WO2016071474A1 - Method for preparing an excipient suitable for preparing creams - Google Patents

Method for preparing an excipient suitable for preparing creams Download PDF

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Publication number
WO2016071474A1
WO2016071474A1 PCT/EP2015/075866 EP2015075866W WO2016071474A1 WO 2016071474 A1 WO2016071474 A1 WO 2016071474A1 EP 2015075866 W EP2015075866 W EP 2015075866W WO 2016071474 A1 WO2016071474 A1 WO 2016071474A1
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WO
WIPO (PCT)
Prior art keywords
weight
components
aqueous
excipient
organic
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Application number
PCT/EP2015/075866
Other languages
French (fr)
Inventor
Johan Van Daele
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Johan Van Daele
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Publication of WO2016071474A1 publication Critical patent/WO2016071474A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/04—Dispersions; Emulsions
    • A61K8/06—Emulsions
    • A61K8/062—Oil-in-water emulsions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/27—Zinc; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
    • A61K8/922—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof of vegetable origin

Definitions

  • the present invention also relates to methods for producing such a cream or excipient. Background of the invention
  • creams are often produced for application to human or animal tissue, often human or animal skin, in order to obtain a medical or cosmetic effect.
  • the starting point for such creams is often an excipient, to which one or more active constituents or components are added, which active components provide the medical or cosmetic effect.
  • the excipient used is, as it were, the carrier of the active components in the creams.
  • excipients which are based on an oil-in-water emulsion, wherein the external phase is aqueous and the internal emulsified phase is oil.
  • oil-in-water emulsion is insufficiently moisturizing and replenishing for dry and damaged skin, and fatty active constituents are not always equally well delivered to the skin because of emulsified.
  • excipient which comprises exclusively fat or oil. Oils of this type have the drawback of closing up the skin, with the result that the skin is no longer able to get rid of its waste substances, which can often cause inflammation and/or slower recovery. In addition, excipients of this type are considered unpleasant to use and do not penetrate well into the skin.
  • Another object of the invention is to develop a water-in-oil cream (also referred to as a w/o cream) which can be combined with a wide range of active constituents, is as hypo- allergenic as possible, and is as low-cost as possible without any detriment to quality.
  • a water-in-oil cream also referred to as a w/o cream
  • One or more of the above objects and/or advantages is achieved by the excipient according to the present invention.
  • a first aspect of the present invention provides an excipient which is suitable for preparing pharmaceutical and/or cosmetic creams.
  • the excipient comprises:
  • aqueous phase which comprises the following
  • organic esters each of the general formula R1-COO-R2, where R1 and R2 are both, independently of one another, a linear or branched alkyl group having 1 1 to 30 carbon atoms;
  • percentages by weight of the components of the organic phase are expressed as the weight of the component over the total weight of the excipient, and the percentage by weight of the aqueous phase is expressed as the weight of the aqueous phase over the total weight of the excipient.
  • the organic components may comprise natural and/or synthetic oils.
  • the organic components may comprise 5% by weight to 15% by weight of one or more organic esters, each having the general formula R1- COO-R2, wherein R1 and R2 are both, independently of one another, a linear or branched alkyl group having 1 1 to 30 carbon atoms.
  • the excipient may be a water-in-oil emulsion.
  • water-in-oil is also written as w/o.
  • the organic phase may comprise 20 to 70% by weight of natural or synthetic oils, preferably selected from the group consisting of paraffin oil, vaseline, preferably white vaseline, and combinations of the two.
  • the organic esters perform a function of auxiliary emulsifier and viscosity regulator whereas the sorbitan esters are used essentially as emulsifier.
  • An excipient is a constituent of a pharmaceutical or cosmetic preparation which dissolves or suspends the other components (for example active components which provide a medical or cosmetic effect if the preparation is applied to tissue, for example skin, of a human or animal) and provides the desired consistency of the preparation.
  • the excipient is what is known as the carrier of the cream, and the cream is based on the excipient.
  • the aqueous phase comprises 98% by weight to 99.5% by weight of purified water, which percentage by weight of purified water is expressed as the weight of the component over the total weight of the aqueous phase.
  • the preservative may comprise one or more components which have a preserving property.
  • the preservative may be a combination of
  • o 0.05% by weight to 0.15% by weight of methyl parahydroxybenzoate o 0.01 % by weight to 0.1 % by weight of propyl parahydroxybenzoate, which percentages by weight of the components of the aqueous phase are expressed as the weight of the component over the total weight of the aqueous phase.
  • the natural or synthetic oil may comprise paraffin oil.
  • the natural or synthetic oil may comprise paraffin oil and vaseline, in which case the weight ratio of paraffin oil to vaseline is greater than 1.
  • the weight ratio of paraffin oil to vaseline is more than 50/50, such as more than 2.5, for example in the range from 80/20 to 99.99/0.01.
  • the use of vaseline as part of the natural or synthetic oils has the advantage that the stability of the excipient, or of the cream based on the excipient, can be made less dependent on the ambient temperature at which the excipient or the cream is stored.
  • the addition of vaseline gives a product which will remain stable for longer in the case of excipients or creams which are stored at higher ambient temperatures, for example in tropical regions.
  • liquid paraffin means Paraffinum liquidum Ph. Eur. having a viscosity of between 1 10 mPa.s and 230 mPa.s determined by method 2.2.9 described in Ph. Eur. 7.0.
  • Ph. Eur. 7.0 means "the European Pharmacopoeia, version 7.0.”
  • the excipient may comprise more than 15% by weight, for example for more than 20% by weight of aqueous phase.
  • the excipient comprises more than 25% by weight, such as 25% by weight or even more than 30% by weight of aqueous phase.
  • the natural or synthetic oil may be present in a concentration of between 53% by weight and 63% by weight.
  • the liquid paraffin can provide a good consistency of the cream, and moreover is hypo-allergenic, making it accessible for wide public use.
  • it forms a base in which lipophilic molecules can be dissolved.
  • Organic esters are esters in which R1 and R2, independently of one another, contain 1 1 to 30, preferably 15 to 24 carbon atoms.
  • Excipients according to the invention are formed in such a way that the excipient forms a water-in-oil base with an optimum spreadability and stability, on the one hand, and which, on the other hand, breaks down when spread, so as to have a cooling effect.
  • the natural or synthetic oils have a viscosity of between 1 10 mPa.s and 230 mPa.s, which viscosity is determined by method 2.2.9 described in Ph. Eur. 7.0.
  • wax may be present in an amount from 5.5% to 9.5% by weight.
  • Wax in particular provides a good consistency of the excipient.
  • the wax used may be cera alba.
  • the one or more organic esters may be present in the excipient in an amount of from 7% by weight to 14% by weight.
  • the one or more organic esters may comprise or be cetyl palmitate.
  • the excipient may comprise:
  • the percentages by weight of the components in the organic and aqueous phase are expressed, unless specified otherwise, as the weight of the component over the total weight of the excipient.
  • the excipient may comprise more than 25% by weight of purified water.
  • the excipient may comprise: • in the aqueous phase the components
  • the percentages by weight of the components in the organic and aqueous phase are expressed, unless specified otherwise, as the weight of the component over the total weight of the excipient.
  • the excipient may comprise:
  • weight ratio of paraffin oil to vaseline is greater than 1 ; o 3 to 8% by weight of cera alba
  • the percentages by weight of the component in the organic and aqueous phase are expressed, unless specified otherwise, as the weight of the component over the total weight of the excipient.
  • the excipient according to the invention serves as a carrier for a cosmetic or medicinal cream, or can either be used as such a cream, for example for the treatment of dry skin, itching, wounds, burns, burns caused by radiotherapy, ichthyosis, dry eczema, bedsores (decubitus), psoriasis, scars, pigment disorders and many other dermatological diseases and skin disorders.
  • the excipient used as a cream can have a cooling, anti-itching, pain- relieving, wound-healing, skin-repairing and nutritive effect on, for example, burns or for example burns caused by irradiation, on dry skin symptoms such as dry skin, dry eczema and ichthyosis, on bedsores, psoriasis, and many other dermatological diseases and skin disorders.
