EP2194953A1

EP2194953A1 - Water- and active ingredient-containing gel

Info

Publication number: EP2194953A1
Application number: EP08785499A
Authority: EP
Inventors: Michael Roreger; Iris Schnitzler; Christian Hausen
Original assignee: ICS Innovative Care Systems Andernach GmbH
Current assignee: LTS Lohmann Therapie Systeme AG
Priority date: 2007-08-20
Filing date: 2008-08-12
Publication date: 2010-06-16
Also published as: WO2009024275A1; US20110182955A1; JP2010536810A; DE102007039229A1

Abstract

The invention relates to a hydrogel comprising water, at least one gel former, at least one pharmaceutical active ingredient or cosmetic ingredient and, where appropriate, further auxiliaries and additives obtainable by a) mixing water and auxiliaries and additives which are present where appropriate, b) adding the gel former and homogenizing the mixture, c) adding the pharmaceutical active ingredient or cosmetic ingredient and, where appropriate, ionic compounds which induce gel formation, and homogenizing the mixture, d) pouring out the mixture onto a support and e) cooling the mixture to form the hydrogel, where steps a) to d) are carried out at a temperature between 79 and 95°C. This hydrogel is suitable for administering cosmetic ingredients onto or via the skin or mucous membrane of a human, in particular in the form of a cosmetic face pack.

Description

Water and medicated gel

The present invention relates to a water-containing gel (hydrogel) which, in addition to water, comprises at least one gelling agent and at least one pharmaceutical and / or one cosmetic active substance or ingredient. The gel according to the invention preferably contains at least one cosmetic ingredient. The invention further relates to a process for the preparation of the gel and its use for delivering said active ingredients and ingredients to or over the skin or the mucous membrane of a human.

Hydrogel films and their use for administering cosmetic ingredients to the skin or mucous membrane of a human are known.

DE 3827561 C1 discloses a flexible, hydrophilic, water-swellable gel film. This gel film has a water content of 0.1 to 70 wt .-% and is characterized by a high water absorption capacity and good mechanical stability. The film contains a cation-active and an anion-active polymer, and its preparation is carried out using a so-called volatile additive in order to suppress the incompatibility reaction of said polymers during the dissolution process. This gel film can be used both in cosmetics in the form of masks or films for skin treatment and as a pharmaceutical preparation for transdermal drug administration.

DE 695 07 818 T2 relates to topical skin care compositions, in particular aqueous topical skin care compositions containing a hydrogel thickener and a water-insoluble silicone conditioning agent. The aim here is to provide skin care compositions that remain translucent, have improved skin feel, and exhibit reduced stickiness. The preparation of the disclosed compositions is carried out by mixing together the ingredients according to the conventional methods of the prior art at room temperature. DE 699 18 418 T2 describes a hair care product in the form of a thickened water-based liquid which has a shearling phase which forms a reversible gel. The shear gel is formed from a variety of separate gel particles. For production, a suitable polymer is subjected to shear during gelation. To form the Schergels a temperature of less than or equal to 25 ⁰ C is required.

DE 10 2004 038 285 A1 relates to drug delivery systems based on polymer matrices containing one or more essential oils. The polymer matrix may be constructed from an agar-agar / polyacrylic acid-based synthetic polymer or gel matrix and contain one or more permeation controlling membranes.

The object of the present invention was therefore to provide a cosmetic and / or pharmaceutical preparation in the form of a gel or gel film for

Administration of cosmetic or pharmaceutical ingredients or active ingredients to or through the skin of a human, in particular for the administration of cosmetic ingredients to the skin or mucous membrane of a human. This

Gel should therefore be particularly suitable for cosmetic use, d. H. be highly hydrated and as skin friendly as possible.

Furthermore, it should be easy to produce without the auxiliary substances and additives described in the prior art and also without the use of so-called. As carrier layers, nonwoven inserts, chemical crosslinkers and the like, can be realized and still have sufficient elasticity and minimum tear strength.

