DE4021083C2 - Phospholipid formulations and their use for the preparation of liposomal medical and cosmetic baths - Google Patents
Phospholipid formulations and their use for the preparation of liposomal medical and cosmetic bathsInfo
- Publication number
- DE4021083C2 DE4021083C2 DE19904021083 DE4021083A DE4021083C2 DE 4021083 C2 DE4021083 C2 DE 4021083C2 DE 19904021083 DE19904021083 DE 19904021083 DE 4021083 A DE4021083 A DE 4021083A DE 4021083 C2 DE4021083 C2 DE 4021083C2
- Authority
- DE
- Germany
- Prior art keywords
- weight
- oil
- phosphatidylcholine
- acid
- cosmetic
- 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.)
- Expired - Lifetime
Links
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Landscapes
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Description
Gegenstand der Erfindung sind Phospholipidformulierun gen, die pharmazeutische oder kosmetische Wirkstoffe enthalten, und ihre Verwendung zur Herstellung liposo maler medizinischer oder kosmetischer Badezubereitun gen.The invention relates to Phospholipidformulierun gene, the pharmaceutical or cosmetic active ingredients contain, and their use for producing liposo painters of medical or cosmetic bath preparations gene.
Badezubereitungen, insbesondere konventionelle Ölbäder, werden in der Medizin und der Kosmetik sehr häufig an gewandt, um der Haut großflächig Wirkstoffe zuzuführen. Dies kann in Form von Teilbädern, wie z. B. Fußbädern, Sitzbädern, Armbädern oder Vollbädern erfolgen. Bath preparations, in particular conventional oil baths, become very common in medicine and cosmetics turned to the skin over a large area to supply active ingredients. This can be done in the form of partial baths, such as. Footbaths, Seating baths, baths or full baths take place.
Der Begriff des Wirkstoffes ist hierbei unterschied lich. Während ein pharmazeutischer Wirkstoff dazu ge eignet ist, Hautkrankheiten zu heilen oder günstig zu beeinflussen, Erkältungskrankheiten zu lindern, auf Kreislauf und Stoffwechsel einzuwirken, hat ein kosme tischer Wirkstoff eine andere Funktion. Ein kosmeti scher Wirkstoff vermindert z. B. die Austrocknung der Haut, bewirkt eine Hautglättung, macht die Haut weich, verbessert die Elastizität der Haut, schützt die Haut vor den Wirkungen der UV-Strahlung.The term of the active ingredient is different Lich. While a pharmaceutical agent to ge is suitable to cure or beneficial to skin diseases affect relieve colds on Circulation and metabolism have a kosme tischer active ingredient another function. A cosmeti scher active ingredient reduces z. B. the dehydration of Skin, smoothes the skin, softens the skin, improves the elasticity of the skin, protects the skin from the effects of UV radiation.
Die wichtigsten Inhaltsstoffe eines Ölbades sind Ölkom ponente, Wirkstoff sowie einer oder mehrere Emulga toren, die eine Dispersion der Ölkomponente und des Wirkstoffes, insbesondere wenn er lipophilen Charakter hat, im Wasser ermöglichen.The most important ingredients of an oil bath are Ölkom component, active ingredient and one or more Emulga which is a dispersion of the oil component and of the Active ingredient, especially if it has lipophilic character has to allow in the water.
Typische Emulgatoren für Ölbäder sind z. B. ethoxylier te oder propoxylierte Fettalkohole, Ester der Phosphor säure, Ricinolsäuresulfate, Alkoholethersulfate etc. Je nach Menge des Emulgatoranteils ergeben sich nach Ver mischen der Formulierung mit dem Badewasser ober flächenspreitende (niedriger Anteil), milchige oder klare Bäder (hoher Anteil), d. h. die Größe der Ölpar tikel der entstehenden Emulsionen wird durch die Emul gatorkonzentration beeinflußt.Typical emulsifiers for oil baths are z. B. ethoxylated te or propoxylated fatty alcohols, esters of phosphorus acid, ricinoleic acid sulfates, alcohol ether sulfates, etc. according to the amount of emulsifier, Ver mix the formulation with the bathwater upper area-spreading (low portion), milky or clear baths (high proportion), d. H. the size of the oilpar Particles of the emulsions formed by the Emul gator concentration affected.
Emulgatoren haben neben ihrem Vorteil, lipophile Stoffe in Wasser dispergieren zu können, zwangsläufig den Nachteil, auf die Haut entfettend zu wirken und somit auch sehr viel Wirkstoff, insbesondere wenn er lipophil ist, im Badewasser zu binden. Auch ist dem Fachmann wohlbekannt, daß Emulgatoren in Abhängigkeit einer ihrer Stoffkonstanten, nämlich der kritischen Micellen konzentration, irritierend auf die Haut wirken können. Je höher die kritische Micellenkonzentration ist, umso höher ist der Anteil nicht-micellar gebundener Emulga tormoleküle und damit das Irritationspotential. Hinzu kommt, daß übliche Emulgatoren, insbesondere anioni sche, in der Hornschicht der Hornschicht der Haut einen starken Quelleffekt bewirken (U. Zeidler, Ärztliche Kosmetologie 19 (3), 208-219 (1989)). Ölbäder sind daher, insbesondere im kosmetischen Bereich, nicht unumstritten.Emulsifiers have besides their advantage, lipophilic substances to be able to disperse in water, inevitably the Disadvantage of degreasing the skin and thus also very much active ingredient, especially if he is lipophilic is to tie in the bath water. Also, the expert well-known that emulsifiers depending on a their substance constants, namely the critical micelles Concentration, can irritate the skin. The higher the critical micelle concentration, the better higher is the proportion of non-micellar bound emulsa tormoleküle and thus the irritation potential. in addition comes that usual emulsifiers, especially anioni in the horny layer of the horny layer of the skin strong source effect (U. Zeidler, Ärztliche Cosmetology 19 (3), 208-219 (1989)). Oil baths are therefore, especially in the cosmetic field, not undisputed.
Man kann daher als Ziel für eine optimale Ölbadkom position definieren, daß die Formulierung möglichst viel Ölkomponente und Wirkstoff enthalten soll, mög lichst wenig Emulgator, der wiederum möglichst wenig entfettend wirkt und außerdem ein möglichst niedriges Irritationspotential aufweisen soll, wobei die Ölkom ponente und der Wirkstoff möglichst gut verfügbar sind.One can therefore as a goal for an optimal Ölbadkom define the wording as possible should contain a lot of oil component and active ingredient, pos As little emulsifier as possible, and as little as possible degreasing and also the lowest possible Irritationspotential should have, the Ölkom component and the active ingredient are available as well as possible.
Hier sind den üblichen Emulgatoren Grenzen gesetzt. Hinzu kommt, daß z. B. bei niedrigen Emulgatorkonzen trationen aufgrund von Aufrahmungserscheinungen der Öl komponente unangenehme und mühsam zu entfernende Fett ränder in der Badewanne entstehen.Here are the usual emulsifiers limits. In addition, that z. B. at low Emulgatorkonzen due to the appearance of oil component unpleasant and difficult to remove fat edges in the bathtub.
Auch ist der Nutzen medizinischer Ölbäder umstritten, da die Bioverfügbarkeit der Wirkstoffe, wie oben dar gelegt, vom Emulgator sehr stark beeinflußt wird.Also, the benefits of medical oil baths are controversial as the bioavailability of the active ingredients, as shown above is very strongly influenced by the emulsifier.