  • a second aspect of the present invention provides a method for producing an excipient, which method comprises the steps of:
  • organic esters each of the general formula R1-COO-R2, wherein R1 and R2 are both, independently of one another, a linear or branched alkyl group having 1 1 to 30 carbon atoms;
  • the organic components may comprise natural and/or synthetic oils. According to some embodiments, the organic components may comprise 1 % by weight to 15% by weight, for example 5% by weight to 15% by weight, of one or more organic esters, each having the general formula R1 -COO-R2, wherein R1 and R2 are both, independently of one another, a linear or branched alkyl group having 1 1 to 30 carbon atoms.
  • said leaving to stand may be such that no action is taken during said leaving to stand, e.g. no heating or no other action.
  • the thorough mixing may take place at a reduced pressure of less than or equal to 0.7. bara.
  • Bara means the absolute pressure, expressed in bar, where 1 bar is equal to 100 000 Pascal. 0 bara therefore means absolute vacuum.
  • first of all a mixture of the aqueous and the organic components may be provided, which mixture of the components is emulsified.
  • the aqueous and organic components if appropriate provided as a mixture, can be heated to a temperature of between 75°C and 80°C.
  • the heating may take place with gentle stirring.
  • gentle stirring is to be understood as meaning the stirring of the components, or if appropriate the mixture, preferably with the aid of a mixer, at a speed of less than 1500 rpm.
  • the mixture after said heating, can be cooled back down until a temperature of below 40°C is reached.
  • the cooling can take place with gentle stirring.
  • the cooling can take place with the aid of forced cooling.
  • Forced cooling means that thermal energy is removed from the product, in this case the emulsion, by means of a cooling fluid which is at a temperature below the ambient temperature, such as cooling water.
  • the temperature of the emulsion may drop at a rate of from 0.5 to 1.5°C per minute.
  • the emulsion can be scraped off the wall of the mixer.
  • the mixture after said heating, can be emulsified in a mixer at a speed of more than 1500 rpm.
  • Stephan(r) mixer which is set at a speed of from 1500 to 4000 rpm in order to emulsify the components in the mixture.
  • the use of the Stephan(r) mixer at 1500 to 4000 rpm delivers high shear mixing. It is preferable to use the Stephan(r) mixer at a speed of around 3000 rpm, for example 3000 rpm. In this way, it is possible to create sufficient small spheres of water in the water-in-oil emulsion.
  • the emulsifying can take place over a period of from 2 to 10 minutes.
  • said steps of heating, emulsifying and cooling in the preparation of a water-in-oil emulsion can take place under a vacuum of less than or equal to 0.7 bara.
  • said heating and cooling can take place under a vacuum of less than 0.7 bara. It is preferable to apply pressure of less than 0.5 bara, or even less than 0.3 bara.
  • the emulsion after said cooling, can be left to stand for a period of at least 4 hours, after which the emulsion is stirred through again.
  • the standing time is preferably more than 6 hours.
  • the temperature can preferably further be brought to ambient temperature, for example to 20 to 25°C.
  • the thorough mixing may take place over a period of from 0.5 to 10 minutes, for example over a period of from 2 to 10 minutes.
  • the components are provided in a weight ratio as described for the excipients according to the first aspect of the invention.
  • the organic and aqueous components may comprise 10 to 73% by weight of aqueous components, which aqueous components comprise the following components:
  • organic components comprise the following components:
  • o 1 % by weight to 15% by weight of one or more waxes o 1 % by weight to 15% by weight of one or more organic esters, each of the general formula R1-COO-R2, where R1 and R2 are both, independently of one another, a linear or branched alkyl group having 1 1 to 30 carbon atoms;
  • the aqueous components may comprise
  • the organic components may comprise
  • the percentages by weight of the components in the organic and aqueous phase are expressed, unless specified otherwise, as the weight of the component over the total weight of the excipient.
  • the organic and aqueous components may comprise more than 15% by weight of aqueous components.
  • the aqueous components may comprise:
  • weight is expressed as the weight of the component over the total weight of the aqueous phase
  • the organic components may comprise
  • the percentages by weight of the components are expressed, unless specified otherwise, as the weight of the component over the total weight of the aqueous and organic components.
  • the aqueous components may comprise
  • weight is expressed as the weight of the component over the total weight of the aqueous phase
  • the organic components may comprise
  • weight ratio of paraffin oil to vaseline varies and is greater than 1 ; o 3 to 8% by weight of cera alba
  • the percentages by weight of the components are expressed, unless specified otherwise, as the weight of the component over the total weight of the aqueous and organic components.
  • an excipient is obtained by using one of the methods in accordance with the second aspect of the invention.
  • active components can be added, in order to obtain a cosmetic or medicinal cream.
  • the methods according to the present invention have the advantage of producing a stable excipient with no or only minimal separation back into an aqueous and an organic phase during storage.
  • the excipient according to the invention may form a pharmaceutical carrier for the processing of one or more active ingredients which give the end product a
  • the excipient according to the invention used as a carrier for a pharmaceutical or cosmetic cream, or as the cream itself, is found to be notably pleasant to use as a result of the cooling effect and good penetration through the skin barrier in the case of dry and/or dehydrated skin, yet a protective but not occlusive film still remains behind, ensuring a prolonged nutritive and therapeutic effect.
  • a third aspect of the invention provides a cosmetic or medicinal cream.
  • cream is used to denote a preparation which is a mixture of lipid phase and aqueous phase, stabilized with an emulsifier.
  • a cream preferably has an optimum viscosity. It is possible for a component to be worked into the cream, either as a solution or as a suspension.
  • a fourth aspect of the invention provides a cosmetic or medicinal cream which
  • this cosmetic or medicinal cream may comprise 75% by weight to 100% by weight of excipient, which excipient has been obtained by one of the methods according to the second aspect of the invention.
  • the one or more active components may comprise one or more components selected from the group consisting of calcium pantothenate, rosemary essential oil, lavender spike essential oil, lemon essential oil and peppermint essential oil.
  • the one or more active components may comprise essential oil of Rosmarinus officinalis var. cineole.
  • the cream may comprise 75% by weight to 99.9% by weight of excipients, and 0.1 % by weight to 25% by weight of one or more active components, the percentages by weight of the components in the cosmetic or medicinal cream being expressed as the weight of the component over the total weight of the cosmetic or medicinal cream.
  • the one or more active components may comprise one or more components selected from the group consisting of calcium pantothenate, rosemary essential oil, lavender spike essential oil, lemon essential oil and peppermint essential oil.
  • the one or more active components may comprise calcium pantothenate.
  • the one or more active components may comprise lavender essential oil.
  • the one or more active components may comprise lavender essential oil and rosemary essential oil.
  • the one or more active components may comprise lavender essential oil, rosemary essential oil and lemon essential oil. According to some embodiments, the one or more active components may comprise lavender essential oil, rosemary essential oil, lemon essential oil and peppermint essential oil.
  • the one or more active components may comprise lavender spike essential oil.
  • the one or more active components may comprise essential oil of Rosmarinus officinalis var. cineole.
  • the one or more active components may comprise one or more zinc-containing compounds.
  • the one or more zinc-containing compounds may be zinc-containing compounds selected from the group consisting of zinc oxide, zinc citrate and zinc sulphate.
  • the one or more active zinc-containing compounds may form 0.1 % by weight to 10% by weight of the cosmetic or medicinal cream, which percentage by weight is expressed as the total weight of the zinc-containing compounds with respect to the weight of the cosmetic or medicinal cream.
  • Zinc-containing compounds may be encountered in various wound-healing, enzymatic systems, and are suitable for use in wound-healing cosmetic or medicinal creams, for example when treating bedsores.
  • a fifth aspect of the invention provides a method for producing a cosmetic or medicinal cream, which cosmetic or medicinal cream comprises an excipient and active compounds.
  • the excipient is produced by one of the methods according to the second aspect of the invention.
  • the one or more active components are added to the excipient and then stirred into the excipient.
  • a sixth aspect of the invention provides a method for producing a cosmetic or medicinal cream, which cosmetic or medicinal cream comprises an excipient and one or more active components.
  • the excipient is produced by one of the methods according to the second aspect of the invention. During the production of the excipient, one or more active components are added.
  • one or more active components can be added after said leaving to stand and before said thorough mixing.
