US 2013 0303470A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2013/0303470 A1 Smothers (43) Pub. Date: Nov. 14, 2013

(54) EXTRACTION METHOD AND Publication Classification COMPOSITIONS (51) Int. Cl. (71) Applicant: Biotechnology, Inc., San C7H I/08 (2006.01) Antonio, TX (US) A68/60 (2006.01) A613 L/7048 (2006.01) (72) Inventor: Donald L. Smothers, Terrell, TX (US) (52) U.S. Cl. CPC ...... C07H I/08 (2013.01); A61 K3I/7048 (21) Appl. No.: 13/944,720 (2013.01); A61K 8/602 (2013.01) USPC ...... 514/26:536/6.3 (22) Filed: Jul. 17, 2013 (57) ABSTRACT Related U.S. Application Data The present invention pertains to methods of extracting car (63) Continuation of application No. 12/578,436, filed on diac systs from arts gy sing play Oct. 13, 2009, now Pat. No. 8524286 material, such as Nerium oteanaer, t rougn use of aloe. It • - s s • L vs. 8 Y-sa-1 is a Y- a • further provides for compositions resulting from Such extrac (60) Provisional application No. 61/105,133, filed on Oct. tions, pharmaceutical compositions, cosmetic compositions, 14, 2008. and methods of treating skin conditions. US 2013/0303470 A1 Nov. 14, 2013

PLANT EXTRACTION METHOD AND bility of the cardiac glycosides to some extent. More recently, COMPOSITIONS U.S. Pat. No. 7,402.325, which is hereby incorporated by reference in its entirety, has described use of supercritical CROSS-REFERENCE TO RELATED CO as extracting higher yields of desired product from pow APPLICATIONS dered oleander . Extraction with supercritical CO 0001. This application is a continuation of U.S. applica necessitates use of high pressure apparatus (above ca. 100 tion Ser. No. 12/578,436, filed Oct. 13, 2009, which claims atmospheres), with all of its attendant hazards. the benefit of U.S. Provisional Application No. 61/105,133, 0007 Accordingly, a need exists for a way to extract ole filed on Oct. 14, 2008. The disclosures of all the above are andrin and other cardiac glycosides more efficiently from incorporated herein by reference in their entireties for all various plant species such as Nerium without use of excessive purposes. heat or high pressure apparatus. SUMMARY OF THE INVENTION FIELD OF THE INVENTION 0008. The present invention provides a method to extract 0002 The present invention pertains to methods of cardiac glycosides from a -containing plant extracting materials from biological sources, and particularly species, such as a Nerium species, through use of aloe, such as from plant matter for cosmetic and medicinal applications. that derived from Aloe vera. It further provides compositions resulting from Such extraction. DESCRIPTION OF THE RELATED ART 0009 Specifically, it provides a method of performing an 0003 Biological sources have provided the bases for extraction of plant material derived from a cardiac glycoside medicines and cosmetics from the earliest days of mankind. containing plant species, such as a species from the genus Most such sources have been , which initially were used Nerium, comprising agitating the plant material in aloe muci as is. Oftentimes, however, it is desirable to extract materials lage and separating the extract from any remaining Solid from plants, as for example when the desired material con material. stitutes only a small proportion of a given plant, or when the 0010. The extraction method optionally involves heating material occurs in the presence of other, undesirable constitu the solution from about 40°C. to about 100° C., optionally entS. including use of extraction adjuvants such as alcohols, 0004 Glycosides represent an important class of com ketones, and esters. pounds extracted from plant sources. Cardiac glycosides, for 0011. An embodiment provides a method of extracting example, are glycosylated Steroids, i.e., steroids conjugated cardiac glycosides comprising intermixing a cardiac glyco to a carbohydrate moiety. Examples of cardiac glycosides side plant species with aloe under conditions selected to form include those useful in the production of Such drugs as an extraction mixture. digoxin and digitoxin. An important class of glycosides 0012. An embodiment further provides conditioning the comes from the genus Nerium, which includes such species as extraction mixture under conditions selected to extract car Nerium indicum, Nerium odorum, and Nerium Oleander, the diac glycosides from the cardiac glycoside plant species to last being the oleander plant native to Asia and the Mediter form a conditioned extraction mixture, wherein the condi ranean littoral and now found also in parts of the United tioned extraction mixture comprises residual cardiac glyco States. The various Nerium species afford Such glycosides as side plant species and a cardiac glycoside aloe mixture. oleandrin, which finds extensive use in medicine. 