WO2001070271A2

WO2001070271A2 - Acid-stable base compositions for preparing surfactant free topical compositions

Info

Publication number: WO2001070271A2
Application number: PCT/US2001/009317
Authority: WO
Inventors: James M. Willmott; Timothy K. Crawford
Original assignee: Collaborative Technologies Inc
Current assignee: Collaborative Technologies Inc
Priority date: 2000-03-23
Filing date: 2001-03-23
Publication date: 2001-09-27
Anticipated expiration: 2002-09-23
Also published as: AU2001245954A1; WO2001070271A3

Abstract

The present invention relates to a base composition for preparing a substantially surfactant free composition for topical, oral, nasal, anal, ophthalmic, or vaginal application. The base composition comprises sclerotium gum and carrageenan. Formulas containing the base composition of the present invention are stable at a pH of about 3.0 and lower. The base compositions are also compatible with cationic dispersions, i.e., unlike prior compositions, mixtures of the base composition and a cationic dispersion do not result in the formation of aggregates or the separation of water and hydrophobic ingredients in the composition. Another embodiment of the invention is a composition for topical, oral, nasal, anal, ophthalmic, or vaginal application comprising the base composition of the present invention and at least one dispersion comprising suspended particles of a hydrophobic active agent, a hydrophobic adjuvant, or a combination thereof. The composition is substantially free of emulsifying surfactants and the suspended particles have a diameter less than about 500 nm. Preferably, the composition comprises at least one cationic dispersion. According to one preferred embodiment, the composition has a pH of less than about 5, preferably a pH of less than about 4, and more preferably a pH of less than about 3. Yet another embodiment is a method of preparing the composition of the present invention.

Description

ACID-STABLE BASE COMPOSITIONS FOR PREPARING SURFACTANT FREE TOPICAL COMPOSITIONS

FIELD OF THE INVENTION The present invention relates to acid-stable base compositions for preparing surfactant free topical, oral, nasal, anal, ophthalmic, or vaginal compositions and a method for preparing such surfactant free compositions.

BACKGROUND OF THE INVENTION Most topical preparations currently sold contain a wide variety of physiologically active agents ("active agents") and/or aesthetic modifying agents. Physiologically active agents are compounds which cause a physiological change to the body following their application. Examples of such agents include alpha hydroxy acids, antioxidants, and vitamins. Aesthetic modifying agents are materials that impart desirable tactile, olfactory, taste or visual properties to the surface to which the composition is applied. Some examples of aesthetic modifying agents include silicone fluids and derivatives thereof, waxes, botanical (vegetable) oils, hydrocarbon-based oils, esters and fragrances.

The performance of these active agents is dependent on delivery,\and delivery is dependent upon the compatibility with the vehicle. These vehicles range from simple solvents, such as water and ethanol, to complex emulsions. Unfortunately not all active agents are completely soluble or compatible with all vehicles. For example, oil soluble active agents are typically not compatible with water or water-based gel vehicles. As a result, many such products exhibit poor delivery of active agents, have poor tactile properties, or are thermodynamically unstable and result in a commercially unacceptable shelf life. Topical preparations having a non- water based solvent do not usually have an aesthetically pleasing appearance, feel, and/or fragrance. Furthermore, non-water based solvents can cause unwanted side effects, such as irritation or damage to the epithelial surface to which they are applied.

To avoid the problems associated with non-water based solvents, stable emulsions are commonly employed to deliver physiologically active agents and aesthetic modifying agents. These emulsions form either spherical micelles of one or more hydrophobic liquid materials in water or spherical droplets of water in a hydrophobic fluid.

Such emulsions are typically formed by separately preparing an oil phase and a water phase. In other words, the hydrophobic ingredients are dissolved in a suitable oil phase and the hydrophilic ingredients are dissolved in water. The two phases are heated to at least 70° C and mixed together. Emulsifying agents are usually added to the mixture in order to reduce the surface tension between the oil and water phases, thereby making the combination of the two phases more stable. The mixture is then slowly cooled to ensure the formation of crystalline structures which enhance the stability of the emulsion. Emulsions prepared by this method usually have a homogeneous opaque white appearance and a smooth or pleasant feeling upon application to the skin or other epithelial surface.

A significant drawback of emulsions is their requirement for surfactants. Surfactants damage the skin's natural barrier and the lipid bilayer of epithelial cell membranes leaving tissue vulnerable and irritating the skin. The damaged barrier permits the passage of other materials that can cause irritation, increase skin sensitivity and bring about allergic reactions. The literature is replete with clinical evidence of the damaging consequences that can occur with the use or overuse of surfactants. For example, Effendy I., Maibach H.I., "Surfactants and experimental irritant contact dermatitis", Contact Dermatitis, 33(4):217-25 (10/1995), indicates that "[m]any surfactants elicit irritant reactions when applied to the skin, partially due to their relative ability to solubilize lipid membranes." In Barany E., Lindberg M, Loden M., "Biophysical characterization of skin damage and recovery after exposure to different surfactants", Contact Dermatitis 40(2):98-103 (2/1999), the authors states that "[t]he majority of adverse skin reactions to personal care products are presumed to be caused by irritant substances, like surfactants."