  • said leaving to stand may be such that no action is taken during said leaving to stand, e.g. no heating or no other action.
  • one or some of the plurality of active components are added as early as during the production of the excipient, and others of the plurality of active components are added after the said standing time and before the said thorough mixing.
  • calcium pantothenate is added as early as during the production of the excipient, more specifically at the beginning of the preparation of the excipient.
  • one or more active components, the aqueous and organic components can be combined before the preparation of the water-in-oil emulsion.
  • the one or more active components may comprise one or more components selected from the group consisting of calcium pantothenate, rosemary essential oil, lavender spike essential oil, lemon essential oil and peppermint essential oil.
  • the one or more active components may comprise calcium pantothenate.
  • the one or more active components may comprise lavender essential oil.
  • the one or more active components may comprise lavender essential oil and rosemary essential oil.
  • the one or more active components may comprise lavender essential oil, rosemary essential oil and lemon essential oil.
  • the one or more active components may comprise lavender essential oil, rosemary essential oil, lemon essential oil and peppermint essential oil.
  • the one or more active components may comprise lavender spike essential oil.
  • the one or more active components may comprise essential oil of Rosmarinus officinalis var. cineole.
  • the one or more active components may comprise one or more zinc-containing compounds.
  • the one or more zinc-containing compounds may be zinc-containing compounds selected from the group consisting of zinc oxide, zinc citrate and zinc sulphate.
  • the one or more active zinc-containing compounds may form from 0.1 % by weight to 10% by weight of the cosmetic or medicinal cream, which percentage by weight is expressed as the total weight of the zinc-containing compounds with respect to the weight of the cosmetic or medicinal cream.
  • a seventh aspect of the invention provides cosmetic or medicinal cream, which excipient was obtained by one of the methods according to the sixth aspect of the invention.
  • the one or more active components in the cosmetic or medicinal cream may, inter alia, be: essential oils, natural moisturizing factors, components for stimulating the generation of skin cells or for promoting the restoration of skin cells, and the like.
  • excipients according to the present invention and those obtained by the method according to the present invention, and creams based on these excipients, are therefore extremely suitable for the treatment of burns or for providing a cooling effect after the application of a tattoo to human or animal skin.
  • the excipients according to the present invention can have a preventive use for preventing or reducing the risk of epidermolysis, erythema, irritation, pain or dryness of the skin, for example caused by radiotherapy.
  • excipients according to the present invention can also have a curative use for epidermolysis, erythema, irritation, burns, pain or dryness of the skin, for example caused by the application of tattoos, radiotherapy, bedsores, eczema, psoriasis, keratosis pilaris and similar disorders, or also as a lubricant for sexual contact, for example during sexual intercourse.
  • Cetyl palmitate is an organic ester having the general formula R1-COO-R2, wherein R1 is a linear alkyl group having 15 carbon atoms and R2 is a linear alkyl group having 16 carbon atoms.
  • liquid paraffin white beeswax, cetyl palmitate and sorbitan
  • aqueous phase referred to above as aqua conservans, forms the remaining 19.21 % by weight.
  • This aqueous phase or aqua conservans consists of:
  • the excipient is formed by combining the ingredients in a suitable container, provided with a mixer, preferably a Stephan mixer and suitable for evacuation.
  • the ingredients are gently stirred using the Stephan (r) mixer while the temperature is increased to 80° Celsius. This is followed by high-shear mixing of the mixture for 3 minutes using the Stephan mixer, mixing at 3000 rpm. Thereafter, the emulsion is actively cooled to below 40° Celsius, if appropriate to room temperature. The vacuum is removed.
  • the excipient obtained in this way is then left to stand for a few hours, at least 2 but preferably 6 hours, and preferably approximately 24 hours.
  • the active components are added, and the excipient (together with any active components) again undergoes high-shear mixing in the Stephan mixer, mixing at 3000 rpm for a few minutes. This mixing may if appropriate takes place after the air has been evacuated from the container to a vacuum of around 0.25 bara.
  • the excipient is also mixed again if no further active components are added in order to obtain a cosmetic or medicinal cream. This is in order to obtain a homogeneous and stable cream or excipient with few or no lumps.
  • This excipient can be used, inter alia, for the production of an itch-reducing and/or burn /wound-repairing cream.
  • the following different active components are added to the excipient in order to obtain a cream, i.e. a w/o emulsion, having the following composition:
  • Peppermint essential oil 0.37 g
  • Sorbitan sesquioleate/arlacel 83 2.97 g
  • liquid paraffin white beeswax, cetyl palmitate and sorbitan
  • sesquioleate together form the organic phase, forming 61.55% by weight of the excipient.
  • the aqueous phase referred to above as aqua conservans, forms the remaining
  • This aqueous phase or aqua conservans is the same as that used in the first embodiment.
  • the excipient is formed using the same procedure as described above in connection with the first embodiment.
  • some of the liquid paraffin is replaced by vaseline, preferably white vaseline, in the same quantities by weight (i.e. 1 g of paraffin is replaced by 1 gram of vaseline).
  • 1 g of paraffin is replaced by 1 gram of vaseline.
  • half or a quarter of the paraffin can be replaced by vaseline.
  • An excipient containing vaseline can be obtained by a similar or even identical preparation method to that explained in connection with the first and second
  • excipients can be used for, inter alia, the production of an itching-reducing and/or burn/wound-repairing cream.
  • the following different active components are added to the excipient in order to obtain a cream, i.e. a w/o emulsion, having the following
  • composition The same quantity of essential oils are added, either after the excipient has been made or before the thorough mixing of the excipient, or added as an additional ingredient to the aqueous and organic components before the heating and emulsifying of these components.

Abstract

A method for preparing an excipient, which method comprises the steps of: ∙ providing aqueous components comprising purified water and a preservative; ∙ providing organic components ∙ preparing a water-in-oil emulsion by - combining the aqueous and organic component - heating to above 60°C, - emulsifying, and - cooling to less than 45°C; ∙ leaving the emulsion to stand for a period of longer than or equal to 2hours; ∙ thoroughly mixing the emulsion obtained to produce the excipient.

Description

METHOD FOR PREPARING AN EXCIPIENT SUITABLE FOR PREPARING CREAMS
Field of the invention The present invention relates to an excipient which is usable as a carrier for
pharmaceutical and/or cosmetic cream per se, and to pharmaceutical and/or cosmetic creams, which creams can be applied to human or animal skin. The present invention also relates to methods for producing such a cream or excipient. Background of the invention
In the pharmaceutical and cosmetics industries, creams are often produced for application to human or animal tissue, often human or animal skin, in order to obtain a medical or cosmetic effect. The starting point for such creams is often an excipient, to which one or more active constituents or components are added, which active components provide the medical or cosmetic effect. The excipient used is, as it were, the carrier of the active components in the creams.
Currently, it is common to use excipients which are based on an oil-in-water emulsion, wherein the external phase is aqueous and the internal emulsified phase is oil. Often, such an oil-in-water emulsion is insufficiently moisturizing and replenishing for dry and damaged skin, and fatty active constituents are not always equally well delivered to the skin because of emulsified.
An alternative is an excipient which comprises exclusively fat or oil. Oils of this type have the drawback of closing up the skin, with the result that the skin is no longer able to get rid of its waste substances, which can often cause inflammation and/or slower recovery. In addition, excipients of this type are considered unpleasant to use and do not penetrate well into the skin.
Attempts have been made to develop a water-in-oil emulsion, in which water is the internal phase and oil is the external phase. Such an excipient could be used as a cream on its own or as an excipient for creams to counteract dry and therefore often itchy skin, or as wound-healing cream. Such excipients have often proven relatively unstable and/or to have little cooling effect, the latter being desirable in order to reduce itching. Summary of the invention
It is an object of the invention to provide an excipient or cream which is a water-in-oil emulsion and which is suitable for use as an excipient or cream per se for
pharmaceutical and/or cosmetic purposes. The excipient according to the present invention has the advantage of remaining stable for a prolonged period of time when stored at room temperature with little or even no separation into an aqueous and an organic phase. Another object of the invention is to provide a method for producing an excipient according to the present invention.