0013 An embodiment further provides separating at least 0005 Extraction of cardiac glycosides from Nerium ole a portion of the cardiac glycoside aloe mixture from the ander facilitates their use clinically by allowing administra residual cardiac glycoside plant species to form a cardiac tion of compositions of known potency and purity. Previous glycoside aloe extract, where the cardiac glycoside aloe methods of extracting these glycosides have employed hot extract comprises cardiac glycosides extracted from a cardiac water, as described in U.S. Pat. No. 5,135,745 and U.S. Pat. glycoside plant species, and where the cardiac glycoside aloe No. 6,565,897, as well as U.S. Patent Publication No. extract is Substantially free of the residual cardiac glycoside 20060188585, each of which is hereby incorporated by ref plant species. erence in its entirety. Owing to the large lipophilic steroidal 0014. In some embodiments the cardiac glycoside plant moiety, however, oleandrin has poor aqueous solubility, species belongs to a family selected from , Bras which limits the effectiveness of aqueous extraction. Further sicaceae, Plantaginaceae, Ruscaceae, or Hyacinthaceae. more, plants generally have waxy cuticles Surrounding their 0015. In some embodiments the cardiac glycoside plant exterior Surfaces to minimize desiccation. This waxy cuticle belongs to the species Nerium indicuin or Nerium Oleander: not only limits the egress of water from the plant to the 0016. In some embodiments the conditioning comprises exterior, but also the ingress of water from the exterior into the heating the extraction mixture to a temperature in the range of plant, and thus further impedes efficientaqueous extraction of about 40°C. to about 100° C. to form the conditioned extrac the desired cardiac glycosides. Also, the desired cardiac gly tion mixture. cosides can hydrolyze or otherwise decompose on long expo 0017. In some embodiments the conditioning comprises sure to hot water. heating the extraction mixture for a heating time in the range 0006. One solution to these problems has been to perform of about 1 to about 10 hours. the extraction not with pure water, but with a mixture of water 0018. In some embodiments the separating comprises and a water-miscible alcohol. Such as methanol or ethanol, as Subjecting the conditioned extraction mixture to a separation described in U.S. Patent Publication No., 20070154573, method selected from the group consisting of filtration, cen which is hereby incorporated by reference in its entirety. Use trifugation, and decanting. of aqueous alcohol increases both the penetration of the 0019. In some embodiments the extraction mixture com extraction solvent into the interior of the plant and the solu prises an amount of the cardiac glycoside plant species in the US 2013/0303470 A1 Nov. 14, 2013

range of about one part to about 50 parts by weight and an 0033. In some embodiments, the extraction mixture com amount of the aloe in the range of about one part to about 100 prises an amount of cardiac glycoside plant species in the parts by weight, based on the total weight of extraction mix range of about one part to about 50 parts by weight and an ture. amount of aloe in the range of about one part to about 100 0020. In some embodiments the extraction mixture com parts by weight, based on total weight of the extraction mix prises an adjuvant selected from the group consisting of alco ture. hols, ketones, and esters. 0034. An embodiment further provides conditioning the 0021. An embodiment provides a cardiac glycoside aloe extraction mixture under conditions selected to extract car composition, comprising aloe and at least one cardiac glyco diac glycosides from cardiac glycoside plant species to form side. a conditioned extraction mixture, wherein the conditioned 0022. In some embodiments, the cardiac glycoside is a extraction mixture comprises residual cardiac glycoside plant cardiac glycoside aloe extract from a cardiac glycoside plant species and a cardiac glycoside aloe mixture. species. 0035 Examples of conditioning the extraction mixture 0023. In some embodiments, the cardiac glycoside aloe composition is a cardiac glycoside aloe extract wherein the under conditions selected to extract cardiac glycosides from cardiac glycoside plant species is Nerium Oleander: cardiac glycoside plant species, include heating the extraction 0024. An embodiment provides pharmaceutical composi mixture, agitating the extraction mixture, and heating the tions comprising aloe, at least one cardiac glycoside and a extraction mixture with agitation. pharmaceutically acceptable carrier. Another embodiment 0036. In some embodiments, conditioning the extraction provides cosmetic compositions comprising aloe, at least one mixture under conditions selected to extract cardiac glyco cardiac glycoside and a dermal agent. sides from cardiac glycoside plant species comprises heating 0025. In certain embodiments, a method of treatment is the extraction mixture to a temperature in the range of about provided comprising identifying a Subject having a skin con 40° C. to about 100° C. to form a conditioned extraction dition and applying an effective amount of the pharmaceuti mixture. cal composition comprising aloe and at least one cardiac 0037. In some embodiments, conditioning the extraction glycoside to the skin of a subject to thereby treat the skin mixture under conditions selected to extract cardiac glyco condition. sides from cardiac glycoside plant species comprises heating 0026. In certain embodiments the skin condition is the extraction mixture for a time in the range of about 1 to selected from the group consisting of