MXPA00008972A - Cyclodextrin flavor delivery systems - Google Patents

Abstract

The invention relates to a process for preparing cyclodextrin inclusion complexes that increases the efficiency of the complexation so that a higher percentage of the active is recovered as a cyclodextrin inclusion complex. The process involves adding a cyclodextrin to a solvent in a reaction vessel, adding an active to the cyclodextrin solution with stirring, and allowing the mixture to stir for an appropriate amount of time and at a sufficient temperature to form an inclusion complex between the cyclodextrin and the active. A solids content increasing agent such as gum acacia, maltodextrin, modified dextrins, or mixtures thereof, is then added to the solution to increase the total solids content of the solution and the solution is at 25 DEG C and 40 DEG C and relative humidity of 53 percent dried to recover the cyclodextrin-active inclusion complex as a dry powder with the amount of active in the powder ranging from 1 to 20 percent by weight of the complex. The invention also relate s to cyclodextrin inclusion complexes prepared by this process.

Description

SYSTEMS OF SUPPLY OF TASTE OF CICLODEXTRINA TECHNICAL FIELD The present invention relates to a method for preparing cyclodextrin complexes of active ingredients, such as flavors, perfumes, pharmaceutical compounds and the like, wherein a higher percentage of active principle is complexed with cyclodextrin, compared to the methods Conventional Cyclodextrin Complex Manufacturing The present invention also relates to novel cyclodextrin inclusion complexes, which can be prepared by the method.

BACKGROUND OF THE INVENTION The use of cyclodextrins as a complexing agent for materials is known. For example, the following US patents. describe the use of cyclodextrins to complex active principles: Patents of E.U.A. Nos. 4,296,137, 4,296,138 and 4,348,416 given to Borden) flavor material for use in chewing gum, dentifrices, cosmetics, etc.): 4,265,779 given to Gandolfo et al. (suppressors of foams in detergent compositions); 3,816,393 and 4,054,736 given to Hyashi et al. (prostaglandins to be used as a pharmaceutical compound); 3,846,551 given to Mifune et al. (insecticidal and acaricidal compositions); 4,024,223 given to Noda et. (menthol, methyl salicylate, and the like); 4,073,931 given to Akito et al. (nitroglycerine); 4,228,160 given to Szjetli et al. (indomethacin); 4,247,535 given to Bernstein et al. (complement inhibitors); 4,268,501 given to Kawamura et al. (anti-asthmatic active ingredients); 4,365,061 given to Szjetli et 1. (complexes of strong inorganic acids); 4,371,673 given to Pitha (retinoids); 4,380,626 given to Szjetli et al.