Another object of the invention is to develop a water-in-oil cream (also referred to as a w/o cream) which can be combined with a wide range of active constituents, is as hypo- allergenic as possible, and is as low-cost as possible without any detriment to quality. One or more of the above objects and/or advantages is achieved by the excipient according to the present invention.
One or more of the abovementioned objects and/or advantages is also achieved by the methods according to the present invention.
A first aspect of the present invention provides an excipient which is suitable for preparing pharmaceutical and/or cosmetic creams. The excipient comprises:
• 10 to 73% by weight of aqueous phase which comprises the following
components
o 0.01 % by weight to 2.25% by weight of preservative;
o 97.75% by weight to 99.99% by weight of purified water;
• organic phase comprising the organic components
o natural and/or synthetic oils and/or fats;
o 1 % by weight to 15% by weight of one or more waxes;
o 1 % by weight to 15% by weight of one or more organic esters, each of the general formula R1-COO-R2, where R1 and R2 are both, independently of one another, a linear or branched alkyl group having 1 1 to 30 carbon atoms;
o 1 % by weight to 8% by weight of sorbitan esters; which percentages by weight of the components of the aqueous phase are expressed as the weight of the component over the total weight of the aqueous phase, the
percentages by weight of the components of the organic phase are expressed as the weight of the component over the total weight of the excipient, and the percentage by weight of the aqueous phase is expressed as the weight of the aqueous phase over the total weight of the excipient.
According to some embodiments, the organic components may comprise natural and/or synthetic oils.
According to some embodiments, the organic components may comprise 5% by weight to 15% by weight of one or more organic esters, each having the general formula R1- COO-R2, wherein R1 and R2 are both, independently of one another, a linear or branched alkyl group having 1 1 to 30 carbon atoms.
According to some embodiments, the excipient may be a water-in-oil emulsion.
The term "water-in-oil" is also written as w/o.
According to some embodiments, the organic phase may comprise 20 to 70% by weight of natural or synthetic oils, preferably selected from the group consisting of paraffin oil, vaseline, preferably white vaseline, and combinations of the two.
Unless specifically stated otherwise, all percentages by weight (% by weight) of a component are based on the total weight of the product in which the component is contained.
The organic esters perform a function of auxiliary emulsifier and viscosity regulator whereas the sorbitan esters are used essentially as emulsifier.
An excipient is a constituent of a pharmaceutical or cosmetic preparation which dissolves or suspends the other components (for example active components which provide a medical or cosmetic effect if the preparation is applied to tissue, for example skin, of a human or animal) and provides the desired consistency of the preparation. The excipient is what is known as the carrier of the cream, and the cream is based on the excipient.
Preferably, the aqueous phase comprises 98% by weight to 99.5% by weight of purified water, which percentage by weight of purified water is expressed as the weight of the component over the total weight of the aqueous phase.
The preservative may comprise one or more components which have a preserving property.
The preservative may be a combination of
o 0.5% by weight to 2% by weight of propylene glycol;
o 0.05% by weight to 0.15% by weight of methyl parahydroxybenzoate; o 0.01 % by weight to 0.1 % by weight of propyl parahydroxybenzoate, which percentages by weight of the components of the aqueous phase are expressed as the weight of the component over the total weight of the aqueous phase.
According to some embodiments, the natural or synthetic oil may comprise paraffin oil. According to some embodiments, the natural or synthetic oil may comprise paraffin oil and vaseline, in which case the weight ratio of paraffin oil to vaseline is greater than 1. Preferably, the weight ratio of paraffin oil to vaseline is more than 50/50, such as more than 2.5, for example in the range from 80/20 to 99.99/0.01. The use of vaseline as part of the natural or synthetic oils has the advantage that the stability of the excipient, or of the cream based on the excipient, can be made less dependent on the ambient temperature at which the excipient or the cream is stored. The addition of vaseline gives a product which will remain stable for longer in the case of excipients or creams which are stored at higher ambient temperatures, for example in tropical regions.
The term "liquid paraffin" means Paraffinum liquidum Ph. Eur. having a viscosity of between 1 10 mPa.s and 230 mPa.s determined by method 2.2.9 described in Ph. Eur. 7.0.
Ph. Eur. 7.0 means "the European Pharmacopoeia, version 7.0."
According to some embodiments, the excipient may comprise more than 15% by weight, for example for more than 20% by weight of aqueous phase.
Preferably, the excipient comprises more than 25% by weight, such as 25% by weight or even more than 30% by weight of aqueous phase.
The addition of more water causes a greater cooling effect when the excipient or a cream based on the excipient is applied to the skin of a human or animal body.
According to some embodiments, the natural or synthetic oil may be present in a concentration of between 53% by weight and 63% by weight.
In particular, the liquid paraffin can provide a good consistency of the cream, and moreover is hypo-allergenic, making it accessible for wide public use. In addition, it forms a base in which lipophilic molecules can be dissolved.
Organic esters are esters in which R1 and R2, independently of one another, contain 1 1 to 30, preferably 15 to 24 carbon atoms.
Excipients according to the invention are formed in such a way that the excipient forms a water-in-oil base with an optimum spreadability and stability, on the one hand, and which, on the other hand, breaks down when spread, so as to have a cooling effect. According to some embodiments, the natural or synthetic oils have a viscosity of between 1 10 mPa.s and 230 mPa.s, which viscosity is determined by method 2.2.9 described in Ph. Eur. 7.0.
According to some embodiments, wax may be present in an amount from 5.5% to 9.5% by weight.
Wax in particular provides a good consistency of the excipient.
According to some embodiments, the wax used may be cera alba.
According to some embodiments, the one or more organic esters may be present in the excipient in an amount of from 7% by weight to 14% by weight.
According to some embodiments, the one or more organic esters may comprise or be cetyl palmitate.
According to some embodiments, the excipient may comprise:
• in the aqueous phase the components
o 16 to 20% by weight of purified water
o 0.8 to 2% by weight of propylene glycol, which percentage by weight is expressed as the weight of the component over the total weight of the aqueous phase
o 0.07 to 0.09% by weight of methyl parahydroxybenzoate, which percentage by weight is expressed as the weight of the component over the total weight of the aqueous phase
o less than 0.03% by weight of propyl parahydroxybenzoate, which percentage by weight is expressed as the weight of the component over the total weight of the aqueous phase
• in the organic phase the organic components
o 53 to 63% by weight of paraffin oil
o 7 to 9% by weight of cera alba
o 7 to 12% by weight of cetyl palmitate
o 2 to 4% by weight of sorbitan sesquioleate
the percentages by weight of the components in the organic and aqueous phase are expressed, unless specified otherwise, as the weight of the component over the total weight of the excipient.
According to some embodiments, the excipient may comprise more than 25% by weight of purified water.
According to some embodiments, the excipient may comprise: • in the aqueous phase the components
o 35 to 41 % by weight of purified water
o 0.3 to 2% by weight of propylene glycol, which percentage by weight is expressed as the weight of the component over the total weight of the aqueous phase
o 0.02 to 0.04% by weight of methyl parahydroxybenzoate, which percentage by weight is expressed as the weight of the component over the total weight of the aqueous phase
o less than 0.01 % by weight of propyl parahydroxybenzoate, which percentage by weight is expressed as the weight of the component over the total weight of the aqueous phase
• in the organic phase the organic components
o 35 to 50% by weight of paraffin oil
o 3 to 8% by weight of cera alba
o 4 to 9% by weight of cetyl palmitate
o 3.5 to 6% by weight of sorbitan sesquioleate
the percentages by weight of the components in the organic and aqueous phase are expressed, unless specified otherwise, as the weight of the component over the total weight of the excipient.
According to some embodiments, the excipient may comprise:
• in the aqueous phase the components
o 35 to 41 % by weight of purified water
o 0.3 to 2% by weight of propylene glycol, which percentage by weight is expressed as the weight of the component over the total weight of the aqueous phase
o 0.02 to 0.04% by weight of methyl parahydroxybenzoate, which percentage by weight is expressed as the weight of the component over the total weight of the aqueous phase
o less than 0.01 % by weight of propyl parahydroxybenzoate, which percentage by weight is expressed as the weight of the component over the total weight of the aqueous phase
• in the organic phase the organic components
o 35 to 50% by weight of paraffin oil and vaseline wherein the
weight ratio of paraffin oil to vaseline is greater than 1 ; o 3 to 8% by weight of cera alba
o 4 to 9% by weight of cetyl palmitate
o 3.5 to 6% by weight of sorbitan sesquioleate
the percentages by weight of the component in the organic and aqueous phase are expressed, unless specified otherwise, as the weight of the component over the total weight of the excipient.
