BE540430A - - Google Patents

Description

       

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  "Dry carriers for vitamins.



   The invention relates to novel compositions of materials and to methods for their preparation. More parti-. Specifically, the invention relates to compositions of materials, new and very useful, containing diposoluble vitamins, particularly vitamin A and / or vitamin D.

   In one of its more specific aspects) the invention is directed to novel compositions of matter containing either of these particular vitamins or both, said novel compositions having a particular range of sizes and the vitamins being very stable in these compositions and easily usable for digest-.on.

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   Feeds for livestock and poultry, as well as customers for humans, have been fortified for many years with these vitamins, but these. products were subject to considerable losses of nutritional value, particularly with regard to vitamin A because this is unstable due to the oxidative influence of the atmosphere and because both vitamin A and vitamin D, are unstable because of the influence of the components of certain foods with which they are mixed. In the previous proposals made in this field, a number of various attempts have been made to protect these vitamins but, if - we except the products disclosed in Belgian patents N 495,896 and N 495,895,

   none of the products offered have been entirely satisfactory, either due to the unstable nature of the products, or the non-digestibility of the products with regard to their vitamin A content, or for one or more of various other known reasons of those who are versed in this field.



   An object of the present invention is to provide new and improved dry carriers for fat soluble vitamins.



   Another object of the invention is to provide, in a dry form, products containing fat-soluble vitamins which are highly resistant to oxidative deterioration.



   Another object of the present invention is to provide a composition of materials containing vitamin A and / or D so that they are very stable and easily usable, that is to say easily digestible.



   Another object of the invention is to provide dry carriers for fat soluble vitamins which, when mixed with feeds or feed components for livestock and poultry, or with feeds for humans, will fortify these materials with fat-soluble vitamins so that these materials retain their vitamin activity

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 fat soluble for very long periods of time, even when fortified products are stored under conditions leading to oxidative deterioration of fat soluble vitamins.



   Other subjects of the invention will be in part obvious and in part will appear in the following,
It has now been found that the above and other objects can be achieved by providing a dry and loose product, composed of a multiplicity of very small particles, each particle consisting of a solid solution of A fat soluble vitamin material, an edible antioxidant and a normally solid resinous ethyl cellulose capable of forming a solid solution with the combination of the vitamin carrier material and the antioxidant.

   In addition to the materials which constitute the basic components of the present invention, other ingredients can be added to the compositions and, in the preferred embodiment of the present invention, very finely divided solid plant materials are incorporated; that is to say, vegetable flours, in each of the innumerable particles which constitute the products of the invention.



   It has been found that the presence of a vegetable flour in the products of the present invention appreciably increases the stability of the vitamins in the products. However, the products of the present invention which do not contain vegetable flour have a very high degree of stability and are. far superior to previous products in this field. Materials such as plant dyes, synergists for antioxidants, surfactants, etc. can also be added to the compositions, if desired, and incorporated into each of the many particles which constitute the products of. invention.



   The compositions of the invention, both the basic behaviors and the preferred embodiment of the invention, contain the fat-soluble vitamins such that
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 these are easily divisible and are very

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 resistant to oxidative destruction, which is evidenced by the fact that the vitamin activity of the products of the invention is not substantially reduced, even after the products have been stored for long periods of time.

   What is more significant, however, is the fact that feeds for livestock and poultry and human feeds which have been fortified with vitamins by the addition of the products of the present invention are extremely stable and produced. very little loss of the activity of the added vitamin, even when these fortified products are stored for periods of six months to a year or more under conditions which are very conducive to the oxidative destruction of the vitamins.

   It is therefore possible by using the products of the present invention to prepare food or feed components for livestock or poultry, enriched in vitamins, then to ship these materials to tongues distances and then to store them for long periods of time before they are released. they are not sold to the end consumer.

   Prior to the present invention, many foods fortified with easily usable vitamin A would not have retained their vitamin A activity over a long practical period of storage, but with the products of vitamin A. present invention, it is possible to prepare such fortified foods which will retain their vitamin A activity for long periods of time at summer temperatures, In addition, ethylcellulose resin. confers very desirable physical characteristics, namely: the hardness and the excellent flow of the finished solid product.

   This means that the products of the present invention are stabilized against any increase in surface area due to the heat and pressure conditions encountered in certain processes including the use of dry carrier products,
The loss of vitamin activity that occurs when products containing easily used fat-soluble vitamins

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 Wheats are stored for, for long periods of time: .r.- COn8 (llent U ", SiLllt: by destruction" oxyé1Jite vitamins. In fact, it is t1'08 likely, however, that at least part of the loss vit.amimiciue activity is due to the destruction of vitamins by a route other than ordinary oxidation.

   In all likelihood, other components in the. composition containing the vitamins catalyzes in one way or another
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 besides the transformation of vitamins into physiologically inactive pb compounds. However, it is common practice to refer to the sum total of all losses of vitamin activity, which are detected by any of the usual methods of analysis, such as biological, chemical or physical methods of analysis. , as being oxidizing destruction of vitamins. In describing the present invention, this practice is adopted.



   One prepares the products of the present invention by forming a homogeneous solid phase comprising the material containing the vitamin, the antioxidant and the resinous ethyl cellulose. When using a vegetable flour, as in the preferred embodiments of the invention, it exists in the form of discontinuous particles uniformly dispersed throughout the continuous mass, formed by the solid solution of matter
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 vita.minée, antioxidant and resinous ethylcellulose.,.