(Hormone regulator of plant growth), 4,438,106 given to Wagu et al. (large chain fatty acids useful for reducing cholesterol): 4,474,822 given to Sato et al. (tea essence complexes); 4,529,608 given to Szjetli et al. (honey aroma), 4,547,365 given to Kuno et al. (active ingredient complexes for hair curling); 4,596,795 given to Pitha (sex hormones); 4,616,008 given -a to Hirai et al, (-antibacterial complexes); 4,636,343 given to Shibanai (insecticide complexes), 4,663,316 given to Ninger et al- (antibiotics); 4,675,395 given to Fukaza et al. (hinokitiol); 4,732,759 and 4,728,510 given to Shibanai et al. (bath additives); 4,751,095 given to Karl et al. (aspartamane); 4,560,571 (coffee extract); 4,632,832 given to Okonogi et al. (substitute for powdered cream); 5,571,782 and 5,635,238 given to Trinh et al. (perfumes, flavors, and pharmaceutical compounds). Cyclocidext complexes are particularly desirable when the active ingredient is a flavoring material. By complexing the flavoring material with a cyclodextrin, the flavor material is protected from degradation as a result of reactions induced by heat, light, and / or reactions with oxygen or other compounds. For example, β-terpinene is a reactive terpene that is important in tangerine flavors. The? -terpineno ea, however, f-á_c-L. e t-e oxidized to p-cymene, which has an unpleasant kerosene note. By complexing the β-pinene with cyclodextrin the compound is protected from the adverse effects of oxygen, and provides a flavor that is stable for a much longer period of time. Complexing the flavoring material with a cyclodextrin also reduces the loss of the material -sab-O-ri-Z-ante by volatilization and / or sublimation. For example, diacetyl. e_s a -volta_compound that has a butter flavor. Because of its volatility the butter flavor is easily lost when food products containing diacetyl are heated. Complex diacetyl with cyclodextrin, ^ ¡^ ^^ ^ - .. > -. »... however, it results in the loss of less butter flavor when a product is heated, heated in a microwave oven. In addition, the cyclodextrin 5 complexes provide standard and standardized powders containing the a-ctive principle which are easy to use. If pnri a powder, the cyclodextrin compl-ajas are easy to measure, handle, and store. The increased flavor stability when complexed with The cyclodextrin provides a flavoring material that can be stored mastrically. As a result of the improved stability, the measurement of quantities of the s-ranges more precise, since the flavor content remains more -cons-t-ante with time. -The times of more prolonged storage., Su. Handling, and simplicity of use reduce costs, and thus they are of commercial importance in the food industry. An additional economic benefit of 1-Lsa.r complexes of ri rl nrlpxf r i a s that q is needed, hands of the campLaj.o cyclodextrin to flavor food, compared to the spice or natural flavor. Yet another advantage of cyclodextrin complexes is that the natural material content of some flavors can be reduced by complexing the flavor component (s) with cyclodextri a, and ^^^^^^^^ yy ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ ^^^^^^^^^^^^^^^^^^^^^^^^ sj ^^ thus the risk of allergic reactions is minimized and the risk of microbial contamination is reduced. The flavor content in conventional cyclodextrin complexes typically ranges from -about 5 to 15 percent, and more frequently from 7 to 10 percent. The flavors typically consist of more than one component, and while it is possible complexing all components of the flavor composition with a cyclodextrin, usually only the most vulnerable components of the composition are complexed flavor. Specific flavors and / or flavor enhancers include, for example, those described in US Patents. Nos. 4,348,416 and 5,571,782. Specific examples of flavors complexed with cyclodextrin include: Patent of E.U.A. No 4,560,571 given to Sato al. which describes an instant drink in which soluble flavors and aromatic components present in roasted coffee beans, roasted beans, or roasted cereal are complexed with cyclodextrins; the Patent of E.U.A. No. 4,529,608 given to Szejtli et al. which describes a process for the preparation of honey powder that preserves the aromatic substance of honey by complexing the aroma components with cyclodextrin; the Patent of E.U.A. No. 3,061,444 given to Rogers et al., Which describes complexing meat and vegetable aromas with cyclodextrin; the patent of E.U.A. No. 4,001,438 given to Marmo et al., Which describes complexes of peppermint and cyclodextrin to flavor chewing gum; and the U.S. Patent. No. 3,140,184 given to Robbins et al., Which describes complexes of acetaldehyde / ethyl acetate and cyclodextrin. Complexing the flavor with cyclodextrin does not adversely affect the taste, texture, or appearance of the food. In fact, in some cases the texture of the food can actually be improved by complexing the flavor with a cyclodextrin. For example, soups and beverages prepared from mixtures can be beneficially thickened when the flavor is complexed with a cyclodextrin. Cyclodextrins are obtained by the action of the enzyme cycloglicosilt ansferasa on starches. In dilute aqueous solutions, the enzyme connects the helices that naturally exist in the starch to form rings or crowns of three-dimensional polyglucose. Cyclodextrins are polyglucose rings created with 6, 7, or 8 glucose units, and are referred to as a, ß, or? cyclodextrins, respectively. The outer part of the crown-like structure consists of primary and secondary hydroxyl groups, and is hydrophilic. The inner part of the crown consists mainly of carbon and hydrogen atoms, and ether junctions, and forms a h-idrophobic cavity. This macrocyclic structure with a hydrophilic exterior and hydrophobic interior allows the cyclodextrin molecule to form complexes. inclusion with a wide variety of chemically different compounds, referred to herein as active principles. The Cyclodextrin behaves like a "host" that can accommodate, and release, the active ingredient or "host" molecule. A variety of methods for forming cyclodextrin complexes are known. All these methods involve contacting the active principle with the cyclodextrin to form the complex. Typically, a hot aqueous solution of the cyclodextrin molecule is mixed with the active ingredient for a sufficient time for the complex to form, followed by removal of the aqueous solvent. Alternatively, the complexing can take place in an organic solvent or an aqueous solvent containing an organic cosolvent. Representative organic solvents include ethanol, isopropanol, acetone, and ethyl acetate. In other Btí-BsBÍ-tii «é- ^ Bi --.-.-. ^^^^^^^^ i ^^^^^^^ 1 ^ 1 ^ - ^^^^^^^^ te method, the The active ingredient is combined with a small amount of solvent to form a paste, and the cyclodextrin and the paste are kneaded together to form the complex, followed by drying the resulting complex. This method is commonly used when a high ratio of active ingredient to cyclodextrin is required. Once the cyclodextrin complex is formed, a variety of methods are available to dry it. Typically, the complex is filtered to remove the solvent, and air-dried, dried in a vacuum oven, or lyophilized. The complex can also be isolated by spray drying. All the methods for forming cyclodextrin complexes involve a balance between the active principle complexed with the cyclodextrin, that is, the complex, and the free active principle, that is, the active principle not complexed with the cyclodextrin. Thus, a specific amount of free active ingredient is always present. When the complex is isolated, some free active ingredient is lost during the filtration and / or drying steps, and thus, the efficiency of the process is much less than 100%. The efficiency of the process is measured with the percent yield for the incorporation of the active principle, that is, the quantity of active principle recovered as a cyclodextrin complex divided by the starting amount of the active principle. For example, efficiency in generally only about 30 percent when cyclodextrin complexes are recovered by spray drying. Thus, when cyclodextrin complexes are spray dried, substantially more than 50 percent of the active ingredient may be lost during the drying step. This loss of the active principle increases the cost of the final product, and is especially problematic for expensive active ingredients. In addition, the costs of cyclodextrins and thus the cost of the resulting cyclodextrin complexes have limited their commercial use. As a result, although cyclodextrin complexes of several active ingredients have been described and discussed in the art, their commercial use has been limited. Thus, there remains the need to reduce the cost of producing cyclodextre complexes, so that they can be commercially valuable. The present invention solves this need.

