DE1617557A1 - Stable oryzanole solution and process for making same - Google Patents

Description

The present invention relates to pharmaceutical, cosmetic and nutritionally useful preparations containing oryzanol in dissolved form. In particular concerns this invention solubilization of oryzanol, thereby it can be incorporated in a stable, dissolved form.

The oryzanol used, was initially believed to it a single compound rather than as a group of vitamins is, includes various kinds of three or more triterpene alcohol esters of 3-Methoay-4-hydroxy ~ olimamicL _f wherein the sum formulas of these Main shares

1098U / 1S8S

- ■ 2 -

^G 40 ^H 58 ° 4 ^{and C} 41 ^H 60 ° 4

are, in terms of its properties, it is a white or awake yellowish-white, noiseless, crystalline Substance or crystalline powder, which is stable in the air and slightly soluble in water, as well only in a corresponding manner in methanol, petroleum ether, each but is fully soluble in acetone and fatty acid ester

An n-heptane solution of oryzanol exhibits a peculiarity Abs orpt ion band open with absorption maxima at 231 mu, 291 mu and 315

The general medicinal value of oryzanol differs from the known hormones and the like too in chemical composition. Oryzanol is a complete new nutrient extracted from vegetable oil, and it was found that oryzanol was mainly so acts on the endocrine system that the function of the same is promoted, the peripheral blood vessels expand so that the blood circulation is noticeably improved, the growth helps to accelerate the disease, has antibiotic and bactericidal effectiveness. In the field of gynecology Oryzanol is remarkably effective in menopausal diseases, with hormones, vitamins, and sedatives similar things were used: In the field of internal medicine can it be used for underdevelopment ia

109Θ1Λ / 1d86 - 3 -

Growth, menopausal fatigue, insomnia, disorders in the bloodstream, decreased performance, etc .; on the In the field of dermatology, oryzanol is used more generally, for example for climacteric chloasma, facial exfoliative eczema, cephalic pityriasis, acne vulgaris, wrinkling, cracking, chronic eczema, faciales Helasma, skin rejuvenation, etc ..

With regard to the water-solubilization of fat-soluble vitamins or other fat-soluble substances, apart of oryzanol, studies have heretofore been made using various kinds of surface treatment agents and accordingly published many reports about it. Nonetheless, most of the same concern solubilization using surface treatment agents, such as polyoxyethylene sorbitan mono-fatty acid ester, Polyoxyethylene fatty acid ester, polyoxyethylene fatty alcohol ether, Polyoxyethylene castor oil derivatives and the like.

These surface treatment agents are essentially non-ionic surface active agents and, moreover, are if they are used as such, limited to those containing polyethylene glycol as the hydrophilic residue for the reason that the hydrophilic Hest des Polyethylene glycol can be modified by changing its degree of polymerization and is not a hydrophilic residue, except

1098U / 198S '_ 4 _

the one mentioned above, available and sufficient is the lyophilic To correspond to the remainder of a long-chain hydrocarbon. It has been found, however, that the solubilization process, using the surface treatment agent, the hydrophilic residue of which is polyethylene glycol is, has the following disadvantages:

1. Polyethylene glycol and surface treatments containing them are completely different from the Substances as they exist in the natural state, but also in living bodies, so that despite the fact that they are not particularly poisonous, due to the Food hygiene laws may not be used.

2. It has already been explained that the fact that a Surface treatment agent with a polyethylene glycol group dissolves in water, due to the fact that a million is formed with the hydrophilic residue, the strives outwards and with the lyophilic residue, which is directed towards the center, and then the ether formation of the polyethylene glycol hydrated and dissolved in water, although the designated bond is extremely weak, so that dehydration when the temperature rises (in the case of the Sterilization by heating) takes place. In addition, the cloud point can be noticeable depending on the

- 5 - 10981 Ul 1985

dissolved substances or additives, at normal temperature fall off, and immersion in warm water may cause cloudiness, so that the practical use of them is sometimes difficult.