The excipient according to the invention serves as a carrier for a cosmetic or medicinal cream, or can either be used as such a cream, for example for the treatment of dry skin, itching, wounds, burns, burns caused by radiotherapy, ichthyosis, dry eczema, bedsores (decubitus), psoriasis, scars, pigment disorders and many other dermatological diseases and skin disorders. The excipient used as a cream can have a cooling, anti-itching, pain- relieving, wound-healing, skin-repairing and nutritive effect on, for example, burns or for example burns caused by irradiation, on dry skin symptoms such as dry skin, dry eczema and ichthyosis, on bedsores, psoriasis, and many other dermatological diseases and skin disorders.
A second aspect of the present invention provides a method for producing an excipient, which method comprises the steps of:
• providing aqueous components comprising purified water and a preservative;
• providing organic components comprising
o natural and/or synthetic oils and/or fats;
o one or more waxes;
o one or more organic esters, each of the general formula R1-COO-R2, wherein R1 and R2 are both, independently of one another, a linear or branched alkyl group having 1 1 to 30 carbon atoms;
o one or more sorbitan esters;
• preparing a water-in-oil emulsion by
o combining the aqueous and organic components
o heating to above 60°C,
o emulsifying, and
o cooling to less than 45°C;
• leaving the emulsion to stand for a period of longer than or equal to 2 hours;
• thoroughly mixing the emulsion obtained, so that the excipient is obtained.
According to some embodiments, the organic components may comprise natural and/or synthetic oils. According to some embodiments, the organic components may comprise 1 % by weight to 15% by weight, for example 5% by weight to 15% by weight, of one or more organic esters, each having the general formula R1 -COO-R2, wherein R1 and R2 are both, independently of one another, a linear or branched alkyl group having 1 1 to 30 carbon atoms.
According to some embodiments, said leaving to stand may be such that no action is taken during said leaving to stand, e.g. no heating or no other action.
According to some embodiments, the thorough mixing may take place at a reduced pressure of less than or equal to 0.7. bara.
Bara means the absolute pressure, expressed in bar, where 1 bar is equal to 100 000 Pascal. 0 bara therefore means absolute vacuum.
According to some embodiments, during the preparation of a water-in-oil emulsion, first of all a mixture of the aqueous and the organic components may be provided, which mixture of the components is emulsified.
According to some embodiments, during the preparation of the emulsion, the aqueous and organic components, if appropriate provided as a mixture, can be heated to a temperature of between 75°C and 80°C.
According to some embodiments, the heating may take place with gentle stirring.
The term gentle stirring is to be understood as meaning the stirring of the components, or if appropriate the mixture, preferably with the aid of a mixer, at a speed of less than 1500 rpm.
According to some embodiments, the mixture, after said heating, can be cooled back down until a temperature of below 40°C is reached.
According to some embodiments, the cooling can take place with gentle stirring.
According to some embodiments, the cooling can take place with the aid of forced cooling.
Forced cooling means that thermal energy is removed from the product, in this case the emulsion, by means of a cooling fluid which is at a temperature below the ambient temperature, such as cooling water.
According to some embodiments, during the cooling the temperature of the emulsion may drop at a rate of from 0.5 to 1.5°C per minute.
According to some embodiments, during the cooling the emulsion can be scraped off the wall of the mixer. According to some embodiments, the mixture, after said heating, can be emulsified in a mixer at a speed of more than 1500 rpm.
It is preferable to use a Stephan(r) mixer which is set at a speed of from 1500 to 4000 rpm in order to emulsify the components in the mixture.
The use of the Stephan(r) mixer at 1500 to 4000 rpm delivers high shear mixing. It is preferable to use the Stephan(r) mixer at a speed of around 3000 rpm, for example 3000 rpm. In this way, it is possible to create sufficient small spheres of water in the water-in-oil emulsion.
According to some embodiments, the emulsifying can take place over a period of from 2 to 10 minutes.
According to some embodiments, said steps of heating, emulsifying and cooling in the preparation of a water-in-oil emulsion can take place under a vacuum of less than or equal to 0.7 bara.
According to some embodiments of the invention, said heating and cooling can take place under a vacuum of less than 0.7 bara. It is preferable to apply pressure of less than 0.5 bara, or even less than 0.3 bara.
According to some embodiments, after said cooling, the emulsion can be left to stand for a period of at least 4 hours, after which the emulsion is stirred through again.
The standing time is preferably more than 6 hours. During the standing time, the temperature can preferably further be brought to ambient temperature, for example to 20 to 25°C.
According to some embodiments, the thorough mixing may take place over a period of from 0.5 to 10 minutes, for example over a period of from 2 to 10 minutes.
According to some embodiments, the components are provided in a weight ratio as described for the excipients according to the first aspect of the invention.
According to some embodiments, the organic and aqueous components may comprise 10 to 73% by weight of aqueous components, which aqueous components comprise the following components:
o 0.01 % by weight to 2.25% by weight of preservative;
o 97.75% by weight to 99.99% by weight of purified water; and wherein the organic components comprise the following components:
o natural and/or synthetic oils and/or fats;
o 1 % by weight to 15% by weight of one or more waxes; o 1 % by weight to 15% by weight of one or more organic esters, each of the general formula R1-COO-R2, where R1 and R2 are both, independently of one another, a linear or branched alkyl group having 1 1 to 30 carbon atoms;
o 1 % by weight to 8% by weight of sorbitan esters;
which percentages by weight of the aqueous components are expressed as the weight of the component over the total weight of the aqueous components, the percentages by weight of the organic components are expressed as the weight of the component over the total weight of the organic and aqueous components, and the percentage by weight of the aqueous components together is expressed as the weight of the aqueous phase over the total weight of the organic and aqueous components.
According to some embodiments,
• the aqueous components may comprise
o 16 to 20% by weight of purified water
o 0.8 to 2% by weight of propylene glycol, which percentage by weight is expressed as the weight of the component over the total weight of the aqueous phase
o 0.07 to 0.09% by weight of methyl parahydroxybenzoate, which percentage by weight is expressed as the weight of the component over the total weight of the aqueous phase
o less than 0.03% by weight of propyl parahydroxybenzoate, which percentage by weight is expressed as the weight of the component over the total weight of the aqueous phase
• the organic components may comprise
o 53 to 63% by weight of paraffin oil
o 7 to 9% by weight of cera alba
o 7 to 12% by weight of cetyl palmitate
o 2 to 4% by weight of sorbitan sesquioleate
the percentages by weight of the components in the organic and aqueous phase are expressed, unless specified otherwise, as the weight of the component over the total weight of the excipient.
According to some embodiments, the organic and aqueous components may comprise more than 15% by weight of aqueous components.
According to some embodiments: • the aqueous components may comprise:
o 35 to 41 % by weight of purified water
o 0.3 to 2% by weight of propylene glycol, which percentage by
weight is expressed as the weight of the component over the total weight of the aqueous phase
o 0.02 to 0.04% by weight of methyl parahydroxybenzoate, which percentage by weight is expressed as the weight of the
component over the total weight of the aqueous phase
o less than 0.01 % by weight of propyl parahydroxybenzoate, which percentage by weight is expressed as the weight of the
component over the total weight of the aqueous phase
• the organic components may comprise
o 35 to 50% by weight of paraffin oil
o 3 to 8% by weight of cera alba
o 4 to 9% by weight of cetyl palmitate
o 3.5 to 6% by weight of sorbitan sesquioleate
the percentages by weight of the components are expressed, unless specified otherwise, as the weight of the component over the total weight of the aqueous and organic components.