Additionally, lowering the surface tension of a topical preparation generally increases the surface exposure of the active agent or aesthetic modifying agent to oxygen and other destabilizing materials. For example, in a topical preparation containing retinol as an active ingredient, the instability of the preparation may decrease the efficacy of the retinol. The instability of an unsaturated fatty acid as an aesthetic modifying agent leads to color changes in the preparation and malodor.

Other drawbacks to emulsions include:

(1) Many materials having aesthetic properties, such as, for example, fluorinated compounds, are not easily incorporated into emulsions; (2) Each time the oil or water phase is changed in an emulsion, the amounts and types of emulsifying agents in the emulsion needs to be readjusted; and

(3) Many active agents and aesthetic modifying agents degenerate during the preparation of an emulsion, for example, during heating, and after the emulsion has been formed. Since the time between manufacturing and sale of a cosmetic product is typically several weeks, the product is often no longer "fresh" or effective since the active agent has degenerated or deteriorated. To offset instability problems, many other materials such as chelating agents, antioxidants and masking agents are usually included in the product.

Typical emulsions are time consuming to prepare, require heating, are produced in multiple phases, are slow cooling, and often require high shear conditions to get the particle size small enough for maximum stability. Larger batches may require 8 to 24 hours to process and can take several days to set up. It is also often difficult to control the process parameters for preparing the emulsion. If any factors such as the heating, cooling or mixing rates are not carefully duplicated, the preparation may have different properties than the preceding batches of the same product. As a result, the stability of the emulsion may vary from batch to batch. Often the difference of a single parameter is significant enough to cause the product to be outside the established optimum specifications. These batches then have to be either discarded or re-worked. The lack of reproducibility is especially problematic when the product contains a physiologically active agent. Lack of reproducibility can effect product performance and end user satisfaction. The lack of reproducibility also results in products having different aesthetic properties which the end user will perceive as a lack of quality and will ultimately lead to consumer dissatisfaction or reduced compliance. Emulsions are typically expensive to manufacture. This is due to a variety of factors including the energy to heat the batch, the specialized equipment required to process the emulsion, such as specialized pumps and cooling/heating equipment, and the time the process ties up equipment and personnel. Moreover, such emulsions cannot be easily processed or customized at the point of purchase. Since most skin care preparations are prepackaged and have predetermined dosages, dermatologists cannot readily administer to patients varying dosages of an active agent. As a result, a patient may need to apply two or more different skin care preparations since a single preparation with all of the prescribed active agents may not be available.

Some dermatologists prepare their own skin care preparations. These skin care preparations typically have poor aesthetic properties resulting in poor patient compliance. Thus, it would be desirable for dermatologists to be able to quickly and easily prepare skin care preparations having varying dosages of active agents and an aesthetically pleasing appearance.

Present cosmetic products contain predetermined amounts of active agents. Customers cannot pick and choose which ingredients to include in these products. Many customers do not purchase certain cosmetic products because of an allergic reaction with one or more of the ingredients included in the product. For example, many customers are allergic to various fragrances. It would therefore be advantageous to prepare the cosmetic product at the point of sale without the fragrances. Also, customers may have to apply two or more different cosmetic products to get a desired effect since a single product with the desired combination of active agents and/or aesthetic modifying agents may not be on the market. Many cosmetic products are sold in only one form, such as a spray, gel or lotion. Customers, however, may prefer other forms of the cosmetic product. Prior to the present invention, it was not practical to prepare custom cosmetic products at the point of sale. The preparation of most current cosmetic products require heating, other energy expensive processes, and/or large industrial equipment. As a result, it was not economically feasible to prepare custom cosmetic products at the point of sale. Furthermore, active ingredients which are heat sensitive and oil soluble could not readily be incorporated into cosmetic products by conventional heating without partially or completely degrading the active ingredient.

For the foregoing reasons, there is a need for a substantially surfactant free cosmetic product which can be prepared at the point of sale. Also, there is a need for a method of preparing such a cosmetic product which is fast and does not require heating or other expensive processing techniques.

SUMMARY OF THE INVENTION

The present invention relates to a base composition for preparing a substantially surfactant free composition for topical, oral, nasal, anal, ophthalmic, or vaginal application. The base composition comprises sclerotium gum and carrageenan.