Eine Verbesserung der Ölbadeigenschaften wurde dadurch erreicht, daß man eine Mischung aus Emulgator (Poly ethylenglykol 400-dioleat), Isopropylpalmitat, Maisöl, Lecithin und Wasser vorgeschlagen hat (M. Singer, Clinical Medicine 71, 1921-1924 (1964)). Diese Mischung ist aber insofern auch nachteilig, als sie einen nicht ionogenen Emulgator benutzt. Nichtionogene Emulgatoren sind dafür bekannt, daß sie im Vergleich zu anderen Emulgatortypen das größte Penetrationsvermögen in die Haut haben (W. Kästner, Seifen, Öle, Fette, Wachse 116 (1), 3-9 (1990)); außerdem enthält das System aufgrund seines Wassergehaltes ein Konservierungsmittel (p-Hydr oxybenzoesäurebutylester). Die Allergieauslösung von Konservierungsmitteln ist hinreichend bekannt, und man versucht daher gerade bei Produkten kosmetischer und medizinischer Art dieses Risiko durch die Verwendung konservierungsfreier Präparate auszuschließen; dies ist jedoch hier nicht möglich. Ein weiterer Nachteil ist die bekannte geringe Haltbarkeit von wäßrigen Leci thinprodukten, da sie durch Hydrolyse der Esterbindun gen langsam Fettsäuren abspalten und sich so die Eigen schaften der Produkte verändern. Darüberhinaus ist die beschriebene Mischung nicht gegen Autoxidation ge schützt. Dies ist jedoch sehr wichtig, da Lecithin durch seinen hohen Linolsäuregehalt besonders empfind lich ist. Diese Empfindlichkeit macht sich, auch für den Laien leicht feststellbar, durch ranzigen Geruch bemerkbar.An improvement of the Ölbadeigenschaften was characterized achieved that a mixture of emulsifier (poly ethylene glycol 400 dioleate), isopropyl palmitate, corn oil, Lecithin and water (M. Singer, Clinical Medicine 71, 1921-1924 (1964)). This mixture but is so far disadvantageous, as they do not used ionogenic emulsifier. Nonionic emulsifiers are known to be compared to others Emulsifier types the greatest penetration capacity in the Have skin (W. Kästner, soaps, oils, fats, waxes 116 (1), 3-9 (1990)); In addition, the system contains due to its water content a preservative (p-hydr oxybenzoesäurebutylester). The allergic release of Preservatives is well known, and one tries therefore especially for products cosmetic and medical nature of this risk by use to exclude preservative-free preparations; This is but not possible here. Another disadvantage is the known low durability of aqueous Leci thin products, since they are obtained by hydrolysis of the Esterbindun Slowly split off fatty acids and so the own changes in the products. Moreover, the described mixture not against autoxidation ge protects. However, this is very important since lecithin particularly sensitive due to its high linoleic acid content is. This sensitivity makes up, too The layman easily detectable, by rancid smell noticeable.
Der Wassergehalt hat noch einen weiteren Nachteil, näm lich, daß Ölkomponente und lipophiler Wirkstoff nur einen beschränktem Gehalt haben können, zum anderen aber auch keine hydrolyseempfindlichen Wirkstoffe wie z. B. Vitamin-A-acetat (Akne-Mittel) formuliert werden können. Letzterer Wirkstoff ist außerdem auch sehr oxidationsempfindlich. Die rückfettende Wirkung von Lecithin und der Ölkomponente kann aufgrund des anwe senden Emulgators immer noch nicht voll ausgenutzt werden.The water content has another disadvantage, viz Lich that oil component and lipophilic drug only may have a limited salary, on the other hand but also no hydrolysis-sensitive agents such as z. For example, vitamin A acetate (acne remedies) can be formulated can. The latter ingredient is also very good sensitive to oxidation. The moisturizing effect of Lecithin and the oil component may due to the anwe Emulsifier still not fully utilized become.
Auch Mischungen von anion- oder kationaktiver Tenside mit Lecithin wurden erwähnt (H. Rebmann, Seifen, Öle, Fette, Wachse 100 (14), 343-346 (1974)). Nachteile dieser Formulierungen sind jedoch auch hier die Anwe senheit von Emulgatoren, die dem Fachmann für ihr Irri tationpotential und/oder ihren Einfluß auf die Horn schichtquellung (siehe oben) bekannt sind. Auch alle anderen Nachteile der oben genannten Mischung konnten nicht beseitigt werden, mit Ausnahme, daß Vitamin E als zuzusetzendes Antioxidans beschrieben wurde. Aber auch hier ist dem Fachmann bekannt, das Vitamin E eine nur beschränkte Wirkung als Antioxidans hat, da es selbst gegenüber Luftsauerstoff sehr empfindlich ist. Also mixtures of anionic or cationic surfactants with lecithin were mentioned (H. Rebmann, soaps, oils, Fats, Waxes 100 (14), 343-346 (1974)). disadvantage However, these formulations are also the Anwe the sensitivity of emulsifiers to the expert for their irri tion potential and / or its influence on the horn layer swelling (see above) are known. All too other disadvantages of the above mixture could can not be eliminated, except that vitamin E as has been described to be added antioxidant. But also Here is the expert known, the vitamin E one only has limited effect as an antioxidant, since it itself is very sensitive to atmospheric oxygen.
Als weitere Lösung für diese Probleme wurden kürzlich liposomale (Öl-)Bäder vorgeschlagen, bei denen Lipo somen als Träger für Öl- und Wirkstoffkomponente dienen (H. Lautenschläger und J. Röding, Parfümerie und Kosme tik 70 (12), 757-764 (1989)).As another solution to these problems have been recently liposomal (oil) baths suggested in which Lipo somen serve as a carrier for oil and drug component (H. Lautenschläger and J. Röding, Perfumery and Cosme Tik 70 (12), 757-764 (1989)).
Liposomen sind Vesikel mit unterschiedlichster Struk tur. Je nach Herstellungsverfahren unterscheidet man unilamellare, oligolamellare, multilamellare oder fusionierte Körper mit Membranstruktur und einem Durch messer von ca. 15-3500 nm. Eine Übersicht gibt H. P. Fiedler, Lexikon der Hilfstoffe für Pharmazie, Kosmetik und angrenzende Gebiete, Verlag Editio Cantor, Aulen dorf 1989, S. 744-746.Liposomes are vesicles of various struc door. Depending on the manufacturing process one differentiates unilamellar, oligolamellar, multilamellar or fused body with membrane structure and a through 15-3500 nm. An overview is given by H. P. Fiedler, Lexicon of excipients for pharmacy, cosmetics and adjacent areas, Publisher Editio Cantor, Aulen village 1989, p. 744-746.
Liposomen im allgemeinen Sprachgebrauch sind aus natür lichen, halbsynthetischen und synthetischen Phospholi piden zusammengesetzt, wobei die Hauptkomponente meist aus Phosphatidylcholin besteht. Nebenkomponenten sind z. B. Phosphatidylethanolamin, Phosphatidylinosit, Phosphatidsäure. Man unterscheidet ungesättigte (natür liche), teilhydrierte und hydrierte Phospholipide gemäß ihrer Fettsäurebesetzung.Liposomes in common usage are from natural semisynthetic and synthetic phospholys piden composed, with the main component mostly is phosphatidylcholine. Secondary components are z. B. phosphatidylethanolamine, phosphatidylinositol, Phosphatidic. One distinguishes unsaturated (natural Liche), partially hydrogenated and hydrogenated phospholipids according to their fatty acid occupation.
Ähnlich wie die biologischen Zellen können Liposomen in den vesikulären Innenbereichen wasserlösliche Substan zen und in den Membranen amphiphile und lipophile Sub stanzen speichern (beladene Liposomen). Beispiele für die Beladungen in den Membranen sind Vitamin E, Reti noide, Steroide, lipophile und amphiphile Wirkstoffe, pflanzliche und tierische Öle.Similar to the biological cells, liposomes in the vesicular interior water-soluble substance and in the membranes amphiphilic and lipophilic sub Save punched (loaded liposomes). examples for the loadings in the membranes are Vitamin E, Reti noide, steroids, lipophilic and amphiphilic drugs, vegetable and animal oils.