In order to eliminate these disadvantages mentioned above, suggested the use of saccharo fatty acid monoesters.

In the accompanying drawing, FIG. 1 shows in a graph the relationship between the concentration and the transparency of aqueous solutions of saccharose esters and

FIG. 2 also shows this in a graphical representation Relationship between the concentration and transparency of the aqueous raffinose esters used in the present invention salvation.

Although saccharo fatty acid esters have long been synthesized, the fact that the monoester can be obtained in its pure form is first described in the report by Osipow and others in Ind.Eng.Chem. 48, published in 1962. Recognizing that the monoesters can be brewed as detergents, food emulsifiers or the like, they created a semi-industrial process, whereby the eggs: r _r? have the following structural formula:

'■'"' ^: ' tm? F _f _ ₆ _

1098U / 19ÖS

CH ₄ OCOR

CHaOH

CH ₂ OH

The monoeaters synthesized according to the designated report are esters of lauric acid, myristic acid, palmitic acid, Stearic acid, oleic acid, caprylic acid and caprylic acid, which are altogether tasteless and odorless, non-toxic and non-stimulating. Lauric acid ester dissolves in water, but the others in solvents such as methanol, ethanol, acetone and the like. These have one quality reduce surface tension and are suitable for food preparation and injections.

The process of solubilization by sucrose ester however, it is not perfect and involves some difficulties which are encountered in practice. One of these difficulties concerns taste and smell. The report by Osipow and others regarding the saocharose esters states that these are boiled and odorless, but sacoharo myristate, laurate, caprate, caprylate and

similar are all bitter in taste, while-inolate and linolenate a strong Ge. you have. Beyond that these are · compounds without exception water-soluble and ' intended for more ala HLB 15. Palmitat, St ear at and 01 «at,

1098U / 1985

which have relatively little taste and smell are not suitable for solubilization. The transparency of aqueous solutions of sucrose esters is shown in FIG.

Accordingly, the method of detachment using sucrose esters is limited because of their usefulness in terms of taste, odor and solvency of these esters, with those having more double bonds being found to be more obnoxious and fatty acid esters having a short carbon chain are more bitter. Furthermore, with regard to the dissolving power of the sucrose ester, the hydrophilic Eest is generally limited to sucrose and is not sufficient to bring about the solubilization of oryzanol and furthermore cannot be adjusted by changing the degree of polymerization as with the polyethylene glycol series, so that ™ qn consequently depends on the fatty acid will make use of the lyophilic residue alone. .

Due to the fact that sucrose has more OH groups than Having sorbitol, sorbitan or similar, their esters are also highly hydrophilic, while the fatty acid esters have more Carbon atoms as palmitic acid, these in water in makes it difficult to dissolve to a high degree and exceeds the limit of the dissolving power. Caproic acid ester, although less carbon atoms are weak lyophilically and

$ 109 8-14 / 198

therefore not suitable for solubilization. Accordingly are for saturated fatty acid esters of normal chain the Saccharo fatty acid esters of 8 to 14 carbon atoms only relatively suitable for solubilization.

Nonetheless, in making the oryzanol solution the use of the sucrose esters given above, with regard to the solvent power, taste and smell of the ^ Sucrose ester, as previously indicated, not sufficient.

It is therefore the subject of the present invention To provide a method of making a stable oryzanol solution which is excellent in taste and smell, and especially in addition to providing a method for the preparation of an oryzanol solution, the opposite seasonal temperature changes is stable.

From the above it follows that soluble- * then do the previously described task with an excellent result are able to dissolve if their hydrophilic property is higher than that of sucrose, so that their dissolving power higher than HLB 15 must be used. As a result of various studies it was found that, provided that the hydrophilic property thereof is higher than that of sucrose, fiaffinose is selected the fatty acid eater the oryzanol solubilization makes successful. "

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ORIGINAL

In other words, the subject matter of the present invention lies in the use of baffino fatty acid esters as a dissolver in the production of the oryzanol solution. Baffinose is naturally found in sugar beets and cottonseed and belongs to the trisacarides, which also, in the effluents of Stephen's process for making contained by sucrose. Its structural formula is as follows:

CH ₂ OH. .