Compositions containing the base composition of the present invention are stable at a pH of about 3.0 and lower. The base compositions are also compatible with cationic dispersions, i.e., unlike prior compositions, mixtures of the base composition and a cationic dispersion do not result in the formation of aggregates or the separation of water and hydrophobic ingredients in the composition.

Another embodiment of the invention is a composition for topical, oral, nasal, anal, ophthalmic, or vaginal application comprising the base composition of the present invention and at least one dispersion comprising suspended particles of a hydrophobic active agent, a hydrophobic adjuvant, or a combination thereof. The composition is substantially free of emulsifying surfactants and the suspended particles have a diameter less than about 500 nm. Preferably, the composition comprises at least one cationic dispersion. According to one preferred embodiment, the composition has a pH of less than about 5, preferably a pH of less than about 4, and more preferably a pH of less than about 3. Yet another embodiment is a method of preparing a composition for topical, oral, nasal, anal, ophthalmic, or vaginal application. The method comprises mixing (a) the base composition of the present invention, and (b) at least one dispersion comprising suspended particles of a hydrophobic active agent, a hydrophobic adjuvant, or a combination thereof. The composition prepared is substantially free of emulsifying surfactants and the suspended particles have a diameter less than about 500 nm. Mixing may be performed with a propeller mixer or manually, i.e., by hand. Preferably, the base composition is premanufactured. According to one preferred embodiment, the composition prepared contains at least one cationic dispersion. Since the composition is simple and quick to prepare, custom cosmetic compositions may be prepared at the point of sale for customers in minutes. Prior to the present invention, such products would take hours to be prepared.

DETAILED DESCRIPTION OF THE INVENTION

Generally, the weight ratio of sclerotium to carrageenan ranges from about 1 :0.8 to about 1 :3. The weight ratio preferably ranges from about 1 : 1 to about 1:1.5 and more preferably is about 1 : 1.33.

The base composition typically contains from about 0.5 to about 10% by weight of sclerotium gum and from about 0.5 to about 12% by weight of carrageenan, based upon 100% total weight of base composition. Preferably, the base composition contains from about 1 to about 4% by weight of sclerotium gum and from about 1 to about 5% by weight of carrageenan, based upon 100% total weight of base composition. According to a preferred embodiment, the base composition contains about 1.5% by weight of sclerotium gum and about 2.0% by weight of carrageenan, based upon 100% total weight of base composition. The base composition may further comprise additional rheology modifying agents. However, the base composition does not contain rheology modifying agents which are not effective in acidic environments, such as, for example, carbomer, acrylate/alkyl acrylate crosspolymers, and carboxymethylcellulose. Preferred rheology modifying agents include, but are not limited to, phosphorylated starch derivatives, acrylates/vinyl isodecanoate crosspolymer, xanthan gum, locust bean gum, guar gum, and any combination of any of the foregoing. The term "phosphorylated starch derivative" includes, but is not limited to, starches containing a phosphate group. Suitable phosphorylated starch derivatives include, but are not limited to, hydroxyalkyl starch phosphates, hydroxyalkyl distarch phosphates, and any combination of any of the foregoing. Non-limiting examples of hydroxyalkyl starch phosphates and, hydroxyalkyl distarch phosphates include hydroxyethyl starch phosphate, hydroxypropyl starch phosphate, hydroxypropyl distarch phosphate, and any combination of any of the foregoing. According to a preferred embodiment, the base composition comprises a hydroxyalkyl distarch phosphate and more preferably hydroxypropyl distarch phosphate.

Another embodiment of the invention is a composition for topical, oral, nasal, anal, ophthalmic, or vaginal application comprising the base composition of the present invention and at least one dispersion comprising suspended particles of a hydrophobic active agent, a hydrophobic adjuvant, or a combination thereof. The composition is substantially free of emulsifying surfactants and the suspended particles have a diameter less than about 500 nm. Typically, besides the base composition, the composition for application only contains water-soluble ingredients and/or dispersions of hydrophobic active agents and/or hydrophobic adjuvants. Generally, hydrophobic ingredients which are not in the form of a dispersion are not included in the composition, or at least not in any substantial amounts.

Other.active agents, aesthetic modifying agents, and adjuvants, such as those described in Remington's Pharmaceutical Sciences, 19^th Edition, A. R. Gennaro (1995) and the International Cosmetic Ingredient Dictionary and Handbook, 7^th Edition (1997), published by The Cosmetic, Toiletry, and Fragrance Association (both of which are hereby incorporated by reference), may be incorporated into the composition. Generally, all hydrophobic ingredients to be included in the final composition are added as dispersions (i.e. a dispersion of the hydrophobic ingredient is prepared before it is mixed with the base composition and the dispersion).

Preferably, the composition contains a cationic dispersion.

