A method of obtaining a water-dispersible composition oryzanol and product

 

(57) Abstract:

The invention relates to a method for producing water-dispersible compositions of oryzanol in which the Sterol is easily applied form. The method includes spray drying the suspension of oryzanol in the presence of monofunctional and polyfunctional surfactants. The product is obtained in a form that can be administered in food or in drink, or in solid or suspension of the standard form. 2 C. and 10 C.p. f-crystals, 2 tab.

Related applications

This application is a partial continuation application US Serial Number 09/025952, filed February 19, 1998, the full contents of which are entered in the description by reference.

Background of the invention

This invention relates to a method for producing a water-dispersible compositions of the Sterol, dried by spraying, in particular to a method for producing dispersible-sitosterol by method of drying by atomization.

As described in U.S. Patent No. 5502045, 5578334 and 5244877, it is known that the consumption-sitosterol reduces cholesterol in the bloodstream. In present-sitosterol is introduced into foods as a food ingredient in their prepara is limited to those products, in which the manufacturer has decided to enter-sitosterol.

It would be very desirable to obtain-sitosterol in a convenient ready-to-use form, in which consumers could use it in food just before eating. A particularly convenient form would be disposable bag-sitosterol, similar to those currently used for artificial sweeteners. The problem of providing-sitosterol in this form is that it is difficult to separate the active ingredient from other sterols, namely from stigmasterol, campesterol etc.

Attempts to solve the problem are described in U.S. patent No. 3881005 and No. 4195084, in which the water dispersible sitosterin get mixed with excipient and suitable surface-active substance. Although these publications discloses water-dispersible sitosterol, it would be very beneficial to improve FotoDepartament-sitosterol, as I think this is a more effective form as agent for lowering cholesterol.

Brief description of the invention

The main scope of the present invention is a method of obtaining a stable spray dried powder of the matrix, which has sluchae introduction-sitosterol in aqueous suspension using a mixed surfactant system, containing monofunctional and polyfunctional surfactant, and drying the suspension of the Sterol with getting in the water dispersible-sitosterol, and this method is performed in the absence of the stages of de-aeration and homogenization.

Detailed description of the invention

-Sitosterin is usually produced from wood or agricultural sources, such as a mixture of soy-based. Except-sitosterol, it is understood that in this description-sitosterol also includes esters-sitosterol, as well as stanol and ester derivatives stanol, which are restored derivatives of sterols. These derivatives are well known in this field and are described in U.S. patent No. 5244887; 5502045 and 5698527. -Sitosterin obtained by this invention are water-dispersible. The term "water-dispersible" in this description means that when dried by spraying the composition-sitosterol is placed in water at least 200 mg composition/ml of water will dispergirujutsja with weak stirring. Qualified in this field specialist understands that typically sitosterin are hydrophobic materials, and adding-sitosterol in is also applicable to another class of compounds, lowering cholesterol - to oryzanol (orynzanol) and its esters. These materials are also known in the field as esters oryzanol (see, for example, U.S. Patent No. 5514398, the content of which is incorporated as reference, and PCT WO 98/1519, published January 15, 1998). This invention also provides oryzanol, esters oryzanol and other related compounds in more dispersible form. Although the following description will relate to-sitosterol, the present invention is equally applicable to the specified oryzanol and related compounds.

For the most effective action if swallowed particle size-sitosterol should be in the range from 10 to 40 microns. More preferably, the particle size should be in the range from about 20 to 35 microns. Any grinding method known in this field can be used for grinding-sitosterol. Suitable methods include poroshkovaya, rotary hammer mill, air grinding, etc., from which air grinding is preferred. Particles of smaller sizes are preferred because the resulting-sitosterol more easily E smaller particle size less than desirable, because they lead to higher corner of the gap, the higher the angle of repose and compressibility. The manufacturability of the product water dispersible-sitosterol can be improved when a larger particle size; however, I believe that this has a deleterious effect on the efficiency-sitosterol in reducing cholesterol in the serum.

In order to obtain water-dispersible-sitosterin required suitable surface-active substances.

The present invention uses a dual surfactant system. However, the surfactant in the system is monofunctional, while the second surface-active agent is polyfunctional. Monofunctional surfactant tend to be more hydrophobic, while the polyfunctional surfactants tend to be hydrophilic. Used in this invention, the system of the two surfactants creates mixed mizlou system, which leads to the production of water-dispersible product. The term "monofunctional" in this invention is used to denote the ability powerglide ability to communicate with-sitosterol, as with other surface-active substance.

Useful for practice of this invention surfactants include esters of polyglycerol, Polysorbate, mono - and diglycerides of fatty acids, esters of propylene glycol, esters of sucrose and fatty acids and polyoxyethylenated complex arbitation fatty acids. These surfactants are well known in this field and are commercially available.

