NZ523505A - Composition containing ceramic calcium phosphate particles for skin application - Google Patents

Abstract

Active materials such as herbal extracts, allantoin, citric acid, vitamins, anti-inflammatory agents, sun blocking agents, emollients or antimicrobial agents are delivered to the skin of a subject in a composition comprising ceramic calcium phosphate particles, such as ceramic hydroxyapatite in a vehicle for topical application.

Description

New Zealand Paient Spedficaiion for Paient Number 523505 52 36 0 5 NEW ZEALAND PATENTS ACT, 1953 No: Divided out of No. 513032 Date: Dated 13 June 1996 COMPLETE SPECIFICATION METHODS OF DELIVERING MATERIALS INTO THE SKIN, AND COMPOSITIONS USED THEREIN I, ZAHRA MANSOURI, a US citizen of 82 Pelican Lane, Redwood Shores, California 94065, United States of America, do hereby declare the invention for which I pray that a patent may be granted to me, and the method by which it is to be performed, to be particularly described in and by the following statement: (followed by page la) INTELLECTUAL PROPERTY OFFICE OF N.Z. - 7 JAN 2003 RECEIVED Field of the Invention The invention relates generally to a method of making skin care products and to methods of using such products. This invention also relates to skin care products which moisturize the skin and prevent excessive drying of the skin.

This invention further relates to skin care products which are antimicrobial and help prevent infection by pathogenic microorganisms, and which mitigate against the spread of such pathogens.

In particular, the invention is concerned with formulations for cleansing and moisturizing skin which are antimicrobial, have a water base, and comprise a micro-carrier to deliver materials into the skin. The formulations are free of alcohol, lanolin, fragrance, petroleum-based components or animal by-products.

This invention still further relates to skin cleansing products which are antimicrobial, and non-irritating and non-drying to the skin after frequent use. The instant invention further relates to skin moisturizing products which are antimicrobial, non-greasy, and which rapidly penetrate the outer layers of the skin, and which form a shield to prevent loss of moisture from the skia Background of the Invention Excessive drying of the skin is a common problem which is often the result of exposure to wind, sun and low humidity, or a combination of these factors. Frequent washing of the hands can also result in excessive drying. This is particularly true if abrasive soaps, alcohol-based products and other harsh chemicals are used for cleansing. la Skin that has been excessively dried is not only unsightly, but also tends to slough off excessively and to crack, leading to abrasions of the skin surface. Because the skin serves a key role as a physical barrier to the entry of parasites and pathogens, excessive drying can lead to a breach of the barrier and infection by pathogenic bacteria and fungi Thus cracks or openings in the skin serve as a portal of entry for pathogens and potential pathogens. Even organisms that are normally considered to be non-pathogens can result in opportunistic infection in immunologically compromised individuals. Infections may be mild or severe and may be localized to the initial site(s) of infection or may be systemic and spread throughout the body. Such spread may occur by direct extension to contiguous tissues, or by way of the lymphatics and ultimately by way of the bloodstream.

Thus, the frequent application of many prior art skin cleansing compositions contributes to skin damage, and therefore may indirectly increase the risk of skin infections. Many prior an skin moisturizers contain petroleum products which dissolve latex gloves as worn by workers in diverse fields, including the health care field.

Similarly, many prior art moisturizers contain animal-derived products, such as lanolin. It is known that certain animal-derived products may cause skin allergies and/or dermatitis.

Skin care products of the instant invention allow for frequent use of the products to protect the skin and prevent damage due to drying. In so doing, skin care products under the invention help to prevent infection of the skin itself and entry of pathogens through the skin where they may infect underlying tissues.

Skin cleansing products of the instant invention are formulated not only to accommodate continued frequent use without causing drying and cracking of the skin but also, by the inclusion of one or more antimicrobial agents, to prevent the transmission and spread of pathogenic or potentially pathogenic microorganisms.

Skin care products of the instant invention are formulated to implement the absorption of the composition by the skin. In particular, sldn care products of the instant invention comprise an absorption implementing micro-carrier material. The absorption implementing micro-carrier material of choice under the invention is a form of ceramic hydroxyapatite. Ceramic hydroxyapatite under the invention is in the form of macroporous spheres of predetermined size range, and ts chemically pure. It is formed by the agglomeration of crystals of hydroxyapatite, of 0.05 to 0.10 micrometer size range, into spherical particles which are then sintered at high temperature.to provide mecharacaOy-physicaliy- and chemically-stable spheres. Ceramic hydroxyapatite which is useful in the practice of the instant invention is exemplified by that manufactured by the Asahi Optical Company, Tokyo. Ceramic hydroxyapatite has been widely used as a chromatographic separation medium (see, for example, R. Kasai et al. J. Chromatography 407,20S (1987); S. Tstmi et al. J. Immunol. Methods 106,169 (1988); T. Kadoya et al. J. Liquid Chromatography 9,3543 (1986); T. Kadoya et al. J Liquid Chromatography 11,2951 (1986).

