin, Zucker(-alkoholen), Stärke, Polysacchariden und deren Mischungen besteht, einen Wassergehalt von 1 ,0 bis 10,0 Gew.-% bezogen auf die Gesamtumhüllung aufweisen. Dabei kommen als Zuckeralkohole für die Umhüllung besonders bevorzugt Sorbitol und als Polysaccharid-Kompo- nente Carrageenane, Alginate und/oder Pektine in Frage. Schließlich sieht die Erfindung auch vor, dass die Umhüllung der Matrix als weitere Zusätze Siliciumdioxid, Calciumcarbonat, lebensmittelgeeignete Farbstoffe, Farbpigmente und/oder Talkum enthält. ln Abhängigkeit von der Zusammensetzung der bioaktiven Komponente und der das Umhüllungsmaterial ausmachenden Substanzklassen kann es für die Produktqualität der erfindungsgemäßen Gesamtmatrix von Bedeutung sein, in welchem Gewichtsverhältnis die Umhüllung und die bioaktive Komponente vorliegen. Hierbei haben sich insbesondere Gewichtsverhältnisse von Umhüllung zur bioaktiven Komponente als besonders geeignet gezeigt, die zwischen 1 : 0,25 bis 10,0 und besonders bevorzugt 1 : 1 bis 5,0 liegen.The coating, which preferably also consists of gelatin, glycerol, sugar (alcohols), starch, polysaccharides and mixtures thereof, should have a water content of 1.0 to 10.0% by weight, based on the total coating. Sorbitol is particularly preferred as sugar alcohols for the coating and carrageenans, alginates and / or pectins as polysaccharide components. Finally, the invention also provides that the coating of the matrix contains, as further additives, silicon dioxide, calcium carbonate, food-grade dyes, color pigments and / or talc. Depending on the composition of the bioactive component and the substance classes that make up the coating material, it may be important for the product quality of the overall matrix according to the invention in what weight ratio the coating and the bioactive component are present. Weight ratios of the coating to the bioactive component, which are between 1: 0.25 to 10.0 and particularly preferably 1: 1 to 5.0, have been found to be particularly suitable.
Abhängig vom jeweiligen Verwendungszweck ist natürlich auch der Gesamtdurchmesser der Matrix, der gemäß vorliegender Erfindung insbesondere zwischen 0,3 und 20 mm betragen sollte.The total diameter of the matrix is, of course, also dependent on the respective intended use, and should in particular be between 0.3 and 20 mm according to the present invention.
Neben der Matrix selbst beansprucht die vorliegende Erfindung auch deren Verwendung, wobei aufgrund der in ihr enthaltenen Komponenten insbesondere die Stärkung der mentalen oder/und körperlichen Belastbarkeit und Leistungsfähigkeit, die Vorbeugung erhöhter Serumcholesterin-Spiegel, die Förderung oder/und Erhaltung der Gesundheit sowie ganz allgemein die Verbesserung des Wohlbefindens im Vordergrund stehen.In addition to the matrix itself, the present invention also claims its use, with the components contained in it in particular strengthening the mental and / or physical endurance and performance, preventing elevated serum cholesterol levels, promoting or / and maintaining health, and in general the focus is on improving well-being.
Mit der erfindungsgemäßen Matrix wurde somit eine Formulierung von Phosphatidylserin und Phosphatidylcholin gefunden, die in wirtschaftlich vertretbarer Weise hergestellt werden kann und die im Gegensatz zu den bekannten anderen Formulierungen eine ausgeprägte oxidative und hydroly- tische Stabilität aufweist. Somit verbindet die erfindungsgemäße Matrix zwei Merkmale, die bislang nicht vereinbar waren, nämlich verkapselbar zu sein und dabei gleichzeitig eine ausreichende Stabilität aufzuweisen. Diese Kombination ist vor allem ausgeprägt bei Matrices mit thixotropen oder scher-verdünnenden Eigenschaften. Sie tritt aber auch bei Matrix-Formen auf, die pastös sind und sich newtonisch verhalten. Die nachfolgenden Beispiele verdeutlichen diese Vorteile der Matrix mit einer bioaktiven, Phospholipid-haltigen Komponente gemäß Erfindung.With the matrix according to the invention, a formulation of phosphatidylserine and phosphatidylcholine was thus found which can be prepared in an economically justifiable manner and which, in contrast to the known other formulations, has a pronounced oxidative and hydrolytic stability. The matrix according to the invention thus combines two features that were previously incompatible, namely being encapsulable and at the same time having sufficient stability. This combination is particularly pronounced for matrices with thixotropic or shear-thinning properties. But it also occurs in matrix forms that are pasty and behave in a Newtonian way. The following examples illustrate these advantages of the matrix with a bioactive, phospholipid-containing component according to the invention.