This object is achieved by the cosmetic and / or pharmaceutical preparation according to the invention in the form of a hydrogel or aqua gel, which is suitable for delivering pharmaceutical or cosmetic active substances or ingredients to or via the skin or the mucous membrane of a human The water-containing gel is preferably in the form of a flat and flexible product, in particular in the form of a so-called gel film. This product or film preferably has a minimum layer thickness of 2 mm. The water content of the preparation is preferably more than 90% by weight, based on the finished preparation. The preparation or hydrogel comprises at least water, one or more gelling agents and one or more active ingredients or ingredients. In addition, the hydrogel according to the invention known in the art other auxiliaries or additives such. As tackifiers for better adhesion of the gel film on the skin, preservatives and disinfectants, pH regulators, antioxidants, emulsion stabilizers, fillers, crosslinking agents, solubilizing and humectants, etc. included; see. z. B. DE 3827561 C1, especially pages 3 to 5. Preferred and to ensure the best possible skin compatibility, the number and amount of these auxiliaries and additives is limited to a minimum. In particular, the preparation according to the invention or the hydrogel film according to the invention can be prepared and used without the use of the aforementioned reinforcing means; Nevertheless, he has the necessary for the pharmaceutical or cosmetic applications elasticity and minimum tear strength.

Furthermore, the gel preparation according to the invention shows improved optical properties, for example, in comparison with the products of the prior art. As regards the translucency and transparency. These improved optical properties have significance, in particular for the cosmetic applications of the preparation, since it depends not only on the effectiveness of the preparation but also on its appearance.

The preferred embodiment of the invention is in the form of the cosmetic preparation and in particular in the use of the hydrogel or gel film according to the invention as a face mask.

Also in cosmetic use, the highly water-containing gel is preferably in the form of a sheet product (eg as a film). The hydrogel comprises, in addition to water, preferably more than 90% by weight, at least one cosmetic see ingredient and at least one gelling agent. Suitable cosmetic ingredients are, for. In INCI (International Nomenclature of Cosmetic Ingredients). Due to the high water content of the hydrogel according to the invention, hydrophilic ingredients are particularly easy to process. The proportion of cosmetic ingredients is preferably 0.1 to 10% by weight. Preferred cosmetic ingredients are, for. As vegetable oils, synthetic oils, vitamins and vitamin derivatives, botanical extracts and active ingredients, moisturizers (moisturizers), skin care substances, skin soothing and skin-smoothing substances, peeling products, antioxidants, emollients, film formers, solubilizers, ionogenic and non-ionic thickeners, penetration enhancers, conditioners, sunscreens, omega-3 and omega-6 fatty acids, amino acids, peptides, surfactants, anti-inflammatories, antimicrobials and their combinations. Dexpanthenol is particularly preferred.

In principle, all gel formers known for the formation of hydrogels can be used as gelling agents, eg. E 400 - alginic acid, E 401 - sodium alginate, E 402 - potassium alginate, E 403 - ammonium alginate, E 404 - calcium alginate, E 405 - propylene glycol alginate, E 406 - agar agar, E 407 - carrageenan, E 407a - eucheuma algae, E 410 - locust bean gum, E 412 - guar gum, E 413 - tragacanth, E 414 gum arabic, E 415 - xanthan gum, E 416 gum karaya, E 417 - tara gum, E 418 - gellan, E 420 - sorbitol, E 421 - mannitol , E 422 - Glycerol or E 425 - Konjac root (E XXX = E number of food additives authorized in the European Union). Particularly preferred as gelling agent are (hydrophilic) polysaccharide derivatives or mixtures containing them with other substances such. As the ^® various types Kelcogel (gellan gum) from CPKelco, Atlanta, USA, or guar gum types or derivatives of guar flour as guar hydroxypropyltrimonium chloride (commercially available from Rhodia, France, from their series with the trademark Jaguar) , The particularly preferred Kelcogel types are mixtures containing gellan gum, which consists of acylated linear chains with glucose, rhamnose and glucuronic acid units. In a particularly preferred variant mixes to the Kelcogel ^® with xanthan gum, a high molecular weight polysaccharide is selected from (1, 4) -linked beta-D-glucose with trisaccharide side chain on each glucose unit at position 3 consisting of a glucuronic acid unit between 2 mannoses, here especially preferably, the Keltrol ^® grades (z. B. Keltrol ^® CG of CPKelco), and konjac mannan, also known as glucomannan, a polysaccharide of beta-linked D-glucose and D-mannose. Preferably, the finished hydrogel product contains from 0.05% to 8.0% by weight of one or more gelling agents.

The auxiliaries and additives described above and used in the prior art in water-containing gels may also be present in the cosmetic preparation according to the invention. Preferably, the hydrogel according to the invention monohydric or polyhydric alcohols, eg. As glycerol, as a solubilizer and humectants, usually to 0.5 to 20 wt .-%. Furthermore, metal salts as crosslinking agents, preferably calcium salts such as calcium chloride, and further ionic polymers can be added to the hydrogel according to the invention in the preparation. The metal salts are preferably in 0.01 to 1, 0 wt .-% and the ionic polymers preferably contain from 0.1 to 5 wt .-% As already stated, in the cosmetic preparation in particular due to the better skin compatibility, the number and the amount of auxiliaries and additives used kept as low as possible. The desired flexibility and minimum tensile strength of the hydrogel product can be achieved without these additives usually. This applies in particular to the sheet-like preparations which exceed the preferred minimum thickness of 2 mm.

