Title: Allergic contact dermatitis treatment and composition therefor
United States Patent: 6,667,026
Issued: December 23, 2003
Inventors: Goldman; Gavriel (Dingmans Ferry, PA); Lapidus; Mitchell (Whippany, NJ)
Assignee: Pocono Falls, Inc. (Whippany, NJ)
Appl. No.: 100476
Filed: March 15, 2002
A topical composition is disclosed for reducing a urushiol-induced allergic response and the dermatitis associated therewith. The composition is a preparation having an acorn derivative and a nontoxic dermatologically acceptable aqueous dispersion material. The acorn derivative is acorn ash, acorn mash, roasted acorn, or acorn extract and comprises about 0.1 to 50 percent by weight of the treating preparation. After the initial preparation, preservatives are then added. Optionally, additional ingredients such as surfactants and emulsifying agents, antihistamines, topical anesthetics, colloidal oatmeal, topical antipruritics, astringents, and emollients may be added to the aqueous acorn dispersion. With processing varied according the examples provided, the ingredients are combined so as to create sprays, creams, gels, ointments, and lotions.
SUMMARY AND DESCRIPTION OF THE PREFERRED EMBODIMENT
In general terms, the invention disclosed hereby includes an aqueous solution of an acorn derivative suitable for application to the site of contact dermatitis. The acorn derivatives as discussed hereinbelow are extracts, suspensions, and dispersions prepared from acorn ash, acorn mash, and roasted acorns. Acorns utilized in the present invention are from Red Oak (Quercus rupra), Black Oak (Quercus shumardi i Buckl.) Scarlet Oak (Quercus coccinea Muenchb.), Willow Oak (Quercus phellos L.) and other species of the Erythrobalanus group.
In the description which follows the term treating preparations is defined as solutions, suspensions, or emulsions in the form of topical ointments, creams, lotions and sprays. In the formulations of the present invention varying amounts of acorn derivatives have been found to be efficacious in treating the allergic response induced by the urushiol resin and the dermatitis arising therefrom. Thus, treating preparations having from 0.1 to 50 percent by weight of acorn derivative are set forth. The treating preparations, namely solutions, suspensions, and emulsions hereof have, in addition to the acorn derivative, a nontoxic dermatologically acceptable aqueous dispersion material.
Various topical compositions forming sprays, creams and ointments require in addition to the acorn derivative and water such inactive components as surfactants, antioxidants, emulsifiers, stabilizers, dispersants, and preservatives. In another aspect of the invention additional active components of the topical composition are disclosed such as anesthetics, antipruritics and antihistamines.
The Prophylactic Effect and the Mechanism of Action of the Acorn Extract
As discussed in some detail in the Background Information, it is believed that the allergic response to urushiol has an initial sensitization phase followed by a delayed hypersensitivity reaction in the dermal layers of the skin. While the exact reaction mechanism is not fully understood, researchers believe that the urushiol resins enter the superficial layers of the human dermis where it attaches to tissue proteins to produce a hapten in about 10 minutes or less. The protein molecules are attached on the surface of specialized white blood cells known as Langerhans cells in the epidermis and to macrophages in the dermis skin layers. The Langerhans cells communicate the antigen information to inducer lymphocyte cells, which proliferate into circulating T-memory and T-effector lymphocytes. The immune lymphocytes are now sensitized to additional urushiol entry into the skin layers.
With subsequent urushiol exposure, the subject has a delayed hypersensitivity reaction, which allows T-cells to invade the skin area containing the newly deposited urushiol. It is further hypothesized that the acorn extract provides a physical and mechanical barrier which protects exposed skin or mucous membrane surfaces from harmful stimuli and annoying irritants. Exposed skin or mucous membranes surfaces are isolated from harmful stimuli and annoying irritants because the physical and chemical properties of acorn derivatives include a protective demulcent effect. It is also hypothesized that the proteins, carbohydrates, lipids, divalent metals in the acorn derivatives, and the Maillard reaction components in the acorn extract preferentially bind and thereby inactivate urushiol resin.
Additionally, the acorn extract also binds and inactivates the urushiol components during the elicitation phase of the antigenic response. The aqueous acorn extract hereof also controls the osmotic pressure of water with respect to the skin and permits adequate water to enter into the stratum corneum. The acorn extract leaves a thin occlusive film or coating on the skin which retains the absorbed moisture. As a result of this coating, a dual action occurs, namely: (1) the acorn extract proteins, carbohydrate, divalent metals and Maillard reaction products bind the urushiol stimuli components and reduce further antigenic response; and, (2) the lipid, protein, carbohydrate, and Maillard reaction components protect against urushiol irritation by moisturizing the skin. Acorn extract thereby acts as an antipuritic and has a generally soothing demulcent effect.