abscesses, acne, actinic about 10 hours to form a conditioned extraction mixture. keratosis, age spots, liver spots, burns, Sunburn, heat burn, 0038. In some embodiments, a conditioned extraction radiation burn, cold Sores, corns, eczema, psoriasis, ring mixture comprises a mixture where a portion of the cardiac worm, Scabies, skin cancers, basal skin cancer, Squamous glycosides from the cardiac glycoside plant species are skin cancer, melanoma skin cancer, skin tags, and warts. extracted into the aloe present in the mixture. Thus, the result 0027. These and other embodiments are described in of conditioning is to form a conditioned extraction mixture greater detail below. that contains residual cardiac glycoside plant species and a cardiac glycoside aloe mixture that contains both aloe and the DETAILED DESCRIPTION OF THE PREFERRED cardiac glycoside(s) extracted into the aloe from the cardiac EMBODIMENTS glycoside plant species. 0028. An embodiment provides a method of extracting 0039. An embodiment further provides separating at least cardiac glycosides, comprising intermixing a cardiac glyco a portion of the cardiac glycoside aloe mixture from the side plant species with aloe under conditions selected to form residual cardiac glycoside plant species to form a cardiac an extraction mixture. glycoside aloe extract. 0029. Examples of cardiac glycoside plant species include 0040 Those skilled in the art will appreciate that the car those in the family Apocynaceae (dogbane), particularly in diac glycoside aloe extract may contain, in addition to cardiac the genera Nerium, Strophanthus, Apocynum, Thevetia, and glycoside(s), other components extracted by the aloe from the Catharanthus, the family Brassicaceae, particularly in the cardiac glycoside plant species, such as, for example, genus Cheiranthus, the family Plantaginaceae, particularly in polysaccharide(s). the genus Digitalis, the family Ruscaceae, particularly in the 0041. Examples of separating at least a portion of the genus Convallaria, and in the family Hyacinthaceae, particu cardiac glycoside aloe mixture from the residual cardiac gly larly in the genus Urginea. coside plant species include filtration, separation, and decant 0030 Examples of particular cardiac glycoside plant spe ing. cies include Nerium oleander. Thevetia nerifolia, Digitalis 0042. In some embodiments, the cardiac glycoside aloe purpurea, Digitalis lanate, Convallaria majalis, Urginea extract comprises cardiac glycosides extracted from the car maritima, Urginea indica, , Apocynum diac glycoside plant species. cannabinum, Cheiranthus cheiri. 0043. In some embodiments, the cardiac glycoside aloe 0031. The term “aloe' refers to a genus of plants native to extract is Substantially free of the residual cardiac glycoside and comprising about 400 species, including Aloe plant species. arborescens, Aloe aristata, Aloe dichotoma, Aloe inveriensis, Aloe varvegata, Aloe wildii, and Aloe barbadensis miller. 0044. In some embodiments, the extraction mixture com 0032. In some embodiments, the conditions selected to prises an adjuvant selected from the group consisting of alco form an extraction mixture comprise mixing aloe with the hols, ketones, and esters. leaves and stems of a cardiac glycoside plant species that are 0045. A further embodiment provides a cardiac glycoside optionally cut into pieces, milled, or powdered to facilitate the aloe composition, comprising aloe and at least one cardiac extraction. glycoside. US 2013/0303470 A1 Nov. 14, 2013

0046. In some embodiments, the cardiac glycoside is a badensis miller, while “mucilage” refers to the mucilage cardiac glycoside aloe extract from a cardiac glycoside plant neous gel obtained from within their leaves. species. 0056. In use, mucilage derived from an Aloe species, such 0047. In some embodiments, the cardiac glycoside aloe as Aloe barbadensis miller, is obtained by methods well composition is a cardiac glycoside aloe extract wherein the known to those skilled in the art. For example, U.S. Pat. No. cardiac glycoside plant species is Nerium Oleander: 4.957.907, which is hereby incorporated by reference in its 0048. An embodiment provides pharmaceutical composi entirety, describes in detail one procedure for extracting aloe tions comprising a cardiac glycoside aloe composition com plant material. prising aloe, at least one cardiac glycoside and a pharmaceu 0057 The aloe is then mixed with plant material in a tically acceptable carrier. Examples of pharmaceutically manner selected to extract cardiac glycosides. For example, acceptable carriers include dermal agents as well as the car the mucilage obtained from an aloe plant is then mixed with riers known to those skilled in the pharmaceutical arts for plant material from a Nerium species, such as Nerium Olean inclusion in orally administrable forms such as pills, capsules der in a ratio of about 1-100 parts of aloe to one of oleander and Sublingual compositions. on a weight basis, and preferably 5-20 parts of aloe to one of 0049. Examples of dermal agents include cosmetic com Oleander, and most preferably about nine parts of aloe to one positions and various ingredients known to those skilled in of Oleander, although the exact proportions are not critical. the art of formulating them, Such as, for example, an oily The plant material can include leaves and stems that are ointment, an aqueous ointment, a cream, a lotion (e.g., a optionally cut into pieces, milled, or powdered to facilitate the cosmetic lotion, a face lotion), an emulsion, a pack, a soap, a extraction. If desired, the plant material can be dried before face wash, a makeup (a body makeup, a face makeup) and extraction and can be powdered to increase the Surface area. combinations thereof. 