BeispieleExamples
Beispiel 1 :Example 1 :
Die harte Matrix enthielt als bioaktive Komponente 20 Gew.-% Phosphatidylserin und 1 5 Gew.-% Phosphatidylcholin. Weitere Bestandteile waren jeweils 3 Gew.-% Phosphatidylinositol und 2 Gew.-% Phosphatidylethanol- amin, 38 Gew.-% einer Mischung aus raffiniertem Soja-, zwei teilhydrierten Sojaölen unterschiedlicher Schmelzpunkte sowie 3 Gew.-% eines Bienenwachses, 2 Gew.-% einer Mischung bestehend aus den Vitaminen E und D, Tocotrieole und R-Carotin. Der Rest zu 100 Gew.-% bestand aus den typischen Lecithinbegleitstoffen wie etwa Glycolipiden, Phytosterinen und Oligozuckern.The hard matrix contained 20% by weight of phosphatidylserine and 15% by weight of phosphatidylcholine as the bioactive component. Further constituents were in each case 3% by weight of phosphatidylinositol and 2% by weight of phosphatidylethanolamine, 38% by weight of a mixture of refined soybean oils, two partially hydrogenated soybean oils of different melting points and 3% by weight of a beeswax, 2% by weight % of a mixture consisting of vitamins E and D, tocotrieole and R-carotene. The remaining 100% by weight consisted of the typical lecithin accompanying substances such as glycolipids, phytosterols and oligosugars.
Die beiden bioaktiven Bestandteile waren dabei in der Matrix, die als Pellets mit einem Durchmesser von 3 bis 8 mm vorlag, homogen verteilt.The two bioactive components were homogeneously distributed in the matrix, which was in the form of pellets with a diameter of 3 to 8 mm.
Beispiel 2:Example 2:
Die harte Matrix enthielt als bioaktive Komponente 20 Gew.-% Phosphatidylserin, 5 Gew.-% Phosphatidylcholin und 4 Gew-% Phosphatidylinositol. Weitere Bestandteile waren jeweils 6 Gew.-% Phosphatidylethanolamin und 2 Gew.-% Phosphatidsäure, 45 Gew.-% Palmkernöl und 5 Gew.-% eines Bienenwachses sowie 0,2 % Vitamin E. Der Rest zu 100 Gew.-% bestand aus den typischen Lecithinbegleitstoffen wie etwa Glycolipiden, Phytosterinen und Oligozuckern. Beispiel 3:The hard matrix contained 20% by weight of phosphatidylserine, 5% by weight of phosphatidylcholine and 4% by weight of phosphatidylinositol as the bioactive component. Further constituents were in each case 6% by weight of phosphatidylethanolamine and 2% by weight of phosphatidic acid, 45% by weight of palm kernel oil and 5% by weight of a beeswax and 0.2% of vitamin E. The rest of 100% by weight consisted of the typical lecithin accompanying substances such as glycolipids, phytosterols and oligosugars. Example 3:
Die harte Matrix enthielt als bioaktive Komponente 30 Gew.-% Phosphatidylserin, 4 Gew.-% Phosphatidylcholin und 2 Gew-% Phosphatidylinositol. Weitere Bestandteile waren jeweils 4 Gew.-% Phosphatidylethanolamin und 1 Gew.-% Phosphatidsäure, 45 Gew.-% Palmkernöl und 5 Gew.-% eines Bienenwachses sowie 0,2 % Vitamin E. Der Rest zu 1 00 Gew.-% bestand aus den typischen Lecithinbegleitstoffen wie etwa Glycolipiden, Phytosteri- nen und Oligozuckern.The hard matrix contained 30% by weight of phosphatidylserine, 4% by weight of phosphatidylcholine and 2% by weight of phosphatidylinositol as the bioactive component. Further constituents were in each case 4% by weight of phosphatidylethanolamine and 1% by weight of phosphatidic acid, 45% by weight of palm kernel oil and 5% by weight of a beeswax and 0.2% of vitamin E. The rest consisted of 100% by weight from the typical lecithin accompanying substances such as glycolipids, phytosterols and oligosugars.