Apart from ceramic hydroxyapatite referred to above, hydroxyapatite has been produced in several other fbnns, each with a characteristic particle morphology, size distribution and surface structure, as observed by scanning electron microscopy (T Kadoya et al. J. liquid Chromatography 9,3543 (1986).

Hydroxyapatite has also been ascribed various non-chromatographic applications. For example, JP 254415 discloses cosmetic materials containing spherical hydroxyapatite. JP 266066 teaches a melanin-lightening composition including ethyl alcohol and sodium hydroxide. JP 007409 teaches the use of hydroxyapatite for the selective removal of protein from the body surface. JP 179074 discloses the use of hydroxyapatite as an abrasive, to assist in the cleaning of inanimate surfaces. JP 238429 discloses a blending agent, comprising polystyrene beads coated with hydroxyapatite.

SUMMARY OF THE INVENTION Skin moisturizing products of the present invention are formulated to protect the skin and maintain the skin in a healthy condition. Skin moisturizing products of the present invention are also formulated to be antimicrobial, thereby further reducing the risk of 10 infection by pathogens. Furthermore, the antimicrobial properties of moisturizing products of the invention reduce the risk of transmission of pathogenic and potentially pathogenic microorganisms. Skin care products of the instant invention are further formulated to rapidly penetrate the skin, whereby ingredients of the formulation are more effective.

The compositions and methods of the instant invention may be used to protect the 15 integrity of the skin. The compositions and methods of the instant invention may also be used to promote and maintain healthy skin The skin cleansing compositions of the instant invention may be used frequently to prevent the spread of pathogenic or potentially pathogenic microorganisms. The skin cleansing compositions of the instant invention may also be used frequently on a continual baas with minimal risk of causing drying, irritation, 20 inflammation, or damage to the akin. The antimicrobial skin moisturizing compositions of the instant invention may be used to minimize the risk of irritation and infection. Theskin cleansing and moisturizing products of the instant invention do not dissolve latex and are fully compatible with the use of latex gloves. Thus, the skin moisturizing compositions of 4 the instant invention may be used with latex gloves without the risk of dissolution of the latex or other damage to the latex barrier.

The methods and compositions of the invention may further be used to implement the rapid absorption of biologically active components by the slrin. In accordance with one 5 embodiment of the invention, the slrin moisturizer composition may be used as a single application, or application may be repeated periodically over an extended time period as needed.

In accordance with another method of the invention, a skin moisturizing composition, under the invention, may be applied specifically or preferentially to the point 10 or area of a minor cut, crack, or abrasion of the skin. Such application may protect the epidermis and the dermis from further damage and promote healing, and/or prevent infection of the skin.

In another aspect, the present invention provides a composition for delivering at least one active agent to the skin of a subject, said composition comprising: at least one active agent loaded into a micro carrier selected from the group consisting of hyaluronic acid and chemically pure ceramic hydroxyapatite.

The above-mentioned aspects of the invention are the subject of New Zealand Patent Specification No. 311461, while the following aspects of the invention are the subject of New Zealand Patent Specification No. 513032.

In a particular aspect, the present invention provides a non-irritating lotion composition comprising: an anti-microbial agent in an amount sufficient to kill microorganisms on said skin without substantially irritating said skin; and at least one emollient.

In another aspect, the present invention provides a water-based cleanser composition comprising: an anti-microbial agent in an amount sufficient to kill microorganisms on said skin; a non-irritating amount of a detergent; and at least one herbal extract. (followed by page 5a) In still another particular aspect, the subject of this specification, the present invention provides & composition of matter for application to the skin, said composition comprising: ceramic calcium phosphate particles; and a physiologically and cosmetically acceptable vehicle; wherein said composition is suitable for topical application to the skin.

DETAILED DESCRIPTION OF THE INVENTION The skin or integumentary system is an essential, physiologically and anatomically specialized boundary lamina. It covers the entire external surface of the body. The total area of skin in an adult is between 12 to 2.2 m\ and comprises about 10% of the total body mass, making it the largest organ of the human body. Functionally, the skin acts as an interface between the internal and external environment, and fulfills thermoregulatory, sensory, and other functions, as well as playing a key role as a highly effective physical barrier against infectious agents and dehydration. The skin also acts as a barrier against mechanical, chemical, osmotic, thermal and photic damage.

