MXPA99008759A - Stable liquid mineral ascorbate compositions and methods of manufacture and use - Google Patents

Abstract

Liquid vitamin C concentrate compositions comprise a mineral ascorbate and a pharmacologically acceptable liquid organic polyol solvent for the mineral ascorbate, the concentrate having a pH between about 5 and 7. The concentrate may also contain an aldonic compound and/or a pharmacologically acceptable zinc compound. The concentrate compositions are prepared by heating the solvent at 50-90°C and mixing the ascorbate and/or aldonic compound and/or zinc compound into the heated solvent, preferably in the absence of oxygen. The concentrate compositions are also characterized as a composition which comprises the reaction product of a mineral ascorbate and a pharmacologically acceptable liquid organic polyol solvent and, optionally, an aldonic compound and/or a soluble non-toxic zinc compound, which reaction product includes 4-hydroxy-5-methyl-3(2H)-furanone and/or 3-hydroxy kojic acid. Finished vitamin C products, characterized by excellent long term vitamin C stability, are conveniently prepared by incorporating the concentrates into finished cosmetic, medical and food products.

Description

"COMPOSITIONS OF STABLE LIQUID MINERAL ASCORBASE AND METHODS OF MANUFACTURE AND USE" FIELD OF THE INVENTION This invention relates to stable vitamin C concentrate compositions for preparing finished products such as cosmetic and dermatological preparations, food products, v.q. processed foods, beverages and nutritional supplements, and medicinal, dental, ophthalmic and surgical compositions, both for enteral and parenteral introduction. In another aspect, the invention relates to finished products prepared from these concentrated compositions. Another aspect of the invention relates to methods of making these concentrated compositions and finished products. In yet another aspect, the invention relates to methods of using these finished products.

BACKGROUND OF THE INVENTION Vitamin C has many known biological functions, e.g. it acts as an accelerator to heal wounds, to prevent or treat periodontal disease, as an enzymatic co-factor, as a "reserve" agent against depletion of vitamin E, as a stimulator of collagen synthesis, etc. Vitamin C is known to counteract oxygen-containing free radicals, including both superoxide and hydroxyl radicals. These oxidative free radicals are generated in vivo under a variety of normal and pathological conditions, and vitamin C is known due to its ability to improve conditions caused by free oxygen radicals, e.g. sunburn, cataracts, premature aging and a variety of other degenerative conditions. Due to the beneficial effects attributed to vitamin C, many attempts have been made to formulate liquid vitamin C compositions. However, due to their marked stability, particularly at higher pH values, pharmacologists and other scientists working in the field have had difficulty formulating stable liquid vitamin C compositions that would be useful for preparing various end-use products. It would be highly desirable to provide compositions of vitamin C concentrate, and products of - - end-use preparations of these concentrates, which have improved physical stability and improved chemical stability under less acidic conditions. It would also be highly desirable to provide these concentrated vitamin C compositions that are specially adapted for use to prepare a wide variety of end-use products, including cosmetic products, medicinal products, including dermatological, dental, ophthalmic and surgical products, wound healing, etc. . and various food products, e.g. processed foods, beverages, nutrition supplements, etc.