According to some embodiments:
• the aqueous components may comprise
o 35 to 41 % by weight of purified water
o 0.3 to 2% by weight of propylene glycol, which percentage by
weight is expressed as the weight of the component over the total weight of the aqueous phase
o 0.02 to 0.04% by weight of methyl parahydroxybenzoate, which percentage by weight is expressed as the weight of the
component over the total weight of the aqueous phase
o less than 0.01 % by weight of propyl parahydroxybenzoate, which percentage by weight is expressed as the weight of the
component over the total weight of the aqueous phase
• the organic components may comprise
o 35 to 50% by weight of paraffin oil and vaseline wherein the
weight ratio of paraffin oil to vaseline varies and is greater than 1 ; o 3 to 8% by weight of cera alba
o 4 to 9% by weight of cetyl palmitate
o 3.5 to 6% by weight of sorbitan sesquioleate
the percentages by weight of the components are expressed, unless specified otherwise, as the weight of the component over the total weight of the aqueous and organic components.
According to a third aspect of the invention, an excipient is obtained by using one of the methods in accordance with the second aspect of the invention.
According to some embodiments of the invention, after the standing time and before the mixing again, active components can be added, in order to obtain a cosmetic or medicinal cream.
The methods according to the present invention have the advantage of producing a stable excipient with no or only minimal separation back into an aqueous and an organic phase during storage.
The excipient according to the invention may form a pharmaceutical carrier for the processing of one or more active ingredients which give the end product a
pharmaceutical or medicinal action.
When the excipient according to the invention is rubbed onto the skin, a cooling effect can occur as a result of the emulsion breaking open and/or the water evaporating out of the cream.
The excipient according to the invention, used as a carrier for a pharmaceutical or cosmetic cream, or as the cream itself, is found to be notably pleasant to use as a result of the cooling effect and good penetration through the skin barrier in the case of dry and/or dehydrated skin, yet a protective but not occlusive film still remains behind, ensuring a prolonged nutritive and therapeutic effect.
A third aspect of the invention provides a cosmetic or medicinal cream. The term
"cream" is used to denote a preparation which is a mixture of lipid phase and aqueous phase, stabilized with an emulsifier. A cream preferably has an optimum viscosity. It is possible for a component to be worked into the cream, either as a solution or as a suspension.
A fourth aspect of the invention provides a cosmetic or medicinal cream which
comprises 75% by weight to 100% by weight of excipient according to the first aspect of the invention. According to some embodiments of the invention, this cosmetic or medicinal cream may comprise 75% by weight to 100% by weight of excipient, which excipient has been obtained by one of the methods according to the second aspect of the invention.
According to some embodiments, the one or more active components may comprise one or more components selected from the group consisting of calcium pantothenate, rosemary essential oil, lavender spike essential oil, lemon essential oil and peppermint essential oil.
According to some embodiments, the one or more active components may comprise essential oil of Rosmarinus officinalis var. cineole.
Calcium pantothenate and rosemary essential oil are added for their tissue-restoring effect. It is preferable to use essential oil of Rosmarinus officinalis var. cineole, although var. camphor and/or verbenone or combinations of these variations are possible. The rosemary essential oil also has an anti-infectious action. Lavender spike (Lavendula spica) essential oil has a wound-healing effect, while lemon essential oil (produced from the peel) and peppermint essential oil both further reinforce the refreshing effect of the excipient.
According to some embodiments, the cream may comprise 75% by weight to 99.9% by weight of excipients, and 0.1 % by weight to 25% by weight of one or more active components, the percentages by weight of the components in the cosmetic or medicinal cream being expressed as the weight of the component over the total weight of the cosmetic or medicinal cream.
According to some embodiments, the one or more active components may comprise one or more components selected from the group consisting of calcium pantothenate, rosemary essential oil, lavender spike essential oil, lemon essential oil and peppermint essential oil.
According to some embodiments, the one or more active components may comprise calcium pantothenate.
According to some embodiments, the one or more active components may comprise lavender essential oil.
According to some embodiments, the one or more active components may comprise lavender essential oil and rosemary essential oil.
According to some embodiments, the one or more active components may comprise lavender essential oil, rosemary essential oil and lemon essential oil. According to some embodiments, the one or more active components may comprise lavender essential oil, rosemary essential oil, lemon essential oil and peppermint essential oil.
According to some embodiments, the one or more active components may comprise lavender spike essential oil.
According to some embodiments, the one or more active components may comprise essential oil of Rosmarinus officinalis var. cineole.
According to some embodiments, the one or more active components may comprise one or more zinc-containing compounds.
According to some embodiments, the one or more zinc-containing compounds may be zinc-containing compounds selected from the group consisting of zinc oxide, zinc citrate and zinc sulphate.
According to some embodiments, the one or more active zinc-containing compounds may form 0.1 % by weight to 10% by weight of the cosmetic or medicinal cream, which percentage by weight is expressed as the total weight of the zinc-containing compounds with respect to the weight of the cosmetic or medicinal cream.
Zinc-containing compounds may be encountered in various wound-healing, enzymatic systems, and are suitable for use in wound-healing cosmetic or medicinal creams, for example when treating bedsores.
A fifth aspect of the invention provides a method for producing a cosmetic or medicinal cream, which cosmetic or medicinal cream comprises an excipient and active compounds. The excipient is produced by one of the methods according to the second aspect of the invention. The one or more active components are added to the excipient and then stirred into the excipient.
A sixth aspect of the invention provides a method for producing a cosmetic or medicinal cream, which cosmetic or medicinal cream comprises an excipient and one or more active components. The excipient is produced by one of the methods according to the second aspect of the invention. During the production of the excipient, one or more active components are added.
According to some embodiments, after said leaving to stand and before said thorough mixing, one or more active components can be added.
According to some embodiments, said leaving to stand may be such that no action is taken during said leaving to stand, e.g. no heating or no other action. According to some embodiments, one or some of the plurality of active components are added as early as during the production of the excipient, and others of the plurality of active components are added after the said standing time and before the said thorough mixing. Preferably, calcium pantothenate is added as early as during the production of the excipient, more specifically at the beginning of the preparation of the excipient.
According to some embodiments, one or more active components, the aqueous and organic components can be combined before the preparation of the water-in-oil emulsion. According to some embodiments, the one or more active components may comprise one or more components selected from the group consisting of calcium pantothenate, rosemary essential oil, lavender spike essential oil, lemon essential oil and peppermint essential oil.
According to some embodiments, the one or more active components may comprise calcium pantothenate.
According to some embodiments, the one or more active components may comprise lavender essential oil.
According to some embodiments, the one or more active components may comprise lavender essential oil and rosemary essential oil.
According to some embodiments, the one or more active components may comprise lavender essential oil, rosemary essential oil and lemon essential oil.
According to some embodiments, the one or more active components may comprise lavender essential oil, rosemary essential oil, lemon essential oil and peppermint essential oil.
According to some embodiments, the one or more active components may comprise lavender spike essential oil.
According to some embodiments, the one or more active components may comprise essential oil of Rosmarinus officinalis var. cineole.
According to some embodiments, the one or more active components may comprise one or more zinc-containing compounds.
According to some embodiments, the one or more zinc-containing compounds may be zinc-containing compounds selected from the group consisting of zinc oxide, zinc citrate and zinc sulphate.
According to some embodiments, the one or more active zinc-containing compounds may form from 0.1 % by weight to 10% by weight of the cosmetic or medicinal cream, which percentage by weight is expressed as the total weight of the zinc-containing compounds with respect to the weight of the cosmetic or medicinal cream.
A seventh aspect of the invention provides cosmetic or medicinal cream, which excipient was obtained by one of the methods according to the sixth aspect of the invention. The one or more active components in the cosmetic or medicinal cream may, inter alia, be: essential oils, natural moisturizing factors, components for stimulating the generation of skin cells or for promoting the restoration of skin cells, and the like.
The excipients according to the present invention, and those obtained by the method according to the present invention, and creams based on these excipients, are therefore extremely suitable for the treatment of burns or for providing a cooling effect after the application of a tattoo to human or animal skin.
Moreover, the excipients according to the present invention, and those obtained by the method according to the present invention, and creams based on these excipients, can have a preventive use for preventing or reducing the risk of epidermolysis, erythema, irritation, pain or dryness of the skin, for example caused by radiotherapy. The excipients according to the present invention, and those obtained by the method according to the present invention, and creams based on these excipients, can also have a curative use for epidermolysis, erythema, irritation, burns, pain or dryness of the skin, for example caused by the application of tattoos, radiotherapy, bedsores, eczema, psoriasis, keratosis pilaris and similar disorders, or also as a lubricant for sexual contact, for example during sexual intercourse.
