The invention concerns a concentrated hormone pharmaceutical composition having from about 0.6 to about 80% of at least one hormone; from about 20 to about 90.4% of at least one solvent, and optionally a pharmaceutically acceptable carrier. The concentrated hormone pharmaceutical composition according to this invention provides a concentrated pharmaceutical composition that is easy to use and saves time and money to the pharmacies dealing with BHRT pharmaceutical products.

Description of the Invention

SUMMARY OF THE INVENTION

The invention offers at least one of the following advantages: a system of concentrated pharmaceutical compositions that is easy to use and saves time and money to the pharmacies dealing with BHRT pharmaceutical products; individualized BHRT products such as ointments, creams, gels, or pastes; and a color-coded hormone pharmaceutical composition.

The concentrated composition of the present invention can be manufactured to contain a higher concentration of hormone (or combination of hormones) than the standard concentration of hormones prescribed by physicians, thus the pharmacist can easily measure the amount required to be incorporated into the BHRT product.

The concentrated composition of the present invention could include any concentration of any hormone or any combination of hormones in any proportion as long as the concentration is greater than the accepted physician prescribed concentrations to treat hormone deficiencies.

The present invention, also relates to a metered dispensing device including the composition of the invention to provide a means to measure and combine, quickly and accurately, quantities of hormones with appropriate ointment, cream, or gel bases by the compounding pharmacist while minimizing exposure to hazardous airborne hormone particles. Thus, airborne particles are drastically reduced because the hormones are incorporated into a liquid or semi-solid form.

The present invention relates to a concentrated hormone pharmaceutical composition comprising: from about 0.6 to about 80% of at least one hormone; from about 20 to about 90.4% of at least one solvent, and optionally a pharmaceutically acceptable carrier.

In the preferred embodiment, the concentrated hormone pharmaceutical composition is chosen from estradiol, estrone, estriol, testosterone, DHEA, pregnenolone, progesterone, or combination thereof.

The invention also relates to a concentrated hormone pharmaceutical composition comprising: from about 0.6 to about 50% of at least one hormone; from about 50 to about 90.4% of at least one solvent, and optionally a pharmaceutically acceptable carrier wherein the at least one hormone is chosen from estriol, estradiol, or combination thereof.

The at least one hormone is a combination of estriol and estradiol in a ratio of 5:5, 6:4, 7:3, 8:2, or 9:1.

Furthermore, the invention concerns a concentrated hormone pharmaceutical composition comprising: from about 0.6 to about 50% of at least one hormone; from about 50 to about 90.4% of at least one solvent, and optionally a pharmaceutically acceptable carrier wherein the at least one hormone is chosen from estriol, estradiol, estrone, or combination thereof.

The at least one hormone is a combination of estriol, estradiol, and estrone in a ratio of 5:4:1, 6:3:1, 7:2:1, or 8:1:1.

Furthermore, the invention concerns a concentrated hormone pharmaceutical composition comprising: from about 0.8 to about 80% of at least one hormone; from about 20 to about 90.2% of at least one solvent, and optionally a pharmaceutically acceptable carrier wherein the at least one hormone is testosterone.

In addition, the invention concerns a concentrated hormone pharmaceutical composition comprising: from about 8 to about 90% of at least one hormone; from about 10 to about 92% of at least one solvent, and optionally a pharmaceutically acceptable carrier wherein the at least one hormone is progesterone.

Furthermore, the invention concerns to a color-coded concentrated hormone pharmaceutical.

Furthermore, the invention concerns a method for producing a concentrated hormone pharmaceutical composition, the method comprising the steps of: measuring at least one hormone, a solvent and/or optionally a carrier by using an electronic balance in a clean room; combining the ingredients of step a by using an industrial scale mixer to ensure thorough mixing; and running the mixture of step b through a large-scale ointment mill or homogenizer to decrease the particle size of the drug, and optionally, heating the concentrate to facilitate the formation of a solution, wherein the hormone concentration is from about 0.6 to about 80%.

Furthermore, the present invention concerns a concentrated hormone pharmaceutical composition comprising: at least one hormone; optionally a powdered base; wherein the at least one hormone is chosen from estriol, estradiol, estrone, or combination thereof; and wherein the composition is in a powdered form.