All wt .-% - information refers to the finished preparation or the finished hydrogel.

The water-containing gel according to the invention or the sheet-like product produced therefrom can have a back layer which is impermeable to the active ingredient or ingredient and to water. Furthermore, the product according to the invention may comprise agents which cause a secure adhesion of the product to the skin or mucous membrane. This can be z. B. be done by the gel with so-called. Sticky as described, or on the side which comes into contact with the skin, has an adhesive layer permeable to the active ingredient or ingredient. Such arrangements are known to those skilled in transdermal therapeutic systems (TTS). In the latter case, the product according to the invention in addition to the optional backing layer also usually has a protective layer or protective film on the adhesive side. Materials for backing layer and protective layer are preferably polymer films such as those described e.g. B. in DE 3827561 C1 on page 5, lines 9 to 33, and the figures mentioned therein are described.

In addition, the gel product according to the invention may have further layers which serve as a reservoir for the active substance or ingredient and / or can exert an additional supporting function. Such arrangements are known to those skilled in the field of TTS and z. B. in DE 3827561 C1 on page 4, lines 56 to 68 described.

All references cited in the description are expressly incorporated by reference. These serve as references and are part of the present description.

The present invention also encompasses a process for the preparation of the hydrogel according to the invention or of a corresponding product, which in particular ensures the obtaining of a hydrogel having the described advantageous properties.

According to the invention, the water and optionally present solubilizers and / or humectants and / or other auxiliaries or additives are mixed and heated to a temperature between 79 and 95 ⁰ C, preferably 85 to 92 ⁰ C, heated. With stirring, the gel-forming substance or a mixture of gel-forming substances is added. Finally, the homogenous mass of the pharmaceutical active ingredients or cosmetic ingredients and, if necessary, the gel compounds inducing ionic compounds (eg crosslinkers in the form of, for example, metal salts and ionic polymers such as anionic polyacrylic acid derivatives) added and homogenized. The resulting liquid is poured onto a carrier layer (eg backing layer) and / or into a desired packaging (eg deep-drawn blister). The temperature when pouring is like that of the foregoing steps also 79-95 ⁰ C ₁ preferably between 80 and 88 ⁰ C. During the subsequent cooling, the aqueous liquid converts to the invention homogeneous hydrogel. In this case, a cooling rate of 2 to 5 ° C / min for the formation of the above-mentioned product properties is particularly preferred

Preferably, the liquid is poured into a thermoforming blister, i. H. into a packaging produced by thermoforming of a defined cavity in a plastic film, in which the hydrogel forms on cooling.

In order to obtain the hydrogel according to the invention with its advantageous properties, compliance with the temperature ranges described above in the individual production steps is crucial. This applies in particular to the filling or pouring out of the initially obtained aqueous, homogeneous liquid. In this step, the liquid must be hot, ie a temperature between 79 and 95 ⁰ C ₁ preferably between 80 and 90 ⁰ C and particularly preferably between 80 and 88 ⁰ C, have.

The hydrogel according to the invention is suitable for dermal, intradermal or transdermal delivery of pharmaceutical active or cosmetic ingredients in humans. In particular, the gel has the property of delivering its active ingredients over a long period of time and at a constant rate per unit time to or over the skin.

Preferably, the use of the hydrogel in cosmetics, and particularly preferably in the form of a sheet-like and flexible product, for. B. as a face mask.

The following examples serve to illustrate the invention without limiting it thereto. example 1

Preparation of a hydrogel according to the invention

Approach:

- Phase 1: Heat water to 90 ⁰ C.

- Phase 2: Mix glycerine, Kelcogel F, Kelcogel Lt 100 and Jaguar and slowly add to the mixture with stirring. Homogenize

- Submit phase 3; homogenize

- Pour out the mixture and let it rise to room temperature over 20 to 30 minutes

Water (1) is heated to 90 ⁰ C. While stirring, a mixture of gel-forming substances (2) is slowly added. Finally, the cosmetic composition, preservatives and the gelation-inducing ionic compounds (3) are added to the homogeneous composition and homogenized with stirring. The resulting liquid is then poured onto a backing or deep drawing die. During the subsequent cooling, the liquid transforms into a homogeneous gel. In a preferred embodiment, the hydrous gel is processed at a temperature above 79 ⁰ C and below 95 ⁰ C, more preferably the pouring takes place between 80 and 88 ⁰ C.