Stabilität der Phospholipide:Stability of the phospholipids:
Die Tabelle 1 zeigt für das beispielhaft in einer Weichgelatinekapsel verkapselte, sehr hydrolyseempfindliche Phosphatidylserin (PS), dass das Einbetten der Phospholipide in der erfindungsgemässen Matrix unter anderem einen stabilisierenden Effekt gegenüber Hydrolyse bewirkt.Table 1 shows that, for example, the very hydrolysis-sensitive phosphatidylserine (PS) encapsulated in a soft gelatin capsule, that embedding the phospholipids in the matrix according to the invention effects, among other things, a stabilizing effect against hydrolysis.
Als Vergleich dienten zwei phospholipidhaltige Lecithine in einer dem Stand der Technik entsprechenden Standardzubereitung, die im Hinblick auf die Verkapselbarkeit nach dem Standard-Rotary-Die Verfahren optimiert waren. Die Lecithine wurden in verkapselter Form bei Raumtemperatur (23 °C) gelagert.Two phospholipid-containing lecithins in a standard preparation corresponding to the prior art, which were optimized with regard to the encapsulability according to the standard Rotary-Die method, served as a comparison. The lecithins were stored in an encapsulated form at room temperature (23 ° C).
Bei den Beispielen 1 bis 3 handelt es sich um die drei beschriebenen Erfin- dungsbeispiele; die Beispiele 4 bis 6 sind Vergleichsbeispiele. Tabelle 1Examples 1 to 3 are the three described examples of the invention; Examples 4 to 6 are comparative examples. Table 1

Claims

Ansprüche Expectations
1 . Matrix mit einer bioaktiven, Phospholipid-haltigen Komponente, dadurch gekennzeichnet, dass sie als bioaktive Komponente 5 bis 981 . Matrix with a bioactive, phospholipid-containing component, characterized in that it is a bioactive component 5 to 98
Gew.-% Phosphatidylserin (PS) und 1 bis 90 Gew.-% Phosphatidylcholin (PC) und darüber hinaus 1 bis 94 Gew.-% mindestens einer weiteren Komponente der Reihe Fett-Komponente pflanzlichen und/oder tierischen Ursprungs, Wachs-Komponente, Polyalkohol- Komponente und weitere physiologisch verträgliche Zusätze enthält.% By weight of phosphatidylserine (PS) and 1 to 90% by weight of phosphatidylcholine (PC) and moreover 1 to 94% by weight of at least one further component of the series fat component of vegetable and / or animal origin, wax component, Contains polyalcohol component and other physiologically compatible additives.
2. Matrix nach Anspruch 1 , dadurch gekennzeichnet, dass die bioaktive Komponente 10 bis 40 Gew.-% und besonders bevorzugt 1 5 bis 30 Gew.-% Phosphatidylserin enthält2. Matrix according to claim 1, characterized in that the bioactive component contains 10 to 40 wt .-% and particularly preferably 1 5 to 30 wt .-% phosphatidylserine
3. Matrix nach einem der Ansprüche 1 oder 2, dadurch gekennzeichnet, dass die bioaktive Komponente 2,0 bis 20 Gew.-% Phosphatidylcholin enthält.3. Matrix according to one of claims 1 or 2, characterized in that the bioactive component contains 2.0 to 20 wt .-% phosphatidylcholine.
