JPH07501259A - self-emulsifying glass - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] ``Giant'' J Pi1 Stand L Noe The fly.

This application was filed on June 1, 1990 and is incorporated herein by reference in its entirety. This is a continuation-in-part of incorporated U.S. Patent Application No. 071,531.847.

Skin care cook The present invention relates to the field of emulsion technology. More specifically, the present invention provides emulsion John and multiple eulsion preparation Compositions and methods for and the pharmaceutics of such compositions and emulsions Concerning applications in the food field, food field or cosmetic field.

My brother's prisoner's back Every year, numerous drugs are abandoned by the pharmaceutical industry due to ~A.

This is because if the compound is found to be inactive (not This is because it cannot be dissolved in FDA-approved solvents for the delivery of this problem is a chemotherapeutic agent (non-polar and therefore has extremely low water solubility or water solubility of 0). t) This is a very common problem. In addition, cosmetics, food, alcoholic beverages, Compounds useful in the photographic, chemical or neuromedical industries in %N are Since there is no effective way to dissolve or suspend the ＼ζA and 0 may occur. Solubilize or suspend such non-polar compounds. The method and medium described above have many pharmaceutical and industrial applications.

In general, the method of preparing a medium for solubilizing non-polar substances is preferably simple. Should. This means that they require many process steps or special techniques to manufacture. You shouldn't. Furthermore, the method should be economical, e.g. Preferably, no input of ghee is required.

The vehicle must be capable of long-term storage without compromising its effectiveness as a delivery agent. No. Media is stored in compact form to reduce transportation and storage costs. It must be possible to store it. For example, storing the medium as a dry solid If possible, it is possible to reduce the weight and volume of the media, and this Transportation and storage costs can be further reduced.

To use such media in pharmaceuticals, foods or other food products, they must contain toxic substances. Must not be doing so. Additionally, such a medium may be used in the edible products in which it is contained. It is preferable not to impart an unpleasant or unpleasant odor to the product. for drugs or cosmetics Vehicles for topical application must be non-toxic and non-irritating. No. Many surfactants are toxic, cause irritation, or Gives off an unpleasant scent. Therefore, they are used in pharmaceutical or edible products. Limited use.

The ideal medium would be stable at a wide range of pHs and temperatures so that it can be used widely. must be fixed.

In certain drug applications, the vehicle is preferably is preferably capable of exiting the vasculature and entering the intracellular fluid. vascular endothelium In order to pass through the intercellular junction, the size of the medium must be approximately 200 angstroms ( 0.2 μm).

Currently existing methods and media for solubilizing lipophilic compounds are complex to manufacture. method, requires a high level of effort, or requires a large input of energy. do. Existing methods and media also contain toxic ingredients or changes in pH and temperature. may contain components that are sensitive to Such methods and media, especially for use in pharmaceuticals. Emulsions containing surfactants and multiphase emulsions are used for this purpose. ions, liposomes, glass dispersions and co-precipitates.

Traditional emulsions solubilize or suspend hydrophobic compounds in an aqueous environment. can be expensive to produce, can be unstable, and are usually toxic. Contains a surfactant. The manufacturing process is expensive because it requires mixing the phases to obtain the appropriate particle size. using an energy-consuming device that provides sufficient shear to create (A, Weiner (1990) BloPha rms: 15-21) o Devices that create shear stress, such as colloid mills , rotary blade mixer, valve homogenizer, microfluidizer - (Microf 1uidizer), French press pressure system, ultrasonic bath or spray equipment, and membrane-based extruders to produce the desired particle size. It requires a considerable amount of energy to produce. operate these devices requires skilled labor and is therefore more expensive (P, Walstra (1983) Encyclopedia of Emulsions: Ba5 ic Theory, Vol. 1:12G (edited by P. Becher)).

Furthermore, devices that generate high shear forces, especially those that are not temperature controlled, In cases where compounds contained in the internal phase can be inactivated (A, 5 adana ( 19119) BloPharm i:14-25; and A, 5adana (1989) BioPhar+eS:2O-23).

Multiphase emulsion systems have recently been described for diverse pharmaceutical and industrial applications. (Davis, S., S., and Walk.

r, J, M, (1987) Meth, Enzy, 149:51-64; Davis, S. S. (1981) Chemistry and Indus try 3- (October): 633-687) For example, water-in-oil-in-water type emulsion to retain, transport or protect water-soluble compounds within it It can be used for. The internal oil phase of such a multiphase emulsion is oil-soluble. compounds can be dissolved. Polyphase emulsions are emulsions of one type. When converting from one mold to another, or when re-emulsifying the primary emulsion. (F　Iorenee, A, T, and and Whitefll, D. (19112) [nt'[, J.

Pharmaceutics 11:277-308; Matsumoto ( 1983) J, Co11oid 1nterface Sci, 94:36 2-368 HFrenkel et al. (1983) J, Co11oid 1n terface Sci, 94:174-178), most frequently used for pharmaceutical purposes. The existing method used requires at least two different surfactants (one with high HL B and the other with low HLB).

However, the practical applications of polyphase emulsions are limited due to their inherent instability. It has been reported that (Omotosho, J., A. et al. (1988) J.

Microencapsulatfon i:183-192; Magdass t, S, et al. (1984) J, Co11oid and Interface Scf, 97:374-379), with low levels of surfactants and substantially More stable multiphase emulsions could greatly expand the useful applications of such media. Probably.

A related system, the gelatin-in-oil-in-water spherical multiphase emulsion, has been proposed for use in drug delivery. (Yoshioka et al. (1982) C Het Phar+s, Bull, 30:1406-1415).

In these systems, the internal water droplets are replaced by gelled gelatin microspheres. It is. In these multiphase emulsions, the S10 type emulsion is a surfactant. formed by sonication of an oil phase and an aqueous gelatin solution (20%) containing Ta. S10/W type emulsion is made by mixing S10 type emulsion with another gelatin aqueous solution ( 1%). Freeze-drying of S10/W type emulsion Drying creates a “bulky pile of oil droplets” which can be replaced with the original S1 if necessary. A 0/W type emulsion was given.

Multi-W10/W emulsion with improved stability forms surfactant film There is a report that this was obtained when a polymerizable nonionic surfactant was used (La W et al. (1984) J, Phar+*, Phar+1aco1.36:50, Law et al. (1984), Int'1. J. Pharma, 21:277-27 8). Adding macromolecules such as albumin to the 'f110/W composition results in a multiphase It has been reported to form a surfactant film that stabilizes the emulsion. these The improved system still requires the use of multiple emulsifiers.

In emulsion production, the input energy required to create the desired particle size is ghee to milk that exactly meets the hydrophilic and lipophilic balance (HLB) requirements of the oil phase. It can be reduced by using a combination of oxidizing agents. (A, We iner (1990) BioPhars: 16-17). Unfortunately, Most of these drugs have irritating properties, which limits their in vivo use (5 Tarbrick, J. (1965) J. Part Sci, 54:1 229) o The need for highly concentrated and irritating emulsifiers is important for emulsification in pharmaceutical applications. can severely limit the use of agent-containing preparations.

Emulsifier-containing emulsions also exhibit instability to changes in pH and temperature. However, as a result, coalescence of emulsion particles occurs and finally phase separation occurs. wake up (J, Co11ett & L, Woo (1975) J, Phar t Sci, 64:1253; and P, Blvorthy & F, Lip sco+*b (1968) J, Phart Phar+gaco1.20:8 17).

Liposomes are thermodynamically stable dispersed systems (H.

■ auser (19g4) Biochem, Biophys, Acta 772 :37) Can dissolve compounds (A, Janoff et al. (1985) Euro, Patent Publ. No. 185680). However, liposo can be unstable under certain conditions (L, Guo et al. (1980), Lip id Res, 21:993; C, Alving & R, Richards ( 1983) The Liposomes (M, 0stro ed, ;D, Papahadjopoulas (1962) Proc, Soc, E xper, Biol, 111:412). Liposomes are antigenic/immunogenic. (C, Alving (1986) Che++, Phys, Lipid s 40:303), and for transport through the intercellular junctions of the vascular endothelium. Can be too large (at least 600 angstroms in diameter) (N, 51m1onesu et al. (1975) J.

Ce1l Biol, 64:586; G, Gregoriadis (197 9) Drug Carriers in Biology and Medi cine, pp, 2B? -341) o In addition, liposome production requires special techniques. can be expensive and energy-intensive in that it requires techniques and equipment ( F. Defrise-Quertain et al. (1984) Liposome Technology, Vol. 2. pp, 1-17; and F, 5zoka & D. Papahadjopoulis (1980) Ann, Rev. , Biophys, Bloeng, 9:41i7; Weiner, A. (199 0) Biopharm i:17-18:0stro (1988) Lip osomes as Drug Carriers, p, 855 (G, Gr egoriadis, ed.))0 glass dispersions incorporate the drug within the melt and allow it to coagulate. It is a solid that is formed by forming a glass dispersion during solidification. the Such substances are used in tablets, capsules, etc. to increase the dissolution, absorption and therapeutic efficacy of pharmaceuticals. used in tablets or other dosage units. The glass solid dispersion dissolves the carrier and drug. Formed by melting or fusing, followed by rapid cooling. The carrier is a solvent Dissolution; upon mixing with the solvent, the carrier is rapidly dissolved and dissolved into the carrier matrix. of the drug becomes a molecular dispersion. One drawback to this method is that the drug or carrier may can be decomposed, vaporized or oxidized during the process (W, Chiou & S, Riegel+zan <1971) J, Pharm, Sci , 60:1283). A further disadvantage is that the production It is in the construction cost. Finally, to form the glass dispersion solid, the fused carriers are The drug must be dissolved or mixed into the body compound. For example, J, K anig (1964) J, Phar+g, Sci, 53: 188-1 92. , researchers dispersed or dissolved castor oil in molten mannitol. I couldn't make them understand.

Literature describing glass solutions using sugars as carrier compounds includes L, A 11en et al. (1977) J, Pharm, Sci, 66:494-496 ; W, Chiou & S, Riegelman (1971) J, Pharm , Sci, 60:1281-1302; and J. Kanig (196 4) is included.

The coprecipitated solid can be mixed with a solvent to form a solution. Co-precipitated solids Forms are prepared by dissolving a physical mixture of two solid components in a common solvent and then (L Chiou & S, Riegel San (1971) J, Part Sci, 60:12B3). The coprecipitate is a seed made of various polymers.

Literature describing such coprecipitates includes W, Chiou & S, Rfegelman (1971) J, PhartScf, 60:1376 -80; E, 5tupak & E, Bates (1972) J, Pha rm, Sci, 6L:400-4034. Chiou & S, Riegel+ nan (1971) J, Pharm, Scf, 60:1281-1302;A , Sihonel 1i et al. (1969) J, Pharm, Sci, 58 :538-549; and T, Tachibana & A, Nakamu ra (1965) Kolloid-Zeitschrift und Zei tschriftfur Polymere 203(2):130-133 included. However, none of these documents deals with coprecipitates containing oil or lipid components. has not been reported. The drawbacks associated with existing coprecipitation methods are that both the drug and the carrier are The problem is that you have to find a solvent that is familiar to you. This indicates that the drug and carrier necessarily limit the possible combinations to those that have a common non-toxic solvent. It turns out.

The novel method of the present invention eliminates many of the problems inherent in the aforementioned methods and systems. The Company provides emulsion systems and multi-phase emulsion systems. this method is free of toxic surfactants (or a multiphase agent) by adding the selected aqueous phase. In the case of emulsions, only one surfactant is required) to form an emulsion We provide new glass that Furthermore, the method of manufacturing this glass is simple. Ru. That is, it is used in the process of making glass and making emulsions from that glass. The equipment uses the energy required to produce liposomes and surfactant-containing emulsions. It requires much less energy than ghee. Emulsion is the invention from a glass by simply contacting the glass with a suitable aqueous phase (e.g. water). can be made and no action is required to form an emulsion. . The resulting emulsion is very stable under various pH and temperature conditions. It is. This emulsion has particles with a diameter smaller than about 0.2 μm and is suitable for blood vessels. Can be formulated to be transported across the intercellular junctions of the endothelium Ru. In contrast to prior art methods, multiphase emulsions simply contain the selected aqueous phase. Made from a solid substance, glass, which has long-term storage stability by adding be able to. In contrast to existing coprecipitation systems, the emulsion of the present invention Contains an oil phase that can optionally be used to solubilize hydrophobic active ingredients. difference Furthermore, since the emulsicon of the present invention contains an oil component, the relationship between the drug and the carrier is Eliminates the problem inherent in known coprecipitation methods of limited combinations.