The above and other features, properties and advantages of the present invention will be explained with the aid of the following examples of embodiments. The description of these examples of embodiments is given by way of explanation, without being intended to restrict the scope of the invention.
Description of examples of embodiments
The present invention is described below making use of specific embodiments.
It should be noted that the term "comprising" as used for example in the claims is not to be interpreted in any limiting sense implying any restriction to the following elements, features and/or steps. The term "comprising" does not exclude the presence of other elements, features or steps. Thus, the scope of an expression "an object comprising the elements A and B" is not limited to an object which includes only the elements A and B. The scope of an expression "a method comprising steps A and B" is not limited to a method which includes only steps A and B.
In the context of the present invention, these expressions mean only that the relevant elements or steps constitute the elements or steps A and B for the purposes of the invention.
In the specification which follows, reference is made to "an embodiment" or "the embodiment". Such reference means that a specific element or feature, described on the basis of this embodiment, is included in at least this one embodiment. The occurrence of the term "in an embodiment" or "in one embodiment" at various places in this description, however, does not necessarily refer to the same embodiment, although it may refer to the same embodiment.
Furthermore, the properties or the features may be combined in any suitable way in one or more embodiments, as will be clear to a person skilled in the art.
An embodiment of an excipient according to the invention has a composition as follows:
Figure imgf000018_0001
Cetyl palmitate is an organic ester having the general formula R1-COO-R2, wherein R1 is a linear alkyl group having 15 carbon atoms and R2 is a linear alkyl group having 16 carbon atoms.
The components liquid paraffin, white beeswax, cetyl palmitate and sorbitan
sesquioleate together form the organic phase, which forms 80.79% by weight of the excipient. The aqueous phase, referred to above as aqua conservans, forms the remaining 19.21 % by weight. This aqueous phase or aqua conservans consists of:
Purified water 99.00 g
Propylene glycol 0.90 g
Methyl parahydroxybenzoate 0.08 g
Propyl parahydroxybenzoate 0.02 g
Total 100.00 g The excipient is formed by combining the ingredients in a suitable container, provided with a mixer, preferably a Stephan mixer and suitable for evacuation.
After the air has been evacuated from the container to a vacuum of around 0.25 bara, the ingredients are gently stirred using the Stephan(r) mixer while the temperature is increased to 80° Celsius. This is followed by high-shear mixing of the mixture for 3 minutes using the Stephan mixer, mixing at 3000 rpm. Thereafter, the emulsion is actively cooled to below 40° Celsius, if appropriate to room temperature. The vacuum is removed.
The excipient obtained in this way is then left to stand for a few hours, at least 2 but preferably 6 hours, and preferably approximately 24 hours.
Then, if appropriate the active components are added, and the excipient (together with any active components) again undergoes high-shear mixing in the Stephan mixer, mixing at 3000 rpm for a few minutes. This mixing may if appropriate takes place after the air has been evacuated from the container to a vacuum of around 0.25 bara.
This produces the excipient according to the invention.
The excipient is also mixed again if no further active components are added in order to obtain a cosmetic or medicinal cream. This is in order to obtain a homogeneous and stable cream or excipient with few or no lumps.
This excipient can be used, inter alia, for the production of an itch-reducing and/or burn /wound-repairing cream. The following different active components are added to the excipient in order to obtain a cream, i.e. a w/o emulsion, having the following composition:
Calcium pantothenate 1.00 g
Rosemary essential oil 0.50 g
Lavender spike essential oil 0.09 g
Lemon essential oil (peel) 0.37 g
Peppermint essential oil 0.37 g
Liquid paraffin/paraffinum liquidum 58.58 g
White beeswax/cera alba 7.61 g
Cetyl palmitate 9.51 g
Sorbitan sesquioleate/arlacel 83 2.97 g
Aqua conservans 19.01 g
Total weight 100 g The active components as listed above are added and mixed with the excipient.
Calcium pantothenate and rosemary essential oil are added for their tissue-restoring effect. It is preferable to use essential oil of Rosmarinus officinalis var. cineole, although var. camphor and/or verbenone or combinations of these variations are possible. The rosemary essential oil also has an anti-infectious action. Lavender spike (Lavendula spica) essential oil provides a wound-healing effect, while lemon essential oil (produced from the peel) and peppermint essential oil both further increase the refreshing effect of the excipient.
Another embodiment of an excipient according to the invention has a composition as follows:
Figure imgf000020_0001
The components liquid paraffin, white beeswax, cetyl palmitate and sorbitan
sesquioleate together form the organic phase, forming 61.55% by weight of the excipient. The aqueous phase, referred to above as aqua conservans, forms the remaining
38.45% by weight. This aqueous phase or aqua conservans is the same as that used in the first embodiment.
The excipient is formed using the same procedure as described above in connection with the first embodiment.
In a third embodiment, some of the liquid paraffin is replaced by vaseline, preferably white vaseline, in the same quantities by weight (i.e. 1 g of paraffin is replaced by 1 gram of vaseline). For example, half or a quarter of the paraffin can be replaced by vaseline. An excipient containing vaseline can be obtained by a similar or even identical preparation method to that explained in connection with the first and second
embodiments.
These excipients can be used for, inter alia, the production of an itching-reducing and/or burn/wound-repairing cream. The following different active components are added to the excipient in order to obtain a cream, i.e. a w/o emulsion, having the following
composition: The same quantity of essential oils are added, either after the excipient has been made or before the thorough mixing of the excipient, or added as an additional ingredient to the aqueous and organic components before the heating and emulsifying of these components.
It will be clear that, although the embodiments and/or the materials have been discussed for the purpose of providing embodiments in accordance with the present invention, various alterations or changes may be made without deviating from the scope and/or the spirit of the present invention.

Claims

Claims
1. Method for producing an excipient, which method comprises the steps of:
• providing aqueous components comprising purified water and a preservative; · providing organic components comprising
o natural or synthetic oils and/or fats;
o one or more waxes;
o one or more organic esters, each of the general formula R1 -COO-R2, wherein R1 and R2 are both, independently of one another, a linear or branched alkyl group having 1 1 to 30 carbon atoms;
o one or more sorbitan esters;
• preparing a water-in-oil emulsion by
o combining the aqueous and organic components
o heating to above 60°C,
o emulsifying, and
o cooling to less than 45°C;
• leaving the emulsion to stand for a period of longer than or equal to 2 hours;
• thoroughly mixing the emulsion obtained, so that the excipient is obtained.
2. Method according to Claim 1 , wherein the thorough mixing takes place at a
reduced pressure of less than or equal to 0.7 bara.
3. Method according to one of Claims 1 to 2, wherein during the preparation of a water-in-oil emulsion, first of all a mixture of the aqueous and the organic component is provided, which mixture of the components is emulsified.
4. Method according to one of Claims 1 to 3, wherein during the preparation of the emulsion the aqueous and organic components, if appropriate provided as a mixture, are heated to a temperature of between 75°C and 80°C.
5. Method according to one of Claims 1 to 4, wherein the heating takes place with gentle stirring.
6. Method according to one of Claims 1 to 5, wherein the mixture, after said heating, is cooled back down until a temperature of between 40°C is reached.
7. Method according to one of Claims 1 to 6, wherein the cooling takes place with gentle stirring.
8. Method according to one of Claims 1 to 7, wherein the cooling takes place with the aid of forced cooling. Method according to one of Claims 1 to 8, wherein during the cooling the temperature of the emulsion drops at a rate of from 0.5 to 1.5°C per minute. Method according to one of Claims 1 to 9, wherein during the cooling the emulsion is scraped off the wall of the mixer.
Method according to one of Claims 1 to 10, wherein the mixture, after said heating, is emulsified in a mixer at a speed of more than 1500 rpm.
Method according to one of Claims 1 to 1 1 , wherein the emulsifying takes place over a period of from 2 to 10 minutes.
Method according to one of Claims 1 to 12, wherein said steps of heating, emulsifying and cooling in the preparation of a water-in-oil emulsion take place under a vacuum of less than or equal to 0.7 bara.
