WO2014098764A1

WO2014098764A1 - Topical treatment delivery system

Info

Publication number: WO2014098764A1
Application number: PCT/SG2012/000485
Authority: WO
Inventors: Pak Ho Henry Leung; Wai To Fung
Original assignee: Conifer Living Formulas Pte Ltd; Clearbridge Nanomedics Pte Ltd
Priority date: 2012-12-21
Filing date: 2012-12-21
Publication date: 2014-06-26

Abstract

A topical treatment delivery system comprising: a backing layer configured to accommodate the facial contours of a user, a soluble nano-fibre membrane affixed to the backing layer, and a TCM extract encapsulated in the membrane configured for topical delivery to the face. Also a method of fabricating a membrane for topical treatment delivery to the face of a user, and a face mask.

Description

Topical treatment delivery system

FIELD

The present invention relates to a topical treatment delivery system. BACKGROUND

It is know to provide various types of dressing for wounds. For example in International Patent publication number WO 2006/036130 a composite dressing is provided for wound care. However the composite nano-fibre is fabricated using needle electro spinning, which has a high energy requirement and is quite slow.

Increasingly alternative or herbal remedies are becoming popular. For certain types of herbal remedy it may be desirable to apply the formula topically. However often such remedies are difficult to apply, especially topically, and are not user friendly. Moreover the composite in WO 2006/036130 is not well suited to delivering such remedies.

Further improvements in treatment delivery devices include International Patent publication number WO 2009/045342, which discloses a solution spinning method for fabricating a nano-fibre including essential oils. Korean Patent number KR20110077792 describes electro-spinning a hydrophilic polyurethane nano-fibre or polyurethane web. Cosmetic treatment is impregnated within the web. US2011229551 is a biodegradable sustained release drug delivery nano-fibre web. The web is then implanted into the vitreous cavity within the eye.

However for remedies such as Traditional Chinese Medicine (TCM), it maybe important for the active compounds in the powered extracts to remain viable throughput the fabrication process. It may also be important to ensure that the active compounds are delivered topically in a controlled and user friend manner.

SUMMARY

It may therefore be desirable to provide a topical treatment delivery system which goes some way to overcoming one or more of the problems mentioned above, or which will at least give the public a useful choice.

In general terms the invention proposes a soluble nano-fibre membrane incorporating a TCM extract. Upon application to a user's skin the membrane may slowly dissolve, which may thereby topically deliver the treatment in a controlled and user friendly manner. The membrane may be in the shape of a facemask to apply the treatment to the face of a user. The treatment may include skin clearing (anti acne), skin whitening, skin rejuvenation and firming, and/or skin lightening (anti-pigmentation). The membrane may be fabricated using needless electro-spinning, which may ensure the over 90% of the active compounds remain viable throughout fabrication, and may provide a lower cost and higher throughput production process. This process may allow for both polar and non-polar chemical compounds from a TCM formulation to be viably incorporated into the membrane and to be controllably topically delivered.

In a first specific expression of the invention there is provided a topical treatment delivery system according to claim 1.

In a second specific expression of the invention there is provided a method of fabricating a membrane according to claim 4.

Embodiments may be implemented according to any of claims 2-3 or 5 to 14. BRIEF DESCRIPTION OF THE DRAWINGS

One or more example embodiments of the invention will now be described, with reference to the following figures, in which:

Figure 1 is a plan view of the facemask according to an example embodiment.

Figure 2 is a flow diagram of a method of fabrication according to an example embodiment.

Figure 3 is a recipe for the TCM Skin Clearing (anti-acne) Formulation.

Figure 4 is a recipe for the TCM Skin Whitening Formulation.

Figure 5 is a recipe for the TCM Skin Rejuvenation Firming Formulation.

Figure 6 is a recipe for the TCM Skin Lightening (Anti-Pigmentation) Formulation.

Figure 7 is a table of the High-performance liquid chromatography (HPLC) analysis before and after electro-spinning.

Figure 8 is a graph of the HPLC analysis of a solution including the TCM formulation for Whitening including with PEO polymer before electro-spinning.

Figure 9 is a graph of the HPLC analysis of an electro-spun membrane encapsulating the Whitening TCM formulation.

Figure 10 is a table comparing the organic and non-organic extraction efficiency for 90% water 0% ethanol buffer, and for the 2 stage extraction process with 9:1 mix ratio. Figure 11 is graphs of the HPLC analysis of the solution after extraction by (a) water, (b) ethanol, (c) 90% water 10% ethanol buffer, and (d) 2 stage extraction process with 9:1 mix ratio.

DESCRIPTION

A topical treatment delivery system 100 is shown in Figure 1 according to the example embodiment. A face mask 102 includes apertures for the user's eyes 104, nose 106 and mouth 108, and slit's 110 to accommodate the typical facial contours around the periphery.