The condition of the skin is generally considered, by medical practitioners and lay people alike, to reflect the state of health, age and other aspects of life of an individual. 5a Histologically, three major tissue layers are identified The uppermost layer, the epidermis, is a relatively thin stratified squamous epithelium which is itself composed of five strata. Subjacent to the epidennis is the dermis, a dense fibroelastic connective tissue stroma. The third layer, lying beneath the dermis is the subcutaneous layer composed of areolar and fatty connective tissue.

There are three basic cell types in the epidermis: keratinocytes which produce keratin, melanocytes which are involved in pigmentation, and Langerhans cells which aid the immune system by intercepting foreign bodies in the skin. In the epidennis a mitotic layer at the base provides keratinocytes which continuously replace those shed at the skin surface.

The epidermis can be divided into layers according to the stage of maturation of keratinocytes within it. These layers are, from deep to superficial, as follows: stratum basale, stratum spinosum, stratum granulosum, stratum lucidum and stratum corneum. The first three of these layers are metabolically active, while the two upper layers which have attained terminal keratinization constitute the cornified zone. Cells of the stratum coraeum eventually become detached from the epidermal surface and are replaced from below. Typically the time taken for a newly-formed keratinocyte to pass to the surface and be shed ranges from 45- 75 days. However, under certain pathological conditions of the skin, turnover rates are much higher. As a result keratinization is incomplete and the normal barrier functions of the skin are lost.

The dermis comprises a strong yet flexible layer which consists primarily of collagen. This layer, which contains naves, blood vessels, hair follicles, sebaceous glands and apocrine glands, fulfills vital roles in thermoregulation and sensory perception. The sebaceous glands produce sebum, a natural lipid material which helps to prevent drying, cricking and excessive shedding of the outer layers of the skin.

Compositions for cleansing and moisturizing the skin according to the invention comprise an antimicrobial agent, an emollient and a micro-carrier in combinations as described below.

L Antimicrobial component.

The present invention provides skin cleansing and moisturizing compositions, comprising an antimicrobial agent which functions to inhibit the growth of pathogemc or potentially pathogemc bacteria and fiingi, or to kill such organisms. Thus the antimicrobial agent may be bacteriostatic, bacteriocidal, fungistatic or fungicidal in its action.

A preferred antimicrobial agent for use under the invention i& Triclosan. This agent used in the formulation has been found effective against the whole genera, of microoranisms, (for example: bacteria, fiingi, Pseudomonas aeruginosa, Pseudomonas capacia. Staphylococcus aureus, Escherichia coli, Candida albicans, Aspergillus niger. Salmonella typhimurium, etc...). Thus, the antimicrobial component of the composition is effective in both preventing infection via the skin and in preventing the spread and transmission of pathogenic microorganisms. The antimicrobial agent is normally present in an amount of from 0.001-5% by weight, preferably from 0.05-2% by weight, and more preferably from 0.1-1% by weight. iL Water activity depressant Compositions according to the invention may also comprise one or more water activity depressants, the function of which is, in part, to inhibit the growth of microorganisms during product storage and to preserve the product. Water activity depressants, with or without the inclusion of an antibiotic chemical, help to prevent the 7 ♦The active agent in Triclosan is 5-chloro-2-(2,4-dich!orophenoxy)phenol. growth of spoilage organisms. Examples of water activity depressants include sorbitol, propylene glycol, sugars, and alkali metal salts, including carboxylates, haHdes, and sulfates. A preferred water activity depressant is sorbitol. The sorbitol component of the composition is preferably present in a concentration of from 1-20% by weight, moire preferably from 1-10% by weight, and most preferably from 1-2% by weight. Mfcrc-ttrricr.

Compositions under the invention may also comprise one or more micro-carriers. The junction of such a micro-carrier is, in part, to implement the uptake of the product by the skin. Uptake of the product prevents excessive loss of moisture from the skin surface and promotes product contact with the metabo&calty active cells of the dermis and epidermis beneath the cornified zone of the stratum lucidum and stratum coraeum.

A preferred micro-carrier is ceramic hydroxyapatite. Ceramic hydroxyapatite also functions as an unbound/excess lipid remover and anti-microbial function enhancer.

Ceramic hydroxyapatite used under the invention is a form of chemically pure calcium phosphate (molecular formula Ca^PO^OHQj), which is produced as spheres with a controlled diameter. Preferably the median diameter of ceramic hydroxyapatite under the invention is in the range of 1-10 micrometers, more preferably in the range of 2-6 micrometers. Ceramic hydroxyapatite spheres are manufactured by the agglomeration of small crystals (50-100 tun size range) followed by sintering at high temperature. As a result of this process, each sphere is porous and can act as a miniature sponge. This characteristic of ceramic hydroxyapatite spheres allows it to absorb, cany, and subsequently release components of the composition to which it has been bound.