0058. In an embodiment, the vessel is then heated to with 0050. An embodiment provides pharmaceutical composi agitation to about 40°C. to about 100° C., for about one to 10 tions comprising a cardiac glycoside aloe extract from a car hours, but the time is not critical. The time to achieve a desired diac glycoside plant species and a dermal agent. degree of extraction can be readily determined by those 0051. In certain embodiments, a method of treatment is skilled in the art. Similarly, agitation can be accomplished by provided comprising identifying a Subject having a skin con shaking, Vortexing, Sonicating, or other method, the choice of dition and applying an effective amount of the pharmaceuti which is not critical. cal composition (e.g., comprising aloe and at least one cardiac 0059. In a preferred embodiment, the vessel is heated with glycoside) to the skin of a subject to thereby treat the skin agitation to about 80°C. for about five hours. The vessel is condition. In this context, the treatment of the skin condition then cooled to room temperature, and the Solids separated does not necessarily imply medical treatment, and thus for from the extract by a suitable method, such as settling, filter example may include providing a benefit typically associated ing, decanting, Screening, or centrifuging, or some combina with the application of a cosmetic. Such as soothing, softening tion of these separation methods. or moisturizing the skin and/or hair. 0060. If desired, the resulting effluent can then be filtered 0052 Examples of a “skin condition' include abscesses, through 1 micron screen, followed by an optional further dry skin, Sun-damaged skin, aging skin, acne, actinic kerato filtration through a screen with openings between about 0.5 sis, age spots, liver spots, burns, Sunburn, heat burn, radiation and 1 micron in diameter. burn, cold Sores, corns, eczema, psoriasis, ringworm, Scabies, 0061. In one embodiment, the extraction is performed by skin cancers, basal skin cancer, Squamous skin cancer, mela immersing material from a cardiac glycoside-containing noma skin cancer, skin tags, and/or warts. plant species, such as Nerium Oleander, in a vessel containing 0053 An embodiment provides a method of extracting the aloe-containing extraction solution. The plant material compounds, including in particular medicinally valuable gly can include leaves and stems that are optionally cut into cosides, from material derived from a cardiac glycoside-con pieces to facilitate extraction. If desired, the plant material is taining plant species. Cardiac glycoside-containing plant spe dried before extraction, and can optionally also be powdered cies are found in the family Apocynaceae (dogbane), to increase the Surface area. particularly in the genera Nerium, Strophanthus, Apocynum, 0062 Similarly, the extraction can be performed at any Thevetia, and Catharanthus, the family Brassicaceae, par temperature above the freezing point of the solution. In one ticularly in the genus Cheiranthus, the family Plantaginaceae, embodiment, the extraction is performed at room tempera particularly in the genus Digitalis, the family Ruscaceae, ture, but if desired, an elevated temperature can also be used, particularly in the genus Convallaria, and in the family Hya as the temperature is not critical. cinthaceae, particularly in the genus Urginea. 0063. Furthermore, if desired, an extraction adjuvant can 0054 Particular species include Nerium oleander. Thev be added to the solution. Such adjuvant can be an organic etia nerifolia, , Digitalis lanate, Conval alcohol, ether, ketone, or ester. Examples include methanol, laria majalis, Urginea maritima, Urginea indica, Strophan ethanol, n- and iso-propanol, methoxyethanol, 2-butoxyetha thus gratus, Apocynum cannabinum, Cheiranthus cheiri. In a nol, diethyl ether, acetone, butanone, and ethyl acetate, and preferred embodiment, the material is derived from Nerium mixtures of Such solvents. Oleander, the well-known Oleander plant. 0064. After extraction has proceeded to the desired extent, 0055. The applicant has found that use of aloe mucilage the extract can be separated from the remaining plant material enhances the extraction efficiency of medicinally useful by a variety of methods, including filtration, centrifugation, extracts from cardiac glycoside-containing plant species, and decantation, all methods well-known in the art, to pro such as those cited above. The term “aloe' refers to a genus of duce the aloe-based extract. plants native to Africa and comprising about 400 species, 0065. The resulting aloe-based extract can be used medici including Aloe arborescens, Aloe aristata, Aloe dichotoma, nally either as prepared, or can be further treated if desired, Aloe inveriensis, Aloe varvegata, Aloe wildii, and Aloe bar for example by evaporation of some of the solution either at US 2013/0303470 A1 Nov. 14, 2013