Insbesondere lipophile Wirkstoffe, pflanzliche und tie rische Öle sind im Kosmetikbereich wichtig für eine optimale Hautpflege, speziell zur Behandlung trockener Haut. Auch bei hochungesättigten Ölen, die z. B. zur Behandlung von atopischer Dermatitis eingesetzt werden (H. P. Nissen, W. Wehrmann, U. Kroll und H. W. Kreysel, Fat. Sci. Technol. 90 (7), 268-271 (1988)), ist die Verteilung und das Eindringen in die Haut von entschei dender Bedeutung. Liposomen sind daher bezüglich Ver teilung und Penetration in die Haut das ideale Träger system.In particular, lipophilic drugs, plant and tie Essential oils are important in the cosmetics industry optimal skin care, especially for the treatment of dry Skin. Even with highly unsaturated oils, the z. B. for Treatment of atopic dermatitis (H.P. Nissen, W. Wehrmann, U. Kroll and H.W. Kreysel, Fat. Sci. Technol. 90 (7), 268-271 (1988)), is the Distribution and penetration into the skin is crucial dender meaning. Liposomes are therefore related to Ver division and penetration into the skin the ideal carrier system.
Bisher bekannte Liposomen haben aber trotz der genann ten idealen Eigenschaften wesentliche Nachteile:So far known liposomes have despite the genann ideal properties, significant disadvantages:
Liposomen klassischer Zusammensetzung sind aufgrund der üblicherweise eingesetzten hochreinen Ausgangsmateria lien - meist sind dies hochangereicherte Phosphatidyl choline - und des komplizierten Herstellungsprozesses wesentlich teurer als übliche Emulsionen mit weniger guten Eigenschaften.Liposomes of classical composition are due to the commonly used high purity starting materials Most of these are highly enriched phosphatidyls choline - and the complicated manufacturing process much more expensive than usual emulsions with less good properties.
Liposomen klassischer Zusammensetzung haben ein nur ge ringes Speichervermögen für lipophile Substanzen. Lipo somen aus ungesättigten Phospholipiden können zwar ca. 10-30% ihres Gewichtes an Triglyceriden aufnehmen, dies bedeutet aber selbst für eine sehr hochkonzentrierte Liposomendispersion mit 10% Liposomengrundstoff (in der Trockensubstanz) eine Endkonzentration von 1-3% Trigly cerid in der Formulierung. In vergleichbaren Öl/Wasser- Emulsionen sind dagegen 10-20% lipophile Komponenten üblich.Liposomes of classical composition have only ge low storage capacity for lipophilic substances. Lipo although unsaturated phospholipids can Take up 10-30% of their weight in triglycerides, this But even means for a very highly concentrated Liposomal dispersion with 10% liposome base (in the Dry matter), a final concentration of 1-3% Trigly cerid in the formulation. In comparable oil / water Emulsions, however, are 10-20% lipophilic components common.
Ein weiterer gravierender Nachteil hinsichtlich des Einsatzes von Liposomen in Badeformulierungen ist die Tatsache, daß fertige liposomale Badeprodukte sehr viel Wasser enthalten (80% und mehr) und in dementsprechend große Gebinde (500-1000 ml) abgefüllt und konserviert werden müssen. Die Formulierungen sind trotz Konservie rung nur beschränkt haltbar, da die Bestandteile der Liposomen zu Hydrolyse-Reaktionen und Oxidierbarkeit neigen und damit die Zusammensetzung während der Lage rung verändert wird. Sie sind daher nur beschränkt lagerfähig. Dies alles ist aus heutiger Sicht unrenta bel und unpraktisch und hat bisher den wirtschaftlichen Durchbruch liposomaler Badepräparate verhindert. Das Problem kann auch damit nicht gelöst werden, daß z. B. gefriergetrocknete oder sprühgetrocknete Instant-Lipo somen eingesetzt werden, da sie einerseits von der Her stellung sehr teuer und damit unwirtschaftlich sind, andererseits gerade flüssige lipophile Komponenten naturgemäß nicht oder nur sehr beschränkt enthalten können. Hinzu kommt, daß derartige Formulierungen ein besonders großes Volumen einnehmen und daher unvorteil haft transportiert werden können.Another serious disadvantage regarding the Use of liposomes in bath formulations is the Fact that finished liposomal bath products very much Contain water (80% and more) and in accordingly large containers (500-1000 ml) bottled and preserved Need to become. The formulations are in spite of preserves Limited shelf life because the components of Liposomes to Hydrolysis Reactions and Oxidizability tend and thus the composition during the situation changed. They are therefore limited storable. All this is unrenta from today's perspective bel and impractical and so far has the economic Breakthrough liposomal bath preparations prevented. The Problem can not be solved so that z. B. freeze-dried or spray-dried instant lipo be used because they are on the one hand from the Her very expensive and thus uneconomic, on the other hand just liquid lipophilic components naturally not included or only very limited can. In addition, such formulations a take up very large volume and therefore unfavorable can be transported safely.
Nun hat sich überraschend gezeigt, daß man die oben genannten Probleme elegant lösen oder umgehen kann, wenn man Phospholipidformulierungen, dadurch gekenn zeichnet, daß sie Phosphatidylcholin (1), eine Ölkompo nente (2), Alkohol (3), Stabilisator (4), Wirkstoff (5) und Hilfsstoff (6) enthalten, bei der Anrichtung des Bades oder Teilbades in das Badewasser gießt, wobei sich in situ die Bildung von mit Öl und mit Wirkstoffen beladenen Liposomen vollzieht.Now it has surprisingly been found that the above elegantly solve or circumvent these problems, when phospholipid formulations, characterized thereby that it is phosphatidylcholine (1), an oil comp component (2), alcohol (3), stabilizer (4), active substance (5) and excipient (6), in the installation of the Bath or partial bath in the bath water pours, wherein in situ the formation of oil and with active substances loaded liposomes.
Die genannten Hauptkomponenten der erfindungsgemäßen Phospholipidformulierungen (1) bis (6) sind:The said main components of the invention Phospholipid formulations (1) to (6) are:
- (1) Phosphatidylcholin: Produkte dieser Art sind unter unterschiedlichen Handelsbezeichnungen im Handel und werden von Lecithinverarbeitern hergestellt. Vorteil hafterweise werden pflanzliche, meist aus der Sojabohne gewonnene, oder tierische, meist aus Hühnerei gewonne ne, Phosphatidylcholine eingesetzt.(1) Phosphatidylcholine: Products of this kind are under different trade names in the trade and are made by lecithin processors. benefit Sufficiently, are herbal, mostly from the soybean won, or animal, mostly from Hühnerei gewonne ne, phosphatidylcholines used.
- (2) Ölkomponente: Diese Komponente kann aus nativem Öl, (teil-)synthetischem Öl, Carbonsäureestern, flüssigen Wachsestern, öligen Kohlenwasserstoffen oder Mischungen derselben bestehen. Unter nativen Ölen versteht man Naturöle pflanzlichen oder tierischen Ursprungs. Pflanzliche Öle sind z. B. Sonnenblumenöl, Distelöl, Avocadoöl, Mandelöl, Sojaöl, Rizinusöl, Erdnußöl, Wei zenkeimöl, Karottenöl, Aprikosenkernöl, Borretschöl, Nachtkerzenöl, Haselnussöl, Palmkernöl, Sesamöl, Lein öl, Macadamia-Nußöl, Maiskeimöl, Rüböl, Mohnöl, Pfir sichkernöl, Olivenöl, Walnußöl. Tierische Öle sind z. B. Nerzöl und Fischöl. (Teil-)synthetische Öle sind hauptsächlich Triglyceride, deren Säurekomponenten aus definierten oder Mischungen aus mittel- oder langket tigen Fettsäuren bestehen, z. B. Capronsäure, Caprin säure, Stearinsäure, Isostearinsäure, Palmitinsäure, Ölsäure, Linolsäure, Ricinolsäure. Zu den synthetischen Ölen gehören auch die Silikonöle. Unter Carbonsäure estern sind z. B. Isopropylpalmitat, Isopropylmyristat, Isopropylstearat, Oleyloleat, Myristyllactat, Cetyl lactat, 2-Ethylhexylpalmitat, Isooctylstearat, Hexyl laurat, Dibutyladipat, 2-Octyldecanol, Isopropyllino leat zu verstehen. Flüssige Wachsester sind z. B. im Jojobaöl enthalten. Auch feste Wachsester sind verwendbar, wenn sie in den oben genannten flüssigen Ölen gelöst werden können. Ölige Kohlenwasserstoffe sind z. B. Paraffinöl, Heptamethylnonan.(2) Oil Component: This component may be of native oil, (partially) synthetic oil, carboxylic acid esters, liquid Waxy esters, oily hydrocarbons or mixtures consist of the same. By native oils one understands Natural oils of plant or animal origin. Vegetable oils are z. Sunflower oil, thistle oil, Avocado oil, almond oil, soybean oil, castor oil, peanut oil, white teat oil, carrot oil, apricot kernel oil, borage oil, Evening primrose oil, hazelnut oil, palm kernel oil, sesame oil, flax oil, macadamia nut oil, corn oil, rapeseed oil, poppy seed oil, peach kernel oil, olive oil, walnut oil. Animal oils are z. B. Mink oil and fish oil. Are (partial) synthetic oils mainly triglycerides whose acid components are made defined or mixtures of medium or langket consist of fatty acids, eg. B. caproic acid, caprin acid, stearic acid, isostearic acid, palmitic acid, Oleic acid, linoleic acid, ricinoleic acid. To the synthetic ones Oils also include the silicone oils. Under carboxylic acid Estern are z. Isopropyl palmitate, isopropyl myristate, Isopropyl stearate, oleyl oleate, myristyl lactate, cetyl lactate, 2-ethylhexyl palmitate, isooctyl stearate, hexyl laurate, dibutyl adipate, 2-octyldecanol, isopropyllino leat to understand. Liquid wax esters are z. In the Jojoba oil included. Also solid wax esters are usable if in the above liquid Oils can be dissolved. Oily hydrocarbons are z. For example, paraffin oil, heptamethylnonane.