Due to the high acidic stability of the base composition of the present invention, the composition may have a pH of less than about 5 and even a pH of less than about 4, about 3, or about 1. Generally, the composition contains from about 0.01 to about 60% by weight, preferably from about 5 to about 85% by weight, and more preferably from about 0.4 to about 6% by weight of the base composition, based upon 100% weight of total composition.

The composition for topical, oral, nasal, anal, ophthalmic, or vaginal application may be prepared by mixing (a) the base composition of the present invention, and (b) at least one dispersion comprising suspended particles of a hydrophobic active agent, a hydrophobic adjuvant, or a combination thereof. The composition prepared is substantially free of emulsifying surfactants and the suspended particles have a diameter less than about 500 nm. The composition preferably comprises less than about 3% by weight and more preferably less than about 1% by weight of dispersion initiator, based upon 100% weight of total composition.

The composition may be a cream, gel, or lotion, serum or spray.

Preferably, the base composition is premanufactured, i.e., prepared at a location remote from where the mixing step is performed or prepared in large quantities. The term "large quantities" is herein defined as a quantity greater than that needed to produce a single final product and is preferably many multiples times that. The base composition is typically premanufactured in large batches.

Mixing is generally performed at a temperature of from about 15 to about 30° C, preferably at a temperature of from about 20 to about 30° C, and most preferably at ambient temperature. Since the hydrophobic active agent or hydrophobic adjuvant is added to the base composition as a dispersion, heating and other expensive processing steps are not required to obtain a homogenous final composition. Preferably, the composition is not heated.

The dispersion is generally a homogenous fluid which is stable for a commercially relevant period of time. The dispersion typically remains stable for at least 2 months and preferably at least 6 months at ambient temperature and in many cases at least 2 weeks and preferably at least 2 months at elevated temperature (50° C).

According to a preferred embodiment, the dispersion is prepared by mixing from about 0.1% to about 70% by weight of hydrophobic active agent and/or hydrophobic adjuvant with from about 30% to about 99.9% by weight of aqueous phase under high pressure and high shear conditions, based upon 100% weight of total dispersion. Suitable high pressure and high shear dispersions are sold under the tradename SanSurf^® by Collaborative Laboratories, Inc. of East Setauket, NY. The aqueous phase contains water and, optionally, other hydrophilic adjuvants. More preferably, the mixing is performed with shearing at a pressure from about 9,000psi to about 25,000 psi to form a dispersion having an average particle size ranging from about 50nm to about 500 nm.

The base composition may be prepared by methods known in the art.

Hydrophobic Active Agent or Hydrophobic Adjuvant Dispersion

A hydrophobic active agent or hydrophobic adjuvant is an active agent or adjuvant which has a non polar property which makes it essentially insoluble in water or water and polar solvent solution. Hydrophobic active agents and hydrophobic adjuvants of the present invention include, but are not limited to, partially and fully hydrophobic active agents and partially and fully hydrophobic adjuvants. For example, hydrophobic active agents encompassed by the present invention include compounds and complexes which contain a hydrophobic moiety.

The composition of the present invention may also include non-hydrophobic active agents and non-hydrophobic adjuvants.

The dispersion containing the suspended particles generally contains from about 0.01 to about 70% by weight of oil, based upon 100% weight of total dispersion. Preferably, the dispersion contains from about 1.0 to about 50% by weight of oil, based upon 100% weight of total dispersion. The oil component of the composition may include active agents and adjuvants which are oils.

The dispersion is a suspension of liquid or solid particles of colloidal size or larger in a liquid medium. Generally, the dispersion contains suspended particles, such as oil particles (or oil droplets), having a diameter less than about 500 nm. The diameter of the suspended particles preferably ranges from about 50 nm to about 500 nm and more preferably from about 250 to about 500 nm. Preferably, the oil droplets contain one or more lipophilic materials. The oil droplets may have a charge as determined by zeta potential measurements. The oil droplets may be prepared by ultra high shear mixing or microfluidization. Preferred oil containing dispersions are sold under the tradename SanSurf^® by Collaborative Laboratories, Inc. of East Setauket, NY, and Dermasomes™ by Microfluidics Corp. of Newton, MA.

Active Agents

Suitable active agents include, but are not limited to acid stable, anti-acne agents, antimicrobial agents, antiinflammatory agents, analgesics, antierythemal agents, antipruritic agents, antiedemal agents, antipsoriatic agents, antifungal agents, skin protectants, sunscreen agents, vitamins, antioxidants, scavengers, antiirritants, antibacterial agents, antiviral agents, antiaging agents, protoprotection agents, hair growth enhancers, hair growth inhibitors, hair removal agents, antidandruff agents, anti-seborrheic agents, exfoliating agents, wound healing agents, anti-ectoparacitic agents, sebum modulators, immunomodulators, hormones, botanicals, moisturizers, astringents, cleansers, sensates, antibiotics, anesthetics, steroids, tissue healing substances, tissue regenerating substances, amino acids, peptides, minerals, ceramides, biohyaluronic acids, and any combination of any of the foregoing.