  In preparing the products of the present invention by the method usually employed, the various components other than vegetable flour are dissolved in. a suitable organic solvent, ie a solvent in which the vitamin material, the antioxidant and the ethyl cellulose are soluble. If a vegetable flour is to be used in the dry carrier products of the invention, it is the uniform scatters
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 (lJ.! 2 (One hundred in all the mixture and incorporated it carefully.



  The mixture is stirred, tI1t: e Until it takes a consistency of soft caramel, and, at this moment, it is removed from the container in which the me lW'l [! (:), t 'Eltè made , it is created (in one layer l1JÜ1CE :.

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 and dried to remove the solvent. When the solvent has been removed, the product is crushed or fed to produce a composition of materials having a special desired particle size. The products of the invention consist of a multiplicity of particles extending throughout the. range of about
1190 to about 149 microns. The preferred particle size range is from about 590 to about 250 microns, and at least 80% of the particles should be within this range.



   While the particular sequence of introducing the components into the mixture is not of critical importance in preparing the composition of the present invention, it has been found that it is best to proceed as follows in the preparation. new dry carrier products of the invention.



   The resinous ethyl cellulose is dissolved in an organic solvent in which the antioxidant and the vitaminized material are soluble. The vitamin material and the antioxidants and other additives are then added to the ethylcellulose solution either as such or in a previously prepared solution of these materials in a certain amount of the chosen solvent.

   The resulting solution is thoroughly mixed and, if vegetable flour is used, it is added, followed by stirring. Obviously, it goes without saying that the order of addition can be changed and that one can first of all prepare a solution of vitamin material and. the antioxidant in a suitable organic solvent, ¯ then add ethyl cellulose and vegetable flour.



   In another process for the preparation of the products of the present invention, the resinous ethyl cellulose, normally solid, is melted by heating it in an inert atmosphere and the fat-soluble vitamin-containing material to be employed is then mixed therein, as well as. edible antioxidant

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 which must be incorporated into the products, while maintaining the high temperature and the inert atmosphere. In preparing the preferred composition of the invention, a small amount of a vegetable flour is also carefully incorporated into the melt.

   Thereafter the liquid mixture which has been thus prepared is formed into a multiplicity of very small solid particles by any suitable method.



   This liquid mass contains all of its components in a uniformly distributed state, with respect to one another. When in said elevated temperature condition, the mass may in any convenient and desired manner be converted or formed into droplets or small globules where the temperature is reduced to convert them to a solid state or to cause their. solidification by any suitable process, for example according to the processes which are disclosed in Belgian patents 495,896 and 495,895 of which the present applicant is one of the inventors. Alternatively, the liquid mass can be allowed to solidify into any shape and the resulting solid can be ground to a desired particle size.

   All operations in which materials are brought to high temperature must be carried out under an inert atmosphere.



   In a very satisfactory process for preparing the products of the present invention, the various components of. the composition are taken up in a suitable solvent, for example ethylene dichloride, and they are mixed homogeneously by thorough agitation in a mixer provided with a suitable means of agitation, for example a grid type agitator. .

   When the mixture becomes uniform and takes on the consistency of a caramel, it is then transferred by a suitable means, for example a downpipe, on a continuous stainless steel belt which passes around two rollers approximately 90 cm in diameter and about 15 meters apart, and the mixture is spread out into a uniform film,

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 approximately 1 to 2 mm thick, with suitable means, for example a scraper. The belt then transports the material first over a suitable heater, for example a steam-heated surface, which dries the material by removing the solvent.

   On leaving the heating zone the product is cooled by a stream of air and removed from the belt by a suitable device such as a scraper. The dry film is pre-cut by a series of rotating blades as it is removed from the belt. It is then collected in a receptacle and fed by any suitable means into a mill where the product is finally reduced to a multiplicity of very small particles having the desired special particle size. The composition is then sieved to remove any particles outside the desired range and then is ready to use as a dietary supplement.



   In most cases, the particles which are obtained will flow freely and will not tend to adhere tightly. appreciable. to each other. If it is found that the particles in fact have a tendency to adhere to each other to some extent, this tendency can be easily overcome by dusting them with a very small amount of a vegetable flour, for example one of the vegetable flours inter. - forming part of the preparation of the preferred compositions of the present invention.



   With the products of the invention, it is possible to employ materials containing fat soluble vitamin which have a substantially lower activity than the activity of the materials containing fat soluble vitamin to be employed with such products. those which are prepared in Belgian patent N 478,155. Obviously, one can use liposoluble vitamin concentrates with very high activity for

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 the preparation of the products of the invention and, if it is desired to obtain dry carriers having a very high activity, it is preferable to employ very active liposoluble vitamin concentrates in the preparation of these carriers.



   When preparing dry supplements to be added to feeds for livestock and poultry in order to enrich their content of the fat-soluble vitamin, it is not necessary to employ very active concentrates of fat-soluble vitamin but rather oils containing. fat-soluble vitamin, having low vitamin activity.

   Many feeds for livestock and poultry are fortified with vitamin A so that they have an activity of approximately 5 units of vitamin A per. gram. In order to prepare dry carriers suitable for fortifying foods to this extent, oils containing fat-soluble vitamin can be used, having a fairly low activity, since dry carriers prepared for this use should not. have an activity that exceeds about 1000 or 2000 units of vitamin A per gram.



   As the source of the fat soluble vitamins, any of the naturally or artificially produced vitamins A and D can be used. Activated sterols such as irradiated ergosterol or irradiated 7-dehydrocholesterol, vitamin A in the alcohol form or preferably in the ester form can be used, vitamin A which has been produced by . synthetic processes or even fish oils, fish liver oils, vitamin concentrates prepared from these oils, etc.