PREVIOUS TECHNIQUE _ __ _ ^ __ U.S. Patent No. 2,822,317 (Gulesich et al.) Discloses a liquid aqueous composition which includes L-ascorbic acid (including ascorbyl fatty acid esters), a ferrous salt (including ferrous sulfate, lactate, gluconate, succinate, glutamate and salts). of choline citrate and complex salts) and a polyhydric alcohol of 5 to 6 carbon atoms. This composition is said to have "satisfactory" stability at a pH = 2.0 to US Patent Number 5,587,149 (Point and others) discloses that solutions of ascorbic acid dissolved in polyethylene glycol ("PEG") and then emulsified in a liquid of silicone to form an emulsion (of ascorbic acid + PEG) -in-silicone are physically "stable" in the sense that "they do not exhibit creaming, sedimentation or phase separation". However, to prevent the chemical degradation of ascorbic acid, these emulsions are encapsulated in "twist" gelatin capsules. U.S. Patent No. 4,938,969 (Schinisky et al.) Discloses a composition of ascorbic acid, tyrosine and water soluble zinc salt, e.g. zinc sulfate, in a "vehicle compatible with the tissue" (e.g., mineral oil + sesame oil + glycerin + PEG), but does not report on the chemical or physical stability of this composition. U.S. Patent No. 5,536,500 (Galey et al.) Reviews various stabilization methods for vitamin C, involving physical techniques (eg, incorporation into zeolites, etc.), chemical modification of the ascorbic acid molecule, such as conversion into a phosphodiester in combination with vitamin E, and functionalization of the enediol group by formation of phosphate, sulfate, ether or ester functions. The - cinnamic acid ascorbyl esters are disclosed but not reported for the physical or chemical stability of these esters in liquid carriers US Patent Number 5,140,043 (Darr et al.) discloses topical compositions of ascorbic acid (or a analogue reducer), in a water carrier (glycol or polyol) It is ensured that shelf stability of 12 weeks (= 100 percent retention of ascorbic acid) is acceptable only if the ratio of water to glycol carrier / polyol is elevated (eg, at least 1: 1) and the pH is maintained at < 3.5 US Patent Number 5,350,773 (Schweikert et al) discloses liquid compositions containing a fat-soluble substance that are stabilized against " microbiological deterioration "for a period as long as six months, by dispersing the fat-soluble substance in a continuous phase of glycerol or glycerol-water containing an" emulsifier "of Ascorbyl fatty acid ester, e.g., ascorbyl palmitate. U.S. Patent No. 5,736,567 (Cantin et al.) Discloses aqueous compositions of ascorbic acid-polyol-oil, with relatively lower water contents than conventional cosmetic or dermatological compositions. ~~ - DESCRIPTION OF THE INVENTION BRIEF DECLARATION OF THE INVENTION I have now discovered that liquid Vitamin C concentrate compositions that have improved stability, which are specially adapted to prepare finished products. These concentrated compositions include at least one mineral ascorbate, dissolved in at least one pharmacologically acceptable liquid organic polyol solvent for the mineral ascorbate (s). The concentrated compositions have a pH of at least about 5, preferably from about 5 to about 7. In accordance with another aspect of the invention, the concentrated composition preferably also contains at least one aldonic compound. In yet another aspect, the concentrated __ composition of the invention preferably also includes a pharmacologically acceptable zinc compound, preferably a water soluble zinc salt. The invention also consists of a liquid vitamin C composition that includes the reaction product of at least one mineral ascorbate and at least one pharmacologically acceptable liquid polyol solvent for mineral ascorbate. The invention also includes liquid vitamin C compositions that include 4-hydroxy-5-methyl-3 (2H) -furanone and / or 3-hydroxy-kojic acid, as well as compositions that also include at least one aldonic compound - and / or a pharmacologically acceptable zinc compound. The invention also proposes the finished products prepared from the concentrated compositions and / or the reaction products defined above. In accordance with another aspect of the invention, the finished emulsion products comprise a continuous phase and a dispersed phase, the concentrated composition being carried in one of these phases. In yet another respect, the invention includes methods for administering vitamin C which includes the step of introducing topically, orally, enterally or parenterally to humans or animals, a finished product prepared from the concentrated composition defined above. In accordance with still another embodiment, the concentrated compositions / reaction products defined above include a compound that is characterized by a high liquid chromatographic maximum. performance (HPLC) 285 nm that appears after the frontal maxima and before the maximum ascorbate, now identified as 4-hydroxy-5-methyl-3 (2H) -furanone, ie 4-hydroxy-5-methyl-3 (2H) -furanone and these compositions and the reaction products that also include 3-hydroxy-kojic acid, i.e., 3-hydroxy-kojic acid Other aspects and features of the invention will become apparent to those skilled in the art from the following detailed description thereof, which is taken together with the drawings.

BRIEF DESCRIPTION OF THE DRAWINGS - - In the drawings, Figure 1 is an HPLC chromatogram which represents the main components of a typical composition of the prior art prepared in accordance with US Patent Number 5,140,043 issued to Darr et al. Figure Ib is a chromatogram representing a control composition that includes the same components minus ascorbic acid; Figure 2a is an HPLC chromatogram representing the major components of a concentrated vitamin C composition of the present invention that includes a zinc compound. Figure 2b represents a control composition that includes the same components except mineral ascorbate; Figure 3a is an HPLC chromatogram representing the major components of a concentrated composition of the present invention that does not include a zinc compound and Figure 3b represents a control composition that includes the same components except mineral ascorbate; Figures 4a and 4b are three three-dimensional HPLC graphs representing the main components of the concentrated compositions such as those typified in Figures 2a and 3a, where the x-axis represents the retention time (minutes), the - axis y represents the absorbance (in response units of the arbitrary detector) and the z-axis represents the wavelength of the light scanned by the diode array detector (nm); and Figures 5a and 5b compare the stability of the typical commercially available liquid vitamin C composition (5a) with the stability of the concentrated vitamin C compositions of the invention (Figure 5b), which are prepared with and without an added aldonic component. and with and without a zinc component.