Preferred anti-acne agents include, but are not limited to, salicylic acid, retinoic acid, alpha-hydroxy acids, benzyl peroxide, sodium sulfacetamide, clindamycin, and any combination of any of the foregoing. Preferred combinations of anti-acne agents to be incorporated in the composition include salicylic acid, retinoic acid, and hydrocortisone; sodium sulfacetamide and clindamycin; salicylic acid and clindamycin; salicylic acid, alpha- hydroxy acids, and tetrahydrozoline.

Suitable antimicrobial agents include, but are not limited to, benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, chloroxylenol, cloflucarban, fluorosalan, hexachlorophene, hexylresorcinol, iodine complex, iodine tincture, para- chloromercuriphenol, phenylmercuric nitrate, thimerosal, vitromersol, zyloxin, triclocarban, triclosan, methyl-benzethonium chloride, nonyl phenoxypoly(ethyleneoxy) ethanol-iodine, para-chloro-meta-xylenol, providone-iodine complex, poloxamer-iodine complex, triclorcarban, undecoylium chloride-iodine complex, and any combination of any of the foregoing.

Suitable anti-inflammatory agents include, but are not limited to, alidoxa, allantoin, aloe vera, aluminum acetate, bismuth subnitrate, boric acid, calamine, casein, cellulose, microporous, cholecatciferol, cocoa butter, cod liver oil, colloidal oatmeal, cystein hydrochloride, dexpanthenol, dimethicone, glycerin, kaolin, lanolin, live yeast cell derivative, mineral oil, peruvian balsam, petrolatum, protein hydrolysate, racemethionine, shark liver oil, sulfur, talc, tannic acid, topical starch, vitamin A, vitamin E, white petrolatum, zinc acetate, zinc carbonate, zinc oxide, hydrocortisone, betamethasone, ibuprofen, indomethicin, acetyl salicylic acid, tacrolimus, flucoinolone acetonide, sodium sulfacetamide, and any combination of any of the foregoing. Suitable analgesics include, but are not limited to, diphenhydramine, tripeiennamine, benzocaine, dibucaine, lidocaine, tetracaine, camphor, menthol, phenol, resorcinol, matacresol, juniper tar, methylsalicylate, turpentine oil, capsicum, methyl nicotinate, b-glucan, and any combination of any of the foregoing.

Suitable antierythemal agents include, but is not limited to, tetrahydrozoline and hydracortisone.

Suitable antipruritic agents include, but are not limited to, benadryl, pramoxine, antihistamines, and any combination of any of the foregoing.

Suitable antiedemal agents, include, but are not limited to, pregnenalone acetate, tanin glyrosides, and any combination of any of the foregoing. Suitable antipsoriatic agents include, but are not limited to, caleipotriene, coal tar, anthralin, vitamin A, and any combination of any of the foregoing. Preferred combinations of antipsoriatic agents include, but are not limited to, hydrocortisone, retinoic acid, and alpha hydroxy acid; dovonex, salicylic acid, and a sunscreen agent; indomethicin, salicylic acid, and urea; anthralin and salicylic acid; and anthralin and indomethicin. Other suitable antipsoriatic agents include, but are not limited to, caleipotriene, coal tar, anthralin, vitamin A, and any combination of any of the foregoing.

Suitable antifungal agents include, but are not limited to, clioquinol, haloprogin, miconazole nitrate, clotrimazole, metronidazole, tolnaftate, undecylenic acid, iodoquinol, and any combination of any of the foregoing.

Suitable skin protectants include, but are not limited to, cocoa butter, dimethicone, petrolatum, white petrolatum, glycerin, shark liver oil, allantoin, and any combination of any of the foregoing.

Suitable sunscreen agents include, but are not limited to, ethylhexyl methoxycinnamate, avobenzone, benzophenone-3, octacrylene, titanium dioxide, zinc oxide, and any combination of any of the foregoing.

Suitable antioxidants include, but are not limited to, scavengers for lipid free- radicals and peroxyl radicals quenching agents, and any combination of any of the foregoing. Suitable antioxidants include, but are not limited to, tocopherol, BHT, beta carotene, vitamin A, ascorbic acid, ubiquinol, ferulic acid, azelaic acid, thymol, catechin, sinapic acid, EDTA, lactoferrin, rosmariquinone, hydroxytyrosole, sesamol, 2-thioxanthine, nausin, malvin, carvacone, chalcones, glutathione isopropyl ester, xanthine, melanin, guanisone, lophorphyrins, 8-hydroxyxanthine, 2-thioxanthione, vitamin B₁₂, plant alkaloids, catalase, quercetin, tyrosine, SOD, cysteine, methionine, genistein, NDG, procyanidin, hamamelitannin, ubiquinone, trolox, licorice extract, propyl gallate, sinapic acid, and any combination of any of the foregoing.