Finally, the invention concerns a kit for producing a liquid or semi-solid concentrated hormone pharmaceutical composition, the kit comprising: at least one hormone; at least one solvent, and optionally a pharmaceutically acceptable carrier, wherein each element is packet in separated graduated dispensing devices.

The foregoing has outlined rather broadly the more pertinent and important features of the present invention in order that the detailed description of the invention that follows may be better understood, and so that the present contribution to the art can be more fully appreciated. Additional features of the invention that will be described hereinafter form the subject matter of the claims of the invention. It should be appreciated by those skilled in the art that the conception and the specific embodiments disclosed might be readily utilized as a basis for modifying or formulating other liquid formulations for carrying the same purposes of the present invention. It should also be realized by those skilled in the art that such equivalent formulations do not depart from the spirit and scope of the invention as set forth in the appended claims.

DETAILED DESCRIPTION OF THE INVENTION

The present invention concerns a pharmaceutical composition, including high concentrations of hormone that can be used by the compounding pharmacist safely, accurately, quickly, and inexpensively to produce individualized BHRT products such as ointments, creams, gels, or pastes.

The present invention concerns a concentrated hormone pharmaceutical composition comprising: at least one hormone; at least one solvent, and optionally a pharmaceutically acceptable carrier wherein the weight concentration of the at least one hormone in said composition is equal or greater than 0.6%.

In one of the embodiments, the concentrated is in a powdered form.

The term "pharmaceutically acceptable" means approved by a regulatory agency of the Federal or a state government or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in animals, and more particularly in humans.

Hormones

The present invention contemplates the use of any one of the steroid hormones derived from cholesterol including, but not limited to, estrogen (estriol, estradiol, or estrone), progesterone, testosterone, dehydroepiandrosterone, norethisterone acetate, norgestrel, levonorgestrel gestodene CPA chlormadinone acetate, drospirorenone, and 3-ketodesogestrel.

The concentrates also could include, but not be limited to, an estriol concentrate, an estradiol concentrate, an estrone concentrate, a combination estriol, estradiol, and estrone (triest) concentrate in any proportion, preferably in a 8:1:1, 5:4:1, 6:3:1, or 7:2:1 ratio; a combination of estriol and estradiol concentrate (biest) in any proportion, preferably in a 5:5, 6:4, 7:3, 8:2, or 9:1 ratio; a combination estriol and estrone concentrate, a combination estradiol and estrone concentrate, a progesterone concentrate, a combination progesterone and estriol concentrate, a combination progesterone and estradiol concentrate, a combination progesterone and estrone concentrate, a combination progesterone and triest concentrate, a combination progesterone, estriol, and estradiol concentrate, a combination progesterone, estriol, and estrone concentrate, a combination progesterone estradiol, and estrone concentrate, any of the previously mentioned concentrates in combination with testosterone i.e. a combination triest, progesterone, and testosterone concentrate, a testosterone concentrate, any of the previously mentioned concentrates in combination with dehydroepiandrosterone (DHEA), and a DHEA concentrate.

In addition, any of the sex hormones may be used. Any androgen including, but not limited to, testosterone may be used. Any progestogen including, but not limited to, progesterone may be used. Any estrogen including, but not limited to, estriol, estradiol, or estrone may be used.

The concentrated composition of the present invention could include any concentration of any hormone or any combination of hormones in any proportion as long as the concentration is greater than the accepted physician prescribed concentrations to treat hormone deficiencies.

The present invention provides a concentrated pharmaceutical composition that contains any ratio of estriol to estradiol (biest) having between 6 mg/g and 900 mg/g of biest, preferably between 8 mg/g and 200 mg/g, even more preferably 10 mg/g to 60 mg/g.

In addition, the present invention provides a concentrated pharmaceutical composition that contains any ratio of estriol, estradiol, and estrone (triest) having between 6 mg/g and 900 mg/g of the triest, preferably between 8 mg/g and 200 mg/g, even more preferably 10 mg/g and 60 mg/g.

Furthermore, the present invention provides a concentrated pharmaceutical composition that contains between 10 mg/g and 900 mg/g of estriol, preferably between 15 mg/g and 300 mg/g, even more preferably 15 and 60 mg/g.