- (3) Alkohol: Hierunter versteht man vorzugsweise Ethan ol mit einem Gehalt von 90-100%. Der Zusatz des gut verträglichen Alkohols hat insbesondere die Funktion, eine homogene Lösung bei der Mischung der Formulie rungsbestandteile herzustellen.(3) Alcohol: This is preferably ethane oil with a content of 90-100%. The addition of the good Compatible alcohol has in particular the function of a homogeneous solution in the mixture of Formulie produce ingredients.
- (4) Stabilisator: Der hier verwendete Stabilisator ist Harnstoff. Er hat die Funktion, einerseits die Oxidationsbeständigkeit der erfindungsgemäßen Phospho lipidformulierungen ganz wesentlich zu erhöhen, ande rerseits die optimale Bildung der Liposomen beim Eingießen in Wasser zu gewährleisten. Zum anderen ist Harnstoff ein für den Fachmann bekannter hautpflegender natürlicher Stoff, der Bestandteil der Haut ist und unter anderem auch den Wasserhaushalt der Haut positiv beeinflußt.(4) Stabilizer: The stabilizer used here is Urea. He has the function, on the one hand the Oxidation resistance of the phospho invention to significantly increase lipid formulations, ande On the other hand, the optimal formation of the liposomes To ensure pouring in water. The other is Urea a well-known for the expert skin care natural substance that is part of the skin and Among other things, the water balance of the skin is positive affected.
-
(5) Wirkstoff: Hierbei kann es sich um einen oder meh
rere kosmetisch wirksame Wirkstoffe oder um einen oder
mehrere pharmakologische Wirkstoffe handeln:
Kosmetische Wirkstoffe der erfindungsgemäßen Phospho lipidformulierungen sind Fette, Vitamine (insbesondere A, B-Komplex, C, E sowie deren übliche Derivate wie z. B. Vitamin-A-palmitat, Vitamin-E-acetat), Provitamine wie β-Carotin, etherische Öle, selbstbräunende Sub stanzen wie Tyrosin; UV-Licht-Absorber wie z. B. Uroca ninsäure und deren Ester, Hautschutzstoffe wie z. B. Ricinolsäurederivate, Phytosterole, Cholesterin, Cho lesterylsulfat, Squalen, Squalan, Palmitinsäure, Stea rinsäure, Isostearinsäure. Wirkstoffe wie Panthenol, Bisabolol, Pflanzenextrakte, tierische Extrakte, Linol säureester, alpha- und gamma-Linolensäurester, Colla gen- und Elastin-Hydrolysate und deren Kondensate mit Fettsäuren, Glutathion, Ceramid, Sphingolipide. Vielfach haben die oben genannten Ölkomponenten (2), wie z. B. pflanzliche, tierische Öle und Wachsester, auf Grund ihrer Zusammensetzung ebenfalls kosmetischen Wirkstoffcharakter.
Pharmazeutische Wirkstoffe der erfindungsgemäßen Phos pholipidformulierungen sind Retinol und deren Ester, Vitamin-A-säure und deren Ester (Tretinoin), Isotreti noin, Retinoide allgemein, Antimykotika, Antiseptika wie Chlorhexidin, juckreizstillende Substanzen, nicht steroidale Antirheumatika und deren Ester wie z. B. Salicylsäure, Salicylsäuremethylester; entzündungshem mende Mittel, durchblutungsfördernde Mittel wie z. B. Nicotinsäurebenzylester; Campher, Corticoide wie Hydro cortison, Betamethason, Triamcinolon, Dexamethason, Prednisolon; Heparin, Zytostatika, Antihistaminika, Antiallergika, Antibiotika wie z. B. Tetracyclin, Erythromycin, Gentamycin, Neomycin; antiparasitäre Mittel, Venenmittel, Wundbehandlungsmittel, Adstrin gentien, Antiaknemittel, Antipsoriatika, Anisebor rhoika, Antisebostatika, Keratolytika, Narbenbehand lungsmittel, Allantoin, Clotrimazol, Guajazulen, Hexyl resorcin, Isoprenalin, Fumarsäure, Fumarsäureethyl ester, Fumarsäurediethylester, Dithranol, Ichthyol, Thymol, Rosmarinöl, Panthenol, Phantothensäure, Kamil lenextrakt, Hamamelisextrakt, Salbeiöl, Eukalyptusöl, Fichtennadelöl, Wacholderbeeröl, Baldrianöl, Baldrian extrakt, Eichenrindeextrakt, Weizenkleieextrakt, Kie fernnadelöl, Borneol, Menthol, Schafgarbenblütenex trakt, Limonen, Heublumenextrakt, Molkepulver, Hopfen extrakt, Lavendelöl, Tannin, Aesculin, Aescin, Salicyl amid, Latschenkieferextrakt, Nicotinsäuremethylester, Nicotinsäureethylester, Salicylsäurenicotinat, Salicyl säureglycolester, Estradiol, Dichlorophen, Undecylen säure, Colecalciferol, Placentaextrakt, Thymusextrakt, Benzalkoniumchlorid, Griseofulvin, Nystatin, Amphoteri cin B, Clotrimazol, Miconazol, Econazol, Tioconazol, Ketoconazol, Isoconazol, Coffein, Ibuprofen, Indo metacin, Etofenamat, Diclophenac, Flufenaminsäure, Silibinin, Silymarin, Linolsäure, alpha-Linolensäure, gamma-Linolensäure, di-homo-gamma-Linolensäure, Eico sapentaensäure, Minoxidil, Superoxiddismutase.(5) Active substance: This may be one or more cosmetically active substances or one or more pharmacologically active substances:
Cosmetic active ingredients of the phospho lipid formulations according to the invention are fats, vitamins (in particular A, B complex, C, E and their usual derivatives such as, for example, vitamin A palmitate, vitamin E acetate), provitamins such as β-carotene, essential Oils, self-tanning substances such as tyrosine; UV light absorber such. B. Uroca ninsäure and their esters, skin protection agents such. As ricinoleic acid derivatives, phytosterols, cholesterol, Cho lesterylsulfat, squalene, squalane, palmitic acid, stearic acid, isostearic acid. Active substances such as panthenol, bisabolol, plant extracts, animal extracts, linoleic acid esters, alpha- and gamma-linolenic acid esters, collagen gene and elastin hydrolysates and their condensates with fatty acids, glutathione, ceramide, sphingolipids. In many cases, the above-mentioned oil components (2), such as. As vegetable, animal oils and wax esters, due to their composition also cosmetic active ingredient character.