H OH '

The position of the ester linkage of raffinose is unknown, but it is believed that it is the 6-division of galactose when considering the Saooharose ester. Monoesters, diesters, triesters, and the like are used in mixtures manufactured.

The designated raffinate fatty acid esters are in high fashion hydrophilic in comparison with the polyethylene glycol series mentioned above and sucrose esters and are suitable for dissolving oryzanol. The designated. Ester occurs naturally, along with fatty acids and baffinose, and is non-toxic, tasteless and odorless. Therefore, the solution of the present invention is not only for. Medicines and cosmetic needs, but also

1098U / 198S

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- ίο -

suitable for food.

In general, the solubilization process consists of fat-soluble vitamins in the fact that you first, to prepare a solution of the solubilizer, a solubilizer dissolves in a dispersion medium (water) and then a dispersion medium (fat-soluble vitamin) is added to make it soluble. In the case of oryzanol, the indicated solubilization can be carried out in the following manner be performed:

First of all, it should be noted that even if the oryzanol added to a mixture of a dispersion medium and a solubilizer (raffinate fatty acid ester) and that designated The mixture is heated and mechanically stirred, the solubilization of oryzanol is difficult, depending on from the concentration of oryzanol, actually solution is not achieved. In this case, however, if the oryzanol in a raffinate fatty acid ester, which has been heated to its softening point, and then the solution is dispersed and dissolved in a dispersion medium, the oryzanol solution can be prepared extremely easily. Further, in this case, it is possible that a small amount of water is present in the raffinate. In other words, the solution of a concentrated raffinate fatty acid ester over # 50, preferably £ 90 and over, duroh

- 11 1098U / 19S5

Dissolving with oryzanol can be prepared with heating, and the vegetable solution can be in a dispersion medium be dissolved by way of dispersion. Hence is it does not matter in the solubilization of oryzanol the hydrophilic residue of a solubilizer is too hydrophilic, and in this regard the raffinate fatty acid ester is a satisfactory solubilizer for oryzanol.

Whether the lyophilic properties of the raffino ester are strong or weak depends on the number of carbons in the fatty acid components. It depends essentially on that Ratio of the designated lyophilicity to the hydrophilicity did from raffinose on, with fatty acid esters from 8 to 20 atoms are suitable, of which the esters of lauric acid, Hyristic acid, palmitic acid and oleic acid die are mostly preferred.

The synthesis of the λ raffinose fatty acid esters used in the present invention is carried out by mixing the fatty acid esters and the raffinose in dimethyl formamide and transesterifying with an alkaline catalyst; in other words, the raffinose completely dehydrates the ester insofar as it usually contains 5 moles of crystallization water.

For example, 3 moles of raffinose will be in 4- 1 dimethyl form ~ amide dissolved with 1 mol of fatty acid methyl ester. The solution

- 12 1098U / 198S.

50 g of potassium carbonate are combined and 5 hours at 95 ⁰ C under reduced pressure of 100 to 200 mm Hg
heated until the transesterification is effected. Thereafter, after the solvent is removed by heating, with
Isopropanol or isobutanol is a separation extracted from the raffinose. The specified solvent is removed by heating and recrystallization with dichloro-pethane is effected. The fatty acids used here should be 90% pure. Depending on the amounts of fatty acid methyl esters, monoesters, diesters, triesters are formed in this way, although any of these esters and their mixtures can be used in a similar manner in the present process.