Several examples of various ointments, creams, aqueous solutions, sprays and the like for the treatment of contact dermatitis are presented hereinbelow. All of the preparations contain a most efficacious active ingredient, namely, a vegetable product derived from the acorn. The acorns utilized can be from Red Oak (Quercus rupra), Black Oak (Quercus shumardi i Buckl.) Scarlet Oak (Quercus coccinea Muenchb.), Willow Oak (Quercus phellos L.) and other species of the Erythrobalanus group. For purposes of this application an acorn derivative is defined as any of the following forms; an acorn powder produced by roasting the acorn nuts, shells and caps and further processing the product thereof by, for example, triturating, grinding, milling, and/or screening; an acorn ash or the solid residue remaining after burning the combustible portion; an acorn mash, namely, a solution of crushed acorn nuts; and, an acorn extract, namely, a suspension or dispersion using powder, ash, and/or mash and suitable aqueous and non-aqueous diluents.
Acorn is composed of water, proteins, lipids, carbohydrates, minerals, and vitamins. When the acorn is roasted, the roasting process generates Maillard or sugar-amine reactions and produces sugar fragmentation and other reaction products. In this regard the acorn extract is distinguished from oak bark and tannic acid mentioned, supra, based on composition and Maillard reaction products. While some tannins may be derived from the acorn shells and hats, the coloration of the roasted product suggests the formation of some melanoids as a result of the roasting process.
In one method, prior to preparing an extract, the raw or roasted acorns are converted into ash by burning off the organic materials. The ash inorganic material is cooled and screened to provide a powder.
Preparing the Acorn Extracts
Acorn extract, suspensions, and dispersions for use in the present invention are prepared from raw acorn mash, roasted acorns or acorn ash. Acorn mash is prepared by breaking up the shells and hats of raw acorns in order to expose the inner nut portion of the acorn. Roasted acorns are prepared by heating raw acorns between about 90oC. and about 350oC. for between about 5 minutes to 10 hours. The preferred roasting conditions are 200oC. for one hour. The roasted acorns are cooled then prepared for extraction by breaking up the shells and hats in order to expose the inner portion of the acorn.
Various extracts, suspensions, and dispersions can be prepared by those familiar with the art. The extracts can be prepared from water, super critical CO2, or various polarity solvents. The solvents include alcohols, ethers, hexanes, methylene chloride, and others. The preferred extract, suspension, and dispersion are prepared using water.
The mash or roasted acorns are extracted in water for a period of time. The water temperature can range from about 10oC to 100oC., with stirring for a period of time ranging from 10 minutes to 24 hours in order to prepare an intermediate. The time temperature relationship is also concentration dependent. The preferred extract, suspension, or dispersion is prepared from about 10% material at 100oC. for 1-hour. The intermediate is screened to remove the large particles and thereby reduces the concentration of the acorn extract to about 5%. These extracts may also be filtered. The aqueous extracts in accordance with the invention are complex mixtures of organic and inorganic materials.
The mash or roasted acorns are extracted in intermediate polarity solvents such as alcohol for a period of time. The preferred alcohol is ethanol at room temperature or with slight heating. The alcohol may also be distilled and condensed over the acorn material to provide continuous extraction with pure solvent similar to that used in a soxlet extractor in order to prepare an intermediate. The time temperature relationship is concentration dependent and varies from one concentration to another. The preferred extract from about 10% material at for 1-hour.
The intermediate is screened to remove the large particles and thereby reduces the concentration of the acorn extract to about 5%. These extracts may also be filtered. The alcoholic extracts in accordance with the invention are complex mixtures of organic and inorganic materials. The alcohol may be evaporated off to produce a concentrated extract or used as is to formulate.
The mash or roasted acorns are extracted in non-polar solvents such as hexane, methylene chloride, and ethers for a period of time. The preferred nonpolar solvent is hexane at room temperature or with slight heating. The hexane may also be distilled and condensed over the acorn material to provide continuous extraction with pure solvent similar to that used in a soxlet extractor in order to prepare an intermediate. The time temperature relationship is also concentration dependent. The preferred extract from about 10% material at for 1-hour. The intermediate is screened to remove the large particles and thereby reduces the concentration of the acorn extract to about 5%. These extracts may also be filtered. The nonpolar solvent extracts in accordance with the invention are complex mixtures of organic and inorganic materials. The nonpolar solvent is evaporated off to produce a concentrated extract. Acorn Ash can be used to formulate directly. Additional nonpolar acorn extracts may be prepared by using super critical CO2 extractions techniques. In particular, compositions containing about 0.1% or more, preferably 0.5 to 75% and more preferably 0.5 to 10% or acorn extract according to the invention can be used to treat poison ivy.