   Also, instead of employing vitamin A in the present products, vitamin A precursors such as carotene can be used. The various forms of vitamin E can also be used. Solid forms of fat-soluble vitamins, such as, for example, crystallized calciferol and crystallized vitamin A acetate, can first of all be dissolved in a liquid which is miscible in the proportions desired with the solvent used to dissolve

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 the antioxidant and ethyl cellulose, and which forms a homogeneous film with said components after removal of the solvent.

   The amount of the fat soluble vitamin containing material in the compositions of the present invention can vary from as little as 1% to as much as about 75% of the total weight of the compositions. The liposoluble vitamin material employed in the production of the compositions of the present invention is. such that, when incorporated with a suitable amount of ethyl cellulose using a mutual solvent, it is capable of producing a dry homogeneous film when the solvent is removed, in a form which may be referred to as d 'generally by the expression solid solution.

   In most cases it is preferred that the products of the invention which are carriers for vitamin A have an activity of at least 1000 units of vitamin A per gram and that the products of the invention which are carriers for vitamin A. are carriers for vitamin D have an activity of at least about 100 vitamin D units per gram.



     The resinous ethyl cellulose employed in the preparation of the products of the invention can be any of the commercially available forms of ethyl cellulose. Although the ethyl content and viscosity of ethyl cellulose exert a profound influence on its physical properties, it has been found that all commercially available forms of ethyl cellulose, ranging in ethoxy content from 44.5% to approximately 50% and varying in viscosity from 6 to 250 centipoise and greater at 25 ° C for a 5% solution in suitable organic solvents, are usable.

   The amount of ethyl cellulose in the compositions of the present invention can vary from a minimum of about 25% to as great as about 75% of the total weight of the compositions. In the preferred compositions of the invention, which - contain vegetable flour, the amount of ethylcellulose

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 can be as low as about 15%, of the total weight of the compositions.



   Among the antioxidants which can be incorporated into the products of the present invention, there may be mentioned compounds such as propyl gallate, butylated hydroxyanisole, nordihydroguaiaretic acid, diphenyl-para-phenylene diamine, etc. These compounds are all edible antioxidants. Other edible antioxidants can also be employed. Likewise) it is possible to use mixtures of antioxidants or mixtures of one or more antioxidants with one or more compounds having little or no antioxidant effect by themselves, but which, when, they are in mixture. - age with antioxidants, have a synergistic effect on them.

   Typical examples of these compounds, which are often referred to as "synergists", are lecithin, and citric acid. With regard to the amount of antioxidant to be incorporated into the products of the present invention, it is preferable to employ at least about 0.05% of antioxidant in most cases, but, the amount of antioxidant to be used will obviously depend to some extent on the effectiveness of the antioxidant. In the majority of cases, the amount of antioxidant that is used will range from about 0.05% up to about 4.0% of the compositions of the invention, in addition to any synergist added.

   When we say that antioxidants are "edible", we mean by this that they can be consumed in the amounts according to which they are used as antioxidants by humans or by animals, without resulting in adverse effects. harmful effects. The antioxidants employed in the production of the compositions of this invention are such that when incorporated with appropriate amounts of ethylcellulose and fat soluble vitamin containing material using a mutual solvent, they are capable of produce by removal of the solvent a dry homogeneous film in a form which

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   one can generally denote by the expression solid solution.



   The amount of vegetable flour which is incorporated into the preferred compositions of the present invention can of course vary, but in any case cannot exceed about 60% of the final product and preferably it should not be more than about 60% of the final product. that about 25% to about 40% of the final product. In order to obtain the maximum profits from the inclusion of vegetable flour in the new products of the invention, the vegetable flour must represent at least 5 ,. about final products. The flour which is incorporated in the composition helps to maintain the stability of the vitamins therein. It is not clear exactly how flour helps maintain vitamin stability, but it has been found that flour does exert such an effect.

   Vegetable flour - also helps to make the vitamins in the products more easily usable for the animal or the man who consumes the food or food enriched with: these products. Vegetable flour helps to make vitamins more readily usable for absorption by the digestive system, since particles of vegetable flour are very easily digested and, when subjected to the action of digestive juices in the digestive tract. 'es- tomac and the intestines, they tend to leave the particles of the vitamin support in a more or less honeycomb state, thus causing the exposure of a much larger surface area of the dry support: to the action digestive juices.



  This obviously has the effect that the vitamins in the carrier. dry are much more easily accessible to the digestive system.



   Among the many vegetable flours which can be employed in the preparation of the preferred compositions of the present invention, there is soybean flour, corn germ flour, cottonseed flour, seed flour. flax, wheat germ flour,

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 March, peanut flour, sifted rice sour polish, wheat flour, etc.

   Vegetable flour consists of relatively finely divided particles of vegetable material the majority of which pass through a sieve at 0.177 mm mesh size, and in most cases it is preferable that. virtually all particles pass through a sieve. 0.177 mm mesh opening, and that the majority of the particles have a size such that they pass through a sieve at 0.149 mm mesh opening.



   The products of the present invention may contain
From about 0.5% to about 40% of an edible surfactant, and this agent will be chosen from a large group of compounds, among which may be mentioned fatty diacid esters of sorbitans and mannitans, products condensation of polyethylene oxide fatty acid esters of sorbitans and mannitans, fatty acid esters of polyethylene glycols, etc. Other edible surfactant materials can also be used.

   When the surfactants are said to be "edible", this is understood to mean that these materials can be consumed by humans or by animals in the amounts in which they are employed in the products of the invention, without that it results in harmful effects.