The following are the physicochemical properties of the raffinate fatty acid monoesters produced in this way
. were obtained, shown in Table 1, and the transparency of the aqueous solution having the same is shown in
Figure 2 shows the relationship between the concentration and the transparency of the aqueous raffinose ester solution used in the present invention
will show.

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I U I /

Myristate white powder.
not altogether
bitter 79.5 .5.8 Palmitate likewise 75.5 4.5 Stearate likewise 81.0 5.5 Oleat likewise 82.5- 7.5

- 15 -

Table 1

Raffino-ex. Ersoheings.- Versatile-free surface »- Ester softening. Fatty acid image and refining tension weight / value point ester properties value nose volume. ( ⁰ C) 1 $ 0.1 $ 0.05 #

Laurat white powder. 81.5 5.4 55.80 58.40 58.20 90.2 85-90 slightly bitter
in taste

57.75 59.50 40.57 85.4 67-69 58.25 40.50 41.75 86.5 60-62 42.78 45.55 44.26 85.5 48-50 59.20 40.87 41.66 77.5 55-54

The amounts of raffinate fatty acid esters used in the present invention do not only change according to the Purposes for which this invention is used, but also according to the carbon number of the fatty acid components, generally 1 part of oryzanol is dissolved in 1000 parts of water, and the amounts indicated are at approximately 10 to 100 parts of raffino / fatty acid ester are around to enable the perfect dissolution of oryzanol.

The oryzanol-containing solution thus obtained according to the invention can be used as food, medicament, Cosmetics are used in the unmodified state, as obtained according to the previous descriptions, however, further investigations were carried out with the addition of components necessary for the respective purposes

1098U / 1985

made to produce an oryzanol containing Solution that is largely more stable in the various ranges of temperature and pH changes.

In general, as the amount of solubilizer increases, the range of stable temperatures of the designated, solubilizing agent Systems move into the lower ranges P and when the concentration of the solubilizer increases, the difference in temperature resistance is increased significantly, as is generally known. In the meantime the cloud point caused by the temperature changes and the cloud formation in the solution do not occur if an ionic surface treatment agent is used, while one of the nonionic surface treatment agent is used own phenomenon can be determined.

* For example, when polyoxyethylene sorbitan mono-Pettsäureester is used as solubilizer, is generally at the turbidity of about 70 to 90 ⁰ C begin to be completely at 100 ⁰ C, and it may occasionally two layers are formed. On cooling, the original transparency will return, while on the other hand the cloud point shows a tendency to lower for a short period of time if the heating and cooling are repeated ^{in the range from 40 to 80 ° C.}

- 15 10Ö8U / 198S

The oryzanol solution of the raffinose fatty acid esters according to the present invention dissolves clearly in the three-component system of fiaffinose-oryzanol-water. Even if briefly heated up to 100 ^° C., no turbidity will occur and even in the event that other substances necessary for practical reasons are added to it, it can be said that it is completely stable to temperature and pH changes. In addition, it may be necessary to add an auxiliary solvent to the oryzanol solution to completely maintain the temperature resistance in a wide range of pH at at least from -20 to 37 ^° C. of seasonal temperature changes, as well as 4-0 to 100 ^° C. temperature changes during production.

As a result of the investigations it has now been found that the practical temperature resistance of the designated solution can be remarkably increased can, if one or more reducing sugars and the water-soluble, metallic complex compounds the same as the auxiliary solvent with the raffinate fatty acid esters available oryzanol solution.

The saccharides used as co-solvents in the present process are the reducing saccharides, such as monosaccharides and disaccharides. Sucrose is in '-'

- 16 1098 U / 198 $

Its reducing property is ineffective and unsuitable. Among the monosaccharides, for example, hexoses such as fructose, glucose, galactose, mannose provide satisfactory ones Results. Invert sac charid, made from a mixture, of fructose and glucose composed can also be used. Fructose and glucose are in some form clockwise or counterclockwise, or as a mixture of these, can be used. Pentose, like ßibose, can do just as well be used. Tetrose such as erythrose or triose such as dihydroxyacetone can also be used, but are not so stable.