Method according to one of Claims 1 to 13, wherein after said cooling the emulsion is left to stand for a period of at least 4 hours, after which the emulsion is stirred through again.
Method according to one of Claims 1 to 14, wherein the stirring-through takes place over a period of from 0.5 to 10 minutes.
Method according to one of Claims 1 to 15, wherein the organic and aqueous components comprise 10 to 73% by weight of aqueous components, which aqueous components comprise the following components:
o 0.01 % by weight to 2.25% by weight of preservative; o 97.75% by weight to 99.99% by weight of purified water; and wherein the organic components comprise the following components:
o natural and/or synthetic oils and/or fats;
o 1 % by weight to 15% by weight of one or more waxes; o 1 % by weight to 15% by weight of one or more organic esters, each of the general formula R1-COO-R2, where R1 and R2 are both, independently of one another, a linear or branched alkyl group having 1 1 to 30 carbon atoms;
o 1 % by weight to 8% by weight of sorbitan esters;
which percentages by weight of the aqueous components are expressed as the weight of the component over the total weight of the aqueous components, the percentages by weight of the organic components are expressed as the weight of the component over the total weight of the organic and aqueous components, and the percentage by weight of the aqueous components together is expressed as the weight of the aqueous phase over the total weight of the organic and aqueous components.
Method according to one of Claims 1 to 6, wherein
• the aqueous components comprise
o 16 to 20% by weight of purified water
o 0.8 to 2% by weight of propylene glycol, which percentage by weight is expressed as the weight of the component over the total weight of the aqueous phase
o 0.07 to 0.09% by weight of methyl parahydroxybenzoate, which percentage by weight is expressed as the weight of the component over the total weight of the aqueous phase
o less than 0.03% by weight of propyl parahydroxybenzoate, which percentage by weight is expressed as the weight of the component over the total weight of the aqueous phase
• the organic components comprise
o 53 to 63% by weight of paraffin oil
o 7 to 9% by weight of cera alba
o 7 to 12% by weight of cetyl palmitate
o 2 to 4% by weight of sorbitan sesquioleate
the percentages by weight of the components in the organic and aqueous phase are expressed, unless specified otherwise, as the weight of the component over the total weight of the excipient.
Method according to one of Claims 1 to 16, wherein the organic and aqueous components comprise more than 15% by weight of aqueous components.
Method according to Claim 18, comprising:
• the aqueous components
o 35 to 41 % by weight of purified water
o 0.3 to 2% by weight of propylene glycol, which percentage by weight is expressed as the weight of the component over the total weight of the aqueous phase
o 0.02 to 0.04% by weight of methyl parahydroxybenzoate, which percentage by weight is expressed as the weight of the component over the total weight of the aqueous phase o less than 0.01 % by weight of propyl parahydroxybenzoate, which percentage by weight is expressed as the weight of the component over the total weight of the aqueous phase
• the organic components
o 39 to 50% by weight of paraffin oil
o 3 to 8% by weight of cera alba
o 4 to 9% by weight of cetyl palmitate
o 3.5 to 6% by weight of sorbitan sesquioleate
the percentages by weight of the components are expressed, unless specified otherwise, as the weight of the component over the total weight of the aqueous and organic components.
Method according to Claim 18, comprising:
• the aqueous components
o 35 to 41 % by weight of purified water
o 0.3 to 2% by weight of propylene glycol, which percentage by weight is expressed as the weight of the component over the total weight of the aqueous phase
o 0.02 to 0.04% by weight of methyl parahydroxybenzoate, which percentage by weight is expressed as the weight of the component over the total weight of the aqueous phase
o less than 0.01 % by weight of propyl parahydroxybenzoate, which percentage by weight is expressed as the weight of the component over the total weight of the aqueous phase
• the organic components
o 39 to 50% by weight of paraffin oil and vaseline wherein the
weight ratio of paraffin oil to vaseline varies and is greater than 1 ; o 3 to 8% by weight of cera alba
o 4 to 9% by weight of cetyl palmitate
o 3.5 to 6% by weight of sorbitan sesquioleate
the percentages by weight of the components are expressed, unless specified otherwise, as the weight of the component over the total weight of the aqueous and organic components.
Method for producing a cosmetic or medicinal cream, which cosmetic or medicinal cream comprises an excipient and one or more active components, wherein an excipient is produced according to one of Claims 1 to 20, and wherein one or more active components are added to the excipient and then stirred into the excipient.
Method for producing a cosmetic or medicinal cream, which cosmetic or medicinal cream comprises an excipient and one or more active components, wherein an excipient is produced according to one of Claims 1 to 20, and wherein, during the production of the excipient, one or more active components are added.
Method for producing a cosmetic or medicinal cream according to Claim 22, wherein, during the production of the excipient, calcium pantothenate is added. Method according to Claim 22 or 23, wherein, after said leaving to stand and before said thorough mixing, the one or more active components are added. Method according to Claim 22 or 23, wherein one or more active components, the aqueous and organic components are combined before the preparation of the water-in-oil emulsion.
Method according to one of Claims 21 to 25, wherein the one or more active components comprise one or more components selected from the group consisting of calcium pantothenate, rosemary essential oil, lavender spike essential oil, lemon essential oil, peppermint essential oil and zinc-containing compounds.
Method according to one of Claims 21 to 26, wherein the one or more active components comprise calcium pantothenate.
Method according to one of Claims 21 to 27, wherein the one or more active components comprise lavender essential oil.
Method according to one of Claims 21 to 28, wherein the one or more active components comprise lavender essential oil and rosemary essential oil.
Method according to one of Claims 21 to 29, wherein the one or more active components comprise lavender essential oil, rosemary essential oil and lemon essential oil.
Method according to one of Claims 21 to 30, wherein the one or more active components comprise lavender essential oil, rosemary essential oil, lemon essential oil and peppermint essential oil.
Method according to one of Claims 21 to 31 , wherein the one or more active components comprise lavender spike essential oil.
33. Method according to one of Claims 21 to 32, wherein the one or more active components comprise essential oil of Rosmarinus officinalis var. cineole.
34. Method according to one of Claims 21 to 33, wherein the one or more active components comprise one or more zinc-containing compounds.
35. Method according to Claim 34, wherein one or more zinc-containing compounds are zinc-containing compounds selected from the group consisting of zinc oxide, zinc citrate and zinc sulphate.
36. Method according to one of Claims 34 to 35, wherein the one or more active zinc-containing compounds form 0.1 % by weight to 10% by weight of the cosmetic or medicinal cream, which percentage by weight is expressed as the total weight of the zinc-containing compounds with respect to the weight of the cosmetic or medicinal cream.
PCT/EP2015/075866 2014-11-06 2015-11-05 Method for preparing an excipient suitable for preparing creams WO2016071474A1 (en)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1599010A (en) * 1977-05-20 1981-09-30 Merck Patent Gmbh Cosmetic compositions for skin tanning
WO2005018599A1 (en) * 2003-08-20 2005-03-03 Avon Products, Inc. Mascara composition
DE202005011257U1 (en) * 2005-07-14 2006-08-24 Schwan-Stabilo Cosmetics Gmbh & Co. Kg Cosmetic preparation in form of oil-in-water emulsion, useful for coloring keratin materials e.g. hair, comprises wax component, fatty acid, polyvalent alcohol, film former, non-ionizable emulsifying agent and gel
JP2014122183A (en) * 2012-12-21 2014-07-03 Kose Corp Dna damage inhibitor

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1599010A (en) * 1977-05-20 1981-09-30 Merck Patent Gmbh Cosmetic compositions for skin tanning
WO2005018599A1 (en) * 2003-08-20 2005-03-03 Avon Products, Inc. Mascara composition
DE202005011257U1 (en) * 2005-07-14 2006-08-24 Schwan-Stabilo Cosmetics Gmbh & Co. Kg Cosmetic preparation in form of oil-in-water emulsion, useful for coloring keratin materials e.g. hair, comprises wax component, fatty acid, polyvalent alcohol, film former, non-ionizable emulsifying agent and gel
JP2014122183A (en) * 2012-12-21 2014-07-03 Kose Corp Dna damage inhibitor

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