BRIEF DESCRIPTION OF THE INVENTION The present invention relates to novel higher charge cyclodextrin inclusion complexes containing one or more active ingredients, and to a process for preparing such complexes. The process comprises the steps of dissolving cyclodextrin in a solvent in a reaction vessel to form a first solution, adding the one or more active ingredients to the first solution with agitation, to form a second solution of the one or more active principles and cyclodextrin , stir the second solution for a sufficient amount of time and at a temperature sufficient to form inclusion complexes between the cyclodextrin and the one or more active ingredients, add an agent that increases the solids content to the second solution, to increase the content of solids of the second solution, and form a third solution, and dry the third solution to form the cyclodextrin inclusion complex as a dry powder. The concentration of cyclodextrin in the second solution can be between about 5 and 40 percent, and the ratio of active ingredient to cyclodextrin can be between about 0.001: 1 and 100: 1. The temperature of the second solution can be between about 4 ° C and 75 ° C. In one embodiment of the process the reaction vessel is sealed, and the active ingredient is added without opening the reaction vessel. The reaction vessel may also be pressurized. The reaction vessel can be pressurized to a value above atmospheric to about 70.3 kg / cm2 (1000 psi). In another embodiment of the process, the second solution is stirred at a first temperature for a first period of time, the temperature of the second solution is then progressively decreased to one or more subsequent temperatures, and the decreased temperature of the second solution is maintained while the second solution is agitated. The agent increasing the solids content is preferably at least one of acacia gum, maltodextrin, or modified starch, and can be added to increase the solids content of the second solution to about 30 to 55 percent by weight of the solution. The solids content of the second solution can conveniently be increased by adding acacia gum in an amount of about 5 to 20 percent by weight of the solution, and the remaining solids content increased by adding about 40 to 60 percent by weight of the solution of a maltodextrin that has a dextrose equivalent of between about -5 and 10.

The active ingredient can be one or more pharmaceutical compounds, perfumes, or flavor components. Preferably, the flavor component may be dimethyl sulfide, methyl mercaptan, acetaldehyde, 2-methyl-3-furantiol, diacetyl, flavors produced by pyrolysis, or mixtures thereof. The invention also relates to cyclodextrin inclusion complexes prepared according to the process of the invention. The cyclodextrin inclusion complex may contain between about 1 and 20 per • cent by weight of the complex, and conveniently it is above 15 percent by weight of complex. As noted above, the active ingredient in the cyclodextrin inclusion complex may be one or more flavors, perfumes, or pharmaceutical compounds. Preferred aspects of the invention can be understood from a review of the following detailed description and Figures, wherein: Figure 1 is a schematic drawing of a reaction vessel for preparing cyclodextrin complexes according to the present invention; Figure 2 is a graph comparing the efficiency of the process of the invention for complexing tomato flavor with cyclodextrins with the efficiency of several other methods of complexing or encapsulating tomato flavor; Figure 3 is a graph that represents the results of a technical evaluation panel that compared the quality of tomato, chicken and shrimp flavors complexed with cyclodextrin according to the process of the present invention with those flavors encapsulated by conventional spray drying; Figure 4 is a graph depicting the results of a technical evaluation panel that compared the flavor quality of tomato complexed with cyclodextrin according to the process of the present invention with tomato flavors encapsulated by conventional spray drying as a function of time; Figure 5 is a graph depicting the results of a technical evaluation panel that compared the flavor quality of chicken complexed with cyclodextrin according to the process of the present invention with chicken flavors encapsulated by conventional spray drying as a function of time; Figure 6 is a graph depicting the results of a technical evaluation panel that compared the flavor quality of complexed shrimp with cyclodextrin according to the process of the present invention with shrimp flavors encapsulated by conventional spray drying as a function of time; and Figure 7 is a graph depicting a comparison of the stability of tomato, chicken, and shrimp flavors complexed with cyclodextrin according to the process of the present invention with those flavors encapsulated by conventional spray drying after storage at 25 ° C. or 40 ° C and a relative humidity of 53 percent.