atmospheric or reduced pressure, and either at room tempera a disease or condition), and the route of application or admin ture or an elevated temperature. Alternatively, if desired, the istration chosen. Any of the well-known techniques, carriers, extract composition can be freeze-dried, or spray-dried, or and excipients may be used as Suitable and as understood in Subjected to liquid-liquid extraction. the art; e.g., in Remington’s Pharmaceutical Sciences, above. 0066. The term “pharmaceutical composition” refers to a 0074 For injection, the aloe extract may be formulated in mixture of a cardiac glycoside aloe extract as described herein aqueous Solutions, preferably in physiologically compatible with other chemical components, such as diluents or carriers. buffers such as Hanks’s solution, Ringer's solution, or physi The pharmaceutical composition facilitates application or ological saline buffer. For transmucosal administration, pen administration of the aloe extract to an organism. Multiple etrants appropriate to the barrier to be permeated are used in techniques of administering a compound exist in the art the formulation. Such penetrants are generally known in the including, but not limited to, oral, injection, aerosol, art. parenteral, and topical application or administration. The 0075 For oral administration, the aloe extract can be for term “pharmaceutical composition' as used herein includes mulated readily by combining with pharmaceutically accept cosmetic compositions and nutraceutical compositions, able carriers well known in the art. Such carriers enable the which are not intended for use in the treatment of a particular aloe extract to be formulated as tablets, pills, Sublingual com disease or condition, and thus the term "pharmaceutical” in positions, dragees, capsules, liquids, gels, syrups, slurries, this context does not necessarily imply that the composition Suspensions and the like, for oral ingestion by a patient to be contains an amount or type of cardiac glycoside aloe extract treated. Pharmaceutical preparations for oral use can be that would render the composition useful as a drug. obtained by mixing one or more solid excipients with the aloe 0067. The term “carrier refers to a chemical compound extract described herein, optionally grinding the resulting that facilitates the incorporation of a compound into cells or mixture, and processing the mixture of granules, after adding tissues. For example dimethyl sulfoxide (DMSO) is a com suitable auxiliaries, if desired, to obtain tablets or dragee monly utilized carrier as it facilitates the uptake of many cores. Suitable excipients are, in particular, fillers such as organic compounds into the cells or tissues of an organism. Sugars, including lactose. Sucrose, mannitol, or Sorbitol; cel 0068. The term "diluent” refers to chemical compounds lulose preparations such as, for example, maize starch, wheat diluted in water that will dissolve the aloe extract as well as starch, rice starch, potato starch, gelatin, gum tragacanth, stabilize the biologically active form. Salts dissolved in buff methyl cellulose, hydroxypropylmethyl-cellulose, sodium ered solutions are utilized as diluents in the art. One com carboxymethylcellulose, and/or polyvinylpyrrolidone monly used buffered solution is phosphate buffered saline (PVP). If desired, disintegrating agents may be added, such as because it mimics the salt conditions of human blood. Since the cross-linked polyvinyl pyrrolidone, agar, oralginic acidor buffer salts can control the pH of a solution at low concentra a salt thereof Such as sodium alginate. tions, a buffered diluent rarely modifies the biological activity 0076 Dragee cores are typically provided with suitable of a compound. coatings. For this purpose, concentrated Sugar Solutions may 0069. The term “physiologically acceptable' defines a be used, which may optionally contain gum arabic, talc, poly carrier or diluent that does not abrogate the biological activity vinyl pyrrolidone, carbopol gel, polyethylene glycol, and/or and properties of the aloe extract. titanium dioxide, lacquer Solutions, and Suitable organic Sol 0070 The pharmaceutical compositions described herein vents or solvent mixtures. Dyestuffs or pigments may be can be administered to a human patient perse, or in pharma added to the tablets or dragee coatings for identification or to ceutical compositions where they are mixed with other active characterize different combinations of active compound ingredients, as in combination therapy, or Suitable carriers or doses. excipient(s). Techniques for formulation and administration 0077. Pharmaceutical preparations which can be used of the compounds of the instant application may be found in orally include push-fit capsules made of gelatin, as well as “Remington’s Pharmaceutical Sciences.” Mack Publishing soft, sealed capsules made of gelatin and a plasticizer, Such as Co., Easton, Pa., 18th edition, 1990. glycerol or Sorbitol. The push-fit capsules can contain the aloe 