WO2021144080A1 - Method for incorporating active substances into the skin - Google Patents
Method for incorporating active substances into the skin Download PDFInfo
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- WO2021144080A1 WO2021144080A1 PCT/EP2020/085451 EP2020085451W WO2021144080A1 WO 2021144080 A1 WO2021144080 A1 WO 2021144080A1 EP 2020085451 W EP2020085451 W EP 2020085451W WO 2021144080 A1 WO2021144080 A1 WO 2021144080A1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/426—1,3-Thiazoles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
- A61K31/728—Hyaluronic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/57—Magnoliaceae (Magnolia family)
- A61K36/575—Magnolia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0009—Galenical forms characterised by the drug release technique; Application systems commanded by energy involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis
Definitions
- the invention relates to an improved method for introducing active ingredients into the skin, in particular the dermis and epidermis.
- the provision of the active ingredient in a matrix represents an improvement in the introduction of the active ingredient.
- the matrix containing an active ingredient is what is typically referred to as a cosmetic or dermatological formulation.
- the active ingredient can "absorb" into the skin over a longer period of time without it being removed from the skin by inadvertent washing or wiping.
- the introduction of the active ingredient through cosmetic or dermatological formulations also has the disadvantage that the absorption takes place to a sufficient extent only in the case of small active ingredient molecules.
- An injury-free method to improve the delivery of active ingredients is to move the skin during or after the application of the active ingredient.
- the active ingredient is "massaged” into the skin, i.e. by rough mechanical movement of the affected skin area the skin "pressed".
- a typical example of this procedure is rubbing in (supply of active ingredients to a delimited body area without systemic stress on the organism.)
- a further increase in the introduction of the active substance can be achieved by using devices (applicators) that generate mechanical vibrations.
- the theory is that ultrasound (rapidly changing high and low pressure acoustic waves) causes cavitation in bodies of liquid. When these cavitation bubbles burst, a high-speed jet hits the solid, creating microchannels that improve penetration (known as Local Transport Pathways). The size and distribution of the cavitation bubbles varies with low ultrasound ( ⁇ 100kHz) and high ultrasound.
- the range of frequencies used extends from a few 10 Hz (so-called vibration devices e.g. US Patent 1594636 from 1926 or DE utility model 92 02 858 from 1992) to the ultrasonic range of 5 MHz. From US 20170196801 A1, the person skilled in the art receives a lot of information on how an improved pain treatment can be achieved with the aid of an ultrasound applicator.
- Ultrasound applicators typically have an elongated body and a mounting head receiving area.
- the elongated body has a cylindrical ergonomic design that provides a comfortable and easy-to-grasp surface.
- the receiving space for the attachment head is designed in such a way that it ensures a large number of attachment head constructions.
- the elongated body carries the ultrasound generating device including batteries or accumulators in its interior.
- the invention therefore relates to an improved method for introducing active ingredients into the skin, in particular the dermis and epidermis, characterized in that in a first step an active ingredient or an active ingredient-containing preparation is applied to a skin area A, the skin area A using an ultrasound device with ultrasound is treated, the frequency of the ultrasound being in the range from 25 to 35 kHz, in particular in the range from 29 to 31 kHz, and the ultrasound having an energy / energy density in the range from 0.5 to 2.0 W / cm 2 , in particular from 1 to 1.5 W / cm 2 .
- the ultrasound generation is pulsed. This means that the generation of ultrasound is temporarily interrupted. Continuous generation of ultrasound can cause skin damage, especially burns. A ratio of on to off time of 1 to 4 is optimal, which means that a 0.1 s long ultrasound pulse is followed by a 0.4 s long phase out ‘.
- a treatment time of three times five minutes with 20% working time of the ultrasound every hour for 3 hours is sufficient.
- the method according to the invention is particularly suitable for active ingredients with a molar mass of ⁇ 60 kDalton and a log P value of less than 4.2.
- the method according to the invention is particularly preferably suitable for introducing active ingredients from the group of magnolia extract (honokiol), resveratrol, thiamidol, hyaluronic acid.
- the active ingredient-containing preparation can comprise a gel, cream or other consistency, including, but not limited to, ointment, lotion, spray, foam, paste, collodion, emulsion, aerosol, solution, suspension or other topical dosage forms and preparations.
- the dermal absorption of active ingredients was tested using a method according to the invention. Depending on the active ingredient, the increase in dermal absorption is 2.5 times to over 5 times compared to dermal absorption without using the method according to the invention.