The present invention provides a concentrated pharmaceutical composition that contains between 1 mg/g and 900 mg/g of estradiol, preferably between 1.5 mg/g and 100 mg/g.

The present invention also provides a concentrated pharmaceutical composition that contains between 1 mg/g and 900 mg/g of estrone, preferably between 1.5 mg/g and 100 mg/g.

In addition, the present invention provides a concentrated pharmaceutical composition that contains between 10 mg/g and 800 mg/g of testosterone, preferably between 15 mg/g and 900 mg/g, even more preferably between 15 mg/g and 300 mg/g, for use in a female BHRT product.

Furthermore, the present invention provides a concentrated pharmaceutical compound that contains between 100 mg/g and 900 mg/g of testosterone, for use in a male BHRT product.

In addition, the present invention provides a concentrated pharmaceutical compound that contains between 200 mg/g and 900 mg/g of progesterone, more preferably between 400 mg/g and 800 mg/g, even more preferably 600 mg/g.

Furthermore, the present invention provides a concentrated pharmaceutical compound that contains between 10 mg/g and 900 mg/g of dehydroepiandrosterone or between 30 mg/g to 800 mg/g of pregnenolone.

The invention also concerns a concentrated hormone pharmaceutical composition comprising: from about 0.6 to about 50% of at least one hormone; from about 50 to about 90.4% of at least one solvent, and optionally a pharmaceutically acceptable carrier wherein the at least one hormone is chosen from estriol, estradiol, or combination thereof.

In addition, the invention concerns a concentrated hormone pharmaceutical composition comprising: from about 0.6 to about 50% of at least one hormone; from about 50 to about 90.4% of at least one solvent, and optionally a pharmaceutically acceptable carrier wherein the at least one hormone is chosen from estriol, estradiol, estrone, or combination thereof.

Furthermore, the invention concerns a concentrated hormone pharmaceutical composition comprising: from about 0.8 to about 80% of at least one hormone; from about 20 to about 90.2% of at least one solvent, and optionally a pharmaceutically acceptable carrier wherein the at least one hormone is testosterone.

The invention also concerns a concentrated hormone pharmaceutical composition comprising: from about 8 to about 90% of at least one hormone; from about 10 to about 92% of at least one solvent, and optionally a pharmaceutically acceptable carrier wherein the at least one hormone is progesterone. Solvent (or Wetting agent)

The solvent or wetting agent can be any liquid that can dissolve, partially dissolve, wet, or suspend the hormone, or reduce the surface tension of a liquid to a value below the hormones critical surface tension.

In order for a solid to be incorporated into a liquid, the solids surface tension must be above the surface tension of the liquid. The best solvents produce a low air liquid surface tension, and are not readily adsorbed by the solid so as to produce nonwetting behavior.

The wetting agent or solvent acts by lowering the contact angle between the surface of the particle and the wetting liquid. Wetting agents replace a solid to air interface with a solid to liquid interface. The solvent or wetting agent should be miscible with the carrier.

The solvent or wetting agent could possibly be, but is not limited to, one or more of the following in any concentration: propylene glycol, ethoxy diglycol, glycerin, mineral oil, fixed oil, emu oil, peanut oil, vitamin E oil, acetone, amylene hydrate, benzyl benzoate, corn oil, cottonseed oil, diethylene glycol monoethyl ether, ethyl acetate, isopropyl alcohol, methyl alcohol, methylene chloride, methyl isobutyl ketone, polyethylene glycol 300, polyethylene glycol 400, polyethylene glycol 600, sesame oil, alcohol, a 50% ethoxy diglycol (diethylene glycol mono-ethyletherand) 50% propylene glycol mixture, water or mixtures threrof. Any combination of solvents may be employed.

The solvent or wetting agent should satisfy the following characteristics: the solvent or solvents should wet the hormone; the solvent should allow the hormone to be incorporated therein; the solvent or solvents should be compatible with the skin with the least possible number of adverse effects; the solvent or solvents should be smooth and pliable with no adverse odor; the solvent or solvents should have a color appealing to the consumer; and the solvent must be stable and must provide a stable vehicle for the medication.

The scope of the present invention is not limited by the solvents mentioned in the present application; any of those known in the pharmaceutical and cosmetic industries may be employed.