   Among the many surfactants which can be employed in the preparation of the products of the present invention are the fatty acid esters prepared from polyethylene glycols having a molecular weight of from about 200 to about 4000. and fatty acids containing 8 to 22 carbon atoms, such as caprylic acid, capric acid, lauric acid, palmitic acid, oleic acid, ricino-leic acid, stearic acid, hydroxystearic acid, arachidic acid, behenic acid, mixtures of these acids, etc.,

     fatty acid esters prepared from sorbitans and mannitans and any of the fatty acids containing

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 8 to 22 carbon atoms such as the fatty acids listed above, condensation products of polyethylene oxide of fatty acid esters of sorbitans and mannitans, said products containing from about 5 to about 50 ethylene oxide units per molecule, etc.

   The surfactant employed in the production of the compositions of this invention is such that, when incorporated with appropriate amounts of ethyl cellulose, antioxidants, and fat soluble vitamin containing materials, with the aid of a solvent, it is capable of producing, on removal of the solvent, a dry homogeneous film in a form which may be generally referred to as a solid solution.



   The solvent employed in the preparation of the novel products of the invention can be selected from organic solvents in which the ethyl cellulose, the fat-soluble vitamin-containing material and the antioxidant are soluble or miscible in the required proportions. When selecting a solvent for this use, care should be taken to select one which is a solvent for an ethyl cellulose having the particular ethoxyl content of the type of ethyl cellulose used in the preparation of the novel products of the invention. . For example, low ethoxylated ethyl cellulose is soluble in relatively few solvents.

   As the ethoxyl content increases, the solubility in all classes of organic solvents improves to optimum solubility which is obtained with an ethoxyl content of about 47.5 to 49. 0% ethoxyl. Above this level of the ethoxyl content, ethylcellulose is soluble only in non-polar solvents such as aromatic hydrocarbons. It has, however, been found that all commercially available types of ethylcellulose are soluble in ethyl acetate and ethylene dichloride, hence it is preferable to employ these solvents in the preparation of the dry products. support of the present invention.

   In particular, it is better to use

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 Ethylene dichloride as a solvent since this material can be readily obtained, is easily removed and does not adversely affect the stability of vitamin A. However, since the effectiveness of a particular solvent given to a particular type of ethyl cellulose can be easily determined either from existing literature or by simple experimentation, it is obvious that solvents can be used if desired. other than ethyl acetate and ethylene dichloride.

   Depending on the particular type of ethylcellulose employed in the preparation of the dry carrier products of the present invention, the following classes of organic solvents can be used: aromatic hydrocarbons such as benzene and toluene, esters such as acetate. ethyl and butyl, ethers such as ethyl ether, ketones such as acetone, and chlorinated hydrocarbons such as ethylene dichloride, carbon tetrachloride and chloroform.



     It has not been clearly established why exactly the products of the present invention are far much more stable than any of the products previously known in the art. However, the products of the invention are absolutely different from the previous products in that the components are intimately combined with each other, in a really new relationship, and in this case the use or digestibility, as well as the The stability of their fat soluble vitamin content has been established to substantially satisfy all practical commercial applications.

   It has been conclusively established that the products of the present invention have a far greater degree of stability than any of the products previously known in this field, other than those disclosed in Belgian Patents Nos. 495,896 and No. 495. 895, and these products are the only ones, apart from

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 those which are revealed in these two patents, for which it was found that when they are mixed with feeds for cattle or poultry and stored in various conditions of temperature and humidity, that they substantially retain their original vitamin activity for periods of six months to a year and more.

   It has not been established for an exact reason why the products of the present invention are so much more stable than the prior products in this field, and this is why it is not desired to be bound by any particular theories tending to explain. the real reason (s) for their much greater stability.



   Therefore, the present invention can be practiced by intimately combining (a) a resinous ethyl cellulose, (b) a combination of two or more fat soluble vitamin containing materials preferably containing vitamin K and / or D, and (c) an antioxidant or a combination of two or more thereof. These substances (a), (b) and (c) are in such a proportion that (a) is present in an amount equal to 10-75% by weight of the total mass. In the preferred embodiment of the present invention, there is also incorporated in the compositions -a component (d) which consists of one or more vegetable flours.

   In this preferred foraae of the invention, said components (a), (b), (c) and (d) "are proportioned so that (d) is present in an amount equal to 5-60%. by weight of the total mass and that (a) is in an amount equal to 10-75% by weight of the total mass.

   although the present invention relates more particularly to the protection of materials containing the fat-soluble vitamin against oxidative aestruction, and this by the formation of a solid solution of said vitamin material in ethylcellulose, we have found that the concept of forming a solid solution of a sensitive material in ethyl cellulose may also be suitable for protection

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 aubrea mati01'i ;;!, 8 susceptible. , 11.111 [11, we have; '.) LwtD.1, that it is possible to prepare phuX'.J1 {¯IC - ::' I.ltiqW) 13 c medical compositions other than vltwIl1nlof materials. donations JHulls the active components are stabilized cfjI1Lr, the ll.t:

  .C '.. U.L'.al - ,. 1..11 caused by external influences, producing the-
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 said compositions in the form (the solid solutions; 1 <; s. ". lil, = components' Hctii's in ihyltell.u.osw. L'rutz; 3 cotuposants cofruhuns to such cotupositions plliJ.1: '! JJLtdeutjJLl (Medical S ut may exist in the continuous phase of the solid solution or, if they are insoluble in ethylce2¯txlo. ^, They may exist under the form of particles discont.inu < : 'G uniformly dispersed throughout the entire continuous phase of the solid solution.



   For a better understanding of the nature and the objects of the invention, reference may be made to the following examples which are given simply as additional explanations of the invention and which need not be. considered ,, as having a limiting nature.