- the formulation was applied repeatedly (three times) to pig skin every hour.
- the ultrasound head of the device was placed on the skin surface for 5 minutes after each application (a total of 15 minutes of ultrasound treatment).
- Frequency 30kHz +/- 1kHz - power 1-1.2W / cm 2 sonication 1 minute ON time corresponds to 5 minutes pulsed on pig ear skin (110Opm thick) - frozen and then thawed to room temperature - all skin samples were checked for integrity by resistance testing.
- the measuring area had an area of 4.9 cm 2
- the amount of active ingredient applied varied from 18 to 80 pg / cm 2 (honokiol 80.09 pg / cm 2 , resveratrol 27.83 pg / cm 2 and thiamidol 17 pg / cm 2 and hyaluronic acid 25 pg / cm 2 (unlabelled), 0.216 ng / cm 2 and 32000 Bq / cm 2 with radioactively labeled tracer)
- magnolia extract - based on honokiol -, thiamidol and resveratrol (without radioactively labeled tracers) as in "In vitro penetration of cosmetic ingredients without radioactively labeled tracer", August 7, 2017 (BDF-internal SOP according to OECD guideline No. 428 and Diembeck W, Beck H, Benech-Kieffer F, et al. Test Guidelines for the In Vitro Assessment of Skin Resorption and Percutaneous Penetration of Cosmetic Ingredients. European Cosmetic, Toiletry and Perfumery Association. Food Chem Toxicol 1999; 37: 191-13. 205).
- test substance in different skin layers (stratum corneum, epidermis, dermis, receptor fluid) is determined using Franz diffusion cells, followed by HPLC analysis.
- the radioactivity was analyzed using a "Tri-Carb 4910 TR" liquid scintillation counter (Perkin Elmer) with automatic quench correction and Ultima Gold TM (Perkin Elmer, Cat. No. 6013329) as the scintillation cocktail.
- the epidermis and dermis were dissolved in SOLUENE®-350 (Tissue Solubilizer, Perkin Elmer, Cat. No. 6003038).
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Abstract
Description
Verfahren zur Wirkstoffeinbringung auf die Haut Method for applying active substances to the skin
1. Gebiet der Erfindung 1. Field of the invention
Die Erfindung betrifft ein verbessertes Verfahren zur Einbringung von Wirkstoffen in die Haut, insbesondere die Dermis und Epidermis. The invention relates to an improved method for introducing active ingredients into the skin, in particular the dermis and epidermis.
2. Beschreibung des Stands der Technik 2. Description of the prior art
Verfahren zur Einbringung von Wirkstoffen in die obersten Hautschichten gibt es im Stand der Technik zur Genüge. Der einfachste Prozess ist die Applikation eines Wirkstoffes in Reinform oder gelöster Form direkt auf das mit Wirkstoff zu belastende Hautareal. Diese Form der Wirkstoffeinbringung hat den Nachteil, dass der Wirkstoff sehr schnell unbeabsichtigt abgewaschen oder abgewischt werden kann. Zudem diffundieren nur sehr kleine Moleküle wie zum Beispiel Glycerin in die Haut, große Moleküle dringen nicht ein. There are enough methods in the prior art for introducing active ingredients into the uppermost layers of the skin. The simplest process is the application of an active ingredient in pure form or in dissolved form directly to the skin area to be stressed with the active ingredient. This form of introduction of the active substance has the disadvantage that the active substance can be accidentally washed off or wiped off very quickly. In addition, only very small molecules such as glycerine diffuse into the skin; large molecules do not penetrate.
Eine Verbesserung der Wirkstoffeinbringung stellt die Bereitstellung des Wirkstoffes in einer Matrix dar. Die einen Wirkstoff enthaltende Matrix ist das, was typischer Weise als kosmetische oder dermatologische Formulierung bezeichnet wird. Durch die Einbindung in die Matrix wird erreicht, dass der Wirkstoff über eine längere Zeit in die Haut .einziehen' kann, ohne das er durch unbeabsichtigtes abwaschen oder abwischen von der Haut entfernt wird. The provision of the active ingredient in a matrix represents an improvement in the introduction of the active ingredient. The matrix containing an active ingredient is what is typically referred to as a cosmetic or dermatological formulation. As a result of the integration in the matrix, it is achieved that the active ingredient can "absorb" into the skin over a longer period of time without it being removed from the skin by inadvertent washing or wiping.