The mask 102 is fabricated from a membrane which encapsulates a TCM formulation. When the mask 102 is applied to the user's face, it will loosely follow the contours of the face while the face is dry due to the slits 110 and apertures 104,106,108. The membrane is activated by the face being completed wetted, either by applying water or a designed activation gel. The membrane then dissolves and the TCM formulation precipitates out as a uniformly distributed solid residue on the user's face. The mask 102 may be left on for 15min or until the membrane has completed dissolved.

The membrane may be fabricated according to the method 200 shown in Figure 2 according to the example embodiment. A TCM formulation is selected and prepared 202 according to any of the recipes show in Figures 1 to 4. The formulation may initially be a dry fine grounded powder mixture. Subsequently a solution including a polymer is prepared 204. The solution is electro-spun 206 into a nano-fibre membrane. The membrane may be a single fibre layer or it may have multiple layers. The different layers may have different TCM extracts for a dual or combination effects mask.

Lastly the membrane is cut and packaged 208. The method 200 is explained in more detail below.

Firstly the active compounds from the TCM formulation powder are dissolved using one or more processes, depending on the type of compounds to be extracted. For example polar, non polar, and essential/crude oil extraction may all be extracted using separate techniques. Some of the extractions may be combined for use in electro-spinning a single layer, or may be used in fabricating separate nano-fibre layers in a multi layer membrane.

Non-polar molecule extraction

100% Ethanol is used to extract non-polar small molecules. The mixture may be left to stand for several hours or may be agitated to increase the rate of extraction. For example, the mixture may be sonicated for about 30-60 minutes, and then Autoclaved at 90 to 130°C eg: 121°C, for 10 to 90 minutes, eg: 20 minutes. Then the mixture is centrifuged at 6,000 rpm for 30 minutes. The solution is filtered using a cellulose filter or membrane filter with pore size around 0.45um.

Polar molecule extraction

The remaining solids are removed from the filter and are mixed into a buffer or aqueous solution at about 0.05-0.5 g/ml at a temperature of between 25°C to 60°C. The buffer or aqueous solution aids to extract polar small molecules in the formulation. The mixture may be left to stand for several hours or may be agitated to increase the rate of extraction. For example, the mixture may be sonicated for about 30-60 minutes, and then Autoclaved at 90 to 130°C eg: 121 °C, for 10 to 90 minutes, eg: 20 minutes. Then the mixture is centrifuged at 16,000 rpm for 30 minutes. The solution is filtered using cellulose filter or membrane filter with pore size around 0.45um.

Extract combining

10-30% of the Ethanol extract solution is mixed with 90-70% of the buffer or aqueous extract solution to result in the final TCM extracted solution. Essential/crude oil extraction

If the TCM extract includes essential or crude oil, this may need to be separately extracted The TGM formulation powders are mixed into a buffer solution or aqueous or organic solvent at about 0.05-0.5 g/ml at a temperature of between 25°C to 60°C. The buffer solution or aqueous or organic solvent aids to extract total molecules in the formulation. The mixture may be left to stand for several hours or may be agitated to increase the rate of extraction. For example, the mixture may be sonicated for about 30-60 minutes, and then Autoclaved at 90 to 130°C eg: 121 °C, for 10 to 180 minutes, eg: 60 minutes. Then the mixture is centrifuged at 16,000 rpm for 30 minutes. The solution is filtered using, cellulose filter or membrane filter with pore size around 0.45um. The solution will evaporate at 60-100°C, example 80°C, under reduced pressure (under vacuum) for 1-6hr, example 2hr. The remaining liquid represents the essential/crude oil extraction from the formulation. Essential/crude oil extraction may be used for direct polymer mixing without further combination. For example it may be provided as a separate layer in a multi layer nano-fibre membrane.

Then the solution is combined 204 with the polymer. Polymer mixing

A polymer (Polyethylene Oxide (PEO), MV 500-700k) is mixed with the final TCM extracted solution at 25°C to 70°C for 1 hour. After mixing, the solution is left to cool for 30 minutes to allow small molecule-polymerization.

The resulting polymer solution is used for membrane fabrication 206 via electro-spinning. Electro-spinning

The solution is provided for needless electro-spinning at 30kV; solution flow rate at 0.8ml/hr and collector rotator speed at 100 rpm. A 80%nylon/20% polyester honeycombed/netting structure based substrate may be the backing layer. This may be done at room temperature and pressure with collection distance at 8 to 12 cm. The membrane thickness is between 15 urn to 50 urn. The needle spec is 0.5 to 1 inch, and 18G to 25G size.

Lastly the membrane is cut and packaged 208. Cutting and Packaging

The membrane will place UV overnight at room temperature and under vacuum before physical cutting, example face-mask design or any other sizes. Correct cutting membrane will be sealed in packaging under vacuum.