Definitions: As used herein, the following terms have the indicated meanings: "Mineral ascorbate" means a pharmacologically acceptable salt of ascorbic acid, including salts and complexes of ascorbate anions with pharmacologically acceptable cations of the alkali elements (sodium, potassium , etc.), alkaline earth elements (calcium, magnesium, etc.), or transition elements (copper, iron, zinc, chromium, etc.). "Liquid" includes lotions and viscous creams that conform to the configuration of the container in which they are placed, as well as self-supporting gels, pastes and the like.

- The "aldonic" component means an aldonic acid, the simplest of which is glyceric acid, the non-toxic salts thereof (eg, sodium, potassium, calcium, etc.) and the open-chain and cyclic condensation products of the same, to Baber, open-chain aldonic esters, aldono-lactones and aldono-lactides. "pH" of the concentrated compositions of the invention is the pH determined potentiometrically by diluting a part of the liquid subject matter with 10 parts of water, as described in U.S. Pharmacop ia XXIII ["The US Pharmacopoeia / The National Formulary (USP 23 / NF 18)", United States Pharmacopeial Convention, Inc., 12601 T inbrook Parkway, Rockville, MD 20852 USA (1995).] "Stability" refers to the ability of a composition to retain at least 90 percent of its nutritional or pharmaceutical potency (ascorbate content), as determined at room temperature (22 ° C), or at an elevated temperature and converted to room temperature based on in the Arrhenius equation, which relates the constant rate of a chemical reaction to the activation energy and absolute temperature.

DETAILED DESCRIPTION OF THE INVETTCTOKr - The concentrated compositions of the invention are adapted to be converted by additional processing steps to a wide variety of end-use products having various consistencies of liquids running to viscous creamy lotions to self-supporting pastes and gels, and even semi-solids, etc. , depending on the other components with which the concentrate is mixed. Even when the concentrates are formulated initially as a "syrup", easily handled, it is also proposed that the concentrates can also be formulated in a "cream" of intermediate emulsion. The "cream" form of the concentrate in turn, can conveniently be incorporated into existing emulsion bases - bases that are commonly used in various finished end-use products, e.g., cosmetics, dermatological preparations, etc. - no main review of the procedures and processing equipment of the final product manufacturers. The mineral ascorbates used to carry out the invention can conveniently be obtained as commercial products of high purity. If a single mineral ascorbate is used, calcium ascorbate is currently preferred, even though it is proposed that two or more mineral ascorbates may be employed, depending on the end-use product involved. The concentration of - Mineral ascorbate can vary from less than 1 to 80 weight percent of the concentrated syrup product, which will vary with the desired viscosity of the syrup and the solubility of the mineral ascorbate (s) employed in the solvents or solvent mixtures employed. For example, the solubility of calcium ascorbate dihydrate in various polyols ranges from less than one weight percent in pure butanediol or certain pure polyethylene glycols, up to 40 percent to 50 weight percent in pure glycerol, to 50 percent to 60 percent by weight in 70 percent of sorbitol and 75 percent to 80 percent in 70 percent of low molecular weight polyethylene glycol. For comparison, the solubility of sodium ascorbate ranges from virtually zero pure butanediol and pure polyethylene glycol to 15 percent to 20 percent by weight in 100 percent glycerol and 30 percent to 35 percent by weight in 70 percent sorbitol. Even when calcium ascorbate is currently preferred, depending on the final use of the finished products, other pharmacologically acceptable mineral ascorbates, illustratively magnesium, sodium, potassium and / or zinc ascorbates and mixtures thereof, are effectively employed.