0071 Suitable routes of application and/or administration extract in admixture with filler such as lactose, binders such may, for example, include topical (e.g., in the form a a cos as starches, and/or lubricants such as talc or magnesium Stear metic composition or hair care product), oral, Sublingual, ate and, optionally, stabilizers. In soft capsules, the aloe rectal, transmucosal, or intestinal administration; parenteral extract may be dissolved or Suspended in Suitable liquids, delivery, including intramuscular, Subcutaneous, intrave Such as fatty oils, liquid paraffin, or liquid polyethylene gly nous, intramedullary injections, as well as intrathecal, direct cols. In addition, stabilizers may be added. All formulations intraventricular, intraperitoneal, intranasal, or intraocular for oral administration should be in dosages Suitable for Such injections. administration. 0072 The pharmaceutical compositions described herein 0078 For buccal administration, the compositions may may be manufactured in a manner that is itself known, e.g., by take the form of tablets or lozenges formulated in conven means of conventional mixing, dissolving, granulating, dra tional manner. gee-making, levigating, emulsifying, encapsulating, entrap 0079 Alternatively, the active ingredient may be in pow ping or tabletting processes. der form for constitution with a suitable vehicle, e.g., sterile 0073 Pharmaceutical compositions for use in accordance pyrogen-free water, before use. with the present invention thus may beformulated in conven 0080. An example of a pharmaceutical carrier for hydro tional manner using one or more physiologically acceptable phobic aloe extracts is a cosolvent system comprising benzyl carriers comprising excipients and auxiliaries which facilitate alcohol, a nonpolar Surfactant, a water-miscible organic poly processing of the active compounds into preparations which mer, and an aqueous phase. A common cosolvent system used can be used pharmaceutically. Proper formulation is depen is the VPD co-solvent system, which is a solution of 3% w/v. dent upon the intended use (e.g., cosmetic versus treatment of benzyl alcohol, 8% w/v of the nonpolar surfactant Polysor US 2013/0303470 A1 Nov. 14, 2013 bate 80TM, and 65% w/v polyethylene glycol 300, made up to been processed to a liquid with a maximum anthraquinone volume in absolute ethanol. Naturally, the proportions of a (aloin and/or aloe emodin) content of 1 ppm, pH of 3.7-4.1, co-solvent system may be varied considerably without and containing 0.1% potassium Sorbate. destroying its solubility and toxicity characteristics. Further I0086. The extraction mixture was agitated until homoge more, the identity of the co-solvent components may be var neous, and the container with the extraction mixture was ied: for example, other low-toxicity nonpolar Surfactants may placed into a temperature controlled water bath with the water be used instead of POLYSORBATE 80TM; the fraction size of level in the water bath maintained at 60%-80% of the level of polyethylene glycol may be varied; other biocompatible the extraction mixture in the container. The water bath was polymers may replace polyethylene glycol, e.g., polyvinyl heated to 80-85°C. and held at that temperature for five hours pyrrolidone; and other Sugars or polysaccharides may substi with no agitation. The conditioned extraction mixture was tute for dextrose. then covered and allowed to cool. 0081 Alternatively, other delivery systems for hydropho 0087. After the conditioned extraction mixture cooled, a bic aloe extracts may be employed. Liposomes and emulsions portion of the cardiac glycoside aloe mixture was separated are well known examples of delivery vehicles or carriers for from the residual cardiac glycoside plant species as follows:. hydrophobic drugs. Certain organic solvents such as dimeth The cardiac glycoside aloe mixture at the top of the condi ylsulfoxide also may be employed, although usually at the tioned extraction mixture was decanted. The cardiac glyco cost of greater toxicity. Additionally, the aloe extract may be side aloe mixture was then separated from the residual cardiac delivered using a Sustained-release system. Various Sus glycoside plant species by Straining. The cardiac glycoside tained-release materials have been established and are well aloe extract liquid was then combined and agitated until known by those skilled in the art. Sustained-release capsules homogeneous. may, depending on their chemical nature, extend the release I0088. The homogenous cardiac glycoside aloe extract was of the aloe extract for a few hours up to a few weeks. then filtered through a medium of approximately 1 micron 0082 Pharmaceutical compositions suitable for use porosity, followed by a second filtration through a medium of include compositions where the aloe extractis contained in an 0.5-1.0 micron porosity, and the resulting cardiac glycoside amount effective to achieve its intended purpose. More spe aloe extract (Substantially free of the residual cardiac glyco cifically, a therapeutically effective amount means an amount side plant species) was stored in a sealed glass container at of aloe extract effective to prevent, alleviate or ameliorate ambient temperature. symptoms of disease or prolong the Survival of the Subject being treated. Determination of a therapeutically effective Example 2 amount is well within the capability of those skilled in the art, especially in light of the detailed disclosure provided herein. I0089. A pharmaceutical composition was created as fol 0083. The exact formulation, route of administration and lows: A cardiac glycoside aloe extract (Substantially free of dosage for the pharmaceutical compositions can be chosen by the residual cardiac glycoside plant species) prepared as the individual physician in view of the patient’s condition. described in Example 1 was combined with a dermal agent in (See e.g., Fingletal. 