Jedoch hat auch die Wirkstoffeinbringung durch kosmetische bzw. dermatologische Formulierungen den Nachteil, dass die Absorption in genügendem Maße nur bei kleinen Wirkstoffmolekülen erfolgt. However, the introduction of the active ingredient through cosmetic or dermatological formulations also has the disadvantage that the absorption takes place to a sufficient extent only in the case of small active ingredient molecules.
Der Fachmann hat sich daher schon lange mit einer Verbesserung der Wirkstoffeinbringung in die Haut beschäftigt. Zum Beispiel führen gezielte Verletzungen der obersten Hautschichten zu einer schnelleren und mengenmäßig höheren Einbringung von Wirkstoffen in die Haut (Nadelroller). Jedoch besteht hier der Nachteil von Infektionen. The person skilled in the art has therefore long been concerned with improving the introduction of active substances into the skin. For example, targeted injuries to the uppermost layers of the skin lead to a faster and more quantitative introduction of active ingredients into the skin (needle roller). However, there is the disadvantage of infection here.
Eine verletzungsfreie Methode zur Verbesserung der Wirkstoffeinbringung ist die Bewegung der Haut während oder nach dem Wirkstoffauftrag. Im einfachen Fall wird der Wirkstoff in die Haut .einmassiert', also durch grobe mechanische Bewegung des betroffenen Hautareals in die Haut .gepresst'. Durch die mechanische Bewegung der Haut, das Massieren, wird die Durchblutung angeregt, die Hautporen öffnen sich teilweise besser und der Wirkstoff kann schneller und tiefer eindringen. Typisches Beispiel für dieses Verfahren ist die Einreibung (Wirkstoffversorgung eines abgegrenzten Körperbereiches ohne systemische Belastung des Organismus.) An injury-free method to improve the delivery of active ingredients is to move the skin during or after the application of the active ingredient. In the simple case, the active ingredient is "massaged" into the skin, i.e. by rough mechanical movement of the affected skin area the skin "pressed". The mechanical movement of the skin, the massage, stimulates the blood circulation, the skin pores sometimes open better and the active ingredient can penetrate faster and deeper. A typical example of this procedure is rubbing in (supply of active ingredients to a delimited body area without systemic stress on the organism.)
Eine weitere Steigung der Wirkstoffeinbringung lässt sich durch Verwendung von Geräten (Applikatoren), die mechanischen Schwingungen erzeugen, erzielen. Die Theorie ist, das Ultraschall (schnell wechselnde akustische Hoch- und Niederdruckwellen) Kavitation in Flüssigkeitskörpern verursacht. Wenn diese Kavitationsblasen platzen, trifft ein Hochgeschwindigkeitsstrahl auf den Festkörper und erzeugt so Mikrokanäle, die die Penetration verbessern (bekannt als Local Transport Pathways). Die Größe und Verteilung der Kavitationsblasen variiert mit niedrigen Ultraschall (<100kHz) und hohen Ultraschall. A further increase in the introduction of the active substance can be achieved by using devices (applicators) that generate mechanical vibrations. The theory is that ultrasound (rapidly changing high and low pressure acoustic waves) causes cavitation in bodies of liquid. When these cavitation bubbles burst, a high-speed jet hits the solid, creating microchannels that improve penetration (known as Local Transport Pathways). The size and distribution of the cavitation bubbles varies with low ultrasound (<100kHz) and high ultrasound.
Der Bereich der genutzten Frequenzen reicht dabei von wenigen 10 Hz (sogenannte Vibrationsgeräte z.B. US Patent 1594636 von 1926 oder DE Gebrauchsmuster 92 02 858 von 1992) bis in den Ultraschallbereich von 5 MHz. Aus US 20170196801 A1 erhält der Fachmann viele Informationen, wie mit Hilfe eines Ultraschallapplikators eine verbesserte Schmerzbehandlung erreicht werden kann. The range of frequencies used extends from a few 10 Hz (so-called vibration devices e.g. US Patent 1594636 from 1926 or DE utility model 92 02 858 from 1992) to the ultrasonic range of 5 MHz. From US 20170196801 A1, the person skilled in the art receives a lot of information on how an improved pain treatment can be achieved with the aid of an ultrasound applicator.