Pharmaceutically Acceptable Carrier

The carrier can be any suitable carrier that can be incorporated into a system, which can deliver bio-identical hormones transdermaly.

The formulations for the delivery of the pharmaceutical composition according to the present invention may be liquid, ointments, and creams.

The carrier can be chosen from ointment base, powder base, cream base, or a gel base.

Ointments are semisolid preparations, which are typically based on petrolatum or other petroleum derivatives. Creams containing the selected active agent, are, as known in the art, viscous liquid or semisolid emulsions, either oil-in-water or water-in-oil.

Cream bases are water-washable, and contain an oil phase, an emulsifier, and an aqueous phase. The oil phase, also sometimes called the "internal" phase, is generally comprised of petrolatum and a fatty alcohol such as cetyl or stearyl alcohol; the aqueous phase usually, although not necessarily, exceeds the oil phase in volume, and generally contains a humectant.

The specific ointment or cream base to be used, as will be appreciated by those skilled in the art, is one that will provide for optimum drug delivery. As with other carriers or vehicles, an ointment base should be inert, stable, nonirritating and non-sensitizing.

Powders may be formulated with the aid of any suitable powder base, such as talc, lactose, starch, and the like.

The pharmaceutical carrier could possibly be comprised of, but is not limited to, any or all of the following ingredients: an oil in water emulsion base, a water in oil emulsion base, an oleaginous base, an absorption base, a water soluble base an anhydrous gel, a pluronic F127/lecithin isopropyl palmitate gel, hydrous gel, purified water, white petrolatum, cetearyl alcohol, ceteareth-20, sorbitol solution, propylene glycol, simethicone, glyceryl monostearate, polyethylene glycol monostearate, sorbic acid, camellia sinensis (green tea) leaf extract, cholesterol, beeswax, cyclomethicone, C12-15 alkyl benzoate, plankton extract, acetyl ponta peptide-2, ocnethera biennis (evening primrose) root extract, dimethicone, hexyldecanol, dextran, stearyl alcohol, cetyl alcohol, pyrus malus (apple) fruit extract, acetyl hexapeptide-2, alnus firmirolia (yashabushi) extract, tocopheryl acetate (vitamin E acetate), glyceryl stearate, thioctic acid (a-lipoic acid), PEG-100 stearate, ascorbyl palmitate (vitamin C palmitate), tocopherol (vitamin E), tetrahexyldecyl ascorbate, sesamum indicum (sesame) seed oil, retinyl palmitate (vitamin A palmitate), prunus armeniaca (apricot) kernel oil, willow bark extract, phenoxyethanol, benzyl alcohol, potassium sorbate, glycerin, panthenol (pro-vitamin B5), retinal (vitamin A), lavandula agustifolia (lavender) oil, allantoin, polysorbate 20, xanthan gum, titanium dioxide, tetrasodium EDTA, topheryl linoleate (vitamin E linoleate), dimethylamino methylpropanol, ceramide 2, quaternium-15, polyacrylamide, magnesium aluminum silicate, laureth-7, citric acid, C13-14 isoparaffin, aloe barbadensis (aloe vera) leaf juice, cetearyl glucoside, 10-hydroxydecanoic acid, hydroxycaprylic acid, prunus amygdalus dulcis (sweet almond)oil, zinc PCA, zinc oxide, acacia, tragacanth, agar, pectin, gelatin, methyl cellulose, carboxymethylcellulose, carbomer, vitis vinifera (grape) seed extract, hibiscus sabdariffa flower extract, triticum vulgare (wheat)germ oil, citic acid, sodium hydroxymethylglycinate, isopropyl palmitate, squalane, cetearyl glucoside, lecithin, pluronic, cucumis sativus (cucumber) fruit extract, cetyl ricinoleate, caprylic/capric triglycerides, allantoin, ubiquinone (coenzyme Q10), helianthus annuus (hybrid sunflower) oil, cyclomethicone sodium PCA, stearic acid, glyceryl stearate, rose canina (rose hips) fruit oil, glycol, glycyrrhiza glabra (licorice) extract,aesculus hippacastanum (horse chestnut)extract, hydrolyzed yeast protein, calendula officinalis flower extract, centella asiatica (gotu kola) extract, ruscus aculeatus (butcher's broom)root extract, cyclopentasiloxane, evening primrose oil, PEG-75, PEG-150, sodium PCA, calendula officinalis flower extract, cyclopentasiloxane, hydrolyzed milk protein, ethoxy diglycol, lupinus albus seed oil, hydrophilic petrolatum, wool alcohol, sodium lauryl sulfate, PEG 4000 , PEG 400, propylene glycol-ethanol, lecithin soya granular, sorbic acid, polyacrylamide, cytel alcohol, magnesium aluminum silicate, aloe vera (aloe barbadensis) prunus amygadalus amara (bitter almond) kenel oil, pro-lipo multi-emulsion liposomic system, propylparaben, methylparaben, imidazolidimyl urea, pluronic F127, alcohol, sodium hydroxide, DMAE, glycolic acid, edetate disodium dihydrate, urea, stearic acid, glyceryl monostearate, isopropyl myristate, polyoxyl 40 stearate, potassium sorbate, anhydrous ointment base, lanolin, anhydrous lanolin, emollient cream base, lanolin alcohol, mineral oil, glyceryl monostearate, stearic acid flakes, sualene, triethanolamine, krisgel 100, borago (borage) officinalis seed oil, simethicone, salicylic acid, dehydroacetic acid, benzyl alcohol, benzoic acid, benzethonium chloride, polysorbate 80, span, PEG-8 distearate/emerest 2712, hydrogenated vegetable oil, mineral oil (heavy), mineral oil (light), microethane FN 501, hydroxypropylcellulose, hydroxymethylcellulose, methylcellulose, avicel, polyglygol 300, polyglycol 8000, paraffin waxes, propylene glycol isostearate, isostearyl alcohol, white ointment USP, yellow ointment NF, oleic acid USP, olive oil USP, paraffin USP, petrolatum NF, spermaceti wax USP, synthetic spermaceti NF, starch glycerite NF, white wax USP, yellow wax USP, dbutylated hydroxy toluene, or combination thereof.