1975, in “The Pharmacological Basis of a ratio of 4 parts by weight of cardiac glycoside aloe extract to Therapeutics' Ch. 1 p. 1). Typically, the dose range of the 1 part by weight of dermal agent, based on the total weight of composition administered to the patient can be from about 0.5 the pharmaceutical composition. The dermal agent contained to 1000 mg/kg of the patient’s body weight. The dosage may Glycerin, Methyl Sulfonyl Methane, Oryzo Sativa (Rice be a single one or a series of two or more given in the course Bran) Oil, Ricinus Communis (Castor) Oil, Glyceryl Stearate, of one or more days, as is needed by the patient. Note that for Styrene/Acrylates Copolymer, PEG-100 Stearate, Cetyl water and CO-based plant extracts mentioned in the present Alcohol, Dimethicone, Carbomer, Caprylyl Glycol, Glyc disclosure, human dosages for treatment of at least some erin, Glyceryl Caprylate, Phenylpropanol, Methyl Paraben, condition have been established. Thus, in most instances, Tocopherol (Vitamin E), and Fragrance. those same dosages may be used for the aloe extracts, or dosages that are between about 0.1% and 500%, more pref Example 3 erably between about 25% and 250% of the established (0090 Subjects were identified who suffered from age/ human dosage. Where no human dosage is established, a liver spots. Each Subjects lesion color was determined on a Suitable human dosage can be inferred from EDso or IDso four-grade color Scale ranging from: black, dark brown, light values, or other appropriate values derived from in vitro or in brown, to same color as Surrounding pigment (age spots no Vivo studies, as qualified by toxicity studies and efficacy longer visible). 14 Subjects used the pharmaceutical compo studies in animals. sition prepared as described in Example 2 to spot treat their 0084. The amount of aloe extract administered will gen age/liver spots. 6 subjects used a pharmaceutical composition erally be dependent on the subject being treated, on the sub containing a cream made with a hot-water Nerium Oleander jects weight, the severity of the affliction, the manner of extract to treat their age/liver spots. administration and the judgment of the prescribing physician. 0091. After treatment, the results were measured accord ing to the following scale: complete healing (complete dis EXAMPLES appearance of age spots), good (3 grades decrease in lesion color), partial (2 grades decrease in lesion color), or poor (1 Example 1 grade decrease or no change in lesion color). 0085. An extraction mixture was created as follows: The 0092 Out of the 14 subjects who used the pharmaceutical dried leaves and stems of a cardiac glycoside plant species composition prepared as described in Example 2, 7 subjects, comprising Nerium oleander (100 g) were milled to a fine or 50%, reported either complete healing or 3 grades of powder, weighed into a glass container and intermixed with decrease in lesion color. Out of the 6 subjects who used the aloe comprised of Aloe barbadensis juice (900 g) that had pharmaceutical composition containing a cream made with a US 2013/0303470 A1 Nov. 14, 2013

hot-water extract, 4 subjects, or 67%, reported either com the solid material from the liquid material, wherein the liquid plete healing or 3 grades of decrease in lesion color. material comprises the cardiac glycoside aloe extract. 2. The composition of claim 1, wherein the cardiac glyco Example 4 side plant species is in a family selected from the group consisting of Apocynaceae, Brassicaceae, Plantaginaceae, 0093 Subjects were identified who suffered from acne. Ruscaceae, and Hyacinthaceae. When 13 Subjects used a pharmaceutical composition pre 3. The composition of claim 1, wherein the cardiac glyco pared as described in Example 2 to treat the acne, 9 subjects, side plant species is in a genus selected from the group con or 70%, found the product to be as good as or better than sisting of Nerium, Strophanthus, Apocynum, Thevetia, Proactive Renewing Cleanser, a face cleanser known for use Catharanthus, Cheiranthus, Digitalis, Convallaria, and by persons having acne and commercially available from Urginea. Guthy-Renker, LLC. 4. The composition of claim 1, wherein the cardiac glyco Example 5 side plant species is selected from the group consisting of Nerium Oleander, Thevetia nerifolia, Digitalis purpurea, 0094 Subjects were identified who suffered from Sun Digitalis lanate, Convallaria majalis, Urginea maritima, burn. When 16 of the subjects used a pharmaceutical compo Urginea indica, Strophanthus gratus, Apocynum cannabi sition prepared as described in Example 2 to treat the Sunburn, num, and Chemanthus cheiri. 