Pharmaceutical agents of Phos pholipidformulierungen invention are retinol and its esters, vitamin A acid and its esters (tretinoin), Isotreti noin, retinoids in general, antimycotics, antiseptics such as chlorhexidine, antipruritic substances, non-steroidal anti-inflammatory drugs and their esters such. Salicylic acid, salicylic acid methyl ester; inflammatory agents, circulation-promoting agents such. B. nicotinic acid benzyl ester; Camphor, corticoids such as hydrocortisone, betamethasone, triamcinolone, dexamethasone, prednisolone; Heparin, cytostatics, antihistamines, antiallergic agents, antibiotics such. Tetracycline, erythromycin, gentamycin, neomycin; antiparasitic agents, venom agents, wound dressings, astringents, anti-acne agents, antipsoriatics, aniseed hormones, antisecretants, keratolytics, scar treatment agents, allantoin, clotrimazole, guaiacids, hexyl resorcinol, isoprenaline, fumaric acid, ethyl fumarate, diethyl fumarate, dithranol, ichthyol, thymol, rosemary oil, Panthenol, phantothenic acid, chamomile extract, witch hazel extract, sage oil, eucalyptus oil, spruce needle oil, juniper berry oil, valerian oil, valerian extract, oak bark extract, wheat bran extract, pine needle oil, borneol, menthol, yarrow flower extract, limonene, hay flower extract, whey powder, hops extract, lavender oil, tannin, esculin , Aescin, salicylamide, mountain pine extract, nicotinic acid methyl ester, nicotinic acid ethyl ester, salicylic acid nicotinate, salicylic acid ester, estradiol, dichlorophene, undecylenic acid, colecalciferol, placental extract, thymus extract, benzalkonium chloride, griseofulvin, nystatin, amphotericin B, Clotrimazole, miconazole, econazole, tioconazole, ketoconazole, isoconazole, caffeine, ibuprofen, indo-metacin, etofenamate, diclophenac, flufenamic acid, silibinin, silymarin, linoleic acid, alpha-linolenic acid, gamma-linolenic acid, di-homo-gamma-linolenic acid, eicosapentaenoic acid, Minoxidil, superoxide dismutase. - (6) Hilfsstoff: Unter Hilfsstoff der erfindungsgemäßen Phospholipidformulierungen sind z. B. Duftstoffe, Parfümöle, Antioxidantien wie z. B. Ascorbinsäure, Ascorbinsäurepalmitat, Butylhydroxytoluol, Butylhydroxyanisol, Propylgallat, Vitamin E, Vitamin-E- acetat, Vitamin-E-palmitat, Antioxidans-Synergisten wie z. B. EDTA, 1-Hydroxyethan-1.1-diphosphonsäure, Citronensäure, Fumarsäure, Harnsäure und färbende Substanzen sowie deren Mischungen untereinander zu verstehen.(6) Excipient: Under adjuvant of the invention Phospholipidformulierungen are z. Fragrances, Perfume oils, antioxidants such. As ascorbic acid, Ascorbic palmitate, butylhydroxytoluene, Butylhydroxyanisole, propyl gallate, vitamin E, vitamin E Acetate, vitamin E palmitate, antioxidant synergists like z. B. EDTA, 1-hydroxyethane-1,1-diphosphonic acid, Citric acid, fumaric acid, uric acid and coloring Substances and their mixtures with each other too understand.
Entsprechend den gewünschten Gehalten der einzusetzen den Wirkstoffe werden die Gehalte der anderen Komponen ten der erfindungsgemäßen Phospholipidformulierungen angepaßt. Die Gehalte der Einzelkomponenten der erfin dungsgemäßen Phospholipidformulierungen können daher in folgenden Grenzen variieren:According to the desired contents of the insert The active substances become the contents of the other components th of the phospholipid formulations according to the invention customized. The contents of the individual components of the inventions Phospholipidformulierungen according to the invention can therefore in the following limits vary:
Vorzugsweise betragen die Gehalte der Komponenten der erfindungsgemäßen Phospholipdformulierungen:Preferably, the contents of the components are Phospholipd formulations according to the invention:
Typische Zusammensetzungen der erfindungsgemäßen Phos pholipidformulierungen sind:Typical compositions of the phos according to the invention pholipid formulations are:
Die erfindungsgemäßen Phospholipidformulierungen können bei Bedarf vollständig aus Naturstoffen oder naturiden tischen Stoffen aufgebaut sein, wie die folgende Formu lierung illustriert.The phospholipid formulations according to the invention can completely made of natural or natural materials if required table materials, such as the following Formu illustrated.
Das Verfahren zur Herstellung der oben aufgeführten er findungsgemäßen Phospholipidformulierungen ist dadurch gekennzeichnet, daß man nacheinander Phosphatidylcholin (1), Alkohol (3), Stabilisator (4), Wirkstoff (5), Hilfsstoff (6) bei 20 bis 60°C, vorzugsweise bei 20 bis 40°C, mittels eines Ankerrührwerkes oder eines anderen üblichen Rührwerks bis zur Lösung rührt und am Schluß die Ölkomponente (2) zumischt.The method for producing the above-mentioned he according to the invention phospholipid formulations is characterized characterized in that successively phosphatidylcholine (1), alcohol (3), stabilizer (4), active substance (5), Excipient (6) at 20 to 60 ° C, preferably at 20 to 40 ° C, by means of an anchor agitator or another usual agitator stirs until solution and at the end the oil component (2) admixed.
Die Zubereitung des Teil- oder Vollbades mit Hilfe der erfindungsgemäßen Phospholipidformulierungen ist da durch gekennzeichnet, daß man die Phospholipidformu lierung einfach in das Badewasser gießt oder mit dem einlaufenden Wasser vermischt, wobei beliebige Konzen trationen eingestellt werden können.The preparation of the partial or full bath with the help of Phospholipidformulierungen according to the invention is there characterized in that the phospholipid formu Simply pour into the bath water or with the water incoming water mixed, with any Konzen can be adjusted.
Das Verfahren der Herstellung eines (Teil-)Bades unter Anwendung der erfindungsgemäßen Phospholipidformulie rungen zeigt keinen der oben für konventionelle Badezu bereitungen erwähnten Nachteile. Dies kommt insbeson dere dem Endverbraucher zugute.The method of producing a (partial) bath under Application of the Phospholipidformulie invention ments does not show any of the above for conventional bathing mentioned disadvantages. This comes in particular benefit the end user.
Die Hauptvorteile der erfindungsgemäßen Phospholipid formulierungen sind: The main advantages of the phospholipid according to the invention formulations are:
Die erfindungsgemäßen Phospholipidformulierungen unter scheiden sich äußerlich nicht von konventionellen Pro dukten und können auch in gleicher Weise benutzt wer den, d. h. die fertigen liposomalen Badezubereitungen bilden sich durch bloßes Eingießen der erfindungsge mäßen Phospholipidformulierungen in Wasser. Komplizier te Schritte zur Herstellung der vorliegenden mit Ölkom ponente und Wirkstoff beladenen Liposomen entfallen völlig. Die erfindungsgemäßen Phospholipidformulierun gen werden durch einfaches Mischen bzw. Lösen der Ein zelkomponenten hergestellt. Die Herstellung der liposomalen Badezubereitungen ist daher besonders kostengünstig.The phospholipid formulations of the invention under do not differ externally from conventional Pro and can also be used in the same way the, d. H. the finished liposomal bath preparations form by mere pouring the erfindungsge according to phospholipid formulations in water. Komplizier te steps to produce the present with Ölkom component and drug-loaded liposomes are eliminated completely. The phospholipid formulations of the invention conditions are by simply mixing or loosening the one made of cellular components. The production of liposomal bathing preparations is therefore particularly inexpensive.
Liposomen werden erst in situ beim Eingießen der erfin dungsgemäßen Phospholipidformulierungen in das Badewas ser an Ort und Stelle gebildet. Es bilden sich dabei besonders hoch mit Ölkomponente und Wirkstoff beladene Liposomen aus. Sie gehören zu den sogenannten lipidrei chen liposomalen Systemen.Liposomes are first in situ when pouring the inventions Phospholipidformulierungen according to the invention in the bath formed on the spot. It is formed here particularly high loaded with oil component and active ingredient Liposomes out. They belong to the so-called lipidrei chen liposomal systems.