Suitable vitamins include, but are not limited to, vitamin E, vitamin A palmitate, vitamin D, vitamin F, vitamin B₆, vitamin B₃ vitamin B₁₂ vitamin C, ascorbyl palmitate, vitamin E acetate, biotin, niacin, DL-panthenol, and any combination of any of the foregoing.

A preferred sunscreen agent is a mixture of ethylhexyl methoxycinnamate, butyl methoxydibenzoylmethane, cyclomethicone, phospholipids, and water, and is available as Solarease^® from Collaborative Laboratories, Inc. of East Setauket, NY.

Suitable amino acids include, but are not limited to, glycine, serine, and any combination of any of the foregoing.

Aesthetic Modifying Agents The composition preferably includes at least one aesthetic modifying agent.

An aesthetic modifying agent is a material which imparts desirable tactile, olfactory, taste or visual properties to the surface to which the composition is applied. The aesthetic modifying agent may be hydrophobic or hydrophilic. The aesthetic modifying agent is preferably hydrophobic and is more preferably an oil, wax, solid or paste. A dispersion of one or more hydrophobic aesthetic modifying agents is preferably prepared before the hydrophobic aesthetic modifying agents are incorporated into the composition. The hydrophobic aesthetic modifying agents may be dispersed into an aqueous phase by methods known in the art, such as by ultra high shear mixing and microfluidization. The final composition may be prepared by mixing the dispersions containing the hydrophobic aesthetic modifying agents with the base composition and any other adjuvants. Since the hydrophobic aesthetic modifying agents are added to the base composition as dispersions, heating and other expensive processing steps are not required to obtain a homogenous final composition. An example of an aesthetic modifying agent is a mono, di, tri or poly alkyl ester or ether of a di, tri, or polyhydroxy compound, such as ethylene glycol, propylene glycol, glycerin, sorbitol or other polyol compound. Examples of such esters and ethers include, but are not limited to, saturated and unsaturated, linear and branched vegetable oils, such as soybean oil, babassu oil, castor oil, cottonseed oil, Chinese tallow oil, crambe oil, perilla oil, danish rapeseed oil, rice bran oil, palm oil, palm kernel oil, olive oil, linseed oil, coconut oil, sunflower oil, safflower oil, peanut oil and corn oil. Preferred saturated and unsaturated vegetable oils are those having fatty acid components with 6 to 24 carbon atoms. A more preferred vegetable oil is soybean oil.

An example of a hydrophobic aesthetic modifying agent is a compound having the formula C_nH_(2n+2.m) where n is an integer greater than or equal to 6 and m is 0 or an even integer no greater than n. Such compounds include, but are not limited to, saturated and unsaturated, linear, branched, and cyclic hydrocarbon chains. Preferred examples of such compounds include, but are not limited to, mineral oil, petrolatum, permethyl fluids, polybutylenes, and polyisobutylenes.

Another example of a hydrophobic aesthetic modifying agent has the formula

R, -O- -R,

O

or the formula

where R, is a saturated or unsaturated, linear, branched or cyclic C,-C₂₄ alkyl; R₂ is hydrogen or a saturated or unsaturated, liner, branched or cyclic C,-C₂₄ alkyl; and n is an integer from 0 to 20. Examples of such aesthetic modifying agents include, but are not limited to, isopropyl palmitate and diisopropyl adipate.

Yet another aesthetic modifying agent is silicone. Silicone may provide lubrication and/or shine to the composition. Preferably, the silicone is insoluble in water. Suitable water-insoluble silicone materials include, but are not limited to, polyalkylsiloxanes, polyarylsiloxanes, polyalkylarylsiloxanes, polysiloxane gums and polyethersiloxane copolymers. Examples of suitable silicone materials are disclosed in U.S. Patent Nos. 4,788,006; 4,341,799; 4,152,416; 3,964,500; 3,208,911; 4,364,837 and 4,465,619, all of which are incorporated herein by reference. Another suitable hydrophobic material which can be suspended in the composition has the formula

where R, is a saturated or unsaturated, linear, branched or cyclic alkyl having 2 to 24 carbon atoms; M⁽⁺⁾ is N⁺R₂R₃R₄R₅; R₂, R₃ and R₄ are hydrogen or a saturated or unsaturated, linear or branched alkyl or hydroxyalkyl having from 1 to 10 carbon atoms; and R₅ is a saturated or unsaturated, linear, branched or cyclic alkyl or substituted alkyl having 2 to 24 carbon atoms. An example of such a material is lauramine oleate.