Ceramic hydroxyapatite having a mean paitide diameter in the range of 2-6 micrometers can act as an efficient absorption implementing agent for liquid phase S materials. The carrier and absorption enhancing properties of ceramic hydroxyapatite is due to both its porosity and its affinity for various substances. For example, ceramic hydroxyapatite has the ability to bind water, charged molecules, lipids, proteins, and nucleic acids. The porous nature of ceramic hydroxyapatite allows it to bind and then slowly release a relatively large volume of liquid-phase-bound materials.

Due to the small spherical nature of the ceramic hydroxyapatite particles, it may also act as a lubricant.

Conventional (i.e. non-ceramic) hydroxyapatite is known to bind to biological molecules, including proteins, lipoproteins, lipids and nucleic acids ((see, for example, D. Josic et aL BioL Chem. Hoppe-Seyler 372,149 (1991); K.J. Primes et al J. Chromatography, 236,519 (1982); S. Hjerten, Biochim. Biophys. Acta, 31,216 (1959); G. Beraardi and W.H. Cook, ibid. 44,96 (1960); R.K. Main et al. J. Am. Chem. Soc. 81,6490 ((1959); A. Tiselius et al. Arch. Biochem. Biophys. Acta 65,132 (1956)). However, in comparison to ceramic hydroxyapatite; conventional hydroxyapatite is produced as particles which are more irregular in shape and in size, and also more fragile. Ceramic hydroxyapatite is also superior to conventional hydroxyapatite in that ceramic hydroxyapatite spheres are resistant to high temperature and pressure, and are much more physically stable titan conventional hydroxyapatite. (T. Kadoya et al J. Liquid Chromatography, 9,3543 (1986). This physical stability allows for the agitation or mixing of ceramic hydroxyapatite without disintegration of the particles. Ceramic hydroxyapatite is also more stable chemically than conventional hydroxyapatite, being stable for at least five years when stored at room temperature in dry or hydrated form.

Because hydroxyapatite binds lipids, see, e.g., KJ. Primes et al. J-Chromatography, 236, 519 (1982)), ceramic hydroxyapatite, under the invention, may bind to lipid constituents of the instant compositions, as well as to lipid components of the skin. Ceramic hydroxyapatite has the additional advantage in tike context of the present invention of binding to protons much more strongly than does conventional hydroxyapatite. In holding to proteins of the skin, ceramic hydroxyapatite under the invention can act as a bridge between the proteins of skin cells and bound lipids. The resulting layer of bound lipid molecules can serve as an effective protective film to prevent dehydration of and damage to, the skin.

Finally, ceramic hydroxyapatite, due to its propensity to bind to biological molecules, may bind to various surface components of microbial cells and promote the immobilization and inactivation of microorganisms.

Ceramic hydroxyapatite is preferably present in compositions under the invention at a concentration of from 0.001-10%, by weight, more preferably 0.01-5% by weight, and even more preferably from 0.05-1% by weight. iv. Vehicle or Delivery System The compositions according to the invention also comprise a liquid, solid or semi-solid physiologically and cosmeceutically acceptable vehicle or carrier. A suitable vehicle, under the invention, may act variously as a solvent, diluent or dispenant for the constituents of the composition, and allows for the uniform application of the constituents into the skin at an appropriate dilution. It wiE be apparent to the skilled artisan that the range of possible vehicles is very broad. In general, compositions according to this invention may comprise at least one physiologically and cosmeceutically acceptable vehicle.

Vehicles that can be used in compositions under the invention may be Squids or solids, including emollients, various solvents, powders, and humectants. Carriers may be used singly or in combination. Suitable carriers may include, but are sot limited to, the following examples: castor oil, ethylene glycol monobutyi ether, diethylene glycol monoethyl ether, corn oil, dimethyl sulfoxide, ethylene glycol, isopropanol, soybean oil, glycerin, soluble collagen, zinc oxide, titanium dioxide, talc, Kaolin, hyaluronic acid.