Preparing the Compositions
The compositions prepared as described in general hereinbelow are prepared from acorn derivatives, including acorn mash, acorn roast and acorn ash. These ingredients which are initially in particulate form are, prior to manufacturing, screened to select particle size using USA Standard Testing Sieves Nos. 70 to 30, preferably No. 50. Prior to final screening, a particle size reduction step is employed utilizing herringbone-perforated or round-hole-perforated reducing screens. For aqueous dispersions, the screened and reduced particle-size acorn material is then mixed with purified water with a commercially available mixer, such as a Lightnin' Mixer.
After mixing, preservatives are then added to the mixture. If desired additional ingredients such as surfactants and emulsifying agents, antihistamines, topical anesthetics, colloidal oatmeal, topical antipruritics, astringents, and emollients may be added to the aqueous acorn dispersion. The ingredients may be added in such a ratio and processing varied as to create a spray, cream, gel, ointment, or lotion.
The most frequently used preservative for the formulations herein are benzoic acid and derivatives thereof, namely, butylparaben, ethylparaben, methylparaben, propylparaben, sodium benzoate, and mixtures thereof. Typical use of benzoic-acid-derived preservative is a mixture of methylparaben comprising up to 0.3 percent by weight of the treating composition and propylparaben comprising up to 0.1 percent by weight of the treating composition.
Other useful preservatives include alcohol, benzalkonium chloride, benzethonium chloride, benzyl alcohol, bronopol, cetrimide, chlorhexidine, chlorobutanol, chlorocresol, cresol, glycerin, imidurea, phenol, phenoxyethanol, phenylethyl alcohol, phenylmercuric acetate, phenylmercuric borate, phenylmercuric nitrate, potassium sorbate, propylene glycol, sodium propionate, sorbic acid and thimerosal.
Among the inactive ingredients are surfactants and emulsifying agents. These ingredients take on importance as the use thereof improves absorption, coverage, appearance, and feel of the product. Some suitable emulsifying agents are acacia, anionic emulsifying wax, carbomer, carboxymethyl cellulose, cetostearyl alcohol, cetyl alcohol, cholesterol, diethanolamine, glyceryl monostearate, hydrous lanolin, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, lanolin, lanolin alcohols, lecithin, methylcellulose, mineral oil and lanolin alcohols, monobasic sodium phosphate, monoethanolamine, nonionic emulsifying wax, oleic acid, poloxamer, polyoxyethylene alkyl ethers, polyoxyethylene castor oil derivatives, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearates, propylene glycol alginate, sodium lauryl sulfate, sorbitan esters, stearic acid, triethanolamine, and xanthan gum. Frequently mixtures of complimentary surfactants are used in a given formulation.
In the examples applying the present invention anionic, cationic and nonionic surfactants are selected. The anionic surfactants are lauryl sulfates, including sodium lauryl sulfate, triethanolamine lauryl sulfate, and ammonium lauryl sulfate; laureth sulfates,including sodium laureth sulfate, triethanolamine laureth sulfate, and ammonium laureth sulfate; sarcosines, including lauryl sarcosine, and sodium lauryl sarcosinate; sulfosuccinates, including disodium oleamine sulfosuccinate, and sodium dioctyl sulfosuccinate; and docusate sodium. The cationic surfactants are benzalkonium chloride, benzethonium chloride, and cetrimide. The nonionic surfactants are glyceryl monooleate, polyvinyl alcohol, sorbitan esters, povidone, crospovidone, polyoxyethylene fatty alcohols, polyoxyethylene sorbitol esters, and alkanolamides. Additionally, in the examples applying the present invention, amphoteric detergents such as betaines, sultaines, and imidazolinium derivatives are used, and particularly ingredients such as cocamidopropyl betaine and sodium lauraminopropionate.
In the ointment and cream preparations hereinbelow, emollients form a vehicle to carry the active ingredients to the site of the urushiol response and the associated dermatitis. The emollient group from which these carriers are selected include allantoin, cetostearyl alcohol, cetyl esters wax, cocoa butter, cholesterol, dimethicone, glycerin, glyceryl monostearate, isopropyl myristate, isopropyl palmitate, kaolin, lecithin, light mineral oil, mineral oil, mineral oil and lanolin alcohols, petrolatum, and petrolatum and lanolin alcohols.