   The analytical methods used in the examples
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 have an experimental error interval of about, 1C,; G for vitamin oh tests and about 25- for bioassays. Therefore, appropriate tolerances should be allowed for the interpretation of the results of these various tests. All vitamin activity, unless otherwise noted, is expressed in U.S.P.
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 l ', ...',:. rrr .e 1, A very stable dry support for vitamins is prepared by dissolving 1: 3,;:,) g of a concentrate of showcase palmitate i,. E tlrrh1-ai x has an activity of 1.000.0iJ0 of U..P units.

   (the. '"" by to "Éi'Ji'I a"' é <2 vital oil, 10 5 g of? é tii, j, 1 cellulose, 0.30U4 g of Vi't, aliiine Dô in corn oil containing 6,670 rC units per gl "8" rn, 0.21-6 e, of di "henyl-pm'a-phenylene diamine, 0.46 g of 2, S-ditGrt. iü.ire-bL1.'tYl-hYdroqL1i-

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   none, 0.46 g of butylated hydroxyanisole, and 3 g of soybean lecithin in 45 cm3 of ethylene dichloride. The mixture is stirred until it acquires a consistency similar to a caramel, after which one, incorporates 18.6 g of wheat germ flour and mix thoroughly into the previous mixture.



  The resulting composition is removed from the mixing vessel, spread into a thin layer and dried under vacuum with. temperature 36.6 ° C. The resulting film was removed, crushed and sieved to obtain the fraction of which 100% of the particles were in a particle size range of 590 to 297 microns. 95 parts of this fraction are sprinkled with 5 parts by weight of a mixture of 0.8 g of wheat germ flour, 0.1 g of diphenyl-para-phenylene diamine and 0.1 g of 2,5-ditertiary -butyl-hydroquinone. The dry carrier from this example was used to fortify a mineral blend consisting of 40 parts of steamed bone meal, 40 parts of crushed limestone and 16 parts of coil to a theoretical level of 1,000 U.S.P. of vitamin A per gram.

   The three components of this mixture. The mineral all tend to accelerate the oxidative destruction of vitamin A. The mixture thus produced is tested according to the Morton-Stubbs process and was found to give 1100 units of vitamin A per gram. The stability of vitamin A in the mixture is then determined by a storage test. The product is stored at 37 C in contact with the atmosphere for a period of 3 months, then tested for the content of vitamin A and found to contain 942 units of vitamin A per gram.

   A similar test carried out on a commercial concentrate of trace minerals, known to be very destructive of the vitamin A content of other products, stored for a period of 3 months at 37 ° C., shows a shelf life of 70%. the theoretical content of vitamin A. While these storage tests

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 are in progress, a further storage test is carried out on a commercially available feed mixture; fortifies to 50,000 U.S.P. per pound (.153 g) with the dry media in this example.

   This mixture is a calf milk substitute known to accelerate the oxidative destruction of vitamin, IL. A test is carried out on the mixture produced and it is found that it contains 4,600 units of vitamin A per gram. It is stored for 3 months at
37 C in contact with the atmosphere and, at the end of this period, a test shows that the mixture contains 36,800 units of vitamin A per gram. The small loss of vitamin A activity shown by the various fortified mixtures under severe storage conditions shows that the vitamin A content therein is very effectively protected against oxidative destruction.



   The theoretical vitamin D3 content of the product of this example is 38.3 C.I. units per gram. We feed with. this produces chickens following the standard A.O.A.C. for chickens and found to have a biological efficacy equivalent to 38 C.I. units per gram. This result demonstrates that the vitamin D3 content of this product is fully biologically usable for chicken.



   Example 2.



   Another excellent dry carrier for fat soluble vitamins is prepared in the same manner as in Example 1.



   In the present example, 13.5 g of the concentrate of vitamin A palmitate of example 1, 27.0 g of ethylcellulose, 0.381 g of the concentrate of vitamin D of example 1 are dissolved,
0.69 g of diphenyl-para-phenylene diamine, 0.69 g of 2,5-ditertiary-butyl-hydroquinone and 0.69 g of butylated hydroxy-anisole as well as 3.0 g of soybean lecithin in
80 cm3 of ethylene dichloride, and stirred until the resulting mixture has acquired a consistency similar to

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 a caramel.

   We then incorporate 1; g of ieri1i flour and the product is mixed until it is uniform. The product is removed from the. mixer, it is spread in one layer, .. ince and dried under vacuum. The resulting film is crushed and sieved; a fraction is obtained in which 100% of the particles are in the range of 590 to 297 rays. This product is sprinkled in the same way as in Example 1.



  The dry support of this example is used to fortify a mineral mixture having the composition of the mutant which was used in the previous example. A test is then made on the resulting product for the determination of the vitamin content.
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 mine and it is found that it has a vitamin 1 content of S80 .ci vitamin bonds. by gra: -i1! 1le. This product is stored at 37 C in contact with the atmosphere for a period of 3 months. We try it again for its content. in vitamin A and we cons-
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 tate that it contains 848 units of -vitamin per gram.

   A si.uilaire test performed on a commercial trace mineral concentrate known to be very destructive of the vitamin A content of other products, is stored for a period of 3 months at 37 µl and observed for shelf life. of 77.5% of the theoretical vitamin content While these tests
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 storage are in progress, another storage test is carried out on a food mixture available in COfufterCe, fortified at SO.0U0 U15.P units, per pound (453-g) with the dry medium of this example.