The carrier should satisfy the following characteristics: the base should allow the wetted hormone to be incorporated therein; the base should be compatible with the skin with the least possible number of adverse effects; the base should be smooth and pliable with no adverse odor; the base should have a color appealing to the consumer; the base must be stable and must provide a stable vehicle for the medication; and the base should be able to readily release the medication incorporated therein into the skin. Additional Ingredients

The concentrated pharmaceutical composition according to the invention optionally can include antioxidants to prevent oxidation of any of the components therein. The antioxidant may include, but are not limited to, ascorbic acid, sodium ascorbate, sodium formaldehyde sulfoxylate, sodium bisulfite, sodium nitrite, sodium thiosulfate, sodium metabisulfite, sodium sulfite, sulfur dioxide, tannic acid, thioglycerol, tert-butyl-hydroquinone, thioglycolic acid, thiolactic acid, thiosorbitol, thiourea, tocopherols, butylated hydroxy toluene, acetone sodium sulfate, acetylcysteine, lipoic acid (sodium salt), tocopherol, ascorbyl palmitate, butylated hydroxyanisole, calcium ascorbate, calcium bisulfite, calcium sulfite, cysteine, dilauryl thiodipropionate, dithiothreitol,dodecyl gallate, ethoxyquin, ethyl gallate, gallic acid, glutathione, gossypol, hydroquinone, 4-hydroxymethyl-2,6-di-tert-butylphenol, hypophosphorus acid, isoascorbic acid, lecithin, monothioglycerol, B-naphthol, nordihydroguaiaretic acid, octyl gallate, potassium metabisulfite, propyl gallate, sesamol, or Vitamin E. These antioxidants are not particularly limited; any of those known in the pharmaceutical or cosmetic industries may be used.