Example 2

A further example of a hydrogel according to the invention is listed below. The preparation is carried out analogously to Example 1

100000

Example 3 Preparation of Hydrogel with Anti-Aging Formulation

1 water 92.5

2 glycerol 4

Kelcogel F 0.1

Keltrol CG 0.7

Konjac Mannan 0.3

3 Dexpanthenol 0.5

Vitamin C 1, 0

Euxyl PE 9010 0.7

Calcium chloride x 2 H ₂ O 0.2

Approach:

- Phase 1: Heat water to 90 ⁰ C.

- Phase 2: Mix glycerin, Kelcogel F, Keltrol CG and Konjac Mannan and slowly add to the mixture with stirring. Homogenize - Submit phase 3, homogenize,

Example 4

Preparation of a hydrogel with oil components

1 water 91, 85

2 glycerol 4

Kelcogel F 0.1

Keltrol CG 0.7

Konjac Mannan 0.3

3 Dexpanthenol 1, 5

Vitamin A palmitate 0.05

Vitamin E acetate 0.1

Rose oil 1, 0

Cremophor RH-60 0.5

Euxyl PE 9010 0.5

Calcium chloride x 2 H ₂ O 0.2

4 perfume 0.2

- Phase 1: Heat water to 90 ⁰ C.

- Phase 2: Mix glycerin, Kelcogel F, Keltrol CG and Konjac Mannan and slowly add to the mixture with stirring. Homogenize

- Submit phase 3, homogenize

- Phase 4: Add the perfume to the mass and homogenize

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Claims

claims

Hydrogel containing water, at least one gelling agent, at least one pharmaceutical active or cosmetic ingredient and optionally other auxiliaries and additives obtainable by

a) mixing water and optionally present auxiliaries and additives, b) adding the gelling agent and homogenizing the mixture, c) adding the pharmaceutical active ingredient or cosmetic ingredient and optionally the gelation-inducing ionic compounds and homogenizing the mixture, d) pouring out the mixture a carrier and e) cooling the mixture to form the hydrogel,

wherein the steps a) to d) are carried out at a temperature between 79 and 95 ⁰ C.

2. Hydrogel according to claim 1, characterized in that it comprises more than 90 wt .-% water.

3. Hydrogel according to claim 1 or 2, characterized in that the gelling agent is a polysaccharide derivative or a mixture of polysaccharide derivatives.

4. Hydrogel according to one or more of claims 1 to 3, characterized in that the gelling agent gellan gum or guar gum or a mixture of these components.

5. Hydrogel according to one or more of claims 1 to 4, characterized in that the hydrogel contains 0.05 to 8.0 wt .-% gelling agent.

6. Hydrogel according to one or more of claims 1 to 5, characterized in that it contains a humectant.

7. Hydrogel according to one or more of claims 1 to 6, characterized in that the humectant is glycerol.

8. Hydrogel according to one or more of claims 1 to 7, characterized in that it contains a gelation inducing ionic compound.

9. Hydrogel according to one or more of claims 1 to 8, characterized in that the ionic compound is a metal salt or an ionic polymer.

10. Hydrogel according to one or more of claims 1 to 9, characterized in that the metal salt is a calcium salt and the ionic polymer is a polyacrylic acid derivative.

11. Hydrogel according to one or more of claims 1 to 10, characterized in that it comprises at least one cosmetic ingredient.

12. Hydrogel according to one or more of claims 1 to 11, characterized in that the cosmetic ingredient is dexpanthenol.

13. Hydrogel according to one or more of claims 1 to 12, characterized in that it is a flat product.

14. Hydrogel according to one or more of claims 1 to 13, characterized in that the flat product has a minimum thickness of 2 mm.

15. A process for preparing a hydrogel according to one or more of claims 1 to 14 comprising the steps a) to e) according to claim 1.

16. The method according to claim 15, characterized in that step d) is carried out at a temperature between 80 and 88 ⁰ C.

17. The method according to claim 15 or 16, characterized in that the mixture obtained in step c) is poured into a deep-drawing blister.

18. Use of a hydrogel according to one or more of claims 1 to 14 for the administration of cosmetic ingredients to or through the skin or mucosa of a human.

19. Use according to claim 18 as a cosmetic facial mask.

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