   The mixture thus produced
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 is tested and found to contain .8: 2Cfl units of vitamin A per gram. It is stored for 3 months at 37 ° C. in contact with the atmosphere and at the end of this period a test shows that the mixture still contains 40,150 units of vitamin ± ± per gram. The results of the above tests show that this product for which we
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 employs a higher ethylcellulose-to-vitaine palmitate ratio than in Example 1, i.e. a ratio of 2 parts ethylcellulose to one part con-

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 EMI21.1
 centered with vitamin ii palmitate,

   is also very thin in preventing destruction of vitamin A content in prepared food mixtures.



   This product has the same theoretical vitamin D content as that of example 1. In a biological test on chickens, it is found that it has an efficiency of 35 C.I. units per gram.



  This result 'shows that it is quite effective as a source of vitamins for chickens,
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 xerrtlē 3
A very stable dry support for vitamin D3 is prepared by dissolving 6.75 g of rice bran oil containing 100,000 IC units of vitamin D3 per gram in the form of irradiated 7-dehydrocholesterol resin, 6.75 g of 'ethylcellulo
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 .se, G = û3 g of diphenyl-para-p} ,: enylene diamine, 0.23 g of 2 5-ditxtis.ize-butyl-hydroquinor: Er, 0.23 g of hydroxy -, - butylated misole and 0.50 g of lecithin in sufficient ethylene dichloride to reduce the mixture to a caramel-like consistency. 9.95 g of wheat germ flour are then incorporated into the mixture.

   The obtained product was spread in a thin layer, dried under vacuum and crushed to obtain a fraction in which all the particles passed through a sieve at 0.59 mm mesh size. This product has a theoretical vitamin D3 content of
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 27.00 Lu. Units per gram and it has the same excellent characteristics as the products of Examples 1 and 2.
 EMI21.5
 



  Dxe uip 7.e ..



   A product analogous to that of Example 3 is prepared by using a solution of vitamin D2 crystallized in rice bran oil instead of the solution of vitamin D3. This product offers the same excellent characteristics as that of Example 3.

 <Desc / Clms Page number 22>

 
 EMI22.1
 



  '' - "" 1 '- 9- * Or pl.'I, J! É.tl'8 a bUpP01't rec tré # stable lice' vJ.tIl1ines 1jpoolUi ,, 18} J of 1.1 @ 1, .in; plain as in the examples axwc, teeth. In the prescribed example, dissolved 1: 3.5 g of concentrate the vitamin palmitaite .., leu, 5 g dlê4liy: Lc, elluloc-e, 0.54 g L1e 'ilij,> licn yl- p ara-iJhéiiylène diwüine, (J35 g of, 5-ditxtiüïre- bat> .1-lij, dr.oEainone, O, to4 gd) butylated hydroxy-anisole and 1.0 g of lcc ithine in a sufficient quantity of dichloride c:. 'c 'ttlyLu'I3E.' to produce a langB me having a consistency similar to that of a sai-cjiiel. Then 1% of wheat germ flour is incorporated into the mixture. We. then unload it onto an endless conveyor belt and spread it there in a thin layer.

   The product is dried at a temperature of 71.1 C for a period of about 3 minutes, then removed. film and crushed to produce a fraction all of the particles of which are included in the
 EMI22.2
 tervalle from ob0 to 2; ùl; microns. The product, which has an active tea activity of S78,000 U.S.P. by gracie, is tried
 EMI22.3
 for its vitafiiine content and it is found that it contains U .N.P units, per grariiffe. The stability of vitamin A in the accelerated storage test is then determined. the product. stores the latter at 450C in contact with 11 ELtrf, oorhère sanding a period of 6 weeks.

   Then, an assay is made to determine the content of vitamin ji and it is determined that it contains 255,000 units of vitmine per x.r.tc.e. The fact that 111., only about vitamin .A is destroyed under these very severe conditions, shows quite conclusively that the new products protect the vitamin very effectively from oxidative destruction.
 EMI22.4
 cQnliùr.JI1 (illt. i8Û .: g- 6, one prepares another excellent S (1) 10x't sec pour vitaiiiille e, 11 ['0 ::

   ollJ¯blES Oor1fJlO dunn exodus 5 using [, l! mes

 <Desc / Clms Page number 23>

 component.a and reported components, except that we use
1.62 parts of diphenyl-para-phenylene diamine in place of the mixture of antioxidants used in the composition of the previous example. The dry support obtained was found to have an original vitamin A activity of 306,000 vitamin A units per gram. Upon expiration of an accelerated storage test such as that described in Example 5, the vitamin A content of the product of this example is found to be 305,000 units of vitamin A per gram. .

   The extremely small loss of activity under the severe conditions of the accelerated storage test employed demonstrates that the product of this example is very effectively protected against loss of activity of vitamin A.



   Example 7.



   The product of this example is the same as that of Example 6 except that the edible antioxidant employed is butylated hydroxyanisole instead of diphenyl-para-phenylene diamine. The product of this example also shows. an effective .... cited in preventing the loss of activity of 'vitamin A by oxidative destruction.



   Example 8.



   CI-1 prepares two dry carrier products using the same components and the same ratio of components employed. in the previous examples 5, 6 and 7, but using hordihydroguaiaretic acid and propyl gallate, respectively, as antioxidant materials. These products have the same excellent characteristics as those of the preceding examples.



  Example 9.



   A very stable dry vitamin A carrier is prepared by dissolving 10.0 g of a crude concentrate of vitamin A palmitate.