In contrast to existing melt-fusion techniques, the method of the present invention allows the solubilized compound to It is not necessary to use high temperatures that could deactivate or decompose the In addition, the main The method described above is based on a solid-state method in which an oil phase can be used to solubilize lipophilic compounds. Can be applied to body/oil removal. Melting-fusion method and coprecipitation method have not been described for the production of multiphase emulsions.

The methods and compositions described herein are useful for a wide range of emulsion applications. , is particularly attractive for applications in the pharmaceutical, food and cosmetic industries.

Random pulse 11 The present invention provides methods and compositions useful for preparing stable emulsicone. Yo In particular, 0 containing oily substances and non-surface active water-soluble matrix compounds. A self-emulsifying glass composition, the glass having a the glass is of about 10% to about 60% fine quality, and the glass is in contact with a sufficient amount of the aqueous phase. Provides a composition in which stable emulsions can be easily formed by . The glass of the present invention is called a self-emulsifying glass. especially oil-in-water emulsions emulsions and multiphase emulsions, including water-in-oil-in-water emulsions; -Providing a composition. Various water-soluble and/or oil-soluble active ingredients are described below. The self-emulsifying glasses and emulsions of the present invention can be prepared using the methods and compositions described above. can be incorporated into the composition.

The self-emulsifying glass of the present invention can be used in emulsions and multiphase emulsions, especially in water. Useful in producing oil-based emulsions and water-in-oil-in-water emulsions. present invention The self-emulsifying glass produced by the Emulsions that are surfactant-free or avoid the use of multiple surfactants It is particularly useful for forming. The compositions and methods of the invention also provide stable multiphase It is particularly useful in applications requiring emulsions. The glass according to the invention is suitable It can be stored for a long time without losing its emulsion-forming ability under appropriate storage conditions. can. The emulsion is contacted, if necessary, with an aqueous phase appropriate for the desired application. It can be produced from glass. The self-emulsifying glass according to the present invention is , are also useful as drug delivery agents. i.e. oral administration to humans or animals incorporated into capsules, tablets or other dosage forms for drug or are useful as a vehicle for the delivery of other active ingredients.

Stable water-in-oil and oil-in-water emuls produced from self-emulsifying glasses of the present invention John does not require art-recognized surfactants or emulsifiers.

The matrix compound of the invention is not a surfactant, surfactant or emulsifier . The stable multiphase emulsions of the present invention, such as water-in-oil-in-water emulsions, are stable. A water-in-oil emulsion is required, preferably a water-in-oil emulsion containing an emulsifier. second water-soluble interface to obtain a multiphase emulsion. No activator is required. Avoiding the use of surfactants is especially important for drug applications, food In applications and cosmetic applications, surfactants may have toxic, irritating or allergenic properties. It is beneficial because of its potential uses. Use of a second surfactant in multiphase emulsions Avoiding the use of surfactants can limit the stability of multiphase emulsions. This will avoid mixing or migration problems.

The emulsion composition produced from the self-emulsifying glass according to the present invention In any application in which emulsions or multiphase emulsions are found to be useful. can also be used commonly. Generally, emulsions carry active ingredients. for conveyance, transportation, delivery, or protection, or as desired for any other use. to separate and isolate components of the mixture or which are not desired from the mixture. used to remove components. The emulsion according to the invention is an emulsion and in all such general applications of polyphase emulsions. .

Monosaccharides, trisaccharides, and non-sugar sweeteners like cyclamates and saccharin , and polyvinylpyrrolidone (PvP), cellulose derivatives and maltode Water-soluble polymers containing kistrin are particularly useful in forming the self-emulsifying glasses of the present invention. Acts as a matrix compound in Sucrose, fructose and trehalose Sugars, including but not limited to, can be used as matrices in glasses according to the invention. acts as a gas compound. Preferred non-polymeric matrix compounds are sweet Molecules that taste and are at least approximately as sweet as sucrose are even more preferred. stomach. sugars, monosaccharides, two types, sugar alcohols, and at least approximately the same as sucrose; Derivatives of sugars such as moderately sweet chlorinated sugars are useful as matrix compounds in the present invention. It is. Non-sugar sweeteners useful as matrix compounds include amino acids, Amino acid derivatives, aspartame (trademark) and its derivatives, and cyclame salt, saccharin, acesulfame (acesulfame S) and their inducers. Various sweet-tasting ingredients including but not limited to sulfamate containing conductors Includes children.

Has a tripartite glucophore A non-polymeric molecule with three structural features, bipolar bonds or ton donors, electronegative atoms, and the possibility of hydrophobic or dispersive bonding. molecule containing a self-emulsifying glass region prepared using the solvent method of the present invention. It is useful as a matrix compound for proton donor, electronegative source It has a tripartite glucophore with three structural features: a child, and a hydrophobic region. The molecules used in the matrix compound in the solvent-based preparation method of glasses of the invention are It is particularly useful as a product. Molecules with such tripartite glucophores are It is particularly useful in glass preparation processes that use water as a medium.

Polymeric matrix compounds useful in the self-emulsifying glasses of the invention include, among others: Includes PVP, maltodextrins and cellulose derivatives. Molecular weight range Cross-linked and non-cross-linked PVP with a The method can be processed to form a self-emulsifying glass. carboxyme cellulose, and hydroxymethyl and hydroxypropyl cellulose Water-soluble cellulose derivatives containing hydroxyalkylcellulose containing It can be processed by the methods described herein to form a self-emulsifying glass.

The maltodextrins of the present invention have a dextrose equivalent weight of about 5 to 25. Dextrose (dextrose) and starch are classified as It is a copolymer with Chunky and non-chunky forms of maltodextrin both work in the compositions and methods of the invention.

Generally, various matrix compounds may be mixed to form the glasses of the invention. . Using mixtures of Matri-Nox compounds, e.g. This can lead to a self-emulsifying glass. The higher the glass transition temperature, the more The more kinetically the glass becomes kinetically stable. Glasses with higher glass transition temperatures Russ is generally stored more stably and has a longer shelf life . Generally, the glass transition temperature is preferably about 20° C. or more above room temperature.

Non-polymeric matrix compounds such as sucrose and maltodextrin A mixture with a polymeric matrix compound is a mixture with a non-polymeric matrix compound. yields a glass with a higher transition temperature compared to glasses formed solely from . In particular, using a mixture of sucrose and maltodextrin as matrix compound. glass with a higher glass transition temperature than sucrose-based glasses. It will be done. Specifically, a mixture of sucrose and 3% by weight maltodextrin was mixed with mineral oil. in combination, and treated by the solvent method described herein, above about 180'C. A self-emulsifying glass with glass transition is obtained.

Oily substances useful in the compositions and methods of the invention include various oils, particularly those that are liquid at room temperature. Contains mold oil. In particular, drug and cosmetic applications of emulsicone and glass. Oils useful for food applications include fluorodecalin, mineral oil (heavy oil or light oil) , vegetable oil, bean oil, soybean oil, safflower oil, corn oil, olive oil, etc. oil components, and mixtures thereof. stomach. Oily substances also include water-in-oil emulsions. In other words, the In Marsicon, the oil phase is the outer phase of the emulsion; has the bulk properties of oil.

The aqueous phase of a water-in-oil emulsion can incorporate water-soluble active ingredients.

The oil phase of water-in-oil emulsions can incorporate fat-soluble active ingredients. one generally manufactured by any known method to produce such emulsicone. Any type of water-in-oil emulsion containing any surfactant useful for acts as an oily substance in the glass of the present invention. water-in-oil emulsion The methods used to manufacture the product are compatible with any active ingredients incorporated therein. must be maintained. Preferred water-in-oil emulsions employ suitable emulsifiers. For example, it may be necessary to use a suitable lipophilic solution to form a water-in-oil emulsion. surfactants having an IB value of less than about 5.5. including, but not limited to, agents.

m) The weight ratio of +71x compound to oily substance is at least about 2=1. This is preferred in the self-emulsifying glass of the present invention. matrix compound The weight ratio of to oily substance is more preferably between about 2:l and 20:1; and most preferably between about 2=1 and 10=1.

Self-emulsifying glasses are preferably prepared by the solvent method described herein. This melt For the solvent method, the non-surface active matrix compound as defined herein and the oily substance should be Stable when combined with a sufficient amount of solvent to dissolve virtually all matrix compounds form a combination that is not an emulsion, and then The process involves removing the solvent from the glass to obtain the glass. to the solvent used water, aqueous solvents, aqueous alcohols, ethanol, and especially chloroform. organic solvents that dissolve matrix compounds, including but not limited to It's not something you can do. Water and aqueous solvents are preferred, including aqueous solvents and aqueous alcohols. Delicious. In addition, chloroform uses PVP polymer as a matrix compound. preferred for. when organic solvents such as chloroform are used, and , if the oily substance is not a water-in-oil emulsion, modify the method if desired. Add enough solvent to dissolve both the matrix compound and the oily substance. I can do it. The matrix compound and the oily substance are suitably combined to form a matrix. The weight ratio of compound to oily substance is at least about 2:1. solvent The removal of most preferably by rotary evaporation. . The preferred solvent used when the substance in oil is an oil-in-water emulsion is water.

The solvent is used until an apparently dry solid, solid foam or film is produced. Remove with .

In some cases, evaporation on a rotary evaporator can When the solvent is removed, the solid obtained has the appearance of a solid foam. I come to do it.

Removing the solvent from the combination of matrix compound and oily substance A solid substance is formed that is lath. non-polymeric matrix compound, or A mixture of a polymeric matrix compound and a non-polymeric matrix compound The glass formed using the some level of short-range or intermediate-range, here called microcrystalline A range of molecular order is often preserved. Completely amorphous by X-ray diffraction and DSC Glasses determined to be of high quality shall be prepared by the solvent method described herein. Can be done. Completely amorphous glass is highly hygroscopic and retains significant amounts of water. Absorption into the water is unfavorable to its functionality and shelf life. hot water Additionally, there is some level of microcrystallinity, approximately 10% to 60% microcrystalline as measured by DSC. Glass that maintains crystallinity is preferred. The glass of the present invention has approximately It does not preserve more than 10% long-range molecular order.

If a non-polymer is used in the matrix compound, the matrix compound Significant, i.e. greater than about 10%, long range due to crystallization of non-polymer components of The solvent must be removed at a rate sufficient to prevent the formation of molecular order in . This means that the rate of solvent removal will vary from the concentration of any matrix component from a solvent solution. This can generally be achieved if the rate is faster than the rate of crystallization.

The process steps can be carried out at approximately room temperature. is preferably carried out at as low a temperature as possible, producing a solid that looks like . More preferably, the process steps are performed at a temperature below about 50°C. child In the solvent method, the process step involves melting or decomposition of the matrix compound. It should be avoided. That is, this process step It should be carried out at a temperature below the approximate melting or decomposition point of the substance. In total Many, if not all, matrix compounds have melting points below about 140'C. ing. If the active ingredient is incorporated into a self-emulsifying glass, the manufacturing process ensures that the active ingredient does not degrade or become significantly inactivated Should be done at temperature.

The fat-soluble active ingredient is added to the oil-based substance before combining with the IJ sock compound. or at the same time assembled into a self-emulsifying glass by being added to an oily substance. I can be accepted. Water-soluble active ingredients are water-in-oil emulsions can be incorporated into the self-emulsifying glasses of the present invention in a pure aqueous phase. oil A water-in-water emulsion is formed before combining it with the matrix compound. There must be.

Emulsions and multiphase emulsions can be made from the self-emulsifying glass of the present invention. An emulsion of the desired type, e.g. For example, an oil-in-water type, a water-in-oil type, or a water-in-oil-in-water type is formed. into a suitable aqueous phase is dependent on the desired emulsion application and ranges from about 1 to 10. Acidic or basic aqueous solutions with less than about 95% (V/V> including, but not limited to, hydroalcohols having a cole content. of the present invention Emulsions are produced simply by contacting a self-emulsifying glass with an aqueous phase. It will be done. No mixing is necessary to produce an emulsion from glass.

Chemical reactants, chelating agents, catalysts, enzymes, biological cells, drugs, cosmetics, and solar radiation personal care products, including antiperspirants, antiperspirants, hypoallergenic agents, etc. nalcare agents), as well as seasonings, colorants, preservatives, etc. The active ingredient, which is a food additive, can be added to the self-emulsifying glass and emulsifier of the present invention. can be incorporated into the composition. Agents useful in the compositions of the invention include proteins, vaccines, therapeutic enzymes, therapeutic antibodies, hormones, antibacterial agents, Poxygenase inhibitors, acyltransferase inhibitors, chemotherapeutic agents, anticoagulants agents, thrombolytic agents, or colony-stimulating factors. . More specifically, the drugs include dismutase, erythroboietin, and interferon. Ron, interleukin, monoclonal antibody, tumor necrosis factor, human growth hormone insulin, ceftriaxone, cephalothorax Sporin, acetaminophen, β-blocker, trandate te), labetol, 5-fluorouracil, methotre xate, mechloresamine hydrochloride, urease, LH-RH analogs, and gona These include, but are not limited to, dotropine free hormone analogs. Main departure The methods and compositions of the present invention are particularly useful for drug delivery for such pharmaceutically active ingredients. Useful in the preparation of substances.