Among the disaccharides, for example, dihexose such as lactose, maltose and cerebiose can be used.

The metals of the water-soluble metal complex compounds of these reducing sugars are calcium, magnesium, Strontium, barium, titanium, vanadium, chromium, manganese, iron, cobalt, nickel, copper, zinc, etc.

The binding of the metal complex compounds of the reducing Types of sugar is from the following examples of gluco iron (lI) complex compound a) and galacto-titanium complex compound b) evident:

- 17 10981 A / 1985

HC - O
HC - ■ O
HIGH

HC —OH HO "

HO
HO

HC <■ - HC -—

- CH

- CH

:H

CH ₂ OH

CH ₂ OH (a)

The proportions of auxiliary solvents, namely one or several kinds of reducing saccharides and the water-soluble metal complex compounds thereof become desirable in the molar ratio of a reducing saccharide to a metal ion of at least 2: 1 and Ma up to preferably 4: 1 to 52: 1 or more is used.

The reason that the reducing saccharide is in excess compared to the metal ion is used, is that 1. the metal ion is a hydroxide with an ÖH ion in a alkaline, aqueous solution, on the other hand, 2. the metal ion forms a complex compound with a saocharide (in a digestive organ for example) among the same alkaline aqueous conditions and it is assumed that a special relationship between the OH-ion and the Saccharide is given. Accordingly, it is required one Excess sugar, to suppress the tendency of the metallic Ions for hydroxide formation to use. In other words, it is desirable to use one

109814/198 * -18-

Hi ^ fslösungamels that the metallic complex compounds the reducing saccharides themselves are stable.

The amount of such auxiliary solvent added will vary according to the different purposes of the preparation, and reducing sugars are mostly preferred

^ admit their molar ratio of metal ions to sugar at least more than 2: 1 and such that the water-soluble complex compounds in the ratio of 0.1 to 0.9 parts to 1 part of oryzanol are present in a solution whose molar ratio of oryzanol to raffinate fatty acid ester to water is 1: 10: 1000 and higher. The addition method can be carried out in any way, either in the previous solution of the auxiliary or by adding it to the oryzanol solution. In the preparation of an oryzanol solution in water by adding this

"to a Haffino fatty acid ester as a solubilizer and further addition of one or more reducing sugar types and water-soluble metal complex compounds thereof as a co-solvent, is the temperature resistance the solution has been greatly improved, so that it is possible to produce a stable solution of oryzanol.

len in a wide range of pH conditions, the practically sufficient -20 to 37 ⁰ C JahreszeitIiok-related temperature changes, such as from 40 to 100 ⁰ C Temperaturände-

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in the manufacturing process.

For solubilizing other additives in the oryzanol containing Solution it is also possible to use a so-called polyethylene glycol solubilizer or a sucrose ester to use.

If it is a matter of components of general drugs, orally applicable drugs, nutrients, cosmetics, which in addition to oryzanol, for example vitamin A oil or palmitate, acetate, alcohol of the same and vitamin Bp, etc. should contain, then these can be used alone, if they are all used are, haze formation, both at -20 ° to 37 ⁰ C, that is, with virtually seasonal temperature changes as a result even with temperature changes on the occasion of the production of 40 to 100 ⁰ C, which is actually a difficulty may occur in the practice of the present invention.

The indicated difficulty can be eliminated using as a co-solvent of one or more other kinds of reducing saccharides and the water-soluble complex compounds thereof.

In the present invention, alcohol can be used as a solvent (dispersion medium) instead of water will. _

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I U I / O O /

example 1

100 mg orizanol be different Raffino-Fettsäureestern which were heated to 90 to 100 ⁰ C, was added and dissolved therein. The mixtures are then dissolved in ethanol and after the ethanol has been removed by heating, 10 ecm of water are added so that orizanol solutions are obtained.