DETAILED DESCRIPTION OF THE PREFERRED MODALITIES The present invention is directed to a process for complexing active ingredients with cyclodextrins. The process of the present invention increases the efficiency of the complexation, so that a greater percentage of the active principle is recovered as a cyclodextrin inclusion complex. The invention is also directed to the product produced by the complexing process. Any active ingredient can be complexed with cyclodextrin according to the invention, including but not limited to flavors, perfumes, and pharmaceuticals. The process is particularly suitable in relation to active ingredients that are flavors, and will be described predominantly in this context. It will be appreciated, however, that this is done for simplicity of description, and the process is not limited to this application. The active principles and cyclodextrins useful for this invention can be found in the patent of E.U.A. No. 5,571,782, the content of which is expressly incorporated herein by reference thereto. The process of the invention involves adding a cyclodextrin to a solvent in a reaction vessel, adding an active ingredient to the cyclodextrin solution with stirring and without opening the sealed reaction vessel, and letting the mixture stir through. an appropriate amount of time and at a temperature sufficient to form an inclusion complex between the cyclodextrin and the active principle. An agent that increases the solids content is then added to the solution to increase the solids content of the solution, and the solution is spray-dried to recover the cyclodextrin-active compound inclusion complex as a dry powder. The reaction vessel can be sealed or unsealed. Preferably the reaction vessel It is sealed to prevent the loss of any volatile component. Any agent that increases the solids content, including but not limited to, corn dextrose equivalents (5, 10, 15 and 20 DE); starches modified by enzymes, oxidized starches (for example oxidized starch with hypochlorite or periodate); corn starch derivatives substituted with amino acids (eg, corn starch oxidized with periodate, corn starch dextrinized with amylase, and corn starch covalently linked to phenylalanine glycoamine); oligosaccharides of starches modified with alpha-amylase of wheat, corn, rice, amilomaz, corn, waxy corn, Chinese melon, and potato; starch treated with octenyl succinate; hydrocolloids (for example, acacia gum, xanthan, guar, carob, tragacanth, and carrageenan); and proteins (e.g., milk powder, whey, and soy). Preferably the agent that increases the solids content is acacia gum, maltodextrin, modified dextrins, or mixtures thereof. According to the invention, any cyclodextrin which forms a complex with the active principle can be used. Typically the cyclodextrin is an α- or β- or β-cyclodextrin. Any solvent that dissolves the cyclodextrin can be used, however, the preferred solvent is water. A cosolvent, such as ethanol or isopropyl alcohol can be added to water. Typically, when a cosolvent is used, it is added to the water in an amount of about 1 or 2 percent. The concentration of cyclodextrin in the solution is preferably between about 5 percent to 40 percent by weight, and preferably between about 15 percent and 20 percent by weight. However, it is not necessary that all of the cyclodextrin be dissolved when it is added to the solvent. This is satisfactory for a balance to be established between dissolved and undissolved cyclodextrin. In general, the concentration of cyclodextrin in solution increases with increasing temperature. The mixture is typically stirred at a rate between about 300 rpm and 1500 rpm, preferably 300 to 500 rpm. The greater the speed of agitation, the faster the rate of formation of the complex of inclusion of ciclodext ri-active principle. The speed of agitation, however, can not be so high as to create enough shear stress to decompose the cyclodextrin molecules. Thus, the speed of agitation should be as high as possible, without damaging the cyclodextrin molecules. The active principle is introduced into the stirred solution of cyclodextrin. Preferably the active principle is introduced into a sealed reaction vessel without opening the reaction vessel. Generally the active ingredient is pumped into the reactor in pure form or as a solution, and the lines of the flavor supply system are rinsed with solvent. When the active principle is added as a solution, it is preferably added at the highest possible concentration. Preferably, the concentration of active principle in the solution is greater than 50 percent by weight, and more preferably greater than 80 percent by weight. When the active ingredient is a flavor, the preferred solvents for the taste are oil based, fixed oil, triacetin, or water. The concentration of active principle present in the resulting solution is determined by the desired flavor load in the final product. The necessary concentration of active ingredient in the final solution can easily be determined by one of ordinary skill in the art with routine experimentation. Typically, the flavor load of the beginning - *. &.; ._ active in the final product is between 1 and 20 percent, preferably between 2 and 10 percent. Generally, the molar ratio of active ingredient to cyclodextrin in the resulting solution is between about 0.001: 1 and about 100: 1, preferably, between about 0.01: 1 and 10: 1, and more preferably between about 0.2: 1. and 1: 5. The temperature of the solution is generally between about 4 ° C and 75 ° C, preferably between about 10 ° C and 40 ° C, and more preferably between about 12 ° C and 30 ° C. The time to form the complex it is typically between 15 minutes and about 24 hours, preferably between 1 hour and 10 hours. In general, the higher the temperature, the shorter the reaction time. Without wishing to be bound by theory, it is believed that shorter reaction times at higher temperatures are due to more of the cyclodextrin being dissolved in the solvent at higher temperatures. Typical reaction times are 4 hours at 25 ° C. In another embodiment of the invention, the complexation can be initiated with stirring at a high temperature, followed by a progressive decrease in temperature. The applicants have unexpectedly found that the formation of .-- > --- «- - -j- ~ -a-ü-IUi inclusion complexes is more efficient when the temperature of the solution is varied. The formation of the inclusion complex can be more efficient when the complexation is initiated with stirring at a high temperature, followed by progressively lower temperatures. For example, the mixture can be maintained under constant stirring for 1 hour at 75 ° C, followed by 3 hours at 25 ° C and 20 hours at 11 ° C. Applicants have also unexpectedly discovered that the efficiency of complex formation of inclusion can be increased if the reaction vessel is maintained under a positive pressure. Thus, in one embodiment of the invention, the formation of the inclusion complex takes place under positive pressure. The pressure can be increased to any value, however, the pressure is typically above atmospheric and up to as high as about 70.3 kg / cm2 (1000 psi, 68 bar), more preferably up to about 7.03 kg / cm2 ( 100 psi, 6.8 bar). Increasing the pressure during complexation is particularly beneficial when the active principle is volatile. Once the formation of the inclusion complex is complete, the total solids content of the resulting paste is increased to about 30 to 55 percent by weight, preferably 35 to 41 percent by weight by adding an agent that increases the content of solids, ie, acacia gum, maltodextrin, modified dextrins, or mixtures thereof. Preferably, the acacia gum is added in an amount between about 5 to 20 percent by weight, preferably about 7 to 15 percent by weight, and more preferably about 8 to 10 percent by weight, and the content of The remaining solids is composed of maltodextrin having a dextrose equivalent (DE) of between about 5 and 10. The maltodextrin is added in an amount of between about 30-80% by weight, preferably 40-60% by weight. The resulting mixture is then dried, preferably using conventional spray-drying techniques which are well known to those ordinarily skilled in the art. The dried cyclodextrin complexes produced according to the process of the present invention have a higher percentage of active ingredient complexed with the cyclodextrin than if the cyclodextrin complex was prepared by traditional methods such as filtering the cyclodextrin inclusion complex and lyophilizing or drying with vacuum filtering, or spray drying a solution of the cyclodextrin inclusion complex without the addition of the agent that increases the solids content of acacia gum, maltodextrin, modified dextrin, or mixtures thereof. Similarly, the process of the present invention complexes a significantly higher percentage of active principle compared to the traditional spray drying process which does not involve forming cyclodextrin inclusion complexes., but merely adsorbs the active ingredient on the surface of, or encapsulates the active principle in the pores of a solid particle such as acacia gum, maltodextrin, or modified dextrins. The increased efficiency is particularly evident when the active principle is volatile. For example, when the active ingredient is dimethyl sulfide typical spray drying has an efficiency of only about 8 percent, and spray drying of a cyclodextrin inclusion complex without acacia gum, maltodextrin, modified dextrin, or Mixtures of them have an efficiency of about 33 percent. According to the process of the present invention, however, wherein the cyclodextrin inclusion complex is spray dried with acacia gum, maltodextrin, modified dextrins, or mixtures thereof, the process efficiency is greater than 75%. Thus, the process of the present invention recovers more of the active ingredient in the form of an inclusion complex compared to other methods of encapsulation of active principles, and results in less loss of the active ingredient. While not wishing to be bound by theory, it is believed that the increased efficiency is a result of a second coating of acacia gum, maltodextrin, modified dextrins, or mixtures thereof which is formed on the inclusion complex of cyclodextrin-active principle. The increased efficiency can also be partially due to the free active ingredient, ie the active ingredient not complexed with cyclodextrin, which is adsorbed on the surface of or encapsulated in the pores of acacia gum, maltodextrin, modified dextrins, or mixtures of the same. As a result of the improved efficiency, less active ingredient is required at the start of the process to prepare a final cyclodextrin inclusion complex having a specified amount of flavor complexed therein. Similarly, for a given starting amount of active principle the process of the present invention produces a cyclodextrin inclusion complex having a higher percentage of active ingredient complexed therein compared to other processes for the preparation of inclusion complexes of cyclodextrin. As a result of the increased amount of active ingredient in the inclusion complex less of the final material is needed to have a given effect, such as producing a flavor in a perfume or a flavor in a food. This increased efficiency means that the cost of producing cyclodextrin inclusion complexes is significantly reduced, in such a way that the process becomes profitable and commercially practical. The process of the present invention is particularly economical for expensive active ingredients or active ingredients that are volatile. On the other hand, the process of the present invention can be used to form an inclusion complex with only a specific component of a flavor or flavor composition, for example, and then dry mix the resulting complex again with the other components of the composition. Preferably, the specific component is a volatile component of the flavor or flavor composition, or a component that is subject to degradation by exposure to air, light, oxygen, or other compounds. Among the flavor components, the process of the invention is particularly useful for forming cyclodextrin complexes with dimethyl sulfide, methyl mercaptan, acetaldehyde, 2-methyl-3-furantiol, and diacetyl. Similarly, the process of the present invention is particularly useful for forming cyclodextrin complexes with pyrolyzed flavors. The pyrolyzed flavors are free fatty acids that are pyrolyzed at a high temperature, and provide a note of grilled meat or fat to food. A problem with pyrolyzed flavors is that they are unstable in the presence of hydrolyzed vegetable proteins, however, if the pyrolyzed flavors are complexed in a cyclodextrin inclusion complex, their stability in the presence of hydrolyzed vegetable proteins is significantly improved. By "flavor component" is meant any compound or mixture of compounds that contributes to the overall taste perception. Flavor components include, but are not limited to, those listed in the 21 FEMA GRAS list, the Codex Alimentarius list, or any other reliably published list, spices, oleoresins, flavor improvers, and the like. The invention is also directed to a composition prepared according to the method described above. The composition comprises one or more active ingredients in powdered form, wherein at least a portion of the active ingredient is complexed with cyclodextrin, and the cyclodextrin is coated with acacia gum, maltodextrin, modified starch, or mixtures thereof. The active ingredient can be a flavor, perfume, pharmaceutical compound, and the like. The active ingredient typically comprises between about 1 and 20 percent by weight of the complex, and frequently more than 15% of the complex. The cyclodextrin complexes of the present invention exhibit the same release and flavor stability as other encapsulated flavors.