13 subjects, or 85%, found the product to be as good as or 5. The composition of claim 1, further comprising polysac better than a commercially available sunburn product (Aloe charides. Vera's After Sun Body Lotion with Tea Oil). 6. A pharmaceutical composition comprising the cardiac glycoside aloe composition of claim 1, and further compris Example 6 ing a pharmaceutically acceptable carrier. 0095. A pharmaceutical composition was created as fol 7. The pharmaceutical composition of claim 6 in pill, sub lows: A cardiac glycoside aloe extract (Substantially free of lingual or cosmetic form. the residual cardiac glycoside plant species) as described in 8. The pharmaceutical composition of claim 6, wherein the Example 1 was mixed with a dermal agent in the manner pharmaceutically acceptable carrier comprises a dermal described in Example 2. The dermal agent contained agent. L-Lysine, Styrene/Acrylates Copolymer, Glycerin, Oryzo 9. The pharmaceutical composition of claim 8, wherein the Sativa (Rice Bran) Oil, Glyceryl Stearate, Cetyl Alcohol, dermal agent is selected from the group consisting of an oily Dimethicone, Carbomer, C14-22 Alcohols and C12-20 Alkyl ointment, an aqueous ointment, a cream, a lotion, an emul Glucoside, Olea Europaea (Olive) Leaf Extract, Caprylyl Sion, a pack, a Soap, a face wash, a makeup and combinations Glycol, Glycerin, Glyceryl Caprylate, Phenylpropanol, thereof. Methyl Paraben, Ascorbic Acid, Citric Acid, Lactic Acid, 10. A method of treating a skin condition, comprising Glycerin, Water, Eugenia Caryophyllus (Clove) Flower Oil, identifying a Subject having the skin condition; and and Camphor. applying an effective amount of the pharmaceutical com position of claim 6 to the subject. Example 7 11. The method of claim 10, wherein the skin condition is selected from the group consisting of abscesses, dry skin, 0096. Subjects were identified who suffered from cold Sun-damaged skin, aging skin, acne, actinic keratosis, age sores. When 19 of the subjects with cold sores applied a spots, liver spots, burns, Sunburn, heat burn, radiation burn, pharmaceutical composition prepared as described in cold Sores, corns, eczema, psoriasis, ringworm, scabies, skin Example 6, the following results were noted: tags, warts and combinations thereof. 0097. Of the 14 subjects who had previously used other 12. A method of treating a skin cancer, comprising cold sore treatments, 4 subjects, or 29%, found that it worked identifying a subject in need of skin cancer treatment; and as well as the previous treatments and 8 subjects, or 57%, administering an effective amount of the pharmaceutical found that it worked better than other previously used prod composition of claim 6 to the Subject. uctS. 13. The method of claim 12, wherein the skin cancer is 0098. When 19 subjects with cold sores applied the phar selected from the group consisting of basal skin cancer, squa maceutical composition, Subjects, or 63%, found that the mous skin cancer, and melanoma skin cancer. pharmaceutical composition decreased the appearance/red 14. A cosmetic composition comprising the cardiac glyco ness of the cold Sore compared with previous product expe side aloe composition of claim 1, and further comprising a riences. dermal agent. 0099. It will be understood by those of skill in the art that 15. The cosmetic composition of claim 14, wherein the numerous and various modifications can be made without dermal agent is selected from the group consisting of an oily departing from the spirit of the present invention. Therefore, ointment, an aqueous ointment, a cream, a lotion, an emul it should be clearly understood that the various embodiments Sion, a pack, a Soap, a face wash, a makeup and combinations of the present invention described herein are illustrative only thereof. and not intended to limit the scope of the present invention. 16. A method of applying a cosmetic, comprising applying What is claimed is: a cosmetically effective amount of the cosmetic composition 1. A cardiac glycoside aloe composition, comprising a of claim 14 to a subject. cardiac glycoside aloe extract, wherein the cardiac glycoside 17. A method of extracting a cardiac glycoside plant, com aloe extract is prepared by extracting a cardiac glycoside prising: plant species with aloe to create an extraction mixture com mixing a cardiac glycoside plant with aloe to form a cardiac prising a liquid material and a solid material and separating glycoside aloe extraction mixture; and US 2013/0303470 A1 Nov. 14, 2013

separating a cardiac glycoside aloe extract from the cardiac glycoside aloe extraction mixture. 18. The method of claim 17, further comprising heating the cardiac glycoside aloe extraction mixture to a temperature in the range of about 40°C. to about 100° C. 19. The method of claim 17, wherein the extraction mixture comprises a solvent selected from the group consisting of alcohols, ketones, ethers, esters and mixtures thereof. 20. The method of claim 17, wherein the extraction mixture is heated for about one to 10 hours.

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