The methods and compositions described herein can be used, for example, to reduce unpleasant taste, systemic irritation, and Is it the effects of drugs that are harmful to the mind and body, such as severe gastrointestinal irritation or toxic effects? can be used to improve the means of drug delivery by protecting patients from

The methods and compositions described herein also provide protection against degradation or inactivation of active ingredients. It can be used to prevent overall

For example, active ingredients that are moisture labile and/or oxygen labile. minutes can be protected. Water-soluble active ingredients can be added to the aqueous phase of the emulsion of the invention or is incorporated into the aqueous phase. The fat-soluble active ingredient is the oily phase of the target emulsicon. Alternatively, it can be incorporated into the oil phase.

The method of the invention does not require the application of high temperatures to produce the subject glass. subordinate Thus, the methods and compositions of the present invention are particularly useful for treating all temperature-labile water-soluble Alternatively, it is useful for fat-soluble active ingredients. The method of the present invention allows temperatures above about 50°C. At temperatures above It is more useful for active ingredients that contain

Brief description of the drawing Figure 1 shows the turbidity as a function of time (minutes) obtained by absorbance measurement at 400n This is a graph of The graph shows two oil-in-water droplets made from self-emulsifying glass. Comparing the turbidity of the mullions. One contains water as the external phase (black diamond); and the other contains normal saline as the external phase (white squares). same ingredients Also shown is a dispersion of a physical mixture of (black squares). This self-emulsifying glass is It was prepared using sucrose and mineral oil in a 6:1 weight ratio. The dispersion is an emulsion A physical mixture of sucrose, mineral oil, and water with the same proportions as the It was prepared by pouring it on a stove (20 minutes). All measurements were performed at 25°C. Ta. A decrease in turbidity indicates cracking of the emulsicone, which is due to phase separation. This is because it occurs due to separation. No phase separation was observed during the experiment for the two emulsicons. There wasn't. Therefore, the observed decrease in turbidity is due to a decrease in emulsion particle size. It depends.

Figure 2 shows the conductivity of emulsion formed from self-emulsifying glass as a function of the weight contained. This is a graph expressed as a number. Water content is expressed as % water weight in the emulsion. has been done. Conductivity is expressed as relative conductivity to water. All measurements are 2 Made at 5°C. Self-emulsifying glass contains sucrose and mineral oil in a 4:1 ratio. It was.

Figure 3 shows the viscosity of an emulsion with a weight ratio of sucrose to mineral oil of 6:1. Figure 2 is a graph as a function of shear rate (rpm) at 25°C. increases shear rate Measurements were performed while increasing (white squares) and decreasing (black diamonds).

Figure 4 shows the amount of sucrose-mineral oil self-emulsifying glass produced by the solvent method of the present invention. It is an X-ray diffraction diagram. The diffraction diagram of the glass (line B) is shown as a physical mixture of sucrose and mineral oil. (Line A).

Figure 5 shows a self-emulsifying glass forming a w107w emulsion in contact with an aqueous phase. 1 is a comparison of differential scanning calorimetry thermograms. Thermogram A is the matrix compound as sucrose and maltodextrin (3% by weight, white Di-Pac and It is a glass prepared using a mixture of (named mixture) Temperature record chart B is a glass prepared using sucrose as the matrix compound.

This graph shows the standardized heat flow rate (watts/grams) as a function of temperature (0C). It is a representation.

Yohadansha Toyohiro Sermon An emulsion is a dispersion of one liquid in the form of droplets in another immiscible liquid. It is a dispersion. Generally, the diameter of the dispersed droplets exceeds 0.1 micron. (P, Becher (1983) Encyclopedia of Emu lsion Technology Vol, 1. (See p. 108). distributed One liquid is the internal phase (or discontinuous phase), and the other liquid is the external phase. It is a department. Emulsions are most typically used for aqueous and oil phases. . In water-in-oil emulsions, an aqueous phase is dispersed within an oil phase. oil-in-water emulsion In cons, an oil phase is dispersed in an aqueous phase. Emulsions are inherently unstable. Ru. The internal phases coalesce over time and the emulsion breaks down.

Emulsifiers (surfactants) are generally required to stabilize emulsions This is recognized. Therefore, conventional stable emulsions contain at least 1 Contains two emulsifiers.

The type of emulsion (water-in-oil or oil-in-water) can be determined in several ways. Ru. Emulsions typically have approximately the appearance of an external phase. Sunawa Well, W10 emulsion looks like oil, and O/W emulsion looks like oil. is water. Yet another quantitative method for determining emulsion type is dye dissolution. degree test (water-soluble dyes dye O7W emulsion, but W10 emulsion conductivity test (W10 emulsion is generally (not).

Multiphase emulsions are a more complex type of emulsion in which dispersed droplets are containing dispersed droplets of smaller immiscible liquids. Water in water oil (W10/ W) Emulsicons contain oil droplets in an aqueous external phase, and the oil droplets are Contains smaller droplets of aqueous phase inside. The external and internal aqueous phases are the same or It can be different. The polyphase emulsion uses the first O/W or W10 emulsion. It is prepared by emulsifying (Davis and Walker (19 87) Multiple Emulsions as Targetable Delivery 5yste+as Meth, Enzyn+o1. 14 9:51-64). Formation of multiphase emulsions generally involves different HLB It is believed that it is necessary to use two surfactants with a value (Da vis and Walker, 1987; Florence and White hill (1981) J, Co11oid Inter, Sci, 7 9:243-256; Martin et al., Physical Phar+*a cy Physical Chemical Pr1nciples int he Pharmaceutical 5 sciences, Lea & Fe biger, Ph1ladelphia, PA pp, 553-565; Frenkel et al. (1983) J, Co11oid Inter, Set , 94:174-178 HGarti et al. (1983) J. Dispers. ion Scl Technol, 4:237-252). surfactant , i.e., the movement between the phases of surfactants with two different HLB values. , is thought to occur in a multiphase system using one or more emulsifiers (F Renkel et al., 1983). of multiphase emulsions by surfactant migration. A collapse occurs. W10/W emulsions typically remain stable for 24 to 48 hours. (Florence and Whitehall, 1981), but the highest can be stable for up to 30 days under conditions of (Davis and Walk er, 1987 and Garti et al., 1983).

The emulsion and multiphase emulsion of the present invention are selected for self-emulsifying glasses. Created by adding an aqueous phase.

This self-emulsifying glass quickly absorbs water-soluble, non-surface active Matri-Nox compounds into oil. A lipophilic active ingredient, optionally dissolved, prepared in combination with an oily material that can become a phase. or the first emulsion. For example, a water-in-oil emulsion is Optionally contains dissolved active ingredients.

The self-emulsifying glass of the present invention forms an emulsion upon contact with a sufficient amount of aqueous phase. do. Formation of emulsions occurs almost immediately and often requires energy input. Not required. Emulsions can be made from glass simply by contacting a solid with an aqueous phase. can be formed. These properties of this glass make it easy to stir, homogenize, and microfluidizing, ultrasonication, or Processing steps involving milk mixing, such as processing in a Lloyd mill, are omitted.

Prior art self-perforating systems (Pouton (1985) Int'l J, Pharmaceutics 27:3335-348) or drying Unlike emulsions, the target glass, which is a precursor for simple emulsions, Contains no art-recognized surfactants. It is a precursor for multiphase emulsions. A self-emulsifying glass with at most one field to form the first emulsion. Only a surfactant is required.

Simple two-phase emulsions and polyphasic (i.e. three-phase) emulsions are defined herein as can be prepared using the self-emulsifying glass described in . In front of W10/W emulsion The self-emulsifying glass, which is the precursor material, is a first water-in-oil emulsion and a water-soluble Prepared from a mixture with a non-surfactant carrier. Polyphase emulsion is the glass may be formed from contact with an aqueous phase.

The self-emulsifying glass of the present invention can be used to store drugs, reactive chemicals, dyes, fragrances, etc. may contain active ingredients. and for the delivery and solubilization of such active ingredients. May function as an excipient.

Lipid-soluble active ingredients can be incorporated into the glass oil-based material. water soluble active ingredient can be incorporated into the aqueous phase of a water-in-oil emulsion of a self-emulsifying glass.

The self-emulsifying glass of the present invention is produced as a solid, preferably a dry, non-oily solid. , prepared. The glass can be in the form of a powder, a solid foam, or a thin film. Ga The lath can last for long periods without loss of emulsion-forming ability if protected from extreme moisture. Can be saved.

In contrast to crystalline materials, glasses and liquids have only short-range molecular order. example For example, in a crystal, the separation distance and bond angle with the nearest neighbor are exactly the same, but In a glass, the separation distance from the nearest neighbor is approximately the same as the distance over two or three molecules. It's only the same. In practice, this predicts the position of the neighbor in the glass. I can't. As a result, by X-ray diffraction, the material that crystallizes can be can be easily distinguished. Glass or liquids can only show weak, diffuse diffraction results. crystals, on the other hand, can exhibit strong sharp diffraction results. In this sense, Glass is also amorphous in X-ray diffraction (G. O. Jones, “Glass -, Wiley, New York, NY, 1971. pp, 5-! l).

The first amorphous materials to be studied in detail were prepared by cooling the melt, hence the ``glass'' The word "glassy" or "glassy" is used in the literature as a synonym for amorphous solid. It has become. In fact, recent literature citations indicate that spraying is accomplished by drying and freeze-drying. An amorphous material is called glass even if it is prepared as (G, W, White and S, H, Cakebread, J, Fd, Tech nol, 1nia 3-82 (1966)).

Glasses characteristically lack long-range order, but regions of fine quality can be seen under electron microscopy and and detected using calorimetry (M, Mathlouthi, ln d, Aliment, Agri, 1279 (1975)).

These results indicate that the material is separated into amorphous regions that appear amorphous by X-ray diffraction. can have many small discontinuous regions (fine-quality regions) of crystallinity that are scattered I understand. The amount of such areas depends on the method of preparation and the physical properties of each material. It seems to depend on the quality.

The self-emulsifying glass of the present invention is an amorphous material when measured by X-ray crystallography. be. Materials with long range crystallinity of about 10% (by weight) or less are It appears amorphous by X-ray method. Some of the glasses of the present invention have differential scanning calorimetry. As measured by DSC, it appears to contain areas of poor quality. in glass The degree of fine quality ranges from virtually no fine quality to about 60% (by weight) of fine quality. There can be a variety of things, including quality. Fine quality degree, glass processing Depends on the degree of crystallization of the components formed during the process. For example, there are few measurable micro-qualities. Some or no glass, siliconized glassware during solvent removal. It has been found that when used, it can be prepared by the solvent method of the present invention. in the glass The degree of fineness varies over a wide range, with gas forming emulsions on contact with the aqueous phase. Does not affect Russ' abilities. Glass with very low levels of micro-quality is highly hygroscopic It is known that this is possible. Therefore, depending on the required application, e.g. Preservation of molded glass requires that some degree of micro-quality, at least at a low level, be present in the glass. Preferably, it exists in Fine quality at least about 10% to about 60% (by weight) Glasses with a fine quality of about 20% to 30% are preferred; preferable.

The self-emulsifying glass of the present invention can be used in conventional dry emulsions and concentrated emulsions. It is different from Because these compositions typically contain at least one This is because it is made from existing stable emulsions containing two emulsifiers. follow Therefore, existing dry emulsicone precursors contain traditional surfactants. . Similarly, existing dry multiphase emulsion precursors The glass of the present invention is made from a surfactant and contains at least two surfactants. It is different from Russ.

The matrix compounds of the glasses of the present invention are water-soluble, non-surface-active compounds.

Two classes of matrix compounds are used to make self-emulsifying glasses. It has been confirmed that this can be done. One class includes sucrose, trehalose, and monosaccharides and trisaccharides such as fructose, cyclamate and saccharin , sweeteners including sweeteners derived from sugars and synthetic sweeteners. One more One class of matrix compounds is water-soluble polymers such as polyvinylpyrrolidone. Contains rimers, water-soluble cellulose derivatives, and maltodextrins.

Mixtures of two or more matrix compounds may also be used as self-emulsifying gases. It can be used to make lath.

Generally, a "sweetener" is any ingredient that has a sweet taste.

As used herein, the term sweetener refers specifically to sugars and sweet-tasting molecules and compounds other than sugars. Alternatively, it is intended to include mixtures.