EXAMPLES The invention is further defined by reference to the following examples, which describe in detail the methods of the present invention. The examples are representative, and should not be construed to limit the scope of the invention in any way. mkx t? Complexes of flavor systems that have a beef flavor (BEEF FLAVOR 1.123.20, commercially available from FIS USA of Solon, OH), chicken flavor (CHICKEN FLAVOR 2.01.03, commercially available from FIS USA of Solon, OH ), grilled meat flavor (GRILED FLAVOR 4.24.20, commercially available from FIS USA of Solon, OH), shrimp flavor (SHRIMP FLAVOR, 5.58.21, commercially available from FIS USA of Solon, OH), flavor pyrolyzed FLAVOR 8251-0, commercially available from FIS USA of Solon, OH), and a tomato flavor (TOMATO BOOSTER 008 7.70.28, commercially available from FIS USA of Solon, OH) were complexed with β-cyclodextrin according to the process described below. The complexes were formed in a 4 liter reactor vessel having a stirrer and temperature control. The reactor vessel is shown in Figure 1. The agitation speed was set at 1500 rpm. 1 liter of a 15% solution of β-cyclodextrin (Cavitron ™, commercially available from Cerestar of Hammond, IN) was heated to 75 ° C and transferred to the reactor vessel. A non-mixed solution of a composite flavor, or a solution of a composite flavor, having more than about 30 percent by weight of the flavor, was then pumped into the reactor vessel. The container containing the taste was rinsed with 100 ml of water, and the water was pumped into the reaction vessel. The sample was continuously stirred at 1500 rpm for 1 hour at 75 ° C, followed by 3 hours at 25 ° C and 20 hours at 11 ° C. Upon completion of the reaction the sealed reactor vessel was opened, and the total solids of the pasta were increased to 35-41%. This was done by adding 8-10% acacia gum (SPRAY GUM C, commercially available from Colloides Natureles Inc. of Bridgewater, NJ) and the remaining solids content was completed with Maltodextrin 5-10 DE (MALTRIN 040, commercially available from GPC of Muscatine, Iowa). The resulting paste was spray dried using conventional spray drying techniques. The amount of flavor component in the inclusion complex was determined using gas chromatography (GC) analysis of the headspace with a gas chromatograph PE8500 (commercially available from Perkin Elmer of Norwalk, CT) equipped with a flame ionization detector . The amount of flavor component was determined based on the maximum response of reference marker molecules for each flavor. External standards were used to establish retention times for the marker molecules. The following analytical procedure was followed to determine the amount of flavor component in each sample: the samples for the analysis were prepared by dissolving 100 mg of the inclusion complex or 25 mg of the inclusion complex formed from the tomato flavor in 1 ml of water in a tight vial of 20 ml. Samples were placed in a PE101 Auto-sampler (commercially available from Perkin Elmer of Norwalk, CT) and heated to 80 ° C. 2 μl of static samples from the upper space were injected to a 75 mx 0.53 mm x 3 micron column J & DB624 W (commercially available from J &W Scientific Co., Folsom, CA). The following chromatographic conditions were used: initial temperature of 70 ° C with a retention time of 3 minutes, followed by a linear temperature gradient from 70 ° C to 150 ° C at a rate of 10 ° C / minute and maintained for 12 minutes at 150 ° C, followed by a second linear temperature gradient from 150 ° C to 230 ° C at a rate of 10 ° C / minute and was maintained for 12 minutes at 230 ° C. The total run time was 43 minutes The maximum responses were determined using an electronic integrator.