4. Matrix nach einem der Ansprüche 1 bis 3, dadurch gekennzeichnet, dass sie 10 bis 70 Gew.-% und besonders bevorzugt 20 bis 50 Gew.-% der Fett-Komponente, und/oder 3 bis 30 Gew.-% und besonders bevorzugt 5 bis 20 Gew.-% der Wachs-Komponente, und/oder 1 bis 30 Gew.-% und besonders bevorzugt 2 bis 20 Gew.- % der Polyalkohol-Komponente, und/oder 1 bis 5 Gew.-% an weiteren physiologisch verträglichen Zusätzen enthält.4. Matrix according to one of claims 1 to 3, characterized in that it contains 10 to 70 wt .-% and particularly preferably 20 to 50 wt .-% of the fat component, and / or 3 to 30 wt .-% and particularly preferably 5 to 20% by weight of the wax component, and / or 1 to 30% by weight and particularly preferably 2 to 20% by weight of the polyalcohol component, and / or 1 to 5% by weight of further contains physiologically compatible additives.
5. Matrix nach einem der Ansprüche 1 bis 4, dadurch gekennzeichnet, dass in ihr raffinierte, hydrierte und/oder fraktionierte Fette und insbesondere solche, die reich sind an Omega-3 und/oder Omega-65. Matrix according to one of claims 1 to 4, characterized in that in it refined, hydrogenated and / or fractionated fats and in particular those which are rich in omega-3 and / or omega-6
Fettsäuren, wie Docosahexaensäure, Arach idonsäure,Fatty acids such as docosahexaenoic acid, arachidonic acid,
Eicosapentaensäure und konjugierte Linolenensäure, freie Fettsäuren, insbesondere Omega-3 und Omega-6 Fettsäuren, Bienenwachs, Candellilawachs, Shellack, Paraffin, Mono- oder Diglyceride, Poly- ethylenglykol, Polysorbat, Polyglycerinester, Zuckerester, Sorbitanester, Tocopherole und deren Derivate, Tocotrienole und deren Derivate, Polycosanole und deren Derivate, Vitamine wie Vitamin C und E, auch in derivatisierter Form, Aminosäuren, insbesondere die essenziellen, verzweigten und nicht proteinogenen wie z.B. Theanin, Aminosäuren-Derivate wie Kreatin, Taurin, Karnitin, Phytosterine und deren Derivate, (poly)-phenolische Verbindungen und deren Derivate wie Catechol, Phenolsäuren wie Gallussäure, Hydroxyzimtsäuren,Eicosapentaenoic acid and conjugated linolenic acid, free fatty acids, in particular omega-3 and omega-6 fatty acids, beeswax, candellila wax, shellack, paraffin, mono- or diglycerides, polyethylene glycol, polysorbate, polyglycerol esters, sugar esters, sorbitan esters, tocopherols and their derivatives, tocotrienols and their derivatives, polycosanols and their derivatives, Vitamins such as vitamins C and E, also in derivatized form, amino acids, in particular the essential, branched and non-proteinogenic such as theanine, amino acid derivatives such as creatine, taurine, carnitine, phytosterols and their derivatives, (poly) phenolic compounds and their derivatives such as catechol, phenolic acids such as gallic acid, hydroxycinnamic acids,
Kumarine, (lso-)Flavonoide wie Quercetin oder Genistein, Lignane und Lignine sowie Tannin, Saponine, Mono-, Sesqui- und Di-Terpe- ne, Carotinoide wie beta-Carotin, Lutein oder Lykopin, Glucosinolate, Ballaststoffe, wie Nicht-Stärke-Polysaccaride, Extrakte pflanzlichen und/oder tierischen Ursprungs, physiologisch aktive Proteine wieCoumarins, (iso-) flavonoids such as quercetin or genistein, lignans and lignins as well as tannins, saponins, mono-, sesqui- and di-terpenes, carotenoids such as beta-carotene, lutein or lycopene, glucosinolates, fiber, such as non-starch -Polysaccharides, extracts of plant and / or animal origin, physiologically active proteins such as
Lactoferrin und Glycomakropeptid, Phospho- und Glycolipide wie z.B. Sphingosin oder (Phyto-) Sphingomyelin, und/oder mineralische Bestandteile enthalten sind.Lactoferrin and glycomacropeptide, phospho- and glycolipids such as e.g. Sphingosine or (phyto-) sphingomyelin, and / or mineral components are included.