Other Adjuvants

Other suitable adjuvants for the composition include but are not limited to pH adjusters, emollients, conditioning agents, chelating agents, gelling agents, viscosifiers, colorants, fragrances, odor masking agents, UV stabilizer, preservatives, and any combination of any of the foregoing. Preferred pH adjusters include, but are not limited to, aminomethyl propanol, aminomethylpropane diol, triethanolamine, citric acid, sodium hydroxide, acetic acid, potassium hydroxide, lactic acid, and any combination of any of the foregoing. Suitable conditioning agents include, but are not limited to, cyclomethicone, petrolatum, dimethicone, dimethiconol, silicone, quaternary amines and any combination of any of the foregoing.

The composition preferably contains less than about 0.5% by weight of preservatives, based upon 100% weight of total composition. More preferably, the composition contains from about 0.25 to about 0.5% by weight of preservatives, based upon 100% weight of total composition.

The following examples are intended to describe the present invention without limitation. Examples 1-3

Preparation of Base Compositions

The base compositions described in Table 1 below were prepared as follows.

Deionized water (A) was heated to about 55-60° C. Propylene glycol and sclerotium gum were added to the water and mixed with a Silverson mixer for about 15 minutes. The speed of the mixer was increased as the viscosity of the solution increased.

In Example 1 , carrageenan and glycerin were added to the solution and mixed until the solution was uniform and homogeneous. Germazide^® MPB was then added to the solution and mixed until the solution was uniform and homogeneous to yield the base composition. In Examples 2 and 3, carrageenan was added to the solution and mixed until the solution was uniform and homogeneous. Germazide^® MPB and glycerin were added to the solution and mixed until the solution was uniform and homogeneous to yield the base composition.

Table 1 -Base Compositions

¹ - The sclerotium gum was Amigel™ available from Alban Muller International of Montreuil, France.

² - The sclerotium gum was Clearogel™ CS 11 available from M.M.P., Inc. of South Plainfield, NJ. - Germazide^® MPB is a mixture of phenoxy ethanol, chlorphenesin, glycerin, methylparaben, and benzoic acid and is available from Collaborative Laboratories, Inc. of East Setauket, NY.

⁴ - Germaben™ II is a mixture of propylene glycol, diazolidinyl urea, methylparaben, and propylparaben and is available from Sutton Laboratories of Chatham, NJ.

Table 2 contains examples of sclerotium/carregeenum base variants which failed to support surfactant free formulations for topical, oral, nasal, anal, opthalmic or vaginal compositions. Table 2 - Saclerotium / Carregeenum Base Variants

Table 3 is an example of sclerotium/carregeenum base variants which failed to support surfactant free formulations for topical, oral, nasal, anal, opthalmic or vaginal compositions. Table 3 -Cationic Base

Table 4 is an example of a surfactant-free formulation using a sclerotium/carregeenum base variant which failed.

Table 4 - Normal/Dry Moisture Cream

Table 5 is an example of a surfactant-free formulation using a sclerotium/carregeenum base variant which failed.

Table 5- Moisture Lotion

Table 6 is an example of a surfactant-free formulation using a sclerotium/carregeenum base variant which failed. Table 6 -Retinol Lotion

Table 7 is an example of three surfactant-free formulations using sclerotium/ carregeenum base variants which failed. Table 7 - Moisture Cream

Example 4

An anti-aging/hype igmentation serum having the formulation of Table 8 below was prepared as follows. All of the ingredients, except the Aculyn 44™ and Chisso beads, were mixed with a propeller mixer until the mixture was smooth and uniform. The Aculyn 44™ and Chisso beads were added to the mixture and mixed until the mixture was smooth and uniform to form the serum. Table 8

⁵ - SanSurf^® Cyclomethicone is a mixture of water, cyclopentasiloxane and phospholipids and is available from Collaborative Laboratories, Inc. of East Setauket, NY.

⁶ - SanSurf^® Polysynlane is a mixture of water, hydrogenated polyisobutene, and phospholipids and is available from Collaborative Laboratories, Inc. of East Setauket, NY. ⁷ - SanSurf^® C.A.P. is a mixture of water, cetearyl alcohol, and phospholipids and is available from Collaborative Laboratories, Inc. of East Setauket, NY.

⁸ - Catezomes™ Petrolatum-50 is a mixture of water, petrolatum, and stearamidopropyl dimethylamine stearate and is available from Collaborative Laboratories, Inc. of East Setauket, NY. ⁹ - Satin Finish is a mixture of water, phenyl trimethicone, cyclomethicone, dimethiconol, phospholipids, carbomer, and triethanolamine and is available from Collaborative Laboratories, Inc. of East Setauket, NY.

¹⁰ - Retinol Catezomes™ is a mixture of water, retinol, PEG-4, behenamidopropyl dimethylamine behenate and is available from Collaborative Laboratories, Inc. of East Setauket, NY.