- The aldonic compound can be obtained from commercial suppliers, e.g., high purity calcium threonate which can be obtained as the hemi-calcium salt of L-threonic acid, manufactured by Farmak Olomouc, distributed by Helm New York, Piscataway, NJ. Alternatively, and preferably the aldonic component is derived from products manufactured under US Patent Nos. 4,822,816; 4,968,716 and 5,070,085 to Markham and corresponding foreign patents. These ascarbato-aldonic mineral combination compositions can be obtained internationally under the trademark of mineral ascorbates of the Ester-C® brand from Inter-Cal Corporation of Prescott, Arizona, United States of America. If this combination of mineral-aldonic compositions are employed, the weight ratio of the mineral ascorbate to the aldonic compound is about 99: 1, or about 80: 1 weight ratio of the ascorbate residue to the aldonic residue. If a separate source of the aldonic compound, eg, calcium threonate, is used as the aldonic component, I prefer to employ the same in approximately the same weight ratio of the ascorbate residue to the aldonic residue as that which is capable of being achieved by use in Ester C® mineral ascorbate, namely a weight ratio of 80: 1. The highest weight ratios, which lead to - lowest absolute concentration of the aldonic residue, are at least partially effective. The lower weight ratios, which lead to higher absolute concentrations of the aldonic residue, are not detrimental but are limited by lower solubility of the calcium salts of the aldonic components in the polyol media. The aldonic component lends potency to the topical, enteral and parenteral efficacy of mineral ascorbates in end-use products prepared from the liquid compositions of the invention, such as potentiating the enteral efficacy of various aldonic vitamin C compositions, as disclosed by the Markham patents, cited above. The organic polyol solvents used to carry out my invention are selected for pharmaceutical acceptability, their ability to solubilize the mineral ascorbate, the aldonic components and the optional zinc components of the concentrate, the water content and the effect on the stability of the ascorbate component. I currently prefer to use commercially available glycerol blends, which usually contain 5 percent or less of water and commercially obtainable sorbitol, which is a saturated solution (70 percent) in water. Generally, I prefer to minimize the water content of the solvent (s), according to - with economic and functional considerations. Although mixtures of commercially available glycerol and sorbitol are not completely free of water, the chemical activity of water is reduced by the high concentration of the other solutes, by hydrogen bonding, with the hydroxyl groups of the solvents and / or coordinated to the cations of the mineral ascorbate (s) and other solutes. Other polyols that may be employed include polypropylene glycol, hexylene glycol, butylene glycol and the almost infinite molecular weight scale of polyethylene glycols, as well as so-called sugar alcohols, e.g., xylitol, and mixtures thereof with other polyols. These concentrates can be prepared entirely with a solvent, e.g. glycerol or sorbitol, or mixtures of solvents. The final selection of the solvent will depend on economic factors and other related factors. The stability of vitamin C is somewhat better in the sorbitol solvent than in pure glycerol. Propylene glycol is the least desirable from the standpoint of stability of vitamin C, even when other factors e.g. The effect of the skin penetration adjuvant may recommend using at least a certain amount of this solvent in combination with other polyols.

If a zinc compound is incorporated into the concentrates of the invention, I currently prefer to employ an amount of the zinc compound in such a way that the weight ratio of the mineral ascorbate to the zinc compound is about 40: 1 although again not damaging somewhat lower relationships and higher relationships are at least partially effective. The zinc compound can be supplied as pharmaceutically acceptable zinc salts, commercially obtainable in high purity, the pharmaceutically acceptable zinc salts, presently preferably, zinc acetate dihydrate. Alternatively, the zinc component of these concentrates can be provided as zinc ascorbate, either alone or in combination with the aldonic components, eg, threonates, such as in the Ester-C® brand mineral ascorbate products that can be obtained from Inter-Cal Corporation of Prescott, Arizona, United States of America. If zinc ascorbate is used as the source of zinc, then the amounts of the other mineral ascorbate (s) used can be adjusted to account for the joint contribution of ascorbate from zinc ascorbate. A huge body of biomedical literature announces the therapeutic effects of zinc applied topically for wound healing, burn treatment and connective tissue repair and a large amount of this literature recognizes the synergetic effects of zin and vitamin C. similar inert and parenteral effects of the combination of vitamin C and zinc in products that are prepared from concentrates of the present invention, the presence of zinc in the concentrated compositions also improves the production of a singular component of the concentrates, which is identified by Xas HPLC techniques that will be described below. The processes for preparing the concentrated compositions of the invention are not highly critical and various modifications of the processes that will be described below will readily occur to those skilled in the art relating to these exposures. In general, the dry components, namely the mineral ascorbate and, optionally, the zinc compound and / or the aldonic compound are mixed separately with the solvent that has been preheated within the temperature range of 70 ° C to 90 ° C. ° C, preferably from 50 ° C to 90 ° C. The suspension of each component is stirred until it is completely dissolved. When cooled, the product is a viscous liquid but capable of being emptied, that is, a "syrupy" liquid that can vary in color from light yellow to honey color.