Sweeteners include sugars, especially sugar alcohols, amino acids, and sulfamates. Contains sweeteners. Sweeteners other than sugars include, for example, sugar alcohols and amino acids. Natural compounds such as acids, or chlorinated sugars, aspartame (aspartyl feces) trademark of Nylalanine methyl ester), cyclamate, or saccharin. It can be a synthetic sweetener. Used as a matrix compound in the solvent method of the present invention Preferred sweeteners are compounds at least as sweet as sucrose or It is a mixture. In applications in the fields of medicine, food, and cosmetics, , the matrix compound is preferably non-toxic.

For non-polymeric matrix compounds, the sweetness of the molecule and its matrixization An experimental correlation was discovered between the ability to make self-emulsifying glasses using It was. Glass made with sucrose and oil (i.e. mineral oil) is not sweet. It turned out that. From this, the formation of a glass that can self-emulsify is important for taste perception. It was shown that the direction had changed to some extent.

Self-emulsifying glasses contain very sweet molecules, namely cyclamate and saccharide. It has been found that sweeteners such as quince can be produced by the method described herein. It was. This suggests that there are , regions or structural features of the molecule, as described herein using water as a solvent. It was suggested that the ability to form self-emulsifying glasses is correlated with .

Self-emulsifying glass uses water as a solvent to contain glucose, lactose, maltose, and It was found that it cannot be easily formed with the sugar alcohols mannitol and sorbitol. It was. Lactose is poorly soluble in water, and a sufficient amount of lactose The glass is insoluble in water and allows glass formation to occur via rotoevaporation. I can't. Glucose, mannitol and sugar alcohols are well soluble in water. Dry solid glass via rotary evaporation It turned out that it was impossible to create. Self-emulsifying glass prepared from trehalose It turned out that it would be done. However, the resulting trehalo space glass is dry A force that cannot be applied to a solid body). Glucose, maltose, lactose, sorbitol, mannitol sucrose, and trehalose all have lower sweetening power than sucrose. has been done. Therefore, when compared to sucrose, potential Matri-Sox compounds The intensity of sweetness of foods and the water-solvent method described herein using the matrix There is a clear correlation between the ability to produce self-emulsifying glasses.

Many attempts have been made to correlate molecular structure to the properties of sweetness (Kier (1972) J, Pharmaceutical Sci, 61:13 94-1397 and recent reviews, Lee (1987) Adv, Carb ohydrate Chet and Biochem, 45:199-35 1, all of which are incorporated herein by reference. straight line Correlation C, not confirmed. Because the type and structure of the sweet molecule ζ This is because it is very diverse. General ranking of sweet molecule classes and sweetness intensity A brief summary of Birch (1987) Endeavor: 21- It is offered during the 24th. Sweet molecules are sugars; hydrogenated, deoxy, anhydrous, and salts Derivatives of sugars, including high-fructose sugar; amino acids; aspartame (trademark) and amino chloride Amino acid derivatives, including acids; saccharin, cyclamate, and acesulfame (acesulfams); aminonitrobenzene; Drochalcone; Isocoumarin; Thaumatin and Hiruna Certain proteins and peptides such as hernadulcin It is found in the de.

Not all compounds of a particular type are sweet (and apparently similar compounds are Among foods, the intensity of sweetness can vary considerably.

In such a case, only one of the pair of mirror images is sweet. sweetness and certain things No general correlation between physical or chemical molecular properties has been established.

There is a certain degree of correlation between sweetness intensity and physical or chemical properties. A limited number of related compounds have been established.

For example, the sweetness of sugar is correlated with its solubility in water, and amine nitrates It has been reported that the sweetness of lobenzene is correlated with its melting point (Lee (1987) p. 206). Due to the correlation within such a narrow range, associated with weak interactions such as hydrogen bonds or hydrophobic and hydrophilic interactions It is suggested that this property may be responsible for some of the sweet taste. for sweetness The most recent theory is that a type of chemical component has a particular three-dimensional structure or arrangement. It is based on the concept of sweet taste receptors that bind to molecules that have a sweet taste. various sweet flavors A concept that rationally explains the sweetness of a certain molecule and relates the tertiary structure and sweetness. includes the tripartite glucophore (LeeS1987.p, 231 and and Kier, 1972). This tripartite glucophore is associated with sweet taste. It is a structural feature that is characterized by polar bonds represented by AH or A, and consisting of a negatively charged atom, and a third characteristic. First, the proton donor or is more commonly a polar bond, and approximately 2.5 to 4.0 angstroms Two structural features, negatively charged atoms separated by a distance of listed as essential (5hal Ienberger and Acree (1967) Nature 2X! L:480).

Examples of AH include cycloalkyl groups or aromatic ring O-H groups, N-El groups, and and C-H groups. Examples of B include an oxygen atom, an oxime group, a nitro group, and a carboxyl group. Included are a bonyl group and an S-0 or so2 group. , cyclamate and salt NH-3O2 is added to the AH1B unit in Karin sweetener. Book The third feature, designated X in the specification, is associated with increased sweetness intensity.

Feature nsch (1966) Nature 211 Near 5), or more generally Specifically, areas where distributed coupling is possible or areas susceptible to electrophilic attacks (K Ier, 1972). Examples of feature X include alkyl groups and and alkenyl groups, cycloalkyl groups and cycloalkyl groups , aromatic ring, C-2 substitution of aminonitrobenzene. All three features has been described as being involved in the binding of sweet molecules to receptors. three The partial glucophore has an AH-B distance of approximately 2.5-4.0 angstroms. Range, AH-X distance ranges from approximately 3.1 to 5.2 angstroms, and B -X distances range from approximately 5.2 to 7.4 angstroms to form a triangle.

The triangular tripartite glucophore structure is narrower, with an AH-H distance of approximately 2.6 ohms. angstrom, the distance of B-X is about 5.5 angstroms, and the distance of X-Al 1 is shown as approximately 3.5 angstroms. The intensity of sweetness is determined by the receptor associated with better fit or improved bonding within the body. three parts Sweet tasting compounds with monoglucophores can be prepared by the aqueous solvent method described herein. Useful for the preparation of self-emulsifying glasses, especially where feature X is a region capable of hydrophobic bonding Things are useful. Compounds with tripartite glucophores that are sweeter than sucrose are It is a preferred matrix compound for use in the methods and compositions of the invention.

Sweetness is commonly compared to that of sucrose. Detects and compares tastes including sweetness There is a lot of literature in the technical field of taste and aroma on how to compare. specific Methods for testing the relative sweetness of compounds are known in the art. qualitative sweetness Evaluation can be simply done by human taste testing of the solid or aqueous solution. death However, when doing a taste test like this, be careful as some sweet compounds can be toxic. ,Caution must be taken. - Human taste tests are inconclusive and impossible. because For example, an individual's taste may be partially lacking in taste compared to the standard, or may have a taste disorder. This is because there are always cases. A qualitative test that compares the relative sweetness of compounds is Generally done by a special test panel. The intensity of sweetness is often determined by the presence of sucrose. Measure the concentration of an aqueous solution with the same sweetness as the one with the same concentration, and rank it by comparing it with sucrose. be done. A variety of literature providing qualitative rankings of sweetness of various compounds is readily available. (e.g. Grant and Hatch's Chetjcal D ictionary (19B?) 5th edition and later, Grant and Grant edition McGraw-Hill, New York; Andres (1977 ) Low Ca1orie and 5special Dietary Fo ods, see CRC Press).

The lipophilic region of the tripartite glucophore, or more precisely, sucrose, sucrose The lipophilic surface of phosphorus or cyclamate can be It is important not to be confused with the lipophilic regions of traditional emulsifiers.

The second type of matrix compound is a non-sweet polymer. These materials The substance appears to have some structural similarity to some sweet-tasting ingredients. However, there is a clear correlation between the structure of polymers and their usefulness in self-emulsifying glasses. No known relationship. The matrix compound of the polymer can contain any number of vinyl Polyvinylpyrrolidone, especially carboxymethylene, including members of the group containing groups Water-soluble celluloses, including cellulose and hydroxyalkylcellulose Derivatives, complete and partial, and starch/dextrose copolymers, including but not limited to maltodextrins .

As long as it is water-soluble and non-surface active, the size of Matri-Nox compounds is Or there is no molecular weight limit. Generally, the matrix compound is the oil component of the formulation. materials, solvents, and aqueous phase components.

The polymeric matrix compounds of the present invention have no sweetness, so they have a sweet taste and a tripartite structure. Correlation between the presence of glucophore and the functionality of compounds in emulsion formation It is clear that the relationship is not absolute. In other words, sweetness is derived from self-emulsifying gas. A sufficient but not necessary condition for matrix compounds to act on the formation of laths. stomach. The correlation between the intensity of sweetness and the function of the present invention as a matrix compound is The suitability for use in the method of the invention can be easily evaluated by following the procedures described in the specification. This is useful for selecting candidate matrix compounds that may be of value.

Surfactants or emulsifiers are molecules that are selectively adsorbed at interfaces. In water systems, Adsorption or accumulation of emulsifier at the water/air interface clearly reduces the surface tension of water. (see Becher, 1983, p. 111). Surfactant accumulation is , until the water/air interface is saturated with the emulsifier, i.e. to the plateau region. Reduces surface tension. After the surface is saturated with emulsifier, further added emulsification The agent results in the formation of associative structures or micelles. Emulsifiers are molecules that form at the water/air interface. to be oriented so that the non-polar regions of the are exposed to air (which is relatively non-polar) This reduces surface tension. The hydrophilic portion of the molecule is oriented towards the water. milk The three basic structures required for a curing agent are (i) a lipophilic region, and (if) a hydrophilic region. , and (iii) the balance between lipophilic and hydrophilic regions. hydrophilic and It is important that there is a balance in lipophilic loading. For example, if the molecule is highly hydrophilic If too much, it will be localized in the part where the water is, ie in the bulk. On the contrary, the lipophilic molecule If it is too strong, it will be completely excluded from the aqueous phase. Lipophilic regions are common It is considered to be the hydrocarbon chain portion of the molecule. These lipophilic regions can be saturated or unsaturated. Can be either a saturated hydrocarbon chain or, less commonly, a complex It can be a ring or an aromatic cyclic structure. In practice, emulsifiers are generally 8 to 18 It is known to have a hydrocarbon chain consisting of methylene groups. The hydrophilic region is , depending on whether the region is anionic, cationic or nonionic. be marked.

The present invention includes certain species that would not be expected to be surface active according to conventional emulsification theory. The use of molecules and classes of molecules is described. These molecules and A class of molecules, referred to herein as matrix compounds, without significantly lowering the surface tension and thus forming associative structures, i.e. micelles. This is not reported or expected.

According to conventional knowledge, the matrix compound of the present invention fulfills the three requirements of an emulsifier. Two of the structures are missing, i.e. they lack lipophilic regions, and therefore are hydrophilic/philic. Lack of oily balance. Therefore, the matrix compound of the present invention It is expected that they will be equally distributed both in the bulk and in the bulk (He et al. (1986)). , “Theory and Practice of the Pharmaceutical Industry”, 3rd edition, edited by Lachman et al., Lea & Fe biger, Philadelphia, Pennsylvania, 9, 104). For example, Shida Sugar is one of the matrix compounds of the present invention. Sugar molecules are considered to be a hydrophilic group. and is not surfactant (J, G, Rless et al., Bfomat, Art,, Ce1ls, Art,, Org,, 162421-430 (1980)). Stearic acid (CI8H3602) and cocoa acid (coco aic acids, Cl1IHI604), imparting a lipophilic region, Therefore, esterification (mono- and It has been demonstrated that surfactants can be prepared from sucrose by Ta.

As used herein, the term "self-emulsifying" refers to a matrix compound and an oily substance. Applied to glass formed from.

This term refers to the property of glass to form emulsions, especially when glass comes into contact with an aqueous phase. Refers to the ability to form an emulsion just by touching it.

The oily substance of the present invention contains oil or glycerides and esters of fatty acids. It is a substance. The oily substance is preferably liquid at around room temperature. Such oil is Natural and synthetic oils, mineral oil, vegetable oil, peanut oil, safflower oil, olive oil, coconut oil oil, soybean oil, castor oil, linseed oil, petroleum oil and its components, fish oil and animal-derived fluorodecalin, including conventional oils, and perfluorodecalin; There is no limitation to these.