Ultraschallapplikatoren weisen in der Regel einen länglichen Körper und einen Befestigungskopfaufnahmebereich auf. Der längliche Körper hat ein zylindrisches ergonomisches Design, das eine bequeme und leicht zu greifende Oberfläche bietet. Der Aufnahmeraum für den Aufsatzkopf ist so gestaltet, dass er eine Vielzahl von Aufsatzkopfkonstruktionen sicherstellt. Der längliche Körper trägt in seinem Inneren die Ultraschallerzeugungseinrichtung inklusive Batterien oder Akkumulatoren. Ultrasound applicators typically have an elongated body and a mounting head receiving area. The elongated body has a cylindrical ergonomic design that provides a comfortable and easy-to-grasp surface. The receiving space for the attachment head is designed in such a way that it ensures a large number of attachment head constructions. The elongated body carries the ultrasound generating device including batteries or accumulators in its interior.
In WO 2019004806 A1 ist der Aufbau einer Ultraschallerzeugungseinrichtung sehr gut wiedergegeben. The structure of an ultrasound generating device is reproduced very well in WO 2019004806 A1.
3. Erfindung 3. Invention
Die im Stand der Technik zu findenden und dem Fachmann geläufigen Methoden zur Wirkstoffeinbringung in die Haut weisen in Hinblick auf große Wirkstoffmoleküle einige Nachteile auf. The methods to be found in the prior art and familiar to the person skilled in the art for introducing active substances into the skin have some disadvantages with regard to large active substance molecules.
Diesen Nachteilen galt es abzuhelfen. Für den Fachmann überraschend war, dass die Wirkstoffeinbringung sehr stark von der Frequenz und Energie abhängt mit der der Wirkstoff oder eine wirkstoffhaltige Formulierung in die Haut ,einmassiert‘ wird. It was necessary to remedy these disadvantages. It was surprising to the person skilled in the art that the introduction of the active ingredient depends very strongly on the frequency and energy with which the active ingredient or an active ingredient-containing formulation is "massaged" into the skin.
Die Erfindung betrifft daher ein verbessertes Verfahren zur Einbringung von Wirkstoffen in die Haut, insbesondere die Dermis und Epidermis, dadurch gekennzeichnet, dass in einem ersten Schritt ein Wirkstoff oder eine wirkstoffhaltige Zubereitung auf ein Hautareal A aufgetragen wird, das Hautareal A mittels einer Ultraschallvorrichtung mit Ultraschall behandelt wird, wobei die Frequenz des Ultraschalls im Bereich von 25 bis 35 kHz, insbesondere im Bereich von 29 bis 31 kHz beträgt und der Ultraschall eine Energie/Energiedichte im Bereich von 0,5 bis 2,0 W/cm2, insbesondere von 1 bis 1,5 W/cm2 aufweist. The invention therefore relates to an improved method for introducing active ingredients into the skin, in particular the dermis and epidermis, characterized in that in a first step an active ingredient or an active ingredient-containing preparation is applied to a skin area A, the skin area A using an ultrasound device with ultrasound is treated, the frequency of the ultrasound being in the range from 25 to 35 kHz, in particular in the range from 29 to 31 kHz, and the ultrasound having an energy / energy density in the range from 0.5 to 2.0 W / cm 2 , in particular from 1 to 1.5 W / cm 2 .
Ist die Intensität und Dauer/Behandlungszeit zu hoch, kann es zu Überhitzungen und Verletzung der Hautstruktur kommen. If the intensity and duration / treatment time is too high, overheating and damage to the skin structure can occur.
Vorteilhaft ist es daher, wenn die Ultraschallerzeugung gepulst ist. Das bedeutet, dass die Ultraschallerzeugung zeitweise unterbrochen wird. Eine durchgehende Ultraschallerzeugung kann Hautschäden, insbesondere Verbrennungen, erzeugen. Optimal ist ein Verhältnis von an zu aus Zeit von 1 zu 4, das bedeutet das auf einen 0,1 s langen Ultraschallpuls eine 0,4 s lange ,Ausphase‘ folgt. It is therefore advantageous if the ultrasound generation is pulsed. This means that the generation of ultrasound is temporarily interrupted. Continuous generation of ultrasound can cause skin damage, especially burns. A ratio of on to off time of 1 to 4 is optimal, which means that a 0.1 s long ultrasound pulse is followed by a 0.4 s long phase out ‘.