- - In accordance with the currently preferred embodiment of the invention, the viscosity of the finished concentrated product can be lowered and the self-stability of the color of the concentrated product which can be made to darken with storage, can be improved by first heating the solvent in a stirred jacketed tank heated to only about 50 ° C at 90 ° C, dissolving the aldonic components and any of the optional zinc components in the heated solvent and then, stopping the external heating, while dissolving the remaining components in the aldonic solvent solution. The final temperature of the concentrated product after dissolving all the components will rise and desirably will not exceed about 60 ° C. To improve the self-stability of the vitamin C of the concentrated product, all the mixing of the components is preferably carried out in the absence of oxygen, under a blanket of an oxygen-free inert gas such as nitrogen or carbon dioxide. This can be achieved by bubbling the inert gas in a ventilated mixing vessel, covered thereby excluding air from the vessel. Otherwise, the cavitation of the mixing propellant tends to introduce air into the mixture, thus inducing the oxidation of the components - - during the mixing operations. According to this preferred embodiment, the accelerated aging tests (which will be described below) indicate that the different compositions of the concentrate product of the invention will retain more than 95 percent of their original vitamin C potency for 25 months at room temperature. ambient . To prepare emulsions of these concentrates, a phase is prepared by mixing the concentrate with the components typically including waxes, oils, bases, preservatives and emulsifiers at a high temperature e.g. of 70 ° C (or a temperature lower than the thermal decomposition temperatures of oil phase components and mineral ascorbates). An aqueous phase is prepared which may contain preservatives, color agents and / or fragrances and / or flavor agents in distilled water and is heated to the same approximate elevated temperature e.g. of 70 ° C. The heated oil phase is placed in a stirred mixing vessel and the concentrate is mixed in the form of a fine emulsion. The aqueous phase is then added slowly with stirring and the mixing is continued for several minutes. The hot emulsion (usually thick, but capable of emptying with difficulty) is then transferred to packaging modules.

- Alternatively, the concentrated compositions of the invention can be incorporated into the aqueous phase of an emulsion by techniques that are well known in the art or additional components capable of being suspended or soluble in polyol (biologically-medicinally active ingredients, preservatives, flavors). , fragrances, etc.) can be dissolved or suspended directly in the concentrates in order to form the finished products by techniques well recognized in the field.

WORK EXAMPLES The following examples are presented to help understand the invention and to illustrate the presently preferred practice thereof. As an illustration, they are not intended to limit the scope of the invention, which is defined only by the appended claims.

Example 1 This example illustrates the preparation of a typical "syrup" concentrate of the invention. 119.05 grams of. a - 70 percent sorbitol solution at a temperature of 70 ° C to 90 ° C. 0.57 gram of calcium threonate is added and the suspension is stirred until the threonate has completely dissolved. 3.32 grams of the zinc acetate dihydrate are added to the hot threonate solution and the mixture is stirred until the zinc acetate has completely dissolved. 119.05 grams of 100 percent glycerol are added and the mixture is heated to a temperature of 50 ° C to 90 ° C. 48.20 grams of calcium ascorbate dihydrate are added to the sorbitol / glycerol solution and the stirring is continued until it has completely dissolved. It results in a viscous solution that, when cooled, yields a syrupy liquid with a light yellow color viscous but capable of being emptied. The pH of the resulting concentrate is 6.65. The composition of this concentrate, excluding anions other than ascorbate, is Vitamin C 13.64 percent by weight Calcium 1.59 Zinc 0.34 Treonic Acid 0.17 Polyols (less water) 69.74 Water (total) 13.90 EXAMPLE This example illustrates the preparation in a concentrated product of the invention containing sodium ascorbate. 842.2 grams of a 70 percent sorbitol solution are heated to a temperature of 60 ° C. 2. OCT grams of calcium threonate are added and the suspension is stirred until the threonate has completely dissolved. 154.80 grams of the sodium ascorbate is added to the hot sorbitol solution, and the stirring is continued until it has completely dissolved. Upon cooling, a viscous pale yellow liquid product is obtained but capable of being emptied. The composition of the liquid concentrated product is, excluding cations other than sodium: Vitamin C 13.7 percent by weight Sodium 1.8 Tetranic acid 0.17 Polyols (less water) 59.01 Water (total) 25.29 This concentrated product has a vitamin C stability comparable to the product of Example 1, is lighter in color, has improved color stability and is less viscous.