For oil-based substances, use perfume oils such as spearmint, peppermint, or koji oil. can be included. However, it is preferred that the perfume oil is not a major component of the oily substance. The oil is as appropriate for the particular application and in coexistence with other components of the emulsion preparation. selected so that it can be used. Certain natural oils contain monoglycerides that can act as emulsifiers. Although it may contain small amounts of cerides or other components, these materials are There is no need to generate a

Oily substances also include water-in-oil emulsions. This kind of emulsion It has bulk properties like an oil, especially like the oil phase of an emulsion. do. W10 emulsions include an aqueous phase dispersed in an oil phase. The oil phase is the oily substance mentioned above. It can include any quality. The aqueous phase can be water, aqueous salt solutions, acidic or basic aqueous solutions ( pH 1-10) and an aqueous alcohol solution. W10 emulsion is applicable The stability of the W10 emulsion can be prepared by any method known in the art. It may contain suitable emulsifiers for formulation. Preferably the 'f110 emulsion is HL Contains a fat-soluble surfactant with a B value of less than about 5.5. water-in-oil emulsion The amount of surfactant added to produce depends on the oil phase and the aqueous phase to be dispersed. .

The "solvent" used in the methods described herein is one that is capable of dissolving the matrix compound. means any liquid that However, the solvent is It must be possible to remove it from the combination by vacuum without using high temperatures. Therefore, it must be volatile. Process temperature is maintained below about 50°C It is preferable. Solvents are water, aqueous alcohol, alcohol, acidic and basic water solutions, and organic solvents such as dichloroform, but are not limited to these. Not possible. Water and aqueous solutions are the preferred solvents for all matrix compounds. be. Additionally, chloroform is a preferred solvent for PvP. water-in-oil type Water is the preferred solvent for preparing self-emulsifying glasses containing emulsions.

Solvents can be self-emulsifying and residual solvent can be retained in the product emulsion. be suitable for the desired use and with other ingredients of the preparation. selected so that they can coexist.

An "aqueous phase" is added to the self-emulsifying glass to create an emulsion. water The phase can dissolve matrix compounds.

The aqueous phase must contain water, and preferably at least about 5% by weight water. It is. The aqueous phase is preferably neutral, acidic and basic, with a pH ranging from 1 to 10. water-soluble or water-miscible organic compounds; is not limited to. The aqueous phase contains those organic compounds alone or as a mixture in water. It can be contained together with. The aqueous phase is based on the desired use and with other ingredients of the preparation. selected so that they can coexist.

As used herein, an "active ingredient" is optionally retained in one of the phases of the emulsion. or an important compound to be dissolved.

Active ingredients can be water-soluble or fat-soluble. Fat-soluble active ingredients are treated as oil-based substances. may be dissolved in oily substances, including the oil phase of the primary emuldimine used in the water soluble The active ingredient can be dissolved in the aqueous phase, either external or internal to the emulsion of the invention. I can understand it. Active ingredients include chemical reactants, catalysts including enzymes and biological cells, and inorganic dyes, chelating agents, complexing agents, drugs, food additives, flavorings, coloring agents, cosmetics Includes products, etc.

Drugs include human and veterinary drugs, therapeutic enzymes, peptides, proteins, therapeutic and diagnostic antibodies, vaccines, recombinant peptides or proteins, painkillers, and chemicals. Includes therapeutic agents, enzyme inhibitors, and the like. emulsion or self-emulsifying gala The amount of active ingredient in the solution is selected to be appropriate for the desired use. lead to the preparation The amount incorporated is limited by the solubility of the component in the aqueous or oil phase.

Generally the other ingredients of the preparation are selected to be compatible with the active ingredient. Similarly, Glasses containing active ingredients and other substances used in the preparation of emulsions The processing steps involved must also be able to substantially retain the activity of the active ingredients.

Emulsions and multiphase emulsions are used to retain, transport, protect or separate active ingredients. Used to separate. Emulsions hold moisture or air sensitive compounds. and to protect the active ingredients from chemical or biological inactivation. It can be used for Emulsions can also be used for pharmaceutical or edible emulsions. or may mask unpleasant tastes, or may mask any irritant or toxic effects of the active ingredients. It can protect the patient from the effects of radiation. Emulsions are used to isolate desired components from a mixture , or used to remove undesirable or unnecessary products from a mixture. It can be done.

Although we do not wish to adhere to any particular theory, the self-emulsifying glass of the present invention is water-soluble and The oily substance is dispersed throughout the non-surface active compounds, i.e. the matrix compound. It is believed to include the formed matrix. Self-emulsifying type as described herein Solvent methods for producing glass therefore involve dispersion of liquid oil in a solid matrix. It is thought that this causes the formation of dispersed particles.

The present invention provides a method for producing self-emulsifying glasses, emulsions, and multiphase emulsions. provide As mentioned above, adding an aqueous phase to a self-emulsifying glass creates a stable solution. Mulsions and stable multiphase emulsions are produced. Emulsions are made with an aqueous phase. can be formed by contact, no vigorous mixing or emulsifying mixing is necessary. (emulsification The term mixed gender is typically used for the production of conventional emulsifier-containing emulsions. Vigorous mixing required, portex, homogenizer, blender, mill etc. Concerning mixing by ) The emulsions and polyphasic emulsions of the present invention are It can be formed by adding an aqueous phase to the glass when desired. This glass is Under suitable storage conditions it can last for a long time (several months) without any adverse effects. Can be stored.

The term "stable emulsion" refers to mixing by portex, homogenizer, etc. from two liquid phases prepared (without emulsifiers) by mixing or other emulsifying mixtures. dispersion, at least with respect to destruction or coalescence. refers to a liquid-liquid dispersion system that is more stable over time. Depending on the liquid phase involved, non- Stable dispersions typically coalesce within minutes or hours.

A stable emulsion does not coalesce for several hours to several days, depending on the ingredients. It is stable. When using the term "stable" for polyphase emulsions, the same Various meanings are intended. The stable oil-in-water emulsion of the present invention (when properly stored) be stable for several months without coalescence, phase separation, or destruction (if was observed. The stable water-in-oil-in-water emulsions of the present invention have a low It was observed to be stable for 0 days.

Oil-in-water or water-in-oil stability can be determined by following changes in emulsion turbidity. can be experimentally monitored by Such measurements determine the particle size in the emulsicon. This means that you are tracking the The decrease in turbidity accompanied by phase separation observed with the naked eye is Showing the destruction of the mullion. Experimental evaluation of the stability of polyphase emulsions is more complex. It's rough. Most generally, stability is defined as the loss of internal phases to external phases. , for example, as the loss of the internal aqueous phase to the external aqueous phase in a W10/W emulsion. can be evaluated. Stability is determined by the size of the oil droplet Davis et al. (1976) J, P herm, Pharmacol, 5uppl 28:60P), and oil Size distribution of drops and internal water droplets (Davis and Burbage (19 77) J, Co11oid Interface Sci, 62:361 ) shows a correlation. Stability by measuring the number and size of droplets inside a multiphase over a period of time Microphotographic methods can be used to evaluate. The stability also depends on the internal droplet Decay can be assessed by the release of certain marker compounds (Magda ssi et al., 1984; Florence and Whitehill, 19 82; Davis and Walker, 1983) o Kita et al. (1 977) J, Cotroid Interface Sci, 62:87 -94 used viscosity measurements to evaluate the stability of multiphase emulsions.

The self-emulsifying glass of the present invention containing PvP as a matrix compound can be and was found to work even after exposure to autoclave pressure . Emulsions prepared from PvP glasses are also resistant to autoclaving. It was stable. This indicates that the self-emulsifying glass of the present invention has a small number (and some After preparation, it can be sterilized with an adverse effect on the emulsion-forming function. shows.

Self-emulsifying glasses are produced using a solvent method, which involves It is believed that liquid oil forms a dispersed glass. This method is water-soluble and non-surfactant. The matrix compound of the oily substance, and the matrix compound is dissolved and including combining with a sufficient amount of solvent to form a combination.

The solvent is then removed from the combination, preferably using reduced pressure, to form a glass get a Removal of the solvent is preferably carried out by rotary evaporation.

Upon removal of the solvent, the glass forms as a foamy solid, film or powder. Ru. Glass can retain some residual solvent. Another method is to use a matrix compound or and the addition of a solvent that dissolves both the oily substance and the oily substance. This method suitable when the chemical compound is PVP and chloroform is used as a solvent. Can be used. This alternative method is useful when the oily substance is a water-in-oil emulsion. isn't it. When combining water-in-oil emulsions with matrix compounds, water or or an aqueous solution is preferred.

In the present solvent method for the preparation of self-emulsifying glasses, the matrix compound is combined with sexual substances. The weight ratio of Madol, Cus compound to oil in the oily substance is (preferably about 2:1. If a two-phase emulsion system is desired, If so, the oily substance is essentially an oil. If the oily substance is a water-in-oil emulsion, e.g. When the It can become up to. The oil in the emulsion oil phase is correspondingly reduced.

The key to optimizing the quality of self-emulsifying glasses is to This is the weight ratio. When the water-in-oil emulsion is the oil phase, the matrix The weight ratio of to oily material can be as low as about 1.2:1. Mad l look When the weight ratio of compound to oil is lower than about 2=1, the The glass may be coated with residual oil. This residual oil can be removed by adding an aqueous phase to the glass. However, some of the emulsions that are formed are not necessarily incorporated. Separate residual oil may remain as a non-dispersed phase, which is undesirable for some applications (λ. The weight ratio of Trix compound to oily substance is about 2:1 to 20:1. more preferably, the ratio is between about 2:1 and 10=1. stomach.

Preferably the solvent is such as to avoid substantial long-range molecular order in the resulting solid. and removed from the combination. In other words, the solid produced is glass. It should be.

The rate of solvent removal is faster than the rate of crystallization of the IJ Fuchs compound from solution. If so, it is conceivable that this can be achieved.

As mentioned above, fine quality regions in the glass are acceptable and do not impair self-emulsifying ability. With no glass, it is rather preferable.

Substantial long-range order due to crystal formation can affect self-emulsifying ability. The gas of the present invention Preferably, the laths do not include substantial long-range order. In particular, glass exhibits X-ray diffraction be determined to be amorphous by a method, that is, less than about 10% by weight of crystalline is preferable.

The solvent is preferably used until an apparently dry solid, foam or film forms. , it is removed from the combination.

In some cases, for example when using trehalose as a matrix compound, , it may be impossible to obtain a completely dry solid in appearance. have a damp appearance The glass can function as a self-emulsifying glass. Extended solvent removal Substances that remain syrupy after removal will give an emulsion when the aqueous phase is added. do not have. Mannitol and hiculcose were prepared by this solvent method using water as the solvent. When processed, a syrup like this was produced.

of the solvent from the combination of matrix compound and water-in-oil emulsion. The zero self-emulsifying glass produced by removal has a dry appearance. However, this The glass retains an internal aqueous phase that is not removed during solvent removal.

The process of the present invention results in a self-emulsifying glass; No stable emulsion is formed.

This glass is a dry emulsion, as the term is commonly used in the field. Or not preemulsicon. Formed from matrix compounds and oily substances The resulting combination is not a stable emulsion.

Typically, the solvent method processing steps of the present invention may be performed near room temperature. Processing is preferable is carried out at a temperature below about 50°C. In processing using solvent methods, the matrix compound , avoid the use of high temperatures that can break down oils or decompose or inactivate active ingredients. Ru. Solvent methods avoid temperatures at which the matrix compound melts or decomposes. this The process should be carried out at a temperature below the melting point of the matrix compound. Main feature of this invention Most Trix compounds melt at temperatures above about 140°C.

As mentioned above, the methods and compositions of the present invention may be used in which temperature-sensitive active ingredients are used. This is particularly useful when As used herein, the term "temperature sensitivity" refers to the active ingredient partial or complete inactivation with respect to any adverse effects of temperature on Includes partial or complete degradation, or partial or complete denaturation. be The active ingredients of seeds, especially some biological substances, are sensitive even at room temperature. present invention method limits the exposure of such active ingredients to higher temperatures. , useful.

Such solid-liquid dispersions also combine liquid oil with a melt of a solid matrix compound. In other words, by the melt fusion method, It can be manufactured as follows. The combination of molten solids and liquid oils is difficult to measure. Completely amorphous materials can be produced without even the slightest possible qualities. Sugars, two types, sweeteners Any matrix compound of the invention that is a sugar alcohol or a sugar alcohol can be melt-fused. Must produce a self-emulsifying glass when combined with an oil-based substance by law . Melt fusion methods are also not successfully processed by the water-based solvent method of the present invention. self from lactose, glucose, maltose, mannitol and sorbitol It must be applicable to the formation of emulsifying glasses. Matrix compounding in melting method Quite high temperatures (above about 100°C) must be used to melt things. Therefore, there are significant disadvantages compared to the solvent method. The melt method also allows temperature-sensitive components It is not preferable to use it in the preparation of glasses containing PVP, cellulose derivative or by melting (or at a temperature close to the melting point), including maltodextrins Compounds that decompose are preferably used as matrices in melt fusion methods Never. Melting methods are preferred for producing glasses containing temperature-sensitive active ingredients. do not have. At temperatures higher than room temperature, the pharmacologically active ingredients of ) become inactivated or decompose. More active ingredients in the matrix compound (for sugars and sugar alcohols, the temperature required to melt the at higher temperatures), it becomes (completely or partially) inactivated or decomposed. deer However, the melt method limits the range of matrix compounds to at least sugars and sugar alcohols. may be useful in that self-emulsifying glasses can be prepared from them. Ru. However, melting methods are not suitable for preparing self-emulsifying glasses, including water-in-oil emulsions. Not applicable.