¹¹ - Grape Seed Extract is a mixture of glycerin, water, and Vitis Vinifera (grape) seed extract and is available from Collaborative Laboratories, Inc. of East Setauket, NY.

¹² - SanSurf^® Bisabolol is a mixture of water, bisabolol, and cyclopentasiloxane and is available from Collaborative Laboratories, Inc. of East Setauket, NY. ¹³ - The Advanced Moisture Complex is a mixture of glycerine , water, sodium PCA, urea, trichalese, polyquatemium 51 and sodium hyaluronate and is available from Collaborative Laboratories, Inc. of East Setauket, NY.

¹⁴ - Aculyn 44™ is a copolymer of polyurethane and polyethylene glycol or polyetherurethanes and is available from Rohm & Haas Co., Inc. of Philadelphia, PA. ¹⁵ - Chisso beads are cellulose acetate and are available from Collaborative Laboratories, Inc. of East Setauket, NY. ¹⁶ - Melarrest^® A is a mixture of glycerin, lactic acid, kojic acid, ascorbic acid, and polyvinylpyrrolidone and is available from Collaborative Laboratories, Inc. of East Setauket, NY.

All patents, publications, applications, and test methods mentioned herein are hereby incorporated by reference. Many variations of the present invention will suggest themselves to those skilled in the art in light of the above, detailed description. All such obvious variations are within the full intended scope of the appended claims.

Claims

What is claimed is:

1. A base composition for preparing a substantially surfactant free composition for topical, oral, nasal, anal, ophthalmic, or vaginal application, the base composition comprising sclerotium gum and carrageenan.

2. The base composition of claim 1, wherein the weight ratio of sclerotium to carrageenan ranges from about 1 : 0.8 to about 1 :3.

3. The base composition of claim 2, wherein the weight ratio ranges from about 1 : 1 to about 1 :1.5.

4. The base composition of claim 3, wherein the weight ratio is about 1 :1.33.

5. The base composition of claim 1 , wherein the base composition comprises from about 0.5 to about 10% by weight of sclerotium gum and from about 0.5 to about 12% by weight of carrageenan, based upon 100% total weight of base composition.

6. The base composition of claim 5, wherein the base composition comprises from about 1 to about 4% by weight of sclerotium gum and from about 1 to about 5% by weight of carrageenan, based upon 100% total weight of base composition.

7. The base composition of claim 6, wherein the base composition comprises about 1.5% by weight of sclerotium gum and about 2.0% by weight of carrageenan, based upon 100% total weight of base composition.

8. The base composition of claim 1, wherein the base composition further comprises a rheology modifying agent selected from the group consisting of phosphorylated starch derivatives, acrylates/vinyl isodecanoate crosspolymer, xanthan gum, locust bean gum, guar gum, and any combination of any of the foregoing.

9. The base composition of claim 8, wherein the base composition is free of carbomer, acrylate/alkyl acrylate crosspolymers, and carboxymethylcellulose.

10. A composition for topical, oral, nasal, anal, ophthalmic, or vaginal application comprising the base composition of claim 1 and at least one dispersion comprising suspended particles of a hydrophobic active agent, a hydrophobic adjuvant, or a combination thereof, wherein the composition is substantially free of emulsifying surfactants and the suspended particles have a diameter less than about 500 nm.

11. The composition of claim 10, wherein the pH of the composition is less than about 5.

12. The composition of claim 11 , wherein the pH of the composition is less than about 4.

13. The composition of claim 12, wherein the pH of the composition is less than about 3.

14. The composition of claim 13, wherein the pH of the composition is less than about 2.

15. The composition of claim 10, wherein the composition comprises a cationic dispersion.

16. A method of preparing a composition for topical, oral, nasal, anal, ophthalmic, or vaginal application, the method comprising mixing (a) the base composition of claim 1 and (b) at least one dispersion comprising suspended particles of a hydrophobic active agent, a hydrophobic adjuvant, or a combination thereof, wherein the composition prepared is substantially free of emulsifying surfactants and the suspended particles have a diameter less than about 500 nm.

17. The method of claim 16, wherein the composition has a pH of less than about 5.

18. The method of claim 16, wherein the dispersion is a cationic dispersion.

19. A method of preparing a composition for topical, oral, nasal, anal, ophthalmic, or vaginal application, the method comprising mixing (a) a premanufactured base composition (b) at least one dispersion comprising suspended particles of a hydrophobic active agent, a hydrophobic adjuvant, or a combination thereof, wherein the composition prepared is substantially free of emulsifying surfactants and the suspended particles have a diameter less than about 500 nm.

20. The method of claim 19, wherein the composition has a pH of less than about 5.

21. The method of claim 19, wherein the dispersion is a cationic dispersion.