Example 2 This example illustrates the preparation of a topical product or cosmetic cream finished from the concentrate of Example 1. (All concentrations are in weight percent).

Phase I (aqueous) Water (deionized) 67.52 Imidazolidinyl urea 0.20 Coloring and Fragrance (optional) 0.51 Phase II (oil) Mineral Oil 5.04 Petroleum 0.52 Lanolin 0.55 Cetyl alcohol 1.12 Stearyl alcohol 0.70 Stearic acid 1.60 Triethanolamine 0.24 Isopropyl myristate 1.38 Glyceryl monostearate 4.12 Esqualeno 0.72 Silicone oils 1.13 Beeswax 0.62 - - Sorbitan monostearate (Span 60) 0.54 Polyoxyethylene sorbitan monostearate (Tween 61) 0.66 Polyoxyethylene cetyl ether 20 (Brij 58) 0.96 Polyoxyethylene stearate 40 (Myrj 52) 1.34 Caprylic / capric triglycerides 1.44 Triglycerides (olive oil) 1.51 Propyl parahydroxybenzoate 0.12 Methyl parahydroxybenzoate _ 0.17 Vitamin C concentrate (Example 1) 7.29 The components of Phase I dissolve and Phase I is heated to 70 ° C. The components of Phase II are melted together by heating them to 70 ° C, adding the concentrate of Vitamin C as the final component. Phase II is stirred with a rotary mixer while Phase I is emptied as a thin stream. The combined phases are stirred-until the mixture is cooled to a temperature of about 45 ° C to 50 ° C, and the cream product is transferred to containers. When the oil phase containing the sirupose concentrate of Example I is combined with the water phase to prepare the final product formulation (at about 7.3 weight percent of the concentrate), a pleasant creamy emulsion results, which has vitamin stability. Excellent C and excellent wetting and emollient characteristics due to the polyols in the concentrate. The final composition of this emulsified product is Vitamin C 1.00 percent by weight Calcium 0.12 Zinc 0.025 Treonic Acid 0.013 Polyols (less water) 5.11 The pH of the final emulsified product is 5.3 and can be made less acidic, e.g., by the inclusion of a higher concentration of triethanolamine.

Example 2a This example illustrates the preparation of a food product, using the concentrated product of the invention, e.g., the concentrated compositions of Examples 1 or. 500 milliliters of dry granulated sugar is added to 125 milliliters of water and 125 milliliters of corn syrup and the mixture is stirred and boiled at 150 ° C. The heating is discontinued and a flavoring agent is added - - of cherry to give it the desired flavor and color. The concentrated product of Example 1 is added and the amount required to obtain the desired Vitamin C content, e.g., 30 milligrams of Vitamin C / grams of the "sweet" food product. The concentrate and syrup-sugar base are mixed vigorously for a sufficient period of time to completely disperse the concentrated product. The portions of the mixture of the hot concentrate and resulting syrup are transferred to the cavities of a sweet mold and cooled to form a hard candy product enriched with Vitamin C.

Example 3 This example illustrates the HPLC method for characterizing the concentrated products of the invention and for comparing these concentrated compositions with the prior art. High Performance Liquid Chromatography (HPLC) is carried out using a Hewlett-Packard Model 1050 instrument equipped with a diode array detector. Phenomenex "Luna 2" reverse phase 5-micron C-18 chromatography columns (4.6 x 250 mm separation column, 4.6 x 30 mm protective column) are used. The mobile phase is 0.2 percent (in volume / volume) of - - Dicyclo-adylamine adjusted to a pH of 5.3 with o-phosphoric acid. All solutions are filtered through a 0.2 micron nylon filter before use. To facilitate comparisons, samples for chromatography are adjusted to a final concentration of approximately 0.3 percent (w / v) ascorbate by dilution in the mobile phase (described above), and injected into the column 100 microliters. The isocratic elution is carried out with the same mobile phase. The wavelength detection using a diode array detector ranges from 200 to 360 nm. The retention time of the presentation column of the 2-dimensional HPLC chromatograms (minutes) on the x-axis and the detector response at 200 nm (absorbance) on the y-axis. The 3-dimensional HPLC chromatograms show retention time-column (minutes) on the x-axis, absorbance (on arbitrary detector response units) on the y-axis and the wavelength of the light scanned by the detector set diode (nm) on the z axis.