Example 1. Comparison of the Process of the Present Invention with Other Flavor Encapsulation Methods Complex tomato flavor with β-cyclodextrin according to the process described above, and the amount of the dimethyl sulphide marker (DMS) molecule in the complex of inclusion determined by GC analysis of the upper space. For comparative purposes tomato flavor was also complexed with β-cyclodextrin according to the process described above, except that acacia gum and maltodextrin were not added to increase the solids content before spray drying. To compare the process of the present invention with conventional spray drying techniques, tomato flavor was also encapsulated by spray drying with acacia gum and maltodextrin only. In this experiment, the process described above was followed, except that the maltodextrin was replaced by cyclodextrin during the complexing, and the resulting paste was spray dried. The efficiency of the process according to the present invention was 75 percent. The spray drying efficiency of the cyclodextrin inclusion complex without acacia gum and maltodextrin was only 33 percent, and the efficiency of the spray-dried encapsulation with acacia gum and maltodextrin was only 8 percent. Figure 2 provides this data graphically. The results show that the process of the present invention is much more efficient than conventional methods of encapsulating flavor components.

Example 2. Comparison of Spray Drying Complexes of ß-cyclodextrin with Acacia Gum and Maltodextrin with Other Drying Methods of the Inclusion Complexes of ß-cyclodextrin For comparative purposes, tomato flavor is complexed with ß-cyclodextrin according to the process described above, except that the pulp was filtered and dried in a vacuum oven at 40 ° C for 12 hours and a pressure of 1035 kg / cm2 (30 inches of Hg), or by lyophilization. Lyophilization was performed using a VERTÍS 50-SRC lyophilizer (commercially available from Virtis Co. of Gardiner, NY). The material was lyophilized using the following cycle: freezing the sample at -36 ° C for 3 hours, applying a vacuum of 2.04 x 10"4 kg / cm2 (150 millitor), increasing the temperature to 25 ° C at a speed of 3 ° C per hour, and 3 release of pressure. Four cycles were performed to dry each sample. Table 1 shows the effect of the different drying methods on the maximum impact area of the flavor compounds retained in β-cyclodextrin.

Table 1. Effect of Different Drying Methods on the Maximum Area of Impact Flavored Compounds in ß-siclsdextrin with Tomato Flavor The results show that the spray drying process of the present invention is more efficient than oven drying, and similar to lyophilization. The high cost of lyophilization, however, makes the process of the present invention more economical than lyophilization.

Example 3. Effect of Complexing Temperature and Time Complex tomato flavor with ß-cyclodext squab as described above. In a separate experiment tomato flavor was complexed with β-cyclodextrin according to the procedure described above, except that the temperature during the complexing period of 24 hours was maintained at 25 ° C. The results are given in Table 2.

Table 2. Effect of the Complexing Temperature on Maximum Areas of Impact Flavored Compounds in ß-cyclodextrin with Tomato Flavor The results indicate that the process is more efficient when the complexation in a sealed vessel is conducted at a high temperature, followed by cooling than when the complexing is conducted at a single temperature.