 <Desc / Clms Page number 24>

 
 EMI24.1
 synthetic mine conUenat 1,414,000 units vJ.r ... 1 '. [.I, .1.I 'Lré: l1J! R.8, 10, ...: .l' .thylce llülo: e: 1.0 b of c,: iyllayl-j, a.x'o- phtGnylène L1L ,, 1.in6 and 1.0 g of lecithin in a C {1le..lJ.1l. (.. sufficient C1u- '' ethylene chloride for? 't, .U1.5.E : Lin f.:ea.iic o, yc1hot a consistency similar to. 1111 decanter 1. Then incorporate uarir, the mixture 14.0 g of wheat flour ger'ff.6. Ga elLIÈ; ve the G ± Once the mixing vessel is removed from the mixing vessel, one layer is removed and vacuum vacuumed. The exiting film is ground to a fraction of which 1 cc of particles pass. with a sieve at 0.64 rr.rï: opening of 3rd mesh.

   Ci, sprinkle 8.75 g of this' 1 = -I'O; llüt with tln 1! Le18? Age of 1.184 g of the wheat germ weapon and 0.066 bzz of diphenyl-para-phenylene âizàLi-
 EMI24.2
 born. Gn tests the product to determine its vitamin content.
 EMI24.3
 mine. and found to contain 33.GOG units of vitamin 11. per gram; l # .e. '. the end of an accelerated deji storage test, where the product is stored at 45 C in contact with
 EMI24.4
 lithosphere over a period of 6 weeks, we observe
 EMI24.5
 that the product has a vitamin A content of 508. SUG units of vitamin r per gracie. The product is used at a rate of
 EMI24.6
 1;,: to fortify a mineral mixture consisting of 40 parts
 EMI24.7
 from p .: glass 6: crushed lime, 40 parts of treated bone water
 EMI24.8
 steamed and 16 parts of salt.

   We find that the product
 EMI24.9
 rainerai has an original vitamin content of CC-0. units of vitecline A per gram. After storage at.¯37 c aa contact with the atr: osphere for a period of 1 l ',, "moi5" on:
 EMI24.10
 notes that the product has a vitamin A content of: 3300
 EMI24.11
 units of vitaiiinc- 1>. by gi <ai = inie.

   The results of the above tests demonstrate the effective efficiency of the new products.
 EMI24.12
 of this example to ensure the protection of their
 EMI24.13
 held in vitamin t, - against oxidative deterioration. Example 10 Another excellent dry support for collapsible display cases is prepared as in Example 10e. ,: 'lke.s

 <Desc / Clms Page number 25>

 components and the same ratio of components, except that the vitamin A palmitate employed in Example 9 is replaced by a crude concentrate of synthetic vitamin A acetate containing 600,000 U.S.P. per gram. The dry carrier of this example is also found to have remarkable effectiveness in preventing the oxidative destruction of the vitamin A contained therein.



   Example 11.



   A very stable dry carrier for fat soluble vitamins is prepared by dissolving 10.0 g of a synthetic concentrate of vitamin A acetate containing 2.3-10,000 U.S.P. per gram, 1.0 g of diphenyl-para-phenylene diamine, 1.0 g of lecithin and 10.0 g of ethylcellulose in a sufficient amount of ethylene chloride to produce a mixture having a consistency like that of a caramel. 14.0 g of wheat germ flour are then incorporated into the mixture.



   The product is spread in a thin layer and dried in vacuo. The resulting film is ground to a product in which the particles are fine enough to pass through a sieve at 0.84 mm mesh size. The product is sprinkled with ', the same way as that of Example 9.



  The particles of this product have a theoretical vitamin A content of 569,000 vitamin units; A per gram. At the end of an accelerated storage test during which the product is stored at 45 C in contact with the atmosphere for a period of 6 weeks, the product is found to have a vitamin A content of 524,000. Units of vitamin A per gram It is therefore clear that the carrier of this example contains vitamin A in a form which is very resistant to oxidative destruction.



  Example 12.



   5.0 g of a concentrate of vitamin A palmitate containing 1,000,000 are dissolved in 15 cm3 of ethylene dichloride.

 <Desc / Clms Page number 26>

 U..P units. of vitamin A per gram, 5.0 g of ethylcellulose 0.2 g of diphenyl-para-phenylene diamine, 0.2 g of citric acid 0.2 g of propyl gallate and 0.2 g of hydroxy -butylated anisole.



  The product is mixed until it is homogeneous, then it is spread in a thin layer. and left to dry under vacuum.



  The dried film is then crushed until 100% of the particles obtained pass through a screen having a mesh size of 0.84 mm. We are trying this product for. its vitamin A content and found that it contains 405,000 U.S.P units per gram. It is stored for 1 month at 45 C in contact with the atmosphere and tested again after storage. At this time, we see that it contains 370,000 U.S, P units. of vitamin A per gram. The product of this example was used at 1% to fortify an inorganic mixture containing 40 parts of crushed limestone, 40 parts of steamed bone meal and 16 parts of salt.

   The mixture was subjected to an initial test and found to contain 4040 U.S.P. of vitamin A per gram. ' A portion is stored for 8 weeks at 37 ° C and retested at the end of this period. It can be seen that its vitamin A content is then 3200 U.S.P. per gram. The results of these tests show the excellent stability of the product of this example, even when it is stored for long periods in a very adverse environment. example 13.



   We prepare a support.sec. very stable for vitamin A by dissolving 5.0 g of a concentrate of vitamin palmitate containing 1,000,000 units of vitamin A per gram, 1.0 g of polyoxyethylene sorbitan trioleate, 5 g of ethylcellulose, 0.2 g of diphenyl-para-phenylene diamine, 0.2 g of citric acid, 0.2 g of propyl gallate, and 0.2 g of butylated hydroxy-anisole in 15 cm3 of ethylene dichloride.