Example 4 This example illustrates the preparation of a vitamin C product as disclosed in the Patent - North American Issue 5,140,043 (Darr et al.) And a comparison control without vitamin C.

Preparation of the Sample: 10.0 grams of ascorbic acid are transferred to a 100 ml volumetric flask. 80.0 milliliters of deionized water are added and the material dissolved. Propylene glycol is added to bring the final volume to 100 milliliters.

Control Preparation: 80.O milliliters of deionized water is added to a 100 milliliter volumetric flask. Propylene glycol is added to bring the final volume to 100 milliliters.

HPLC procedure: 7.5 grams of the aforementioned sample and the control preparations are transferred to 100 milliliter volumetric flasks. The flasks are brought to a volume with deionized water and the material is completely dissolved and mixed well. 4.0 milliliters of each of these solutions are transferred to separate 10 milliliter flasks that are brought up to the volume with the HPLC mobile phase. Samples are filtered through a - 0.2 micron filter and 100 microliters of each are injected. The resulting chromatogram is illustrated in Figure 1 (test) and Figure Ib (control).

Example 5 This example illustrates the preparation of a vitamin C product as disclosed in U.S. Patent No. 4,983,382 and a comparison control prepared without vitamin C.

Preparation of the sample: 5.0 grams of ascorbic acid, 10.0 grams of deionized water, 21 grams of propylene glycol and 61.1 grams of ethanol are transferred to a 100 milliliter capacity flask. The flask is placed in a sonicator and it is observed that the ascorbic acid dissolves completely. Control preparation: 10.0 grams of deionized water, 21 grams of propylene glycol and 61.1 grams of ethanol are transferred to a 100.0 milliliter capacity flask. The flask is placed in a sonifier and mixed thoroughly.