Die erfindungsgemäßen Phospholipidformulierungen werden wasserfrei hergestellt und sind damit hydrolytisch sta bil, wobei Restwassermengen, die naturgemäß in den Ein zelkomponenten enthalten sind, keinen Einfluß auf die Lagerstabilität haben. Eine Oxidationsanfälligkeit der Phospholipidformulierungen ist durch Anwesenheit des Stabilisators und des Hilfstoffs, der gegebenenfalls Antioxidantien und Antioxidans-Synergisten enthalten kann, bei geschlossenem Gefäß, das aus diffusions sicherem Material wie z. B. Glas bestehen sollte, auch über Jahre nicht gegeben.The phospholipid formulations according to the invention are produced anhydrous and are therefore hydrolytically sta bil, wherein residual amounts of water, naturally in the A zelkomponenten are included, no effect on the Have storage stability. An oxidation susceptibility of Phospholipid formulations are due to the presence of the Stabilizer and the excipient, if necessary Contains antioxidants and antioxidant synergists can, with the vessel closed, the diffusion safe material such. As glass should exist, too not given for years.
Für ein gewöhnliches Vollbad reichen je nach Dosierung der Wirkstoffe 10-100ml der erfindungsgemäßen Phospho lipidformulierungen aus. Dies ist für eine liposomale Badezubereitung sehr wenig. For an ordinary full bath depending on dosage the active ingredients 10-100ml of the phospho invention lipid formulations. This is for a liposomal Bathing preparation very little.
Die erfindungsgemäßen Phospholipidformulierungen lassen sich bei Bedarf ausschließlich aus Naturstoffen her stellen.Leave the phospholipid formulations according to the invention If necessary, only from natural substances put.
Die erfindungsgemäße Phospholipidformulierungen benö tigen für ihre Anwendung keinen konventionellen Emulga tor. Ein Emulgator wäre, insbesondere in größeren Men gen, sogar geradezu schädlich für die Ausbildung der späteren liposomalen Strukturen, da Emulgatoren im allgemeinen die Bilayer der Liposomen zerstören (H. Hauser, Chimia 39, 252 (1985).The phospholipid formulations according to the invention are required do not use conventional emulsions for their application gate. An emulsifier would be, especially in larger men even harmful to the training of the later liposomal structures, since emulsifiers in the general destroy the bilayer of the liposomes (H. Hauser, Chimia 39, 252 (1985).
Die Liposomengrundstoffe wie das in den erfindungsge mäßen Phospholipidformulierungen verwendete Phosphati dylcholin sind dafür bekannt, daß sie selbst in oder durch die Haut penetrieren, auf der anderen Seite aber vollständig ohne Nebenwirkungen sind, da sie körper eigen vorkommen. Sie zeigen im Gegenteil sehr positive Wirkungen auf die Physiologie der Haut, wie z. B. eine Reduzierung des transepidermalen Wasserverlustes. Phos phatidylcholin ist daher auch als kosmetischer Wirk stoff anzusehen (H. Lautenschläger, J. Röding und M. Ghyczy, Seifen, Öle, Fette, Wachse 114 (14), 531-534 (1988). So werden Liposomen heute als Bilayerquelle angesehen, die die bei strapazierter Haut geschädigten Bilayer der Hornschicht wiederherstellen können, ein Effekt der bei Verwendung konventioneller Emulsionen nicht eintreten kann. Ein weiterer Vorteil der Pene tration ist die Einschleusung kosmetischer Wirkstoffe in die Hornschicht der Haut, die eine Depotfunktion hat, und der Transport pharmakologisch aktiver Stoffe in und durch die Haut. Die Stoffe gelangen dabei auch an Körperstellen, die mit üblichen Formulierungen nur schwer erreichbar sind. Dies ist z. B. wichtig bei Teilbädern mit antimykotisch wirksamen Wirkstoffen gegen Mykosen, insbesondere den Nagelmykosen.The liposome bases such as those in the erfindungsge According Phospholipidformulierungen phosphati used dylcholine is known to be in or of itself penetrate through the skin, but on the other side are completely without side effects as they are body own occurrence. On the contrary, they show very positive Effects on the physiology of the skin such. Legs Reduction of transepidermal water loss. Phos phatidylcholine is therefore also as a cosmetic active (Lautenschläger, J. Röding and M. Ghyczy, soaps, oils, fats, waxes 114 (14), 531-534 (1988). This is how liposomes are today used as bilayer sources considered that the damaged on damaged skin Bilayer can restore the horny layer, a Effect of using conventional emulsions can not occur. Another advantage of the Pene tration is the introduction of cosmetic agents in the horny layer of the skin, which has a depot function and transport of pharmacologically active substances in and through the skin. The substances also get there at body parts, with usual formulations only are difficult to reach. This is z. B. important Partial baths with antifungal active ingredients against mycoses, especially nail mycoses.
Phosphatidylcholin wirkt bekanntermaßen nicht entfet tend, da es sich im Gegenteil teilweise mit dem Keratin der Hornschicht zu Komplexverbindungen verbindet. Dies bewirkt eine starke rückfettende Wirkung. Diese rück fettende Wirkung ist besonders ausgeprägt, da die er findungsgemäßen Phospholipidformulierungen keinen kon ventionellen, d. h. naturgemäß entfettenden Emulgator enthalten.Phosphatidylcholine is known to be not removed on the contrary partly because of the keratin the horny layer connects to complex compounds. This causes a strong moisturizing effect. This back Greasy effect is particularly pronounced as he According to the invention phospholipid formulations no con conventional, d. H. naturally degreasing emulsifier contain.
Die Verwendung von Phosphatidylcholin in den erfin dungsgemäßen Phospholipidformulierungen hat den Vor teil, daß diese Verbindung eine extrem niedrige Micel lenkonzentration besitzt (R. Smith und C. Tanford, J. Mol. Biol. 67, 75-83 (1972)) und daher im Vergleich zu konventionellen Emulgatoren, deren kritische Micellen konzentration um mehrere Zehnerpotenzen höher liegen, keinerlei irritierende Wirkung auf die Haut ausübt.The use of phosphatidylcholine in the invention Phospholipidformulierungen according to the invention has the Vor In part, this compound has an extremely low micelle lenkonzentration has (R. Smith and C. Tanford, J. Mol. Biol. 67, 75-83 (1972)) and therefore in comparison to conventional emulsifiers, their critical micelles concentration by several orders of magnitude higher, no irritating effect on the skin.
Die erfindungsgemäßen Phospholipidformulierungen benö tigen für ihre Haltbarkeit keinerlei Konservierungs mittel und sind daher besonders hautfreundlich. Konser vierungsmittel-Allergien oder -Empfindlichkeiten sind daher nicht zu befürchten. Deshalb sind die erfindungs gemäßen Phospholipidformulierungen insbesondere für Menschen mit sehr empfindlicher Haut, für Allergiker, Psoriatiker, Atopiker, Neurodermitiker und andere unter Dermatosen, wie z. B. der Ichthyose, leidenden Menschen geeignet. Die erfindungsgemäßen Phospholipidformulie rungen können auch direkt zur Behandlung dieser Krank heiten eingesetzt werden, wenn entsprechende pharmazeu tische Wirkstoffe in die erfindungsgemäßen Phospholi pidformulierungen eingearbeitet sind. Auch die Behand lung von Sonnenbränden läßt sich sehr vorteilhaft gera de mit stark linol- und linolensäurehaltigen Phospho lipidformulierungen durchführen.The phospholipid formulations according to the invention are required do not give any preservation for their durability medium and are therefore particularly kind to the skin. konser agent allergies or sensitivities therefore not to be feared. Therefore, the invention appropriate phospholipid formulations especially for People with very sensitive skin, for allergy sufferers, Psoriatiker, Atopiker, Neurodermitiker and others under Dermatoses, such. Eg ichthyosis, suffering people suitable. The phospholipid formulation according to the invention Conditions can also be used directly to treat this condition be used when appropriate pharmazeu table active ingredients in the phospholides according to the invention pidformulierungen are incorporated. Also the treat Sunburn can be very beneficial de with strong linolenic and linolenic phosphorous perform lipid formulations.