The non polar solvent may be 100% ethanol. For other application it may also be methanol, dichloromethane, acetone nitrate etc. .

The polar solvent may be distilled water or a salt solution, which reduces undesirable compounds, especially polar compounds. For example, sodium phosphate, sodium acetate, and sodium bicarbonate, or alternatively a mild acid such as acetic acid. Suitable concentrations of the buffer solution using these various compounds are in the range of about 0.05 -0. 5M, most suitably about a 0.1 M solution of sodium phosphate, sodium acetate or sodium bicarbonate, or a 0.5% acetic acid solution.

The polymer may be any soluble and insoluble polymers, for example Poly(acrylamide/acrylic acid); Poly(Diallyl Dimethyl Ammonium Chloride); Poly(2- vinylpyridine N-oxide); Poly(ethylene glycol); Poly(ethylene oxide) ; Polyvinylpyrrolidone); Polyvinyl alcohol); Polypropylene. Suitable molecular size of soluble and insoluble polymers are range of about 1000 - 100,000 MW. The extraction process might be expected to deliver 120 mg of soluble and insoluble small molecules for every per gram of dry powder TCM formulation. In turn more than 97% of those soluble and insoluble small molecule might be expected to be viably retained in polymer mixture and/or the polymer membrane after electro-spinning. Figures 7 to 9 and show that the electrospinning methodology encapsulates over 75% of the starting compounds.

Figures 10 and 11 show that 90% water-10% Ethanol pre-mixed extract buffer allows 94% of total water soluble compounds to be extracted with 6% of total organic compounds to be extracted. Using the two step 100% ethanol followed by water extraction mentioned above (with a 9:1 mixing ratio) allows 90% of total water soluble compounds to be extracted with more than 10% of total organic compounds to be extracted. This represents a two fold increase in organic compounds present compared with the standard prior art extraction method.

The small molecule level of each sample was assay by standard laboratory small molecule assay, for example a Lowry Potein Assay.

While example embodiments of the invention have been described in detail, many variations are possible within the scope of the invention as claimed as will be clear to a skilled reader.

Claims

CLAIMS:

1. A topical treatment delivery system comprising:

a backing layer configured to accommodate the facial contours of a user, a soluble nano-fibre membrane affixed to and/or supported by the backing layer, and

a TCM extract encapsulated in the membrane configured for topical delivery to the face.

2. The system in claim 1 wherein the membrane thickness is between 15 um to 50 um.

3. The system in claim 1 wherein the TCM extract is configured for treatment of skin clearing (anti acne), skin whitening, skin rejuvenation and firming, and/or skin lightening (anti-pigmentation).

4. A method of fabricating a membrane for topical treatment delivery to the face of a user, comprising:

dissolving a TCM extract in solution,

mixing the solution with one or more polymers to allow soluble and insoluble small molecule polymerisation, and

electro-spinning the polymerised solution into a nano-fibre membrane

5. The method in claim 4 further comprising electro-spinning a different polymerised solution, encapsulated a TCM extract configured for treatment of a different condition, into a second nano-fibre membrane on the first second nano-fibre membrane

6. The method in claim 4 or 5 wherein the dissolving step comprises dissolving the TCM extract in a non-polar solvent.

7. The method in claim 6 wherein the dissolving further comprises independently dissolving the TCM extract in a polar solvent.

8. The method in claim 7 wherein the dissolving further comprises

sonicating the solution for 30-60 minutes,

autoclaving the sonicated at 90 to 130°C, for 10 to 90 minutes,

centrifuging the autoclaved solution at 16,000 rpm for 30 minutes, and filtering the centrifuged solution.

9. The method in claims 7 or 8 wherein the polar solution is combined with the non- polar solution using a ratio of between 9:1 and 7:3.

10. The method in any one of claims 4 to 9 wherein the mixing comprises adding Poly(acrylamide/acrylic acid); Poly(Diallyl Dimethyl Ammonium Chloride); Poly(2- vinylpyridine N-oxide); Poly(ethylene glycol); Poly(ethylene oxide) ; Poly(N- vinylpyrrolidone); and/or Poly( vinyl alcohol) to the solution

11. The method in claim 10 wherein the mixing occurs at between 25°C to 70^bC for 1 hour.

12. The method in any one of claims 4 to 11 wherein the electro-spinning comprises applying a voltage of 30kV; a solution flow rate of 0.8ml/hr, collector rotator speed at 100 rpm, a collection distance of 8 to 12 cm, a needle spec is 0.5 to 1 inch, and/or 18G to 25G size.

13. The method in any one of claims 4 to 12 wherein the soluble nano-fibre membrane is multi layer.

14. The method in claim 13 wherein a first layer of the multi layer membrane encapsulates an essential oil or crude oil extraction.

15. A face mask fabricated according to the method of any one of claims 4 to 14.