   The product is mixed until it is homogeneous then it is incorporated

 <Desc / Clms Page number 27>

 
9.2 g of soy flour and continue mixing until the whole mass is homogeneous. The mass is spread in a thin layer and allowed to dry at: Room temperature under vacuum. The resulting film is ground to pass through a sieve at 0.84 mm mesh opening. This product is tested for stability by storing it in air at 45 C. After one month of such storage, the product shows the same excellent preservation, of its vitamin A content as the products of the previous examples. .

   When the product of this example is incorporated at the rate of 1% in a mineral mixture containing 40 parts of crushed limestone, 40 parts of steamed bone meal and 16 parts of salt, and that it is tested for its vitamin A content after storage for one month and 2 months at 37 ° C., it is observed that the vitamin content ,,. is substantially retained in its entirety.



     Example 14.



   A stabilized composition containing procaine penicillin is prepared by dissolving 10 g of crystalline procaine penicillin, 10 g of ethylcellulose having an ethoxy content of 45.5 to 46.8% and a viscosity of 14 centipoise. , 25 g of butylated hydroxyanisole and 0.50 g of soybean lecithin in a sufficient quantity of ethylene dichloride to produce a mixture having a consistency similar to that of a caramel, then 5 g are incorporated. wheat germ flour and mix the mass thoroughly.

   This is spread in a thin layer and dried in vacuo. The resulting film is ground to produce a fraction in which 100% of the particles can pass through a sieve at 0.84 mm mesh size. This product is very effective in protecting the procaine penicillin contained therein from destruction when mixed and processed with a number of other materials in the presence of which it is ordinarily unstable.

 <Desc / Clms Page number 28>

 
 EMI28.1
 



  .sXêp: f11SLli.1 a. prepares a stabilized composition which is identical to that of Example 1 = to, except that we include orp oz ¯. .G g of cod liver oil in the composition and qG1.a la. The product of this example is likewise very effective in protecting its procalne-penicillin content from destruction.



    Example 16.¯
A stabilized composition containing vitamin Z is prepared by dissolving 1.25 g of natural distilled tocopherols containing 340 mg of mixed tocopherols per gram.
 EMI28.2
 



  4.0 g of fish liver oil = 0.75 g of dphenyl-para-phenylene diamine and 5.0 g of ethylcellulose in a sufficient amount of ethylene dichloride to produce a mixture having a consistency similar to that of a caramel. The mass is spread in a thin layer and dried in vacuo. The resulting film is ground to produce a fraction having an approximate particle size of 840 microns. This product is very effective in protecting the vitamin E content therein from destruction.
 EMI28.3
 



  The ethyl cellulose employed in Examples 1 to 13 and 16 is a commercially available ethyl cellulose having an eta ethoxyl content of 44.5% to. 45.5% and one ..
 EMI28.4
 viscosity of 40 to 52 centipoise at 25 C a coneI1; trti of 5% in a solvent mixture composed of 80 parts of toluene and 20 parts of ethanol. However, we used with
 EMI28.5
 successful all types of ethylcel1Uloses existing commercially, having ethoxyl contents ranging from 44.5% to over 49% and viscosities from 4 to 5000 centiposes.



  Representative examples of other types of ethyl cellulose which were used are disclosed in Examples 14 and 15.



   The present application relates to the subject of patents
 EMI28.6
 Belgian N 4'j5.µ56 and N '4U5.8'd5.


    

Claims (1)

EMI29.1 R. V Iv v I C A 0'1 'I 0 N S. 1. Very stable composition of matter, digestible and containing liposoluble vitamin, characterized in that it comprises a multiplicity of small solid particles consisting of EMI29.2 both essentially of (a) ethyl cellulose, (b) fat-soluble vitamin-containing material selected from the group consisting of, fat-soluble vitamin A-containing material, vitamin D-containing material fat soluble and fat soluble vitamin E containing material, and (c) an edible antioxidant, said substances (a), (b) and (c) being combined together homogeneously into a solid solution, the amount thereof being weight of (a) in said particles representing about 25% to about 75% of the weight of the product, and a major portion of the product comprising particles capable of passing through a 1.19 mm sieve. EMI29.3 open, and capable of being retained on a sieve at 0.14 mm opening. 2. A composition of matter according to claim 1, characterized in that (b) is a material containing liposoluble vitamin A. 3. Composition of matter according to claim 2, characterized in that (b) is vitamin A acetate. 4. Composition of matter according to claim 2, characterized in that (b) is vitamin A palmitate. 5. Very stable composition of matter, digestible and containing fat soluble vitamin, characterized in that it comprises a multiplicity of small solid particles consisting essentially of (a) ethylcellulose, (b) material containing the selected fat soluble vitamin. from the group consisting of material containing fat-soluble vitamin A, material containing fat-soluble vitamin D and material containing fat-soluble vitamin E, (c) <Desc / Clms Page number 30> an antioxidant. edible and (d) of a vegetable flour, the said substances (a), (b), (c) and (d) being intimately combined with each other, said particles comprising (a), (b) and (c) in a substantially solid solution forming a continuous phase, with particles of (d) suspended in said solid solution and constituting from about 5% to about 60% of the combined weight of (a), (b), (c) and (d), the amount by weight of (a) being from about 15% to 75% of the weight of the total product, a major portion of said particles capable of passing through a 1.19 mesh size sieve and capable of being be retained on a sieve at 0.149 mm opening. 6. Compositionde materials according to claim 5, characterized in that (d) is wheat germ flour 7. Composition of matter according to claim 5, characterized in that (b) is a liposoluble vitamin A containing material. 8. A composition of matter according to claim 7; characterized in that (b) is vitamin A acetate. 9. Composition of matter according to claim 7. characterized in that (b) is vitamin A palmitate.