Die Liposomen und die darin enthaltenen Öl und Wirk stoffkomponenten, die bei Anwendung der erfindungs gemäßen Phospholipidformulierungen entstehen, sind so fein im Wasser verteilt, daß eine sonst bei konven tionellen Ölbädern zu beobachtende Aufrahmung der Ölkomponente nicht stattfindet. Die Problematik der nach Ablassen des Badewassers zurückbleibenden schwer zu entfernenden Fettränder gibt es daher bei Anwendung der erfindungsgemäßen Phospholipidformulierungen nicht.The liposomes and the oils and active substances contained therein fabric components which, when using the invention are formed according to phospholipid formulations, are so finely distributed in the water, that otherwise at konven oil baths to be observed Oil component does not take place. The problem of after draining the bathwater remaining heavy There are therefore to be removed fat edges in use not the phospholipid formulations according to the invention.
Die Liposomen, die bei Anwendung der erfindungsgemäßen Phospholipidformulierungen entstehen, besitzen je nach Zusammensetzung der Formulierung eine durchschnittliche Größe von 100-2000 nm, d. h. die Größe ist durch Art und Menge der Einzelkomponenten steuerbar.The liposomes, when using the inventive Phospholipidformulierungen arise, depending on Composition of the formulation an average Size of 100-2000 nm, d. H. the size is by type and quantity of the individual components controllable.
Je nach Zusammensetzung der Komposition können sehr unterschiedlich geformte Vesikel entstehen:Depending on the composition of the composition can be very different shaped vesicles arise:
- (a) Klassische uni-, oligo-, multi-lamellare Liposomen bei hohen Gehalten an Phosphatidylcholin (1) und nie drigen Gehalten der Ölkomponente (2) und des Wirkstof fes (5);(a) Classic uni-, oligo-, multi-lamellar liposomes at high levels of phosphatidylcholine (1) and never Drigen Content of the oil component (2) and the Wirkstof fes (5);
- (b) Sogenannte Propeller-Liposomen bei vergleichbaren Gehalten an Phosphatidylcholin (1) und Ölkomponente (2) und/oder Wirkstoff (5). Propeller-Liposomen sind da durch gekennzeichnet, daß sie aus Aggregaten von Öl tröpfchen und klassischen Liposomen bestehen.(b) so-called propeller liposomes in comparable Levels of phosphatidylcholine (1) and oil component (2) and / or active ingredient (5). Propeller liposomes are there characterized in that they are aggregates of oil droplets and classic liposomes exist.
- (c) Chylomikronenartige Liposomen bei hohen Gehalten an Ölkomponente (2) und Wirkstoffes (5) und niedrigen Ge halten an Phosphatidylcholin (1). Chylomikronenartige Liposomen zeichnen sich dadurch aus, daß sie bei Beibe haltung der lamellaren liposomalen Struktur, die größ tenteils durch das Phosphatidylcholin (1) gebildet wird, eine mehr oder weniger stark ausgeprägte ölige Innenphase besitzen, die durch die Ölkomponente (2) bzw. den Wirkstoff (5) gebildet wird. Im Extremfall kann die Innenphase völlig mit amphiphilen und lipo philen Komponenten ausgefüllt sein. Diese Zubereitungen sind besonders interessant, da sie durch Verwendung von nur wenig Phosphatidylcholin, im Extremfall 5 Gew.-%, sehr preiswert sind und vorteilhaft mit kosmetisch und pharmakologisch wirksamen Eiweißhydrolysatkondensaten als Wirkstoffkomponente (5) kombiniert werden können. Als Wirkstoffkomponenten können z. B. Palmitoyl-colla genhydrolysat, Capryloylcollagenhydrolysat, Undecenoyl collagenhydrolysat sowie die acylierten Hydrolysate des Caseins, des Keratins und des Hydroxyprolins eingesetzt werden. Selbstverständlich können diesbezüglich auch definierte Reinsubstanzen wie z. B. die N-Palmitoyl derivate der Glutaminsäure, des Arginins, der Aspara ginsäure, des Lysins, des Serins, des Isoleucins ver wendet werden.(c) Chylomicron-like liposomes at high levels Oil component (2) and active ingredient (5) and low Ge hold on to phosphatidylcholine (1). Chylomikronenartige Liposomes are characterized by the fact that they in Beibe Attitude of the lamellar liposomal structure, the larger Partly formed by the phosphatidylcholine (1) is, a more or less pronounced oily Possess internal phase, which by the oil component (2) or the active ingredient (5) is formed. In extreme cases The inner phase can be completely with amphiphilic and lipo philen components are filled. These preparations are particularly interesting as they are made by using only a little phosphatidylcholine, in extreme cases 5% by weight, are very cheap and beneficial with cosmetic and pharmacologically active protein hydrolyzate condensates as active ingredient component (5) can be combined. As active ingredient components z. B. Palmitoyl colla genhydrolysate, capryloyl collagen hydrolyzate, undecenoyl collagen hydrolyzate and the acylated hydrolysates of the Caseins, keratin and hydroxyproline become. Of course, in this regard too defined pure substances such. B. the N-palmitoyl derivatives of glutamic acid, arginine, aspara ginsäure, lysine, serine, isoleucine ver be used.
Welche Art von liposomalen Vesikeln gebildet werden, ist daher stark vom Zweck des Einsatzes der erfindungs gemäßen Phospholipidformulierungen bestimmt, da hiervon die zu wählende Zusammensetzung abhängig ist.What kind of liposomal vesicles are formed is therefore strongly dependent on the purpose of the use of the invention determined according to phospholipid formulations, since thereof the composition to be selected is dependent.
Je nach Zusammensetzung der erfindungsgemäßen Phospho lipidformulierungen können auch Mischungen von klassi schen Liposomen, Propeller-Liposomen und Chylomikronen artigen Liposomen entstehen.Depending on the composition of the phospho invention lipid formulations can also be mixtures of classical liposomes, propeller liposomes and chylomicrons arise like liposomes.
Die Herstellung der erfindungsgemäßen Phospholipid formulierungen und ihre Anwendung bei Nutzung unter schiedlicher Komponenten wird in den folgenden Beispie len illustriert. Das in den Beispielen verwendete Phos phatidylcholin ist ca. 90%ig angereichert, stammt aus der Sojabohne und ist im Handel unter dem Namen Phos pholipon 90 erhältlich. Ähnliche Produkte sind auch unter anderen Namen, z. B. Lipoid S 100, Epikuron 200, Sternlipid PC-90, käuflich. Selbstverständlich lassen sich auch niedriger konzentrierte Produkte einsetzen, wenn sie mit den übrigen Komponenten kompatibel sind. Die den Komponenten vor- oder nachgestellten einge klammerten Zahlen von (1) bis (6) entsprechen der in der Beschreibung angegebenen Klassifizierung: (1) für Phosphatidylcholin, (2) für Ölkomponente, (3) für Alkohol, (4) für Stabilisator, (5) für Wirkstoff und (6) für Hilfsstoff, wobei wie in der Beschreibung aus geführt, die Komponenten wiederum aus Mischungen von Einzelkomponenten bestehen können.The preparation of the phospholipid according to the invention formulations and their use under use different components will be described in the following example illustrated. The phos. Used in the examples phatidylcholine is approximately 90% enriched, comes from of soybean and is commercially available under the name Phos pholipon 90 available. Similar products are too under other names, eg. B. Lipoid S 100, Epikuron 200, Star lipid PC-90, commercially available. Of course, let to use even lower-concentration products, if they are compatible with the other components. The components preceding or following the components are inserted clement numbers from (1) to (6) correspond to those in the classification given in the description: (1) for Phosphatidylcholine, (2) for oil component, (3) for Alcohol, (4) stabilizer, (5) active ingredient and (6) for excipient, as in the description of led, in turn, the components of mixtures of Individual components may exist.