The active constituents of the skin care compositions according to the invention may be soluble or insoluble in a liquid earner. If the active constituents are soluble in the carrier, the carrier acts as solvent for the active ingredient. If the active constituents are insoluble in the carrier, they are dispersed in the carrier by means of; for example, a suspension, emulsion, gel, cream or paste, and the like. Various oils, such as vegetable oils obtained from any of com, sunflower, saf&ower, soybean, canola, and the like, may 11 also be used as a vehicle, either alone or in combination; Various oils may also be used in combination with water following emulafication. v. Water In general, compositions according to this invention nay comprise water. When water is used in the invention, preferably the water is daonized. Water is a preferred solvent and/or diluent for the active constituents in the compositions of the present invention. Water may be used singly or in combination with another solvent and/or diluent. vLBiuasEtint Compositions under the invention may optionally comprise one or more humectants, for example: dibutyi phthalate, gelatin, glycerin, soluble collagen, sorbitol, sodium 2-pyrroIidone-5-carboxylate A preferred humect ant, under the invention, is glycerin. riL Eosliisni Compositions under the invention may optionally comprise one or more emollients, for example, butane-1,3-diol, ceryl palmitate, dimethylpolysiloxane, 12 glyceryl monoridnoleate, glyceryl monosteaiate, isobutyi paimitate, isocetyl stearate, isopropyl paimitate, isopropyl stearate, butyl stearate, isopropyl Iaurate, hexyl Iaurate, decyl oleate, isopropyl myristate, lauryl lactate, octadecan-2-ol, caprylic triglyceride, capric triglyceride, palmitic acid, polyethylene glycol, propane-l,2-diol, stearic acid, methylene glycol, sesame oil, coconut oil, safflower oil, isoamyl Iaurate, nonoxynol-9, panthenol, hydrogenated vegetable oil, tocophcryl acetate, tocopheryl linoleate, allantoin, propylene glycol, arachis oil, castor oil, iso stearic acid, palmitic acid, isopropyl linoleate, lauryl lactate, myristyl lactate, decyl oleate, myiistyi myristate. viiL SnqP^hmgAgCTf Tbe compositions, according to the invention, may optionally comprise a sun blocking agent. A preferred sun blocking agent under the invention is octyt paimitate. ii. Anti-inflammatory Agent The compositions, according to tbe invention, may optionally comprise an anti-inflammatory agent. Preferred anti- inflammatory agents, under the invention, include extracts of Aloe vera, panthenol, tocopheryl acetate, and tocophcryl linoleate. 14 x. Preservative Other than water activity depressants and antimicrobial components, such as Triclosan, the compositions, according to the invention, may optionally comprise one or more preservatives such as polymethoxy bycyclic oxazolidine, methyl paraben, propyl paraben and DMDM hydantdn. iL Viscosity Enhancer or Thickening Agent The compositions, according to the invention, may optionally comprise a viscosity enhancer or thickening agent Viscosity enhancers of various classes may be chosen, including microbial polysaccharides, such as xanthan gum; cellulose derivatives, such as methylcellulose, carboxymethylcellulose, hydroxypropylmethylcellulose and hydroxyethyiceflulose; and sorbitol. xii. Emulsificr The compositions, according to the invention, may also comprise one or more emulsifiers. Preferred emulsifiers under the invention include: polysorbate-60, sorbitol, and sortman stearate. Such emulsifiers may be incorporated into the instant compositions singly or in any combination. xiii. Vitamins. Proteins arid Derivatives Thereof The compositions, according to the invention, may also comprise one or more ingredients which are vitamins, proteins or derivatives thereof other than those which may be present in otter components of the instant compositions Vitamins, proteins or derivatives thereof may be incorporated into the compositions of the invention either singly or in an combination. Examples of vitamins, proteins or derivatives thereof which may be included in the compositions under the invention include: tocopheryl acetate, tocopheryl linoleate, panthenol, wheat oligosaccharides and hydrolyzed wheat proteins. riv. Surfactant The compositions, according to the invention, may optionally comprise one or more surfactants. Surfactants used under the invention are preferably mild or very mild detergents. Preferred surfactants under the invention include: sodium iaureth sulfate and cocamide DEA. iv. Citric add The compositions according to the invention may also comprise citric acid, a naturally occurring compound present in both plant and animal cells as an intermediate of the Tricarboxylic acid cycle and in relatively high concentrations in citrus fruit. It is preferred that only plant and no animal byproducts are used. Under the invention, citric add is preferably present in a concentration of from 0-10% by weight, more preferably from 0-5% by weight, and most preferably from 0 to about 2% by weight The concentration of citric add may be adjusted slightly to provide a suitable pH. ivi. AHantoin The composition according to the invention may also comprise allantoic Allantoin is a natural product which occurs in both plants and animals, plants being preferable here. Allantoin is considered to stimulate cell proliferation and promote healing of the skin. The allantoin component of the composition is preferably present in a concentration of from 0-5% by weight, preferably from 0.01-2% by weight xviL Aloe vera component* ;The composition according to die invention also comprises a cosmetically and physiologically acceptable preparation obtained from tbe Aloe vera plant. Constituents of this plant are reported to prevent infection, promote wound healing, and to have antifungal properties. The gd obtained from Aloe vera leaves are said to be useful for dry ;16 ;skin conditions. The Aloe vera gel has also been recommended for treating fungal skin infections. The Aloe vera component of the composition is preferably present in a concentration of from 0.1-10% by weight, more preferably from 0.2-5% by weight, and most preferably from 0.5-1.5% by weight. ;xvBi. Natural Scents ;The composition according to the invention also comprises one or more natural scents. Natural scents added to the skin care compositions under the invention impart a pleasant, mild scent, and are formulated to avoid any negative impact on the skin such as drying, irritation or allergies. For example, natural scents may be obtained from plant materials in tbe form of essential oils by the process of fractional distillation, thus avoiding extraction procedures involving organic solvents. ;g*. Other na"t or Msrfrtl fotrerts The compositions according to the invention also comprise one or more natural plant or herbal extracts, including matricaria extract, comfrey extract, and cucumber extract. Under the invention, natural plant extracts are preferably present in a concentration of from 0-5% by weight, more preferably from 0-2% by weight, more preferably from 0 to about 0.8% by weight.