Because these secondary emulsions cannot be stable at the required high temperatures. It is from.

The glasses of the invention can be used in drug delivery, cosmetics, food and food additives, personal care. - products, toxic and hazardous waste treatment, and continuous extraction systems. It can be used for various purposes. The glass of the present invention can dissolve compounds that are only slightly soluble in water. To increase solubility, to increase the absorption of drugs, to mask unpleasant tastes, Water-soluble compounds can be acidified and basicized to protect compounds that are sensitive to moisture. to protect against the environment, to prevent gastrointestinal irritation, and of various compounds. Can be used to reduce toxicity.

The glasses of the present invention can be used as delivery agents for many active ingredients that are oil-soluble or water-soluble. It can be used as The active ingredients here are transferase inhibitors, cephalosporins phosphorus, chemotherapeutic agents, anticoagulants, thrombolytic agents, colony stimulating factors, dismutases, Erythropoietin, human growth hormone, enzymes, vaccines, interferon, Interleukin, monoclonal antibody, peptide, insulin, L)l-R ) I analog, tumor necrosis factor, factor VII [factor, epidermal growth factor, insulin-like Including growth factors, rCD, and other drugs.

Embodiments of the present invention are useful as drug delivery agents while protecting active ingredients from degradation. Protects, helps limit toxicity, and even helps mask unpleasant tastes. be. The glasses of the invention also include insulin and LH-RH analogs. can be used to orally administer peptides and proteins.

Lll-RH analogues include gonadal drugs such as leuprolide. A stimulatory hormone-releasing hormone that is useful in the treatment of advanced prostate cancer. Book The invention provides stable solid-phase drugs that can be administered orally, including peptides including insulin. can be used to prepare a It can be resolved.

Similarly, the present invention describes the safe use of ceftriaxone. Achieving stable solid-phase orally administered drugs. Ceftriaxone is the drug of choice for gonorrhea. - Enterobacter%5erratia.

against infections caused by Nfluenza and other bacteria. is also a widely used third generation cephalosporin. ceftriaxo Although it is easily soluble in water (approximately 40g/10+gl at 25℃), it is unstable in acids. Not active orally.

The present invention also provides stable solid phase excipients for the delivery of lipoxygenase inhibitors. It can be used to serve. Lipoxygenase inhibitors are a variety of arachidonic acid. It is a water-insoluble compound that inhibits the conversion to leukotrienes. leukotrienes It can be a mediator of asthma, allergic reactions, pain, etc. These compounds are Oral drugs are usually oil-soluble and have poor bioavailability. Preventing administration.

The glasses of the present invention allow for easy delivery of lipoxygenase inhibitors to the patient's system. ing.

The glasses of the invention also contain ACAT inhibitors (acyltransferasein). inhibitor), e.g. Belfosdil. used for. ACAT inhibitors block cholesterol absorption from the gastrointestinal system. It's a new class of compounds that cause harm. They are usually oil-soluble, but the gas of the present invention Russ is delivered orally in solid form.

How the invention can be used to mask substances that exhibit an unpleasant taste An example of this is the use of glasses of the invention containing acetaminophen. . Acetaminophen is a documented antipyretic with a bitter taste. It is a drug and analgesic. Its solubility is 1 g per 70111 of water, but its Taste is an obstacle to oral administration. Made according to the invention containing acetaminophen The manufactured glass masks this bitterness.

The glasses of the present invention may also be used with various drugs, such as labetalol. l) and beta-blockers such as trandate). Used to enhance absorption. Labetalol is used for hypertension and angina pectoris. It is a non-selective alpha and beta blocker used for This is water-soluble (approximately 20 mg /ll1) and is usually administered orally. However, this meridian is not available Only about 25% of the tea is metabolized by heavy snow during its first passage.

Similarly, the glasses of the present invention can be used for chemotherapeutic agents such as 5Fυ (5-fluorouracil). Used to enhance absorption of pharmaceutical agents. 5FU is a chemical that acts as an anti-metabolite It is a therapeutic agent. It is selected in combination with other drugs in the treatment of rectal cancer. It is an antitumor drug that is used to treat breast cancer, squamous cell carcinoma of the head and neck, and small cancers of the lungs. non-s all cell cancer, testicular and prostate cancer; Providing chemotherapy as the first choice for other treatments. It's an intravenous injection administered locally and locally.

Oral administration is desirable, but is currently not possible due to the high degree of excretion through secondary metabolism. It is. Its water solubility is 1 g in 80 parts of water, and it can be dissolved in aqueous solution by increasing the pH. The solubility of increases.

The glasses of the present invention are suitable for use with toxic drugs such as methotrexate and hydrochloride. Useful for administering chloretamine. Methotrexate (MTX) is an anti- It is a chemotherapeutic agent that acts as a metabolic agent. It is C in acute lymphoblastic leukemia. It is the anti-tumor drug of choice for NS prophylaxis. It is acute lymphoblastic leukemia, cervical Introduction in cervical cancer, breast cancer, non-Hodgkin's lymphoma and i<-Kit lymphoma and are the components of the combination of first choice for maintenance. Mechloretami hydrochloride Nitrogen mustard is an acylating agent called nitrogen mustard. That is MOPP (mechlorethamine, vincristine, procarbazine, prednisone) and The combination known as MOP (MOPP without prednisone) It is used as Namely, these are the two first choices for Hodgkin's disease. Used in therapy. It dissolves very well in water but is highly toxic. Its use is limited, and acute administration by intravenous injection is also limited.

The glasses of the invention when used as drug delivery agents can be used in dry powder form, capsules, etc. compressed tablet form, solid foam form and emulsion It can be administered to humans or animals in a variety of forms, including in the form of a gelatin.

Another use of the invention is in the field of blood substitutes. Fluorodecalin (Fluoro decalins> is used with blood substitutes that include perfluorodecalin. However, it requires unstable emulsions that require high levels of surfactants. There is a problem of forming a tunnel. Emuls of the invention using perfluorodecalin John is more stable and is formed without the use of surfactants. According to the present invention Many emulsions made by , thus providing a new blood substitute.

in many applications including enzymatic reactions and cleaning of toxic and hazardous wastes. However, there are problems with phase separation. Separation is often done in a series of batches. Ru. The emulsions of this invention are useful as continuous extractants.

For example, in enzymatic reactions, the emulsions of the invention may be used as waste or cell products. aids in the sequential separation of enzymes or cells. The emulsion of the present invention is made of heavy metals. Useful in continuous extraction systems to separate genera. For example, the system This creates a gradient that draws heavy metals into the internal phase of the emulsion. Separation is performed by Such systems e.g. A shift or chelation technique may be used. Related uses of the glasses of the invention include: Performed in the field of enzyme immobilization.

(Margin below) 1 fruit J Actual 501 P3jlb Rigaras no I° appearance Linear PVP (approximately 30.00 077) having a molecular weight>1. mixed with og. Analytical grade Add methanol in sufficient amount to dissolve all the PVP. Ta. This methanol was then transferred to a Buchi rotary evaporator with an upright condenser. By performing rotary evaporation using a vaporator, PvP- Oil-evaporated from methanol.

In addition, during rotary evaporation, Stirring was performed with a stirring bar in the flask.

A flaky solid was obtained. Approximately 2+al of twice-distilled water is added to approximately 200mg of this solid. Upon addition, an oil-in-water emulsion was formed.

Support plate 1 Sho -v + Glass -1 Mix sucrose (2.2 g) with enough double-distilled water to dissolve it. Ta. Heavy mineral oil (USP, >0.5g) was then added to this solution. Gentle heating (i.e., at a temperature below about 50°C), the rotor of this mixture Lee evaporation was performed. The resulting solid has a fluffy appearance. When about 2 ml of twice-distilled water was added to about 200 mg of this solid, , an oil-in-water emulsion was easily formed.

This oil-in-water emulsion incorporating sucrose was tested for taste properties (quali There is almost no sweetness in tative taste test) or Not detected.

Sotachigo 1 Sho -Olive' 1 glass -1 Sucrose (2.0 g), 0.5 g of olive oil, and enough amount to dissolve the sucrose. of double-distilled water. The resulting mixture dries and spreads onto the inner wall of the flask. The mixture was rolled until a well coated (11ned) transparent film was obtained. - Tally evaporated. Add enough double-distilled water to coat the film. In addition, an oil-in-water emulsion was obtained.

Must be added to certain self-emulsifying glasses to form oil-in-water emulsions A certain minimum amount of aqueous phase can be determined by qualitative visual observation or even quantitatively. can be easily measured by standard measurements. As is well known in the art, the external phase Oil-in-water emulsions, which are water or an aqueous solution, are similar in nature to the external aqueous phase. It has the bulk characteristics of a species. For example, is this emulsion visually oily? , or no oily texture. More quantitative analysis of whether water is an external phase The analysis involves adding a small amount of water-soluble colorant to the emulsicon. colorant is outside When dispersed in the external phase (i.e. when the emulsion is colored), the external phase It is in the aqueous phase.

The actual amount exceeding the minimum amount of aqueous phase added to form an oil-in-water emulsion The amount depends on what the emulsion will be used for.

Support A Carboxymethyl cellulose - Rigaras carboxymethyl cellulose (Plastic) Aqualon (Wilmington, Ware) and heavy mineral oil (USP) at a 4:1 ratio. were combined at a weight ratio of

Then double-distilled water in an amount sufficient to dissolve the carboxymethyl cellulose added. This combination was rotary evaporated to dryness.

By adding approximately 1 oaf of double-distilled water to this film, a viscous oil-in-water A mold emulsion was formed.

Shishigaoka i take progesterone Shiko -Safflower' Glass- Progesterone (0.5 g) was dissolved in 0.5 g of safflower oil. Sucrose (2, Og) was combined with progesterone-oil solution. Next, double distilled water is added to sucrose. was added in an amount sufficient to dissolve. The combination obtained in a flask with a stirring bar The nation was rotary evaporated to dryness. When combined with water, benefits The solids formed form an oil-in-water emulsion with progesterone in the oil phase. did.

A similar preparation was made using mineral oil in place of safflower oil. This progesterone was found to be more soluble in safflower oil than in mineral oil.

five points PVP-F’” glass-chloroform “linear PVP (molecular weight approx. 30.0 00> and heavy mineral oil (USP) were combined in a weight ratio of 4:1. This oil and PV Sufficient chloroform was added to dissolve both P. Bring the resulting solution to room temperature The solvent was evaporated and a dry solid was obtained. Dried water distilled twice In addition to solid matter, an oil-in-water emulsion was formed. Similar dry solids The solvent is removed by rotary evaporation. The prepared sodium cyclamate was thus combined with mineral oil in a weight ratio of 3.5:1.

Then add enough double-distilled water to dissolve the sodium cyclamate. added to the combination. This controller is equipped with a rotary evaporator. Bination color water was removed. A glassy solid was obtained. water to this solid An oil-in-water emulsion was formed by adding .

Soluble saccharin, i.e. saccharin sodium dihydrate, with mineral oil at 3.5: Combine in a weight ratio of 1 part and add enough water to dissolve the saccharin. The emulsified glass is then extracted from this combination by rotary evaporation. Prepared by removing water. Adding water to the glassy solid obtained An oil-in-water emulsion was prepared.

Cyclamate and saccharin based emulsions are Qualitative taste property direct test method g) was found to retain sweetness.

However, these emulsions have significantly lower sweetness than an equivalent amount of the sweetener itself. It had taste.

Yuko Soutane 95 Enol °'INHC and INNaO Emulsion of- A mixture of sucrose, heavy mineral oil (υsp) and double distilled water was heated in a rotary evaporator. A self-emulsifying glass was prepared by carrying out irradiation. This mixture and The weight ratio of sucrose to mineral oil in the resulting product and in the glass was 4:1. there were.

An amount between about 1001 g and about 200+*g of this solid is dissolved in 95% ethanol water. solution, about 1 ml each of 181 (C1 and 1) l Na011 and about 2 Il Mixed with an amount between 1. In each case, a stable oil-in-water emulsion is formed. It was.