Die Dosierung beträgt etwa 50 ml Formulierung pro Vollbad, wobei die Wassermenge ca. 150-200 l beträgt. Die Formulierung wird entweder in das einlaufende Wasser gegossen oder unter Verteilung mit der Hand in das bereitstehende Wasser gegeben, wobei sich das Wasser schwach milchig trübt. Die Wassertemperatur ist beliebig und beträgt im Regelfall etwa 35-45°C. Die Formulierung kann auch für Teilbäder genutzt werden, wobei entsprechend weniger Formulierung eingesetzt wird. Bei besonders stark wirkenden Wirkstoffkompo nenten wird die Dosierung zweckmäßigerweise gesenkt.The dosage is about 50 ml of formulation per Full bath, the amount of water is about 150-200 l. The wording is either in the incoming Water poured or under distribution by hand in given the available water, with the Water slightly cloudy milky. The water temperature is arbitrarily and is usually about 35-45 ° C. The Formulation can also be used for partial baths, with correspondingly less formulation used becomes. For particularly strong Wirkkompomp The dosage is expediently lowered.
Herstellung und Verwendung der folgenden Beispiele ist analog zu Beispiel 1:Preparation and use of the following examples is analogously to Example 1:
Claims (4)
- 1) einen Gehalt an Phosphatidylcholin von 5 Gew.-% bis 70 Gew.-%, und
- 2) 3 Gew.-% bis 55 Gew.-% Ölkomponente,
- 3) 3 Gew.-% bis 39 Gew.-% Ethanol,
- 4) 0.1 Gew.-% bis 10 Gew.-% Harnstoff als Stabilisator,
- 5) 0.1 Gew.-% bis 50 Gew.-% medizinischen oder kosmetischen Wirkstoff,
- 6) 0.1 Gew.-% bis 10 Gew.-% Hilfsstoff enthält.
- 1) a content of phosphatidylcholine of 5 wt .-% to 70 wt .-%, and
- 2) from 3% to 55% by weight of the oil component,
- 3) 3% by weight to 39% by weight of ethanol,
- 4) from 0.1% by weight to 10% by weight of urea as stabilizer,
- 5) 0.1% to 50% by weight medicinal or cosmetic active ingredient,
- 6) 0.1 wt .-% to 10 wt .-% adjuvant.
- 1) 10 Gew.-% bis 40 Gew.-% Phosphatidylcholin,
- 2) 20 Gew.-% bis 40 Gew.-% Ölkomponente,
- 3) 20 Gew.-% bis 39 Gew.-% Ethanol,
- 4) 1 Gew.-% bis 7 Gew.-% Harnstoff als Stabilisator,
- 5) 1 Gew.-% bis 10 Gew.-% medizinischen oder kosmetischen Wirkstoff,
- 6) 0.1 Gew.-% bis 5 Gew.-% Hilfsstoff.
- 1) 10% to 40% by weight phosphatidylcholine,
- 2) from 20% to 40% by weight of the oil component,
- 3) 20% by weight to 39% by weight of ethanol,
- 4) 1% to 7% by weight of urea as stabilizer,
- 5) 1% to 10% by weight of medicinal or cosmetic active substance,
- 6) 0.1 wt .-% to 5 wt .-% excipient.
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DE19904021083 DE4021083C2 (en) | 1990-07-03 | 1990-07-03 | Phospholipid formulations and their use for the preparation of liposomal medical and cosmetic baths |
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DE19904021083 DE4021083C2 (en) | 1990-07-03 | 1990-07-03 | Phospholipid formulations and their use for the preparation of liposomal medical and cosmetic baths |
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DE4021083C2 true DE4021083C2 (en) | 1995-08-17 |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE19852508A1 (en) * | 1998-11-16 | 2000-05-18 | Georg Huebner | Use of fat-soluble substance obtained from avocado oil as an antiphlogistic, antirheumatic, antimycotic or antiscabiotic agent, or as a toothpaste, lipstick, leather treatment agent or in bandages |
DE10347487A1 (en) * | 2003-09-30 | 2005-04-21 | Kneipp Werke Kneipp Mittel Zen | Cosmetic or dermatological composition for topical use |
Families Citing this family (14)
Publication number | Priority date | Publication date | Assignee | Title |
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FR2686509A1 (en) * | 1992-01-29 | 1993-07-30 | Oreal | COSMETIC COMPOSITION INTENDED TO BE ADDITIONED TO THE WATER OF A BATH. |
DE4205548C3 (en) * | 1992-02-24 | 1998-07-23 | Merz & Co Gmbh & Co | Bath and shower additive with vesicle-forming properties, its production and use |
DE4322158C2 (en) * | 1993-07-03 | 1997-04-10 | Rhone Poulenc Rorer Gmbh | Phospholipidic composition and use of such a composition |
GB9409763D0 (en) * | 1994-05-16 | 1994-07-06 | Phares Pharma Holland | Liposome forming compositions |
PT909164E (en) * | 1996-05-10 | 2002-12-31 | Yamanouchi Europ Bv | IMMEDIATE VESICULAR PRODUCT |
DE19735518C1 (en) * | 1997-08-16 | 1999-03-11 | Friedrun Geier | Rinsable emulsions for use as tallow-dissolving preparations |
DE19904801A1 (en) * | 1999-02-05 | 2000-08-10 | Klossner Axel | Agent containing urea, sulfur and Calendula extract, useful for topical treatment of skin disorders, especially neurodermatitis |
WO2001017484A2 (en) * | 1999-09-07 | 2001-03-15 | D.T.R. Dermal Therapy Research Inc. | Topical urea composition |
DE10124475A1 (en) * | 2001-05-19 | 2002-11-21 | Beiersdorf Ag | Cosmetic or dermatological composition containing ketohexose, useful for treating e.g. inflammation, pigment disorders, and skin aging, promotes barrier function |
DE10133202A1 (en) * | 2001-07-07 | 2003-01-16 | Beiersdorf Ag | Topical compositions containing osmolytes, useful e.g. for treating or preventing dry skin or inflammatory conditions of the skin, e.g. eczema, polymorphic light dermatosis or psoriasis |
DE10326010A1 (en) * | 2003-06-10 | 2005-01-05 | Henkel Kgaa | Preparation for the skin |
DE102004031210A1 (en) * | 2004-06-28 | 2006-02-09 | Trommsdorff Gmbh & Co. Kg | MLV cosmetic |
FR2958851B1 (en) * | 2010-04-16 | 2012-06-29 | Xeda International | NEW ACTIVE INGREDIENT (S) FORMULATIONS OF VEGETABLE ORIGIN OR THEIR SYNTHETIC OR PLANT EXTRACT (S) CONTAINING THEM, AND LECITHIN |
DE102010054461A1 (en) | 2010-12-14 | 2012-06-14 | Merz Pharma Gmbh & Co. Kgaa | Liposome-forming aqueous bath preparations with high active ingredient content and their cosmetic / dermatological / medical application |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS607932A (en) * | 1983-06-29 | 1985-01-16 | Dai Ichi Seiyaku Co Ltd | Preparation of liposome |
FR2597367B1 (en) * | 1986-04-22 | 1988-07-15 | Oreal | PROCESS FOR FACILITATING THE FORMATION OF LIPID SPHERULES DISPERSION IN AN AQUEOUS PHASE AND FOR IMPROVING THEIR STABILITY AND THEIR ENCAPSULATION RATE, AND CORRESPONDING DISPERSIONS. |
-
1990
- 1990-07-03 DE DE19904021083 patent/DE4021083C2/en not_active Expired - Lifetime
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE19852508A1 (en) * | 1998-11-16 | 2000-05-18 | Georg Huebner | Use of fat-soluble substance obtained from avocado oil as an antiphlogistic, antirheumatic, antimycotic or antiscabiotic agent, or as a toothpaste, lipstick, leather treatment agent or in bandages |
DE19852508C2 (en) * | 1998-11-16 | 2002-09-26 | Georg Huebner | Use of the unsaponified components from avocado |
DE10347487A1 (en) * | 2003-09-30 | 2005-04-21 | Kneipp Werke Kneipp Mittel Zen | Cosmetic or dermatological composition for topical use |
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Owner name: LAUTENSCHLAEGER, HANS, DR., 42799 LEICHLINGEN, DE |