Medicinal use of the herb known as comfrey dates back at least to the time of the Ancient Egyptian civilization, and it has been widely used as a herbal remedy for hundreds if not thousands of years (see, for example, P. Ody (1993) The Complete Medicinal Herbal, Doriing Kindersley, London, New York, Stuttgart). Nicholas Culpeper, an Elizabethan herbalist listed comfrey as bdng amongst the most effective natural healing agents. The English physician Charles J. Macalister, M.D. used comfrey topically to treat serious skin lesions — with remarkable results (C. J. Macalister (1936) Narrative of an 17 Investigation Concerning an Ancient Medicinal Remedy and its Modern Utilities, Republished 1955, The Lee Foundation for Nutritional Research, Milwaukee, WI). One constituent of comfrey considered to be responsible for its medicinal properties is allantoin.

Matricaria is another berb that has been used medicinally since antiquity. Among the skin conditions for which Matricaria has been recommended are: various sores and wounds, eczema and inflammation.

Without being limited by any theory of mode of action of any of these constituents, it is believed that topical use of the instant skin care compositions not only helps to maintain treated skin in a healthy condition, but also promotes healing df dry, cracked sore, or damaged skin. sx.j2g In the case of the skin cleanser composition, the preferred pH is in the range of 6.0 to 8.0; more preferably the pH is in the range of 6.5 to 7.5.

The preferred pH of the skin moisturizer composition is in the range of 5.0 to 8.0; more preferably the pH is in the range of 6.0 to 7.0.

In one embodiment, the composition of a skin moisturizer under the invention comprises for example, a humectant, an emollient, a earner or micro-carrier, an antimicrobial agent, an antimicrobial function enhancer, an unbound/excess lipid remover, a vitamin, protein or derivative thereof plant extract, natural scents, and water.

In a preferred embodiment, the composition of a skin moisturizer under the invention comprises, for example, the following: a humect ant, such as glycerin; 18 a carrier or micro-carrier, such as hyaluronic acid or ceramic hydroxyapatite, an antimicrobial function enhancer, such as ceramic hydroxyapatite, an unbound/excess lipid remover, such as ceramic hydroxyapatite; an emollient, such as glyceryl stearate, allantoin, or nonoxynol-9; an antimicrobial agent, such as Triclosan; an anti-inflammatory agent, such as Aloe vera extract, or panthenol; an emulsifier, such as polysorbate 60; a preservative, such as DMDM hydantoin; a sun block agent, such as octyl paimitate; a vitamin or derivative thereof, such as tocopheryl acetate or wheat oligosaccharides; a proton or derivative thereof such as hydrolyzed wheat protons; a plant extract, such as comfrey extract, or Matricaria extract; a natural seem, such as oil of citrus fruit; and water.

Methods, under the invention, for preparing a skin moisturizer composition comprise the steps of formulating the constituents of each composition as four separate Phases, and subsequently combining each Phase.