6. Matrix nach einem der Ansprüche 1 bis 5, dadurch gekennzeichnet, dass sie eine wasserhaltige Umhüllung aufweist.6. Matrix according to one of claims 1 to 5, characterized in that it has a water-containing coating.
7. Matrix nach Anspruch 6, dadurch gekennzeichnet, dass die Umhüllung einen Wassergehalt von 1 ,0 bis 10,0 Gew.-%, bezogen auf die Gesamtumhüllung, aufweist.7. Matrix according to claim 6, characterized in that the covering has a water content of 1.0 to 10.0% by weight, based on the total covering.
8. Matrix nach einem der Ansprüche 6 oder 7, dadurch gekennzeichnet, dass die Umhüllung aus Gelatine, Glycerin, Zucker(-alkoholen), Stärke, Polysacchariden und deren Mischungen besteht. 8. Matrix according to one of claims 6 or 7, characterized in that the coating consists of gelatin, glycerol, sugar (alcohols), starch, polysaccharides and mixtures thereof.
9. Matrix nach Anspruch 8, dadurch gekennzeichnet, dass die Umhüllung als Zuckeralkohol Sorbitol und als Polysaccharid Carrageenane, Alginate und/oder Pektine enthält.9. Matrix according to claim 8, characterized in that the coating contains sorbitol as sugar alcohol and carrageenans, alginates and / or pectins as polysaccharide.
10. Matrix nach einem der Ansprüche 7 bis 9, dadurch gekennzeichnet, dass die Umhüllung als weitere Zusätze Siliciumdioxide, Calciumcar- bonat, Lebensmittel-geeignete Farbstoffe, Farbpigmente und/oder Talkum enthält.10. Matrix according to one of claims 7 to 9, characterized in that the coating contains, as further additives, silicon dioxide, calcium carbonate, food-grade dyes, color pigments and / or talc.
1 1 . Matrix nach einem der Ansprüche 1 bis 9, dadurch gekennzeichnet, dass das Gewichtsverhältnis von Umhüllung zur bioaktiven Komponente 1 : 0,25 bis 10,0 und besonders bevorzugt 1 : 1 bis 5,0 beträgt.1 1. Matrix according to one of claims 1 to 9, characterized in that the weight ratio of coating to bioactive component is 1: 0.25 to 10.0 and particularly preferably 1: 1 to 5.0.
12. Matrix nach einem der Ansprüche 1 bis 1 1 , dadurch gekennzeichnet, dass ihr Gesamtdurchmesser 0,3 bis 20 mm beträgt.12. Matrix according to one of claims 1 to 1 1, characterized in that its total diameter is 0.3 to 20 mm.
13. Verwendung der Matrix nach einem der Ansprüche 1 bis 12 zur Stärkung der mentalen oder/und körperlichen Belastbarkeit und Leistungsfähigkeit, zur Verbesserung des Wohlbefindens, zur Förderung oder/und Erhaltung der Gesundheit und zur Vorbeugung erhöhter Serumcholesterin-Spiegel. 13. Use of the matrix according to one of claims 1 to 12 to strengthen the mental and / or physical resilience and performance, to improve well-being, to promote or / and maintain health and to prevent increased serum cholesterol levels.
EP03722502A 2002-04-19 2003-04-17 Matrix comprising a bioactive component containing phospholipid Withdrawn EP1503742A2 (en)

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DE10217558 2002-04-19
DE10217558 2002-04-19
DE10250727A DE10250727B4 (en) 2002-04-19 2002-10-31 Matrix with a bioactive phospholipid-containing component
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PCT/EP2003/004030 WO2003088949A2 (en) 2002-04-19 2003-04-17 Matrix comprising a bioactive component containing phospholipid

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US20050232996A1 (en) 2005-10-20
AU2003229693A8 (en) 2003-11-03

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