Example 4. Effect of Pressure on Complexing Efficiency The effect of pressure on the efficiency of complexation was evaluated by complexing the tomato flavor components with β-cyclodextrin according to the process described above. The complexation was conducted at atmospheric pressure, 7.03 kg / cm2 (100 psi), and 70.3 kg / cm2 (1000 psi). Table 3 shows that increasing the pressure improves the efficiency of the process, measured by the maximum area from the upper CG space, for dimethyl sulfide and isobutyl thiazole. Table 3 also shows that for ß-damescenone and cis-3-hexenol increasing the pressure initially resulted in an increase in the amount of flavor complexed with the cyclodextrin, but the effect was leveled. For phenolic alcohol, however, an increase in pressure resulted in a decrease in the amount of flavor complexed with the cyclodextrin. The results show that increasing the pressure can improve the efficiency of the complexation for some flavor components. The improvement in efficiency is more pronounced for highly volatile compounds, such as dimethyl sulfide. gg? j ^^^^^ - ^ - ^ ------ Table 3. Effect of Complexing Pressure on Maximum Areas of Impact Flavored Compounds in ß-cyclodextrin with Tomato Flavor Example 5. Comparison of Taste Quality for Complex Flavors with β-Cyclodextrins According to the Process of the Present Invention with Spray Dried Flavors with Acacia Gum and Maltodextrin Samples of tomato, shrimp and chicken flavor were complexed with β-cyclodextrins as described above. By comparison, they were also encapsulated - ,. .. s, fe 4 samples by conventional spray drying of these flavors with acacia gum and maltodextrin. Conventional spray drying of these flavors was performed as described in Example 1 for tomato flavor. The encapsulated flavors were added to a dehydrated TRIOMR system (commercially available from Nestle Food Service of Solon, OH) to produce a flavor base system. The TRIOMR system is a natural flavor powder for preparing sauces. Flavor based systems were prepared by adding the chicken and shrimp complexes to the TRIOMR system at a 10 percent concentration, and adding the tomato complex at a 5 percent concentration. The flavor base systems were then rehydrated with hot water (100 ° C) and tested by a technical evaluation panel. The bases containing the chicken and shrimp complexes were tested as a 2 percent solution in hot water, and the bases containing the tomato flavor were tested as a 4 percent solution in hot water. The technical evaluation panel had a minimum of eight members in each test session. An intensity scale of 10 points was used to judge the intensity of the flavors, where 0 indicated an aversion to taste, and 10 indicated an extreme taste taste. The samples were first evaluated by the panel, and an arbitrary unit on the 10-point scale was selected to evaluate the model system, which was fresh spray-dried powder. An arbitrary unit was also selected to evaluate the spray-dried powder and the flavor complexed with β-cyclodextrin, which compared these flavors relative to the model system. These values were designated as zero time values for each flavor. The subsequent evaluations were based on this scale. In each new evaluation, the evaluation panel was provided with the model system and the value of the unit that was assigned to the model system, the samples were then evaluated in the 10 point scale relative to the 15 model system. Figure 3 shows the results of the technical evaluation panel for tomato, chicken, and shrimp flavors. The results show that with rehydration the taste complexed with β-cyclodextrin 20 according to the present invention performed the same or better than its counterpart spray-dried. The same samples were also kept at 70 ° C (160 ° F) for 6 hours, and were tested every hour by the panel. A recent reference sample 25 was prepared for each session every hour. The results of the panel ^^ > ^ M ^^^^^^^^^^^ A ^^^^ _ ^ j ^^^^^^^^^ ^^^^^^^^^^^ - ^ - ^^^^^ - ^^^ i ^ as a function of time are shown in Figures 4-6 for the tastes of tomato, chicken, and shrimp, respectively. The results show that even when the intensity results for the β-cyclodextrin taste complexes were generally slightly better after 6 hours compared to the flavors prepared by conventional spray drying, the degradation slopes for both the complexes of flavor with ß-cyclodextrin and the spray-dried complexes were almost the same. This shows that the flavor complexes of ß-cyclodextrin release their flavor at the same speed as the flavors encapsulated by traditional spray drying. The best result for the panel after 6 hours is the result that more flavor is incorporated into the flavor complex of ß-cyclodextrin at the start.

Example 6. Stability of Flavor Complexes with β-20 Cyclodextrin Tomato, beef and chicken flavor samples were complexed with β-cyclodextrin as described above. For comparison, samples were also encapsulated by spray drying Conventional of these flavors with acacia gum and A * aj * toAt maltodextrin following the procedure described in Example 1 for the tomato flavor. The samples were then stored at a temperature of 25 ° C or 40 ° C in a desiccator containing a saturated solution of magnesium nitrate, to control the relative humidity at a level of 53%. The 40 ° C samples were evaluated by upper space chromatography at 1 week intervals for 8 weeks, and the 25 ° C samples were evaluated at 3 and 5 month intervals. Samples were also evaluated by the technical panel at time zero and after 8 weeks for samples stored at 40 ° C, and after 3 months for samples stored at 25 ° C. Figure 7 shows the results of the technical panel for each flavor. It was again observed that flavor complexes with β-cyclodextrin had a higher flavor intensity compared to their spray-dried counterparts. That is, the higher intensity for flavor complexes with β-cyclodextrin is again attributed to the fact that there was more flavor incorporated into the flavor complex with β-cyclodextrin at the start.