In addition, the concentrated pharmaceutical composition according to the invention optionally may include preservatives to prevent the growth of bacteria or fungi in the final product. These may include, but are not limited to, thimerosal, benzyl alcohol, imidazolidinyl urea, quaternium-15, benzalkonium chloride, chlohexidine, chlorbutanol, phenol, cresol, chlorothymol, chloroxylenol, P-chlorometaxylenol, sodium benzoate, potassium sorbate, boric acid, methyl paraben, propylparaben, sorbic acid, alcohol, benzethonium chloride, benzoic acids and salts, benzyl alcohol, sodium benzoate, boric acids and salts, cetylpyridinium chloride,cetyltrimethyl ammonium bromide, chlorbutanol, clorocresol, imidazolidinyl urea, metacresol, myristylgamma picolinium chloride, nitromersol, parabens(benzyl, butyl, methyl, propyl), phenol, phenyl phenol, phenylethyl alcohol, phenylmercuric acetate/nitrate, sorbic acids and salts, thimerosal, hydroxybezoate esters and phenyl ethyl alcohol. These preservatives are not particularly limited; any of those known in the pharmaceutical or cosmetic industries may be used.

Further, the concentrated composition of the invention optionally can include chelating agents and synergists added, which may include, but are not limited to, EDTA and salts, alkyl gallates, ascorbic acid, boric acid, citraconic acid, gluconic acid, hydroxyquinolone sulfate, maleic acid, phosphoric acid, polysorbates, saccharic acid, tartaric acid, tryptophan and citric acid. These chelating agents and synergists are not particularly limited; any of those known in the pharmaceutical or cosmetic industries may be used.

Further, the concentrated composition of the invention optionally can include emulsifying agents to facilitate the formation of an emulsion. The emulsifying agents may include, but are not limited to acacia, tragacanth, agar, pectin, gelatin, methyl cellulose, carboxymethylcellulose, PEG-40 castor oil, PEG 300, polysorbate 20, polysorbate 40, polysorbate 80, sorbitan monopalmitate, simethicone, or any synthetic anionic, cationic, or nonionic emulsifying agents. These emulsifying agents are not particularly limited; any of those known in the pharmaceutical or cosmetic industries may be used.

Further, the concentrated composition of the invention optionally can include suspending agents to increase viscosity. The suspending agents may include, but are not limited to, acasia, bentonite, carboxymethylcellulose, methycellulose, hydroxypropylcellulose, carbomer resins, colloidal silicon dioxide, sodium alginate, tragacanth, agar, alginic acid, attapulgite, bentonite, carrageenan, cellulose, microcrystalline cellulose, microcrystalline carboxymethylcellulose, dextrin, gelatin, guar gum, hydroxyethylcellulose, hydroxypropylmethyl-cellulose, magnesium aluminum silicate, pectin, polaxamer, polyethylene oxide, polyvinyl alcohol, povidone, propylene glycol alginate, xanthan gum, and veegum. These suspending agents are not particularly limited; any of those known in the pharmaceutical or cosmetic industries may be used.

Further, the concentrated composition of the present invention optionally can include stiffening agents to increase viscosity. The stiffening agents may include, but are not limited to, hydrogenated castor oil, cetostearyl alcohol, cetyl alcohol, cetyl esters wax, hard fat, paraffin, synthetic paraffin, stearyl alcohol, emulsifying wax, white wax, and yellow wax. These stiffening agents are not particularly limited; any of those known in the pharmaceutical or cosmetic industries may be used.

Further, the concentrated composition of the present invention optionally can include any substance, which can increase or decrease the pH of the system added. The pH modifiers can be either acidifying agents or alkalizing agents. The pH can be modified to any pH, which is deemed suitable.

These pH modifiers may include but are not limited to, (acidifying agents) acetic acid, acetic acid glacial USP, citric acid, hydrochloric acid, fumaric acid, lactic acid, nitric acid, phosphoric acid, sodium phosphate monobasic, sulfuric acid, malic acid, tartaric acid propionic acid, (alkalizing agents) ammonia solution, ammonium carbonate, diethanolamine, monoethanolamine, sodium bicarbonate, sodium borate, sodium phosphate dibasic, trolamine, potassium hydroxide, sodium hydroxide, and sodium carbonate. These PH modifiers are not particularly limited; any of those known in the pharmaceutical or cosmetic industries may be used.