- - DETAILED DESCRIPTION OF THE DRAWINGS Figures la and Ib illustrate that the product of the liquid ascorbic acid solution typical of the prior art does not contain any major components other than those at the solvent front 1 and the intact ascorbic acid components 2. As shown, the maxima of Figure la are identical to the control shown in Figure Ib with the exception of the maximum 2 ascorbic acid at 26-30 minutes retention time, and the maximum at 4.3 minutes which is a maximum of solvent disturbance. HPLC chromatograms of the typical concentrated compositions of the invention, prepared with and without a zinc component, but without an added threonate, are shown in Figures 2 and 3, respectively. Figures 2a and 3a are test preparations containing ascorbate; Figures 2b and 3b are control preparations without ascorbate. As will be evident, there is a maximum 3 principal that represents a compound that appears between the frontal maxima of solvent 1 (retention time of 2-3 minutes) and both the maximum 4 treonato (retention time ~ 18 minutes) and the maximum 2 ascorbate (retention time of 26-32 minutes) both in Figures 2a and 3a, which do not appear in their control chromatograms - respective, Figures 2b and 3b. This establishes that the compound represented by the maximum 3 that is not ascorbate in both cases was due to the presence of the ascorbate-aldone components of the compositions and that the presence of zinc favors the production of the compound characterized by this maximum 3 which It is not ascorbate. Note that the thronate is formed during the preparation of a typical concentrate, even when it is not deliberately added as a raw material component. Figures 4a and 4b are three-dimensional HPLC chromatograms collected with the use of the diode array detector, which more clearly illustrates the maximum 3 that is characteristic of the compound appearing between the front 1 max of the solvent and both the maximum 2 of ascorbate and the maximum 4 of treonato. In these chromatograms, the retention time forms the x-axis (left-right), the detector response (absorbance, or light absorption) forms the x-axis (vertical) and the wavelength of the detector forms the z-axis ( frontal-posterior). Figures 4a and 4b are produced using the same chromatographic data as that used in Figures 2a and 3a, respectively, with the exception that the elution profile is truncated at approximately 26 minutes prior to the elution of the large ascorbate maximum, - in order to clarify the positions of the compounds formed during the preparation of the concentrated compositions. The maximum 3 appears in Figures 4a and 4b, between approximately 13-14 minutes of retention time, and has an absorption maximum at approximately 285 nm. This maximum, even though it is prominent at approximately 285 nm, shows little absorbance at 200 nm, which is the wavelength commonly used in the routine chromatographic detection of HPLC. The compound represented by the maximum 3 is 4-hydroxy-5-methyl-3 (2H) -furanone. This furanone derivative is present in the concentrated products of the present invention in an amount of about 0.001 weight percent upwardly of about 0.1 weight percent or more. the concentrated compositions of the invention also contain 3-hydroxyl acid? kojic, the compound, represented by the maximum 3a of Figure 4a. This kojic acid derivative is a known skin bleaching agent. In accordance with my present information, it appears that this kojic acid derivative is present in the concentrated products of the present invention in an amount of 0.001 weight percent upwardly of about 0.1 weight percent or more. The previously identified furanone and kojic acid derivatives are present in the - Concentrated compositions of the invention, whether or not an aldonic compound has been added to the reaction mixture from which these concentrated compositions are obtained. Figure 5a illustrates the stability of a typical commercially available liquid vitamin C composition based on U.S. Patent Number _5, 140, 043 (Darr et al.). Figure 5b illustrates the superior stability of vitamin C in the typical concentrated compositions of the invention, illustrating the comparable stabilities of four different mixtures having different ascorbate, aldonic zinc and polyol compositions. These concentrated compositions vary with respect to the concentration of ascorbate (from 10 to 15 weight percent of Vitamin C as calcium ascorbate), the presence or absence of added aldonic compounds (threonate), and the presence or absence of other elements of trace (zinc), and have variable ratios of the polyols in the solvent that is used (glycerol, versus 70 percent sorbitol). The stability of each of these four compositions is evaluated by taking samples of the stored mixtures either at -22 ° C (room temperature) at 40 ° C. (accelerated aging) and measuring the remaining ascorbate by colorimetric procedures. Because the - Chemical decomposition is accelerated by elevated temperature, the time scale of accelerated aging tests is adjusted to "room temperature" by an appropriate factor predicted by the Arrhenius equation. Several concentrated compositions of the invention retain more than 90 percent of their original vitamin C potency for 25 months at room temperature (Figure 5b). In contrast, a commercially available liquid vitamin C composition retains 90 percent of its original potency for only about one month (Figure 5b). Having described my invention, in terms in order to allow those skilled in the art to understand and carry out the same and having identified the currently preferred modes for the practice thereof, I CLAIM:

Claims (16)

CLAIMS:

1. A concentrated liquid vitamin C composition comprising: (a) at least one mineral ascorbate; and (b) at least one pharmacologically acceptable liquid organic polyol solvent for the mineral ascorbate; the composition has a pH of between 5 and 7

2. The liquid concentrate composition of claim 1, which also includes at least one aldonic compound.

3. A liquid concentrated composition of liquid vitamin C, comprising the reaction product of a reaction mixture including: (a) at least one mineral ascorbate; and (b) at least one pharmacologically acceptable liquid organic polyol solvent for the mineral ascorbate; the concentrated composition has a pH of about 5 to 7.

The liquid concentrate composition of claim 3, wherein the reaction mixture includes an aldonic compound.

5. The liquid concentrate composition of claim 3, wherein the reaction mixture includes a pharmacologically acceptable zinc compound.

6. The concentrated composition of claim 5, wherein the zinc compound is a water soluble zinc salt.

7. The concentrated composition of claim 6, wherein the reaction mixture includes an aldonic compound.

8. A vitamin C product prepared from the concentrated composition of claim 1.

9. The method for application of vitamin C comprising introducing into the human body the vitamin C product of the re-fractionation 8.

10. The reaction product of the reinvidication 3 containing a compound characterized in that the maximum HPLC having an absorption maximum at about 285 nm and appears after the front maxima of the solvent and before the ascorbate maximums.

11. The reaction product of the claim 3 containing 4-hydroxy-5-methyl-3 (2H) -furanone.

12. The reaction product of claim 3 containing 3-hydroxy-kojic acid.

The composition of claim 1 containing 4-hydroxy-5-methyl-3 (2H) -furanone.

14. The composition of claim 1, which contains 3-hydroxy-kojic acid.

15. The product of claim 8 which contains 4-hydroxy-5-methyl-3 (2H) -furanone.

16. The product of claim 8 which contains a 3-hydroxy-kojic acid.