One of the functions of the formulations is to remove the urushiol resin from the skin. This requires astringent activity, and while the acorn derivative provides a satisfactory level of astringency the addition of aluminum acetate, zinc oxide, zinc acetate, sodium bicarbonate, calamine, witch hazel, zinc carbonate, and aluminum hydroxide has been employed to enhance this physical property.
It has been found that the antipruritic activity of the acorn derivative hereof is compatible with other well-known antipruritic agents and when combined therewith provide unexpected synergy. Such agents include phenol, camphor, menthol, hydro-cortisone, hydrocortisone acetate, camphorated metacresol, phenolated sodium, and mixtures thereof. As is shown in the examples which follow the effect is gained by the addition of menthol comprising up to 0.2 percent by weight of the formulation or the addition hydrocortisone acetate comprising up to 1.0 percent by weight of the formulation.
The antihistamines added to the topical compositions are typically from the structural classes of ethylenediamines, aminoalkylethers, and alkylamines. Among the ethylenediamine group are such antihistamines as antazoline phosphate, clemizole hydrochloride, chlorcyclizine hydrochloride, chlorothen, methapheniline hydrochloride, dorastine hydrochloride, methdilazine hydrochloride, promethazine hydrochloride, pyrathiazine hydrochloride, pyrilamine maleate, quinetolate, thenaldine, thenyldiamine hydrochloride, thonzylamine hydrochloride, tripelennamine, and zolamine hydrochloride. Among the aminoalkylether group are such antihistamines as chlorphenoxamine hydrochloride, carbinoxamine maleate, clemastine, diphenhydramine hydrochloride, diphenylpyraline hydrochloride, doxylamine succinate, and pyroxamine maleate. Among the alkamine group are such antihistamines as azatadine maleate, bromdiphenhydramine hydrochloride, cyproheptadine hydrochloride, dimethindene maleate, phenindamine tartrate, pheniramine maleate, brompheniramine maleate, dexbrompheniramine maleate, chlorpheniramine maleate, dex-chlorpheniramine maleate, closiramine, cycliramine maleate, mianserin hydrochloride, pyrrobutamine phosphate, terfenadine, and triprolidine hydrochloride. Besides the above, some compositions in structural groups, which groups are not primarily antihistamines such as phenothiazines, piperidines, and piperazines, have antihistaminic characteristics. These groups include promethazine, astemizole, fexofenadine, loratadine, desloratadine, terfenadine, cetirizine, and meclizin, which are antihistaminic.
Another active ingredient used in the formulations hereof is the employment of a topical anesthetic in conjunction with the antipruritic and demulcent effect of the acorn derivative. Here in by the addition of this class of compounds, the user experiences the reversible abolition of sensory perception, especially the sensations of pain and extreme irritation. While some of these topical anesthetic compounds are structurally related to the antihistamines in the preceding paragraph, the compounds take on a disinct role in preparations described. The first group are esters of benzoic acid and diethylaminoethyl alcohols, namely, benzocaine, chloroprocaine, procaine, and tetracaine. Other synthetic anesthetic compounds, which are not esters of benzoic acid and are pharmacologically grouped together, are bupivacaine, dibucaine, lidocaine, mepivacaine, and prilocaine. Besides these two groups, the compounds of etidocaine and pramoxine are also applicable. In one of the topical spray formulations described below the anesthetic, pramoxine hydrochloride, comprises up to 1.0 percent by weight thereof.
Colloidal oatmeal, when used in the formulations hereinbelow, because of the hydrophilic nature thereof, acts at the site of application to control the osmotic pressure of water with respect to the skin and permits adequate water to enter into the stratum corneum. Oatmeal leaves an occlusive film on the skin that serves to hold in moisture, which protects the skin against irritation and acts as an antipruritic. The USP grade of colloidal oatmeal described in this invention was obtained from Beacon CMP Corporation, 611 Springfield Road, Kenilworth, N.J. 07033.
Claim 1 of 10 Claims
What is claimed is:
1. A topical spray formulation for reducing a urushiol-induced allergic response and the dermatitis associated therewith, said spray formulation comprising:
an aqueous roasted acorn extract and a nontoxic dermatologically acceptable dispersant material; and,
said acorn extract having 1.0 to 25% percent solids by weight thereof.