This 95% ethanol, Na0tl and HCI sucrose-mineral oil emulsion was sealed. It was stored in a sealed container at room temperature for one week. During that period, any of these emulsions No phase separation was observed in the sample.

A similar emulsion is made by adding absolute ethanol to a self-emulsifying glass solid. Attempts to prepare emulsions did not form. This glass is water free It did not dissolve or appear to be hydrated in ethanol. this glass remained at the bottom of the container. No oil release was observed.

These results demonstrate that the emulsifier formed from the self-emulsifying glass of the present invention is Under conditions that normally break down surfactant-containing emulsions (addition of alcohol, high p H) shows that it is very stable. Furthermore, the weight of the water content of the aqueous phase The major change is that of compromising the emulsion composition. outside is acceptable, but at least the aqueous phase to ensure emulsion formation. There must be a small percentage of water. It's obvious.

1st ■1 Cane sugar and castor oil were combined in a weight ratio of 2=1. To dissolve this sucrose A sufficient amount of double distilled water was added. Rotary evaporate the resulting mixture A dry, non-oily solid was produced. Approximately 200 m of this dry solid glass g was added to approximately 2 ml of double-distilled water to form an oil-in-water emulsion.

This emulsion is then frozen at about -7°C and thawed at about 25°C. was performed consecutively at least 40 times. This emulsion is produced by this process. Not destroyed. After each freeze-thaw cycle, light scattering, i.e. emulsion The particle size function of the Bausch and Lomb spectrophotometer 100 (Bausch and Indirectly using Low + b Spectrophotometer 100) was measured. This repeated freezing-thawing cycle changes the particle size of the emulsion. had no effect.

L1 Takumi Royal Shower emulsion By using self-emulsifying glass with sucrose and mineral oil in a 6:1 weight ratio, Prepared as described in Example 2. Add distilled water or normal saline to this glass. Additionally, an oil-in-water emulsion was prepared. Furthermore, the physical relationship between oil, sucrose, and water milk mixture (in a similar weight ratio to the emulsion prepared from glass) for 20 minutes. subject to oxidation mixing, that is, with vigorous vortex mixing. ing) Dispersions were manufactured (400nm The turbidity was compared as a function of time (up to about 22 hours). double distilled A control tube containing 3 ml of water was used to compensate for drift in each permeation measurement. Corrected.

The particle size of the emulsion is determined by the turbidity of the sample. more sun Turbidity in the pull indicates breakage of the emulsion or disruption of the dispersion. decrease. Changes in particle size are distinguished from breakage of the emulsion. why If so, the breaking of the emulsion is accompanied by visible phase separation.

Results of turbidity measurements in emulsions and dispersions containing mineral oil and sucrose. The results are shown in Figure 1. Emulsions prepared from glasses are produced with visible phase separation. It was found that the dispersion was considerably more stable than the dispersion in which a decrease in turbidity was observed after 5 to 10 minutes. Ta.

Water-based emulsions exhibit constant turbidity for 4-5 hours, after which the turbidity decreases over time. It declined gradually. In contrast, standard saline emulsions have approx. After 10 minutes, the turbidity decreased even more rapidly over time. But minutes Compared to a dispersion, this emulsion is also destroyed due to the lower turbidity. There wasn't. No phase separation was detected during the experiment.

The significant decrease seen in turbidity is due to the particle size in the emulsion with time. This is thought to result in a reduction in the size of the

When normal saline is employed as the aqueous phase, this effect is short-lived (less (both in terms of speed) and even more remarkable.

Upper five branches PvP: v Emulsion Heavy mineral oil (USP) and linear pvp <molecular weight approximately 30,000) at 1:5 weight They were mixed in quantitative ratios. Add enough analytical grade methanol to dissolve the PvP. , added to the oil and PvP combination.

The resulting mixture was rotary evaporated to remove methanol. obtained The solid (100 mg) was combined with approximately 3 liters of double-distilled water to create an oil-in-water emulsion. tion was formed.

For comparison with the above emulsion, heavy mineral oil (USP) and linear PVP (wt. dispersion in distilled water (same volume as used in the emulsion) in a ratio of 1:5). , prepared as follows. In other words, the combined ingredients are colloid milled (temperature controlled). or maximum turbidity (assessed by visual inspection). It was prepared by stirring until it was mixed. These dispersions do not contain emulsifiers and showed a suitable comparison to non-emulsifier based oil/PVP emulsions.

The turbidity of the emulsion [transmittance (%) at 400 nm] and the The two prepared dispersions were incubated for up to about 22 hours as described in Example 10. Measured as a number. and that the system is subject to any physical change, e.g. For example, visual observations were made for phase separation. Formed from PVP versus oil self-emulsifying glass The emulsion prepared was significantly more stable than any of the dispersions prepared. stirring Both in the dispersion obtained by stirring and in the dispersion prepared in a colloid mill. , a rapid phase separation was observed within almost 5 minutes. In contrast, this emulsion tion was found to be stable for at least approximately 20 hours of founder separation.

A very gradual decrease in the turbidity of the PvP versus oil-based emulsion was observed over a period of about 7 hours. It was observed standing up. This decrease in turbidity is not accompanied by any visible phase separation and is therefore No significant destruction of the mullion was demonstrated. Emulsion gradually over several days John became visually transparent. This clearly indicates the particle size in the emulsion. This is the result of the reduction in

real ff One stitch of emulsion A portion of the double distilled water was added to the self-emulsifying gas prepared by the method described in Example 2. It was added little by little to 0.4615 g of rice. Add water to conductivity of the sample obtained Measured every degree. The conductivity is the resistance value measured with a Fluke 73 multimeter. Obtained from. The data are summarized in Figure 2. In Figure 2, the conductivity of the sample is at 25°C. The conductivity of water is shown in comparison to that of water.

Conductivity results obtained from emulsions formed from self-emulsifying glasses are consistent with known A unique pattern is observed when compared to similar measurements of standard emulsions containing emulsifiers. It shows.

According to FIG. 2, it can be said that the electrical conductivity increases as a function of the weight fraction of water.

As shown in the shaded area in Figure 2 (approximately 90% to 96% water), there is a region where the conductivity fluctuates. be observed. In this region, the conductivity of the sample is either conductive or non-conductive. fluctuate between Reasons for this variation in conductivity in the emulsion of the present invention It is not clear. Water-in-oil emulsion and oil-in-water emulsion No variation is observed in relation to the transition between. Weight of water at which fluctuations are observed The exact range of fractions depends on the matrix compounds and oil content of the self-emulsifying glass. It was thought that it differed depending on the relative amount of (In some cases, many variables The dynamic range was observed as a function of water weight. of these emulsions Although the phenomenon of conductivity fluctuations is not well characterized, these fluctuation regions is assumed to be related to the presence of a liquid crystalline phase in the emulsion of the invention. Either However, it is important to note that there are relatively large regions of varying conductivity, and that in some cases However, the presence of multiple regions where such fluctuations occur is a sign of the self-emulsifying glass. It is thought to be unique to emulsions formed from

Discontinuities in conductivity are caused by percolation transitions. ) has been observed in microemulsions related to (Legues and 5 (1980) Phys, Chet 84:3503). My The leaching of the chloemulge depends on the length of time it lasts and the hardness of the interface. has been reported. (de Gennes and Taupin (1982) J , Phys, Chet 86:2294; Law et al. (19g?) J, Co1 1oid Interface Set, f20:30; and Guest (1985) J, Physique Lett, ■: L-1055).

In contrast, water-in-oil to oil-in-water emulsions containing emulsifiers The change to Marsicon is abrupt, as indicated by a rapid shift in conductivity. It is reported that there are (K, 5 hinoda, H, Arat (1967) J, C o11oid 1nterface Sci, l:429).

The relative conductivity of the emulsion of the invention above the "fluctuation" region is less than 1. It's also big. That is, the conductivity of the continuous phase is greater than the conductivity of the bulk water. this is , possibly due to the formation of liquid crystals, due to emulsion particles when the water content is high. This places an orderly or structural burden on the external phase of water, which makes the aqueous phase more This is thought to be because it easily conducts current. The conductivity in the area below the fluctuation range is Lower values are associated with more complex structures and lower entropy.

Jitsu 11 Ranjo”- 1 m of distilled water distilled 52 times by 1° of emulsicone 1 to 552.411 g of the sila sugar-mineral oil solid prepared by the method described in Example 2. The addition formed an oil-in-water emulsion. The obtained emulsion Stir at approximately 6 Orpm until minimum viscosity reading (approximately 1 hour).

Special Table Sen7-501259 (21) Additionally, the viscosity of the emulsion was measured periodically under minimal shear stress. The viscosity is Brookf 1eld cone/plate viscometer Set the spindle rotation to the minimum value of 0.3 rpm using Established. The spindle was rotated with a length long enough to allow viscosity measurements. The result Shown in Table ■.

Table 1 , - The purpose of the experiment was to determine whether the structure of the emulsion formed during preparation After application of force (60 rpm stirring), it was to be determined whether it was regenerated or not.

As shown in the data in Table I+, the emulsion slowly loses viscosity over time. It can be seen that this causes the destroyed structure to slowly regenerate.

The emulsion structure contains an oil core wrapped in a shell of sucrose molecules, and water molecules are Assuming that it is hydrogen bonded to the acid group, the results in Table 11 can be explained as follows. can be done.

The emulsion particles lose hydration during the initial shearing and therefore their viscosity decreases.

The hydrated structure is regenerated into the emulsicon, all the while increasing its viscosity. Shear response Emulsion grains that can restore the destroyed structure by applying force The stability of the emulsicone particles observed by the ability of the particles to break down and the failure due to shear stress. The resistance to destruction can be rationally explained.

Support craftsmanship earthworks ゛'Toshite Shiko゛　゛　゛　゛　　゛　　゛　゛　　゛　　゛　゛　　゛　゛　　゛　゛　゛　゛　゛　゛　゛　　゛　゛ The viscosity of the sugar-mineral oil emulsion as a function of temperature compared to the control sucrose solution. The viscosity of For the emulsion, 1 ml of twice-distilled water was added to Example 2. It was prepared by adding it to 0.5224 g of glass prepared by the method described in . S The sucrose solution was prepared in an amount equal to the amount of sucrose present in 0.5224 g of said glass (0. , 450 g) in 1 ml of water. Then increase the temperature to 40 The viscosity of both samples was measured while decreasing the temperature from °C to 5 °C. all viscous The spindle speed is measured using a Brook cone/plane viscometer. The temperature was set to 6 Orpm. The results are shown in Table I+.

(Margin below) Table II table! From the result of (2), the viscosity of the emulsion becomes smaller than the viscosity of the sucrose solution as the temperature decreases. It can be seen that the rate also increases rapidly. The viscosity of the sugar-mineral oil emulsion decreases with temperature. of the emulsion by increasing relative to the viscosity of the sucrose solution as a function of The structure is more complex than that of a sucrose solution.

The data show that as the emulsion cools, an additional degree of hydration force of 5 is applied. consistent with theory.

real fl The average of 7 Emulsion Oil-in-water emulsion prepared from self-emulsifying glass with a 6:1 ratio of sucrose and mineral oil. The viscosity of the solution was determined as a function of shear rate at 25±0.2'C. The conclusion of this study The results are shown in Figure 3. The viscosity is high at low shear rates (0,3 rp+*) (30 cps), the shear rate increases; it tangles and decreases. The macromolecule is this sea 11i completely absent in emulsions based on Therefore, thixotropic You cannot expect to observe behavior. Observation of thixotropic-like behavior is due to emulsion as a result of an ordered structure, e.g. associated with the formation of liquid crystals, in , can be explained.

Branch supervisor earthworks vP-′ emulsion size Heavy mineral oil (UPS, 0.25 g) was mixed with 1.25 g of linear PVP <molecular weight approx. 3 0,000) and approximately Zoo+al of analytical grade methanol.

This mixture was then rotary evaporated until dry. a few milligrams Water was added to the resulting solids of rum to form an emulsion. emulsion particles particle size +i, measured on a Hiac/Royco particle size analyzer, approximately 0.5 and and about 5.0 micrometers, with an average of about 4 micrometers.

Soketsu Masujou PvP-゛ Emulsion 5 To determine the rate of emulsion formation from the solid of Example 16, double distillation was carried out. water (31) was added without mixing to the solid sample (127.5 mg) at 0:00, The turbidity of the sample was measured. The absorbance of the samples was measured periodically. Table II+ shows the results. Summarize.

Table I+1 A plateau in absorbance after a period of time indicates that emulsion formation is complete. shows. These data demonstrate that emulsions can be formed without mixing the components. It shows.