Eine Behandlungszeit von drei mal fünf Minuten mit 20% Arbeitszeit des Ultraschalls stündlich für 3 Stunden ist ausreichend. A treatment time of three times five minutes with 20% working time of the ultrasound every hour for 3 hours is sufficient.
Das erfindungsgemäße Verfahren ist insbesondere für Wirkstoffe mit einer Molmasse von < 60 kDalton und einem log P Wert von kleiner 4,2 geeignet. The method according to the invention is particularly suitable for active ingredients with a molar mass of <60 kDalton and a log P value of less than 4.2.
Besonders bevorzugt ist das erfindungsgemäße Verfahren zur Einbringung von Wirkstoffen aus der Gruppe Magnolienextrakt (Honokiol), Resveratrol, Thiamidol, Hyaluronsäure geeignet. The method according to the invention is particularly preferably suitable for introducing active ingredients from the group of magnolia extract (honokiol), resveratrol, thiamidol, hyaluronic acid.
Die wirkstoffhaltige Zubereitung kann ein Gel, eine Creme oder eine andere Konsistenz umfassen, einschließlich, aber nicht beschränkt auf Salbe, Lotion, Spray, Schaum, Paste, Kollodium, Emulsion, Aerosol, Lösung, Suspension oder andere topische Dosierungsformen und -Zubereitungen. Die dermale Absorption von Wirkstoffen wurde unter Anwendung eines erfindungsgemäßen Verfahrens geprüft. Die Steigerung der dermalen Absorption beträgt je nach Wrkstoff das 2,5-fache bis über das 5-fache gegenüber einer dermalen Absorption ohne Anwendung des erfindungsgemäßen Verfahrens. The active ingredient-containing preparation can comprise a gel, cream or other consistency, including, but not limited to, ointment, lotion, spray, foam, paste, collodion, emulsion, aerosol, solution, suspension or other topical dosage forms and preparations. The dermal absorption of active ingredients was tested using a method according to the invention. Depending on the active ingredient, the increase in dermal absorption is 2.5 times to over 5 times compared to dermal absorption without using the method according to the invention.
Der Vergleichsversuch wurde wie folgt durchgeführt: The comparison test was carried out as follows:
Jede Stunde wurde die Formulierung wiederholt (dreimal) auf Schweinehaut aufgetragen.The formulation was applied repeatedly (three times) to pig skin every hour.
Der Ultraschallkopf der Vorrichtung wurde nach jeder Auftragung 5 Minuten lang auf die Hautoberfläche aufgesetzt (insgesamt 15 Minuten Ultraschallbehandlung). The ultrasound head of the device was placed on the skin surface for 5 minutes after each application (a total of 15 minutes of ultrasound treatment).
Alle Tests wurden unter folgenden Bedingungen durchgeführt: All tests were carried out under the following conditions:
Frequenz 30kHz +/-1kHz - Leistung 1-1.2W/cm2 Beschallung 1 Minuten ON time entspricht 5 Minuten gepulst auf Schweineohrhaut (110Opm dick) - gefroren und dann aufgetaut auf Raumtemperatur - alle Hautproben wurden durch Wderstandsprüfung auf Unversehrtheit überprüft. Frequency 30kHz +/- 1kHz - power 1-1.2W / cm 2 sonication 1 minute ON time corresponds to 5 minutes pulsed on pig ear skin (110Opm thick) - frozen and then thawed to room temperature - all skin samples were checked for integrity by resistance testing.
Das Messareal hatte eine Fläche von 4,9 cm2 The measuring area had an area of 4.9 cm 2
Die aufgebrachte Wrkstoffmenge variierte von 18 bis 80 pg/cm2 (Honokiol 80,09 pg/cm2, Resveratrol 27,83 pg/cm2 und , Thiamidol 17 pg/cm2 und Hyaluronsäure 25 pg/cm2 (unmarkiert), 0,216 ng/cm2 und 32000 Bq/cm2 mit radioaktiv markiertem Tracer) The amount of active ingredient applied varied from 18 to 80 pg / cm 2 (honokiol 80.09 pg / cm 2 , resveratrol 27.83 pg / cm 2 and thiamidol 17 pg / cm 2 and hyaluronic acid 25 pg / cm 2 (unlabelled), 0.216 ng / cm 2 and 32000 Bq / cm 2 with radioactively labeled tracer)
Um vergleichbare Bedingungen für behandelte und unbehandelte Haut zu schaffen, wurde die Oberfläche unbehandelter Haut (kein Ultraschall) mit einem Gewicht von 0,1 kg (5 min pro Stunde, insgesamt 15 min) abgedeckt. In order to create comparable conditions for treated and untreated skin, the surface of untreated skin (no ultrasound) was covered with a weight of 0.1 kg (5 minutes per hour, a total of 15 minutes).