Suitable esters of polyglycerol include triglyceridesanother, exerciserelated, hexaglycine-palmitate, exerciserelated, demilitarization, lecapitalhumain, decapitalised, dialyzability, lecapitalhumain, decapitateddoctor, activitiesmore, occupierinvestors and de-capitalinvestment.

Other useful surfactants include Polysorbate obtained from the reaction product of monoglycerides or complex arbitation with ethylenoxide. Examples of useful polysorbates include polyoxyethylene 20 mono - and diglycerides of saturated fatty acids, polyoxyethylene 4 carpetmuncher, polyoxyethylene 20 suttirat, carbamaepine, arbitrageurs, propilenglikolmonostearata, glycerylmonostearate, DigitalMaster, glyceryltrinitrate.

Other suitable surfactants include (in brackets are the values of the products HLB) decapitationalbany [15.5]; demilitarization [10.5]; decapitalised [10.5]; lecapitalhumain [11.0]; decapitateddoctor [13.0]; demilitarizarea [13.5]; exeperimental[12.0]; exeperimental [10,5]; hexaglycine slabomineralizovannykh (hexaglycerolmonoshortening) [12.0]; polyoxyethylene (20) arbitrageurs [16.7]; polyoxyethylene (4) arbitrageurs [13.3]; polyoxyethylene (20) carbamaepine [15.6]; polyoxyethylene (20) servicemonitor [14,9]; polyoxyethylene (20) arbitrational [10.5]; polyoxyethylene (20) orbitonasal [15.0]; polyoxyethylene (5) orbitonasal [10.0]; polyoxyethylene (20) sorbifolia [11.0]. For qualified specialist is obvious that the products HLB value for surfactants is the expression of its hydrophilic-lipophilic balance, i.e. the balance of the size and strength of the hydrophilic (polar) and lipophilic (non-polar) groups of the surfactant.

Derivatives breast kigo surfactant is typically from about 1 to about 10 wt.% with respect to the final dried weight-sitosterolemia product, preferably from about 1.5 to about 4, and most preferably from about 2.0 to about 2.5 wt.%. The content of the polyfunctional surfactant is typically from about 0.5 to about 10 wt.% with respect to the final dried weight-sitosterolemia product, preferably from about 2 to about 4, most preferably from about 2.0 to about 2.5 wt.%. TWEEN 40 is a preferred monofunctional surfactant, SPAN 80 is a preferred polyfunctional surface-active substance. A suitable ratio of monofunctional/polyfunctional surface-active substances, which form a mixed micelle include ratio in the range of from about 1:6 to about 1.5:1, preferably from about 1:4 to about 1.3:1, most preferably a ratio of about 1:1. The content of the used surfactant is in the range of from about 0.5 to about 8 wt.% the total mass of surfactant system, preferably from 1 to about 6, naibolee surfactants upon receipt of the suspension in the composition (formulation) before spray drying add other excipients, supplements for tabletting and so on, It is convenient to introduce additives for tableting and other necessary ingredients, whereby is eliminated or reduced the number of stages of manufacture. If necessary, the ingredients can also be added to-sitosterol after spray drying.

For example, the suspension may be added lubrication, substances that improve slip, media, sweetening agents, disintegrators, preservatives and other ingredients in an amount of from about 5 to about 40 wt.%, usually from about 10 to about 30% and most preferably from about 20 to about 25%. Suitable ingredients include connecting components, which are vegetable glue Arabian gum, mucilage of starch, pre-gelatinising starch, sodium alginate, hypromellose (receiver array), starch paste; polyvinylpyrrolidone, carboxymethylcellulose, dextrin, ethylcellulose, polyethylene glycol, yeasty resin, Zein, hydroxyethyl cellulose, hydroxypropylcellulose, methylcellulose, polymethacrylates, and carboxymethylcellulose.

Dezintegriruetsja agents include microcrystals resin (for example, Ac-Di-Sol (R), stitched provide, alginic acid and alginates, pre gelatinising starch sodium glycolate, starch sodium starch glycollat) (e.g., Explotab R, Primojel R), modified corn starch (e.g. starch 1500R), starch (e.g. potato/maize starch), and ion-exchange resins, such as palacin(polacrin) potassium (e.g., Amberlite IRP-88).

Examples of the water-soluble soluble fillers are lactose, compressible sugar, confectionery sugar, dextrose, mannitol, sodium chloride, sorbitol, xylitol. Examples of water insoluble fillers are calcium carbonate, magnesium carbonate, calcium phosphate (e.g., di - and trehosnovnoy calcium phosphate), calcium sulfate, kaolin, microcrystalline cellulose, powdered cellulose, pre-gelatinising starch, barium sulfate, magnesium trisilicate, aluminium hydroxide.