Further, the concentrated composition of the present invention optionally can include any solubilizing agent. These agents may include but are not limited to, benzalkonium chloride, cetylpyridium chloride, benzethonium chloride, docusate sodium, nonoxynol 9, octoxynol 9, polaxamer(s), polyoxyl 35 castor oil, polyoxyl 40 hydrogenated castor oil, polyoxyl 10 oleyl ether, polyoxyl 20 cetostearyl ether, polyoxyl 40 stearate, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, sodium lauryl sulfate, sorbitan monolaurate, sorbitan monooleate, sorbitan monopalmitate, sorbitan monostearate, and tyloxapol. These wetting and/or solubilizing agents are not particularly limited; any of those known in the pharmaceutical or cosmetic industries may be used.

Further, the concentrated composition of the present invention optionally can include any substance, which can increase the shelf life of said product. These agents may include but are not limited to, vitamin E and ascorbic acid. These substances are not particularly limited; any of those known in the pharmaceutical or cosmetic industries may be used.

In one embodiment, the concentrated hormone pharmaceutical composition contains 32 mg/g estriol, 4 mg/g estradiol, and 4 mg/g estrone concentrates (triest) in 960 mg/g of a mixture of 50% ethoxy diglycol/50% propylene glycol. The estriol, estradiol, and estrone are present in the composition at 8:1:1, 6:3:1, 5:4:1 or 7:2:1 ratios.

After extensive research, the present inventor discovered that the combination of ethoxy diglycol and propylene glycol in any ratio has the ability to dissolve the combination of estriol, estradiol, and estrone (triest) in any ratio or testosterone alone better than using any of the solvents alone.

In another embodiment, the concentrated hormone pharmaceutical composition contains 32 mg/g estriol and 8 mg/g estradiol concentrates (biest) in 960 mg/g of a mixture of 50% ethoxy diglycol/50% propylene glycol. The estriol and estradiol are present in the composition at 8:2, 5:5, 6:4, 7:3, or 9:1 ratio.

In another embodiment, the concentrated hormone pharmaceutical composition contains 64 mg/g testosterone concentrate in a mixture of 50% ethoxy diglycol/50% propylene glycol for women and 150 mg/g of a mixture of 50% ethoxy diglycol/50% propylene glycol for men.

In another embodiment, the concentrated hormone pharmaceutical composition contains 600 mg/g of progesterone concentrate in vanishing cream type oil in water emulsion base.

In another embodiment, the concentrated hormone pharmaceutical composition contains 0.8 g/g estriol, 0.1 g/g estradiol, and 0.1 g/g estrone (triest) in a powdered form optionally mixed with any amount of a filler or in the following ratios: 8:1:1, 7:2:1, 6:3:1, or 5:4:1.

In another preferred embodiment, the concentrated hormone pharmaceutical composition contains 0.8 g/g estriol and 0.2 g/g estradiol (biest) in a powdered form optionally mixed with any amount of a filler or in the following ratios: 5:5, 6:4, 7:3, 8:2, or 9:1.

In another preferred embodiment, the concentrated hormone pharmaceutical composition comprises: at least one hormone; optionally a powdered base; wherein the at least one hormone is chosen from estriol, estradiol, or combination thereof; and wherein the composition is in a powdered form.

The at least one hormone a combination of estriol, estradiol in a ratio of 5:5, 6:4, 7:3, 8:2, or 9:1.

In another preferred embodiment, the concentrated hormone pharmaceutical composition comprising: at least one hormone; and optionally a powdered base; wherein the at least one hormone is chosen from estriol, estradiol, estrone, or combination thereof; and wherein the composition is in a powdered form.

The at least one hormone is a combination of estriol, estradiol, and estrone in a ratio of 5:4:1, 6:3:1, 7:2:1, or 8:1:1.

Examples of powdered bases suitable for use in the pharmaceutical compositions disclosed herein include, but are not limited to, talc, calcium carbonate, microcrystalline cellulose, powdered cellulose, dextrates, kaolin, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, mannitol, silicic acid, sorbitol, starch, pre-gelatinized starch, and mixtures thereof.

In another embodiment of the present invention, the at least one hormone is combined directly with the pharmaceutically acceptable carrier (ointment, cream, powder or gel base) without the prior use of a solvent or solvents.

In a further embodiment of the present invention, the hormone is weighed and packaged unadulterated in an appropriate container. The solvent or solvents and/or optionally the ointment, cream, gel base, or powdered base are packaged in a separate container. The two products are sold together as a kit. The two components are to be combined by whoever purchases the kit to formulate the hormone concentrate system.