The skin moisturizer composition may be formulated according to the following Example. 19 EXAMPLE 1 Formulation of Skin Moisturizer Composition a) Phase IM A suitable volume of deionized water at ambient temperature was metered into a first stainless steel vessel or tank, and the mixer was turned on. Ingredients of Phase LM, comprising nonoxynol-9, Aloe vera extract and panthenol were then added, and the mixture was slowly heated to a predetermined temperature. Preferably Phase 1M of the composition is heated to a predetermined temperature in the range of 30 to 95 °C, more preferably in the range of 40 to 90° C, and most preferably in the range of 50 to 80° C. In a preferred embodiment, methyl paraben is added after heating has begun, when the temperature of Phase 1M is in the range of 30 to 95" C, more preferably when the temperature of Phase 1M is in the range of 40 to 90° C, and most preferably when the temperature of Phase 1M is in the range of 50 to 80° C. b) PfrasgZM The ingredients of Phase 2M, comprising glycerin and ceramic hydroxyapatite, were combined in a suitable second vessel and mixed thoroughly until completely homogeneous. Phase 2M was added to the first vessel when the predetermined temperature for Phase 1M had been attained. c) Phase 3M The constituents of Phase 3M, comprising stearic acid, octyl paimitate; tocopheryl acetate, safflower oil, and hydrogenated vegetable ofl, were combined in a stainless steel third vessel, and the mixture was heated towards a predetermined temperature. Preferably the predetermined temperature for Phase 3M is in the range of 30 to 95° C, more preferably in the range of 40 to 90°C, and roost preferably in the range of 50 to 80° C.

When most of the solid constituents had melted the mixer for the third vessel was turned on. When the temperature of the contents of both tbe third and first vessels attained their respective predetermined temperatures. Phase 3M was added to the first or main vessd, and the contents were mixed well.

After thorough mixing, heating was discontinued and tbe contents of the first vessel were allowed to cool. d) Phase 4M The ingredients of Phase 4M, comprising tocopherol iinoieate, matricaria extract and comfrey extract, were combined in a suitable fourth vessel, and heated to a predetermined temperature. Preferably the predetermined temperature for Phase 4M is in the range of 30 to 60° C, more preferably in the range of 35 to 55° C, and most preferably in the range of 40 to 55° C. When the temperature of the contents of the first vessd were al the same or a similar temperature as the predetermined temperature for Phase 4, the ingredients of Phase 4 were transferred from the fourth vessd to the first vessd with thorough mixing. Heating was discontinued and the mixture was allowed to cool.

When the mixture was at a suitable temperature, preferably in the range of20-40° C, more preferably in the range of25-35° C, natural scent was added, and the mixture was thoroughly stirred until homogeneous.

The skin moisturizer composition of the current invention provides a smooth moisturizer, which is white or slightly off-white in color, and has a delicate scent of citrus fruit. At a temperature of 25° C, it has a pH in the range of 6-7, a viscosity in the range of3500-6500 and preferably 4,400-5,100 cenhpoise, and a specific gravity near 1.0.

In one embodiment, the composition of a skin cleanser under the invention comprises, for example, an antimicrobial agent, a viscosity enhancer, a carrier or micro-carrier, an 21 antimicrobial function enhancer, and an unbound/excess lipid remover, a vitamin, protein or derivative thereof; plant extract, natural scent, and water.

In a preferred embodiment, the composition of a skin cleanser under tbe invention comprises, for example, the following: an antimicrobial agent, such as Triclosan; an antimicrobial function enhancer, such as ceramic hydroxyapatite, and an unbound/excess lipid remover, such as ceramic hydroxyapatite; an emollient, such as propylene glycol, nonoxynol-9; an anti-inflammatory agent, such as Aloe vera extract, panthenol; a surfactant, such as cocamide DEA, sodium Iaureth sulfate; an emulsifier, such as polysorbate 60, sorbitan stearate; a preservative, such as propyl paraben, methyl paraben; a sun block agent, such as octyl paimitate, a vitamin or derivative thereof; such as tocopheryl linoleate or wheat oligosaccharides; a protein or derivative thereof such as hydrolyzed wheat protein; a plant extract, such as comfrey extract, or matricaria extract; a natural scent, such as oil of cucumber, and water.

Methods, under die invention, for preparing the skin cleanser composition comprise the steps of formulating the constituents of each composition as four Phases, and subsequently combining each Phase sequentially.