Nachweis der Absorption: Proof of absorption:
Für Magnolienextrakt - bezogen auf Honokiol -, Thiamidol und Resveratrol (ohne radioaktiv markierte Tracer) wie in „In-vitro-Penetration von kosmetischen Inhaltsstoffen ohne radioaktiv markierten Tracer", 7. August 2017 (BDF-interne SOP nach OECD-Richtlinie Nr. 428 und Diembeck W, Beck H, Benech-Kieffer F et al. Prüfrichtlinien für die In-vitro-Beurteilung der Hautresorption und der perkutanen Penetration kosmetischer Inhaltsstoffe. European Cosmetic, Toiletry and Perfumery Association. Food Chem Toxicol 1999; 37: 191 & ndash; 205) beschrieben. For magnolia extract - based on honokiol -, thiamidol and resveratrol (without radioactively labeled tracers) as in "In vitro penetration of cosmetic ingredients without radioactively labeled tracer", August 7, 2017 (BDF-internal SOP according to OECD guideline No. 428 and Diembeck W, Beck H, Benech-Kieffer F, et al. Test Guidelines for the In Vitro Assessment of Skin Resorption and Percutaneous Penetration of Cosmetic Ingredients. European Cosmetic, Toiletry and Perfumery Association. Food Chem Toxicol 1999; 37: 191-13. 205).
Für kurzkettige Hyaluronsäure: „In-vitro-Penetration kosmetischer Inhaltsstoffe mit radioaktiv markiertem Tracer“, August 2017(BDF-interne SOP nach OECD-Richtlinie Nr. 428 und Diembeck W, Beck H, Benech- Kieffer F et al. Prüfrichtlinien für die In-vitro-Beurteilung der Hautresorption und der perkutanen Penetration kosmetischer Inhaltsstoffe. European Cosmetic, Toiletry and Perfumery Association. Food Chem Toxicol 1999; 37: 191 & ndash; 205) For short-chain hyaluronic acid: “In-vitro penetration of cosmetic ingredients with radioactively marked tracer”, August 2017 (BDF-internal SOP according to OECD guideline No. 428 and Diembeck W, Beck H, Benech-Kieffer F et al. Test guidelines for in-vitro assessment skin resorption and percutaneous penetration of cosmetic ingredients. European Cosmetic, Toiletry and Perfumery Association. Food Chem Toxicol 1999; 37: 191-205)
Analyse: Analysis:
Bestimmung der Bioverfügbarkeit einer Testsubstanz in verschiedenen Hautschichten (Stratum Corneum, Epidermis, Dermis, Rezeptorflüssigkeit) erfolgt unter Verwendung von Franz-Diffusionszellen, gefolgt von HPLC-Analyse. The bioavailability of a test substance in different skin layers (stratum corneum, epidermis, dermis, receptor fluid) is determined using Franz diffusion cells, followed by HPLC analysis.
Ebenfalls möglich ist die Analyse von radioaktiv markierten Substanzen. The analysis of radioactively marked substances is also possible.
Die Radioaktivität wurde unter Verwendung eines Flüssigszintillationszählers "Tri-Carb 4910 TR" (Perkin Eimer) mit automatischer Abschreckkorrektur und Ultima GoldTM (Perkin Eimer, Kat.-Nr. 6013329) als Szintillationscocktail analysiert. Epidermis und Dermis wurden in SOLUENE®-350 (Tissue Solubilizer, Perkin Eimer, Kat.-Nr. 6003038) gelöst. The radioactivity was analyzed using a "Tri-Carb 4910 TR" liquid scintillation counter (Perkin Elmer) with automatic quench correction and Ultima Gold ™ (Perkin Elmer, Cat. No. 6013329) as the scintillation cocktail. The epidermis and dermis were dissolved in SOLUENE®-350 (Tissue Solubilizer, Perkin Elmer, Cat. No. 6003038).