The transparency of the designated solutions was measured with a Beckmann B-type spectrophotometer (wavelength used = 650 mu). The result is from the following Table II can be seen. Solutions of more than $ 93 Transparencies are macroscopically clear.

Table II: Transparency

Raffinose ester Laurate Myristate Palmitate Oleat Amounts to be added ⁺ 1: 10: 1000 87.5 - - - 1: 15: 1000 93.0 93.0 - 92.5 1:20: 1000 96.0 97.0 85.0 94.0 1: 25: 1000 97.5 98.5 93.0 95.0 1:30: 1000 - - 94.0 96.0 1:35 5 10000 - 96.0 98.0

The amounts added are the weight ratio of orizanol to raffinose ester to water.

- 21 10981 Ul 198S

From the previous one. Description can be seen that to create stable solutions containing orizanol

Use of baffino fatty acid esters as solubilizers gives excellent results at concentrations suitable for practical use.

Example 2

A: Baffinose myristine acid ester 1500 mg "

Orizanol 100 mg

Glueo-iron (II) .complex compound 10 mg

Fructose 5000 mg

Water 100 ml

B: L-isoleucine 90 mg

L-leucine 100 mg

L-Lysine Hydrochloride 110 mg

L-phenylalamin 60 mg

L-methionine 90 mg

L-threonine 60 mg

L-Triptophan 50 mg a

L-valine 90 mg

L-arginine hydrochloride 210 mg

L-histidine hydrochloride 100 mg

L-potassium aspartate 100 mg

L-magnesium aspartate 100 mg

Glycine 300 mg

Eatrium glutamate 50 mg

D-pantothenyl alcohol 30 mg

Vitamin Bg 5 mg

Citric acid 200 mg

d, l-maleic acid 100 mg

Lactic acid 0.3 ml

Sorbitol 5000 mg

109814/1985 - 22 -

Raffinose ester is heated to 90 ⁰ C. and crystals of orizanol be added, which are completely melted. The mixture is slowly added to a solution formed by previously dissolving a gluco-iron (II) complex compound and! Fructose. After determining that the resulting solution was not cloudy, becomes

the remaining solution was added all at once and cooled down to 20 ° C and combined with the B mixture to make a total solution.

The orizanol solution thus obtained is satisfactory seasonal temperature changes, there it is very stable, and it can be considered enriched, excellent Nutrients, for example one that can be used orally Medicines are used.

Example 3

A: raffinose palmitic acid ester 100 mg Orizanol 10 mg Pruct o-calcium complex compound 10 mg glucose 50 mg Calcium gluconate 5 mg water 100 ml
r B: thiamine chloride 5 ng Vitamin B ₂ 0> 5 mg Pyridoxine hydrochloride 1st floor Ascorbic acid 25 mg Nicotinic acid amide 10 mg

- 23-1098U / 19IS

The above substances become a similar one Method as in Example 2, a very stable orizanol-containing preparation prepared as a hypodermeintramuscular Injections is available.

Example 4

A: Eaffinose oleic acid ester to 100 mg

Orizanol 10 mg "

Fructo-magnesium complex compound 10 mg, glucose 50 mg

Sourling (water with carbon dioxide) 100 ml

B: fruit essence 1000 mg

Sucrose 10000 mg

Citric acid 5 mg

Treating the foregoing substances by a procedure similar to Example 2, whereby very stable, orizanol- ^ containing nutritious beverages can be obtained. G

Example 5

A: fiaffinose lauric acid ester 300 mg

Orizanol 30 mg

Lacto-titanium complex compound 10 mg

Cerebiosis 50 mg

Water 100 ml

B: Vitamin Bg 5 mg

Oalcium pantothenate 10 mg

- 24 - 1098U / 1985

B: allantoin 10 mg

Dihydro-sodium-acetoacetate 1 mg

Ethyl alcohol 10000 mg

Sodium arginate 50 mg

Paraoxybenzoic acid methyl ester 10 mg

Perfume in an appropriate amount

The foregoing substances are processed in a similar procedure as in Example 2, creating a very stable, orizanol containing nutrient solution for beauty care is obtained.