The skin cleanser composition may be formulated according to the following Example 22 EXAMPLE2 Formulation of Skin Cleanser Composition a) Phase ]C A statable volume of deionized water at ambient temperature was metered into a first stainless steel vessel or tank, and the mixer was turned on. Ingredients of Phase 1C, comprising sodium Iaureth sulfate. Aloe vera extract, citric acid and panthenol were then added, and die mixture was thoroughly stirred. b) Phase 2C The ingredients of Phase 2, comprising sorbitol and ceramic hydroxyapatite, were combined in a suitable second vessel and mixed thoroughly until completely homogeneous. Phase 2 was added to the first vessel. c) Phase 3C The constituents of Phase 3C, comprising propylene glycol, Polymethoxy Bycyclic Oxazolidine and Tridosan, were combined in a suitably azed third vessel, and the contents were thoroughly mixed. Mixing was continued and the mixture was heated until the mixture was homogeneous and it attained a predetermined temperature. Preferably die predetermined temperature for Phase 3C is in the range of 35 to 95° C, more preferably in the range of 45 to 85° C, and most preferably in the range of 55 to 75° C. Heating was discontinued and the mixture was allowed to cool. When the temperature of Phase 3C in the third vessel was in the range of 15 to 35s C, and preferably in the range of 18 to 25s C, Muse 3C was transferred to die first vessel, and die contents were mixed well. 23 d)Phase_4C Mixing of the contents of tbe first vessel was continued while the ingredients of Phase 4C at ambient temperature, comprising nonoxynot-9, cocaxmde DEA, comfrey extract, and matricaxia extract, were added sequentially to the first vessel.

Finally, natural scent was added to the mixture in the first vessd, and the mixture was thoroughly stirred until homogeneous.

The skin cleanser composition of tbe current invention provides a smooth, viscous liquid which is dear to siightty opaque, and has a slight scent of cucumber. At a temperature of 25° C, it has a pH in the range of 6.5-7.5, a viscosity in the range of3,000-4,000, even more preferably in the range of3200-3800 centipoise, and a specific gravity near approximately 1.0.

A preferred embodiment of the skin moisturizer composition according to the invention comprises the constituents shown in the following Example.

EXAMPLE 3 Skin Moisturizer Composition Phase 1 comprises: Deionized water, to 100% w/w; Panthenol, up to 10% w/w; Methyl paraben, up to 5% w/w, and Aloe vera extract, up to 7% w/w.

Phase 2 comprises: Glycerin, up to 10% w/w, and Ceramic hydroxyapatite, up to 5% w/w.

Phase 3 comprises: Stearic add, up to 10% w/w, 24 Tocopherol acetate, up to 5% w/w; Octyl paimitate, up to 10% w/w; Safflowcr oil, up to 10% w/w, Hydrogenated vegetable oil, up to 10% w/w.

Propyl paraben, up to 5% w/w; and Triclosan, up to 1% w/w.

Phase 4 comprises: Plant extract - for example, extract of comfrey, matricaria, up to 5% w/w, Tocopheryl linoleate, up to 5% w/w, Allantoin, up to 5% w/w; and Oligosaccharides and Hydrolyzed wheat protein.

A further constituent of a preferred embodiment of the skin moisturizer composition is natural oil of citrus in the range of 0.01-0.1% w/w.

A preferred embodiment of tbe skin cleanser composition according to the invention comprises the constituents shown in the following Example.

EXAMPLE 4 Skin Cleanser Composition Phase 1 comprises: Deionized water, to 100% w/w; Panthenol, up to 10% w/w; Aloe vera extract, up to 7% w/w; and Citric acid, up to 10% w/w.

Phase 2 comprises: Sorbitol up to 10% w/w; and Ceramic hydroxyapatite, up to 5% w/w.

Phase 3 comprises: Methyl paraben, tip to 5% w/w, Propyl paraben, up to 5% w/w, Propylene glycol, up to 10% w/w; Disodium ethylenediaminetetraacetic acid, up to 2% w/w; and Tridosan, up to 1% w/w.

Phase 4 comprises- Plant extract - for example, extract of comfrey, Matricaria up to 5% w/w; Nonoxynol-9; Hydroxypropyi methylceflulose; and Wheat Oligosaccharides and Hydrolyzed wheat protein.

A further constituent of a preferred embodiment of the slrin cleanser composition is natural oil of cucumber in the range of 0.01-0.1% w/w.

The present invention having been described in various embodiments, it will be apparent to one of ordinary skill that many modifications can be made thereto which nevertheless utilize the methods and compositions of the invention as disciosed. The scope of the invention is defined by the appended claims rather than by the embodiments presented above. 26

Claims (4)

WHAT WE CLAIM IS:

1. A composition of matter for application to the skin, said composition comprising: ceramic calcium phosphate particles; and a physiologically and cosmetically acceptable vehicle; wherein said composition is suitable for topical application to the skin.

2. The composition of matter according to Claim 1, wherein said ceramic calcium phosphate is sintered.

3. The composition of matter according to Claim 2, wherein said calcium phosphate is hydroxyapatite.

4. A composition according to Claim 1, 2 or 3, substantially as herein described. END OF CLAIMS 27 INTELLECTUAL PROPERTY OFFICE OF N.Z 2 6 MAR 2004 RECEIVED