Claims (21)

1. RE IVINDICATIONS 1. A process for preparing cyclodextrin inclusion complexes of one or more active ingredients, comprising the steps of: dissolving cyclodextrin in a solvent in a reaction vessel, to form a first solution; adding one or more active ingredients to the first solution with agitation, to form a second solution of the one or more active principles and the cyclodextrin; stirring the second solution for a sufficient amount of time and at a temperature sufficient to form inclusion complexes between the cyclodextrin and the one or more active ingredients; adding an agent that increases the solids content to the second solution, to form a third solution having an increased solids content; and drying the third solution, to form dry powder of the cyclodextrin inclusion complexes containing the active ingredients in an amount of about 1 to 20 percent by weight of the complex.
2. 2. The process according to claim 1, wherein the agent increasing the solids content is at least one of acacia gum, maltodextrin, modified starch, or mixtures thereof.
3. 3. The process according to claim 1, wherein the concentration of cyclodextrin in the second solution is between about 10 of 5 and 40 percent, and the ratio of active ingredient to cyclodextrin is between about 0.001: 1 and 100: 1.
4. 4. The process according to claim 1, wherein the temperature of the second solution is between about 4 ° C and 75 ° C.
5. 5. The process according to claim 1, wherein the reaction vessel is sealed, and wherein the one or more active principles are added without opening the reaction vessel.
6. 6. The process according to claim 1, further comprising pressurizing the reaction vessel. ^^^^^^^^ & ^ ot ^^^^^^ J ^^^^^^^^^^^^^^^^^^^^^^^^^^^ ^^ _ ^^^^ j ^^^^^ = ^^^ 4 ^^^^^ _ ^ ri ^^^^^^^^^^^^^ j ^^^^^ i ^^^^ ^^ H¿ ^^^^^^^ - ^^^
7. 7. The process according to claim 6, wherein the reaction vessel is pressurized to a value above atmospheric to about 5 of 70.3 kg / cm2 (1000 psi).
8. 8. The process according to claim 1, further comprising stirring the second solution at a first temperature for a first period of time, progressively lowering the temperature of the second solution to one or more subsequent temperatures, and maintaining the decreased temperature of the second solution while stirring.
9. 9. The process according to claim 1, wherein the agent increasing the solids content is added to the second solution to form a third solution having an increased solids content of about 30 to 55 percent by weight. Weight of the solution.
10. 10. The process according to claim 9, wherein the solids content of the second solution is increased by adding acacia gum in an amount of about 5 to 20 percent ^^^^^^^^^ ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ ^^^^^^^^^^^^^^ F ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ ^^^^^^^^ by weight of the solution, and adding maltodextrin that has a dextrose equivalent of between about 5 and 10 in an amount of about 40 to 60 percent by weight of the solution.
11. 11. The process according to claim 1, wherein the active ingredient is one or more pharmaceutical compounds or perfumes.
12. 12. The process according to claim 1, wherein the active ingredient is one or more flavor components.
13. 13. The process according to claim 12, wherein the one or more flavor components is dimethyl sulfide, methyl mercaptan, acetaldehyde, 2-methyl-3-furan thiol, diacetyl, a pyrolyzed taste, or mixtures thereof.
14. 14. A cyclodextrin inclusion complex prepared according to the process of claim 1.
15. 15. The cyclodextrin inclusion complex according to claim 14, wherein the active ingredient is one or more flavors, perfumes, or pharmaceutical compounds.
16. 16. The cyclodextrin inclusion complex according to claim 15, wherein the active ingredient is dimethyl sulfide, methyl mercaptan, ace taldehyde, 2-methyl-3-furan thiol, diacetyl, a pyrolyzed taste, or mixtures thereof.
17. 17. The cyclodextrin inclusion complex according to claim 14, wherein the agent that increases the solids is at least one of acacia gum, maltodextrin, or modified starch.
18. 18. A cyclodextrin inclusion complex comprising an agent that increases the solids content and one or more active ingredients in an amount of about 1 to 20 percent by weight of the complex.
19. 19. The cyclodextrin inclusion complex according to claim 18, wherein the active ingredient is one or more flavors, perfumes, or pharmaceutical compounds.
20. 20. The cyclodextrin inclusion complex according to claim 19, wherein the active ingredient is dimethyl sulfide, methyl mercaptan, acetaldehyde, 2-methyl-3-furan thiol, diacetyl, a pyrolyzed taste, or mixtures thereof.
21. 21. The cyclodextrin inclusion complex according to claim 18, wherein the The agent that increases the solids content is at least one of acacia gum, maltodextrin, or modified starch. SUMMARY OF THE INVENTION The present invention relates to a process for preparing cyclodextrin inclusion complexes that increase the efficiency of complexation, so that a higher percentage of the active principle is recovered as a cyclodextrin inclusion complex. The process involves adding a cyclodextrin to a solvent in a reaction vessel, adding an active ingredient to the cyclodextrin solution with stirring, and allowing the mixture to stir for an appropriate amount of time, and at a temperature sufficient to form a inclusion complex between the cyclodextrin and the active principle. An agent that increases the solids content such as acacia gum, maltodextrin, modified dextrins, or mixtures thereof, is then added to the solution, to increase the total solids content of the solution, and the solution is dried to 25 ° C and 40 ° C and a relative humidity of 53 percent to recover the inclusion complex of cyclodextrin-active principle as a dry powder, with the amount of active principle in the powder in the range from 1 to 20 percent by 25 weight of the complex. The invention also relates to «A-fcj - Jkt * uBß & ?? ~ xA. > . [- t. - -. , < > -. «.» . ,,. , -. -. j Ga ?, _ - - fa-ri-. inclusion complexes of ciclodextpna prepared by this process. -_ _--- j_?