Wirkstoff Anteil an absorbierter Menge in der . Schicht ohne erfindungsgem. Verf. mit erfindungsgem. Verf. SteigerungActive ingredient Percentage of amount absorbed in the. Layer without invention. Author with invention. Av. Enhancement
Mangolia extrakt 0,5 % 2,5 % 5-fach (bezogen auf Honokiol) Mangolia extract 0.5% 2.5% 5-fold (based on Honokiol)
Resveratrol 1 ,2 % 6.7 % 5.6-fachResveratrol 1, 2% 6.7% 5.6-fold
Thia idol 3,4 % 8.8 % 2.6-fachThia idol 3.4% 8.8% 2.6 times
Hyaluronsäure 4,6 % 8,7 % 1 ,9-fach Hyaluronic acid 4.6% 8.7% 1.9 fold
Claims
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102020200423.4A DE102020200423A1 (en) | 2020-01-15 | 2020-01-15 | Method for the introduction of active substances into the skin |
| DE102020200423.4 | 2020-01-15 |
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| Publication Number | Publication Date |
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| WO2021144080A1 true WO2021144080A1 (en) | 2021-07-22 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP2020/085451 Ceased WO2021144080A1 (en) | 2020-01-15 | 2020-12-10 | Method for incorporating active substances into the skin |
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| Country | Link |
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| DE (1) | DE102020200423A1 (en) |
| WO (1) | WO2021144080A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116554122A (en) * | 2023-06-29 | 2023-08-08 | 南京桦冠生物技术有限公司 | α-keto acid amide or substituted oxalic acid amido ester compound and composition thereof |
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| US6002961A (en) * | 1995-07-25 | 1999-12-14 | Massachusetts Institute Of Technology | Transdermal protein delivery using low-frequency sonophoresis |
| WO2001076553A2 (en) * | 2000-04-06 | 2001-10-18 | Sontra Medical, Inc. | Method and device for enhanced transdermal drug delivery |
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| WO2017053453A1 (en) * | 2015-09-22 | 2017-03-30 | Johnson & Johnson Consumer Inc. | Methods for enhancing topical application of a benefit agent |
| US20170196801A1 (en) | 2016-01-12 | 2017-07-13 | Flexxsonic Corp. | Application of topical product using a sonic device |
| WO2019004806A1 (en) | 2017-06-30 | 2019-01-03 | ㈜아모레퍼시픽 | Ultrasonic beauty device using nonconductive material, and manufacturing method therefor |
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| US5618275A (en) * | 1995-10-27 | 1997-04-08 | Sonex International Corporation | Ultrasonic method and apparatus for cosmetic and dermatological applications |
| DE102008009472A1 (en) * | 2008-02-15 | 2009-08-20 | Beiersdorf Ag | Increasing skin moistness, comprises applying a cosmetic preparation on the skin to be treated and subsequently incorporating into the skin to be moistened with the help of an ultrasonic applicator |
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2020
- 2020-01-15 DE DE102020200423.4A patent/DE102020200423A1/en active Pending
- 2020-12-10 WO PCT/EP2020/085451 patent/WO2021144080A1/en not_active Ceased
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| US1594636A (en) | 1924-04-18 | 1926-08-03 | Fitzgerald Mfg Co | Liquid-reservoir applicator for massage vibrators |
| US6002961A (en) * | 1995-07-25 | 1999-12-14 | Massachusetts Institute Of Technology | Transdermal protein delivery using low-frequency sonophoresis |
| WO2001076553A2 (en) * | 2000-04-06 | 2001-10-18 | Sontra Medical, Inc. | Method and device for enhanced transdermal drug delivery |
| WO2006091719A2 (en) * | 2005-02-23 | 2006-08-31 | Sontra Medical Corporation | Compositions and methods enhancing transdermal delivery of drugs and biologics |
| WO2017053453A1 (en) * | 2015-09-22 | 2017-03-30 | Johnson & Johnson Consumer Inc. | Methods for enhancing topical application of a benefit agent |
| US20170196801A1 (en) | 2016-01-12 | 2017-07-13 | Flexxsonic Corp. | Application of topical product using a sonic device |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116554122A (en) * | 2023-06-29 | 2023-08-08 | 南京桦冠生物技术有限公司 | α-keto acid amide or substituted oxalic acid amido ester compound and composition thereof |
| CN116554122B (en) * | 2023-06-29 | 2023-09-19 | 南京桦冠生物技术有限公司 | α-keto acid amide or substituted oxalic acid amide ester compounds and compositions thereof |
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|---|---|
| DE102020200423A1 (en) | 2021-07-15 |
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