Color Coded-concentrated Pharmaceutical Composition

The present invention also provides a color-coded concentrated hormone composition to help the pharmacist quickly choose the composition to be used.

The advantage of having color-coded concentrates are as follows: helps to rapidly identify the concentrate. ensures that all concentrates required to be contained in a final product are present in said final product. This is made possible because each combination and permutation of the concentrates will result in a distinct color profile. If the final product does not match the color profile for that medication, you know you have done something wrong; and

ensures complete mixing of the final product. When the final product is a uniform color throughout, adequate mixing will have taken place.

The coloring agent could possibly be, but is not limited to one of the following: acid red 52, basic fuchsin USP, brilliant green, caramel NF, carmine NO.40, congo red, D&C green NO.5, D&C green NO.6, D&C green NO. 8, D&C orange NO.4, D&C red NO.4, D&C red NO.6, D&C red NO.17, D&C red NO. 22, D&C red NO.28, D&C red NO.33, D&C .violet NO.2, D&C yellow NO.8, D&C yellow NO.10, D&C yellow NO.11, F.D. &C. blue NO.1, F.D. &C. blue NO.2, F.D. &C. green NO.3, F.D. &C. red NO.3, F.D. &C. red NO.19, F.D. &C. red NO.40, F.D. &C. yellow NO.5, F.D. &C. yellow NO.6, malachite green oxalate, rose Bengal, saffron, scarlet red, and any food color in liquid or powder form. The coloring agent is not particularly limited; any of those known in the pharmaceutical or cosmetic industries may be employed. Preferably, the coloring agent will not noticeably color the skin. It should be compatible with the skin with the least number of adverse effects.

The concentrates according to the present invention would be manufactured using extensive safety measures. These include, but are not limited to, the use of custom built clean rooms (a room designed specifically for compounding with hazardous materials), high velocity air flow units fitted with high emission particulate air (HEPA) filters, custom built ventilation systems, protective suits, protective eyewear, protective gloves, and protective HEPA filter masks.

A pharmacist or technician trained in the art of compounding BHRT ointments, creams, gels, and pastes will manufacture these concentrates.

An advantage of the present invention is the composition contains a high concentration of hormones (higher than the prescribed levels), thus the pharmacist can easily use the concentrates to produce a custom tailored BHRT product without risking his own health.

The present invention also contemplates a method for producing the concentrated composition of the present invention. The method comprises the steps of: measuring at least one hormone, a solvent and/or optionally a carrier by using an electronic balance in a clean room; combining the ingredients of step a by using an industrial scale mixer to ensure thorough mixing; and running the mixture of step b through a large-scale ointment mill or homogenizer to decrease the particle size of the drug, and optionally, heating the concentrate to facilitate the formation of a solution, wherein the hormone concentration is from about 0.6 to about 80%.

The concentrated hormone pharmaceutical composition of the present invention may be further divided with similar or different carrier materials to concentrations that are suitable for practical use by the compounding pharmacist.

If the medication is not thoroughly mixed, then it will not contain a uniform concentration of the drug throughout. A solution will provide the best distribution of drug throughout the system.

Running the mixture through a large-scale ointment mill or using a homogenizer decreases the particle size and increases the absorbability, because smaller drug particles will more readily penetrate the dermis. This process also ensures a non-gritty, pharmaceutically elegant, and cosmetically pleasing final product.

The present invention is also in combination with a dispensing device to provide a means to measure and combine, quickly and accurately, quantities of hormones with appropriate ointment, cream, or gel bases while minimizing exposure to hazardous airborne hormone particles. Thus, airborne particles are drastically reduced because the hormones are incorporated into a liquid or semi-solid form.
 

Claim 1 of 29 Claims

1. A concentrated liquid hormone composition for use in compounding a pharmaceutical product for topically delivering one or more steroid hormones to a subject in need of hormone replacement therapy, comprising one or more naturally occurring steroid hormone(s) dissolved in a solvent mixture consisting of ethoxy diglycol and propylene glycol.

 

____________________________________________
If you want to learn more about this patent, please go directly to the U.S. Patent and Trademark Office Web site to access the full patent.