- 25 - 1098U / 1 985

Claims (15)

1 61 7 b 5 7 - 25 patent claims 1. Process of converting Orizanol into a pharmaceutical, Dissolved form which can be used cosmetically and also in edible form, characterized in that orizanol in a solubilizing Means of fatty acid esters from Baffinose is resolved. 2. The method according to claim 1, characterized in that the fatty acid esters laurate, myristate, palmitate, stearate and oleat are. 3. Pharmaceutically, cosmetically and edibly usable solution of orizanol in a solubilizing agent of fatty acid esters from Haffinose. 4 · A pharmaceutically, cosmetically and usable edible solution of orizanol in a solubilizing agent of Fettsau- g re-eetern of ßaffinose, characterized in that the weight ratio of orizanol to Solubilizing agent to water is about 1:10 to 100: 1000th 5. Process of converting Orizanol into a pharmaceutical, Cosmetically and edibly usable, dissolved form, characterized in that oriznaol in a solubilizing Means of fatty acid esters dissolved from affinoae and also an auxiliary solvent is used which is composed of one or more reducing sugars and / or 1098 U / 1 98 5 - 26 - water-soluble metal complex compounds thereof consists. 6. The method according to claim 5, characterized in that the reducing saccharides mono-saccharides, such as fructose, Glucose, galactose, mannose, ritose, or a mixture of Are fructose and glucose. 7. The method according to claim 5, characterized in that the reducing sugars are di-saccharides, such as lactose, maltose and cerebiose. 8. The method according to claim 5, characterized in that the water-soluble metal complex compounds are glucometal complex compound and / or galactomet all-complex compound are, in which metals are used, such as calcium, magnesium, strontium, barium, titanium, vanadium, chromium, W Manganese, iron, cobalt, nickel, copper, zinc. 9. Pharmaceutically, cosmetically and edibly usable solution of oryzanol characterized in that it comprises a solubilizing agent of fatty acid esters of ßaffinose, together with a co-solvent of one or more reducing saccharide species and / or water-soluble Metal complex compounds thereof. 10. Pharmaceutically, cosmetically and edibly usable solution of oryzanol characterized in that it comprises a 1098 U / 198 5 - 27 - solubilizing agent of fatty acid esters of raffinose, together with an auxiliary solvent such as fructose, glucose, Galactose, mannose, ribose or a mixture of fructose and glucose. 11. Pharmaceutical, cosmetic and edible solution of oryzanol characterized in that it comprises a solubilizing agent of fatty acid ester of raffinose and a co-solvent such as lactose, maltose, cerebiose and a mixture thereof. 12. Pharmaceutically, cosmetically and edibly usable, stable solution of oryzanol, characterized in that it comprises a solubilizing agent of fatty acid ester or raffinose and an auxiliary solvent, such as a gluco-metal complex compound and / or galacto-metal complex compound, for this compounds of metals are used, such as calcium, magnesium, strontium, barium, titanium, like vanadium, chromium, manganese, iron, cobalt, nickel, copper, zinc, and the molecular weight ratio of reducing saccharide to the metal ion 2: 1 and more. 13. Pharmaceutically, cosmetically and edibly usable solution of oryzanol characterized in that a solubilizing Agent and an auxiliary solvent in a weight ratio of ' Oryzanol 'to a solubilizing agent to an auxiliary - 28 1 0 9 8 U / 1 9 8 5 Solvents from about 1:10 / to 100: 0.1 to 9.0 are used will. 14. Method of converting orizanol into a pharmaceutically acceptable, dissolved form, such as essentially described in one of the specific examples above. ™ 15. Dissolved orizanol, as essentially in one of the specific examples described here. 1098U / 1985