Usually greases are used in smaller quantities. Examples of lubricants include stearates (for example, magnesium stearate or calcium), talc, polyethylene glycol, liquid paraffin, nutriceuticals, magnipapillata, colloidal silicon dioxide, palmitostearate, stearic acid, zinc stearate, gidrirovannoe vegetable oil. Prov.Omnia, such as colloidal silica (such as AEROSIL), pyrogenic silicon dioxide, hydrogenated silicoaluminate sodium, colloidal silicon dioxide.

Flavoring agents include oranges, cherries and strawberries, raspberries, grapes and fruit of the passion flower.

Sweeteners include, for example, saccharin sodium, aspartame, confectionery sugar, sorbitol, xylitol and mixtures thereof.

-Sitosterol and other ingredients in suspension must be uniformly mixed. Preferably, the suspension is mixed by stirring, preferably using high-speed mixer. The particle size of the micelles formed in the suspension is from about 50 to about 400 microns, preferably from about 100 to about 300 microns, and most preferably from about 150 to about 250 microns. The size of the micelles formed in the suspension can be measured using turbidimetry. At higher turbidity formed larger micelles. It is expected that higher turbidity, i.e. larger micelles, provides a more efficient form-sitosterol to reduce cholesterol when used. Preferred levels mutn who eat 3000 Neyolova Units Turbidity (Nepthialic Turbidity Units - NTU). In this description, the term "turbidity" is used as defined by the USP (United States Pharmacopeia) , the effect of light scattering from suspended particles and turbidity as a measure to reduce the intensity of the incident beam per unit length of the suspension. The range of values of turbidity ranges from 0 to 20,000 NTU. As a point of reference turbidity the turbidity of water is used, set to 0. The turbidity of the samples was measured at room temperature.

After the formation of a suspension with particles of a suitable size, the suspension is dried. Suitable drying methods include drying, freezing, drying rotation, vacuum drying and spray drying, of which the spray drying is preferred. The final moisture content of dried-sitosterol is preferably less than 1 wt.% water. Lower moisture content usually provides fluidity.

When drying the suspension by spraying preferably, the inlet temperature is from about 100 to 120C, preferably from about 105 to about 115S and most preferably from 107 to about 112C. the outlet Temperature of the spray dryer is between about 65 and 85C and most preferably from bring the product out. The resulting water-dispersible-sitosterol consists of more than 50 wt.% Sterol, more than 4 and preferably from about 5 to about 10 wt.% surfactants. In a very preferred embodiment of sitosterin also includes approximately 5% starch and about 5% silicon dioxide.

After removal-sitosterol from the dryer, it will be packaged in any form suitable size, which may be required. The form in which-sitosterol is used varies, depending on consumer preferences. Suitable forms include tablets, dosage for grinding, cooking and beverages, as well as for use in prepared drinks and food. In the preferred embodiment-sitosterol can be Packed in disposable packages containing from about 5 to about 50 grams per package.

This invention provides advantages in comparison with the previous level that provides a water dispersible-sitosterin while some expensive and long process steps are eliminated. In the previously described methods to obtain water dispersible-setdisplay-sitosterol by applying the selection of preferred combinations of surface-active substances. Hereinafter the invention will be illustrated in the following examples which are not limiting. In the examples, the starch is ground to particle size of approximately 10 microns. In these examples, all parts are weight percents unless otherwise indicated.

The following starting materials are available from the following suppliers.

CAB Of SIL - colloidal silicon dioxide from Degussa Corp.

AEROSIL A200 - colloidal silica from Cabot Corp.

EAT Compress - dibasic calcium phosphate dehydrate from Edward Mendall Compress Co., Inc.

M100 - maltodextrin (dextrose equivalent of about 10) from the Grain Process Corp.

Pluronic L-44 - a copolymer of polyethylene-propylene glycol from BASF Corp.

SPAN 80 - orbitonasal from ICI Americas, Inc.

Starch: Starch NF - from National Starch and Chemical. Inc.

Sterols: Generol 122N available from Henkel Company, Ambler, PA.

TWEEN 40 (polyoxyethylene 20 carbamaepine from ICI Americas Inc.

TWEEN 60 is polyoxyethylene 20 carbamodithioate from ICI Americas Inc.

In the examples, the phytosterol is-sitosterol or oryzanol.

EXAMPLE 1

This example discloses the composition of the spray dried material containing priblizitelen fatty acids.

The sample was prepared as follows: to TWEEN 60 add 500 grams of water and the mixture is stirred on heating the tile at 60C until a homogeneous mixture. The solution is transferred into a container of larger size by washing with water. Add the remaining 9500 g of water. Starch, Maltrin M100, Aerosil 200 and sterols are weighed and added to the solution. The resulting solution is stirred by a stirrer with large shear effort for approximately 1 hour. Immediately after this, the suspension is dried by atomization.

The turbidity of 100 mg of the resulting powder, spray dried 25 ml of water, approximately 300 NTU.

EXAMPLE 2

The following example is dried by spraying a composition containing approximately 75 % of the sterols (relative to dry mass).

The sample was prepared as follows: sodium docusinate weighed in a beaker, add 500 grams of water and the mixture is stirred on heating the tile at 60C until a homogeneous mixture. The solution is transferred into a large container, rinsing water. Add the remaining 9500 g of water. Starch, Maltrin M100, Aerosil 200 and sterols are weighed and added to the solution. The resulting solution was stirred using a stirrer with large/P>The turbidity of 100 mg of the resulting powder, spray dried, 25 ml of water is approximately 2400 NTU.

EXAMPLE 3

The following example is dried by spraying a composition containing approximately 75 % of the sterols (relative to dry mass). Instead of Pluronic L-44 may be any poloxamer.

The sample was prepared as follows: Pluronic L-44 is weighed in a beaker, add 500 grams of water and the mixture is stirred on heating the tile at 60C until a homogeneous mixture. The solution is transferred into a large container, rinsing water. Add the remaining 9500 g of water. Starch, Maltrin M100, Aerosil 200 and sterols are weighed and added to the solution. The resulting solution was stirred using a stirrer with large shear effort for approximately 1 hour. Immediately after this, the suspension is dried by atomization.

The turbidity of 100 mg of the resulting powder, spray dried, 25 ml of water is approximately 2600 NTU.

EXAMPLE 4

The sample was prepared as follows: Tween and Span is weighed in a beaker, add 500 grams of water and the mixture is stirred on heating the tile at 60C until a homogeneous mixture. The solution is transferred into a Bo added to the solution. The resulting solution was stirred using a stirrer with large shear effort for approximately 1 hour. Immediately after this, the suspension is dried by atomization.

The turbidity of 100 mg of the resulting powder, spray dried in 26 ml of water, approximately 3500 NTU.

EXAMPLE 5

Three separate experience drying spray performed using 3 different photoactive connection. Photoactivity connections are-sitosterol, -sitostanol and oryzanol A. Other formulations containing photoactive compounds include

Turbidity received 100 mg spray dried powder in 25 ml of water is equal to:

EXAMPLE 6

Dried by spraying the material obtained in accordance with the method described in example 5, together with inactive ingredients to obtain tablets in accordance with the composition and method described below

A. All of the ingredients together in a plastic bag and mixed for 5 minutes.

b. The mixture is pressed into tablets using a Carver press (Carver) with a force of 900 pounds (approximately 4032 Newton) for 3 seconds, using machining perforated ka is metrov).

Tablets are compressed up to the following parameters:

Average weight (mg): 763

Thickness (mm): 6,36

Test results:

Hardness (average) 11 CR

The disintegration time*: 20 minutes

* Apparatus: USP 23 <701> R. 1791 with 900 ml deionized water at 37C.

1. A method of obtaining a water-dispersible composition oryzanol, comprising a) providing an aqueous stream; (b) adding to the water flow monofunctional surfactant in an amount of from about 2 to 2.5 wt.% and polyfunctional surface-active agents in amounts of from about to 2.25 wt.% obtaining water-surfactant mixture; c) adding to the aqueous surfactant mixture oryzanol with getting the suspension oryzanol; (d) drying the suspension oryzanol to highlight water-dispersible oryzanol;

2. The method according to p. 1, in which the drying is carried out by spray drying.

3. The method according to p. 2, in which the monofunctional surfactant is polyoxy-etilendiaminmonoatsetat and polyfunctional surface-active substance is orbitonasal.

4. The method according to p. 1, where WM is carried out at a temperature from about 65 to about 85C.

6. The method according to p. 1, in which the mass ratio of monofunctional surfactant to polyfunctional surfactant is approximately 1:1.

7. The method according to p. 1, in which the suspension oryzanol get when using a high speed mixer.

8. The method according to p. 1, in which oryzanol crushed.

9. The method according to p. 8, in which oryzanol crushed before receiving suspension oryzanol.

10. The product obtained by the method according to p. 1.

11. The product p. 10 provided in a single package, providing from about 5 to about 50 grams of water-dispersible oryzanol.

12. The product under item 10 in the form of tablets.

 

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