The data also show that a wavelength of 400 nm produces the Tyndall effect due to emulsion particles. It is also shown that Therefore, the particle size in the emulsion is 400 rv There must be at least some particles larger than (0.4 μm). emma The lusion is cloudy and larger than 0.05μ (the minimum that can be observed with the naked eye). Indicates the presence of particles of the same diameter.

After the above measurements, the samples were stored at room temperature for 2 weeks. After this period, the emulsion It was observed that the sample became transparent even without separation. This means that when Over time, the particle size of the emulsion decreases to less than about 0,05 μm. It is further shown that emulsions with large particle sizes are formed.

Fruit 1 vice [ Shopam and Shopam's X manufactured by the method of Japanese invention X-ray diffraction patterns of the prepared sucrose-mineral oil solid and a simple mixture of sucrose and mineral oil. I got it.

Each sample contained sucrose and heavy mineral oil (IJSP) in a weight ratio of 3.5:1. was. In sample 1, the oil and sugar were mixed manually. In sample 2, dissolve the sucrose and then as described above in this example. The water was removed by rotary evaporation to produce a self-emulsifying solid.

Each sample was then packed into a 1 x 3 am sample hole and packed into a US powder tube. Scintag/USA Powder) X-ray diffractometer and Cukα, a wavelength of 1.54 angstroms, and a scan rate of 3°C/min. I measured it. FIG. 4 shows the diffraction diagram of each sample.

This diffraction pattern shows that sucrose in a simple mixture maintains its crystal structure as expected. and In contrast, the treated sucrose and mineral oil glasses are rendered amorphous by this experimental method. It became very clear that this was the case. Based on the crystal structure, X-ray diffraction method shows that more than about 10% Long-range molecular order can be detected.

Sucrose-mineral oil solid emulsions with weight ratios of sucrose to oil of 2.5:1 and 4:1 We also measured the diffraction of the This self-emulsifying solid is also shown to be amorphous by X-ray diffraction. It became clear that

Real 11 Ran 1”- Approximately 200 mg of Emulsion Example 2 Approximately 2 Ill of double-distilled water is added to a sucrose-mineral oil solid emulsion of A mullion was formed.

Subsequently, an additional 21 ml of heavy mineral oil (USP) was added to the emulsion. Attachment The added oil was observed to immediately disperse into the system, with no evidence of phase separation. . Dispersion was accomplished without adding any work (eg, stirring) to the system. This example Therefore, it is not necessary for the oil to go through the method of the invention in order to dissolve into the emulsion particles. It shows that something is wrong.

The first emulsion was mixed with a fat-soluble surfactant: Ar1acel-C, 5pan80 Or 5pan 85 (Trademark ICI Americas Inc., USA) It was prepared by emulsifying heavy mineral oil and an aqueous solution to which was added. the surfactant is added to the oil and the mixture is passed through a Prinkmann homogenizer (with a small rotating blade). Brink*an Homogenizer) (Sybron Corp. homogenize for 60 seconds at 40 forces). Next, remove the aqueous phase by boiling I added it slowly. After the addition is complete, homogenize until the desired water-in-oil emulsion is obtained. Genized. 70% to 79% bwt/wt heavy mineral oil, 5.5% to 7.2% weight jl/wt surfactant (HLB 1.8 to 4.3), and 21% to 3 A 0% aqueous phase emuldicon was prepared.

Sucrose was combined with the first Who emulsion in a weight ratio of approximately 78:22. next Double distilled water was added to dissolve the sucrose. Rotary this combination It was subjected to evaporation (at about 5 mwHg). A frame with a combination The lasco was rotated on a rotary evaporator at approximately 17 to 25 rpm; The temperature of the flask was then maintained at approximately 32°C. A dry “foam-like” substance forms Drain and remove water from the combination until complete. Collect the solid as a powder It was stored in a desiccator at room temperature. This solid self-emulsifying glass is This method can be used for a relatively long time (weeks or even months) without losing its emulsifying properties. It turns out that it can be saved in

Addition of the aqueous phase to this solid forms a multiphase W10/11 emulsion. Ru. For example, 5 liters of water, 1N HCI, or 1N NaOH to 1g of solid When added to , a stable multiphase emulsion is formed. In contrast, its solid does not disperse in heavy mineral oil; this is because the density of the glass solid is greater than that of the oil. The solids settle to the bottom of the mineral oil container. This result indicates that the solid is in water or in an aqueous phase. 1) of the emulsion.

The crow was analyzed using differential scanning calorimetry. In that case, please refer to this specification. Ford and Tinuoins (1989) Phar mechanical thermal analysis Ellis Ho rwood Ltd., England. This was done using a known method (see Figure 5, thermogram). The glass transition of this glass is found to be approximately 57°C, and the recrystallization of sucrose is approximately 120°C. Finally, at approximately 185°C, all the crystalline sucrose was observed to become a glass melt. did.

DSC analysis was performed on self-emulsifying glasses produced using sucrose and mineral oil.

DSC thermogram of sucrose-mineral oil glass shows glass transition, sucrose recrystallization and Thermogram A of Figure 5, sucrose/first emitter, where the characteristics of sucrose melting are observed. It is similar to the thermogram of Luchon glass. P on the melting of crystalline sucrose The relative size of the glass will vary depending on the amount of fines in the glass. DSC measurement can be easily used in practice to measure the amount of fine particles in individual glass samples. Ru. Glass transition temperatures can vary depending on the exact composition of the glass.

A DSC thermogram of a physical mixture of sucrose and mineral oil shows no glass transition. Not shown. The thermogram is characteristic of the melting of crystalline sucrose at about 185°C. It only contains

A first emulsion was prepared as described in Example 21. 3% (weight/weight A mixture of sucrose containing maltodextrin in an amount of about 78: 22 and sufficient water to dissolve the sucrose-maltodextrin. Dissolved.

Removal of water by rotary evaporation produces dry solids that come into contact with the aqueous phase. It was found that a W10/W emulsion was formed. For example, 5 ml of water, I When NHCI, IN Na01+ is added to 1 g of solid, a stable multiphase emulsion is formed. A mullion is formed.

The glass was analyzed using differential scanning calorimetry (see Figure 5B). this glass The glass transition temperature of was significantly increased compared to the sucrose-containing glass of Example 21. (until the temperature exceeds about 180'C). No recrystallization of sucrose was detected; and observe the crystalline sucrose in the glass melt. Ma to sucrose carrier The addition of rutodextrin produces a higher glass transition temperature than sucrose alone.

Higher glass transition temperatures are associated with increased stability of self-emulsifying systems in the solid state; and extend the shelf life of these glasses and products based on these glasses. It seems that it does.

Actual 11 skin appearance emulsion 90 Water-soluble and/or fat-soluble dyes can be added to emulsions formed from these glasses. In order to investigate the structure of the compound, it was incorporated into self-emulsifying glass.

The first emulsion was prepared with heavy mineral oil and surfactant as described in Example 20. It was prepared as follows. Add the fat-soluble dye D&C Purple 2 to the oil phase, and add the water-soluble dye FD& C Red 17 was added to the internal aqueous phase.

Prepare a sucrose/first emulsion glass containing both dyes and add water to it. was added to the glass to form a W10/W emulsion. Next, that emulsion Examine the sample under the microscope (400x magnification) and visually observe the red internal phase and blue-gray oil. It was found that it contains phases. Droplets of three types of w1o7w emulsion Observed in mullions. i.e., smaller inner droplets surrounding one larger inner droplet. droplets with a large external droplet (type A), a larger one with a smaller multiphasic internal droplet droplets (type B) consisting of a large external phase, and an innumerable number of small Droplets with a homogeneous, larger external oil phase containing water droplets (type C).

Type A, B, and C droplets were previously described as multiphase emulsions. (see Florence and Wbitehill (1981)).

The multiphase emulsions formed based on sucrose that were investigated showed that approximately 80% of the results were based on type. It consisted of droplets. The rest are either type B or type C droplets. .

The particle size of the W10/W emulsion formed based on these sucrose is was measured as a function of time after John preparation.

Particle size measurements were taken at the time of preparation, 7 days after preparation and 30 days after preparation. workman The average diameter of the outer and inner membranes of the emulsion droplets is immediately after emulsion preparation. 12.4 each! microns and 3.9 microns. These diameters are There was no significant change after 7 or 30 days of preparation. The emulsion is Also, visually inspected under a microscope 60 and 90 days after preparation, and It was found that it remained in its original condition.

glass out The following general procedure uses a water-soluble non-surfactant matrix compound (polymer) of the present invention. (polymer or non-polymer) and especially sucrose, fructose, trehalose, cyclam malt, saccharin, and water-soluble polymers PVP cellulose derivatives and malts Any water-in-oil emulsion containing dextrin may be used.

The first water-in-oil emulsion is prepared using a conventional method known in the art using a fat-soluble surfactant. Formed by law. Suiko Marujo surface active agent is used. anionic, positive Ionic or nonionic surfactants may be used. The aqueous phase is mixed with oily substances. and surfactant and the first W10 emulsion, mix vigorously. (i.e. emulsion mixing) to form.

Once the first emulsion is produced, it is mixed with the desired matrix compound and its of the aqueous solution in an amount sufficient to dissolve the matrix. Next, the resulting transformation Removes water from the compound, creating a dry-looking foam or thin film. dry The apparent solid turns out to be a self-emulsifying glass. enough water to fill the glass Adding a phase creates a stable multiphase emulsion (i.e. W10/W emulsion) form. Table IV lists the preparations of self-emulsifying glasses containing water-in-oil emulsions. A representative list is provided. various vegetable or hydrocarbon oils, especially tow Sorghum oil, bean oil, olive oil, safflower oil, soybean oil, castor oil and mineral oil was used in these examples.

No significant differences were observed between these oils. Oil in the first emulsion used The phase ratio (V/V) of the water sealing phase ranged from approximately 4=1 to 2=1. Illustrated glass, a nonionic surfactant with the indicated ILB value, e.g. Arlacel C (Arlacel C) (trademark) was used. Particularly illustrated matrix compounds The product is sucrose, PVP and a mixture of sucrose and maltodextrin.

In particular, the weight ratio of the emulsion to matrix is about 1:1 to 9:1. range (typical weight ratios of matrix to oil from about 1.2:1 to about 10 :1 range).

In each of the combinations listed in Table IV, the addition of an aqueous phase creates a multiphase emulsion. A self-emulsifying glass was formed.

In some exemplary systems, the active ingredient was mixed into the aqueous phase of the first emulsion. 1st The aqueous phase of the water-in-oil emulsion is the aqueous water-in-oil emulsion inside the W10/W emulsion. phase (that is, the second aqueous phase). water soluble such as dyes and drugs Active ingredients are illustrated. The aqueous phase of the first emulsion has a pH of 10 to 1. and may include inorganic salts. The oil phase of the first emulsion is also commonly It may also contain active ingredients, which are usually fat-soluble.

Surfactant Arulacellu C () ILB 3.7, Trademark ICI Americas A first emulsion is created by emulsifying heavy mineral oil and an aqueous solution to which Rougeon was prepared. The aqueous phase is 0.0614M or 0.0614M of canrenoic acid 4 salt. 439M. Adding surfactant to oil and mixing it A Prinkmann homogenizer (Sybron Cor) with a small rotating blade homogenization for 40 to 60 seconds. next, The aqueous phase was slowly added to the oil phase. After the addition is complete, the desired water-in-oil emulsion is obtained. Homogenization was continued until the The first emulsion contains approximately 71.4% mineral oil; It contained about 21.4% aqueous phase and about 7.1% surfactant. Sucrose is The first W10 emulsion was combined in a weight ratio of about 78:22. Then distilled twice Water was added to dissolve the white sugar. Rotary Evaporation ration to produce a dry "foam-like" solid. add water to the solid , resulting in a W10/11 emulsion. Immediately after preparing the emulsion, infrared When examining the external aqueous phase of a multiphase emulsion using a photometer, it was found that canrenonic acid was present in the external phase. total (not detected). Canrenonic acid was found to be more active in multiphase emulsions as a function of time. Released slowly from the internal phase. Multiphase emulsions such as those illustrated are suitable for sustained release drugs. It can function as an agent delivery system.

Actual temperature LLi OW emulsion I- A concentrated solution of lipoxygenase inhibitor dissolved in olive oil in a flask. It was created. PVP is added in a ratio of 8.4:1:PVP:oil solution. The water Add until PvP is dissolved, resulting in a two-phase system. Next, pour the water into a rotary evaporator. Remove using a rotator to form a solid foam-like substance. Water or other aqueous phase When added to a solid, it produces a stable O/Vl emulsion.

A concentrated solution of lipoxygenase inhibitor dissolved in olive oil in a flask. Create. Add PvP at a ratio of 8.4:1::PVP:oil solution. Chrollo Add foam until PVP is dissolved. The chloroform is then transferred to the rotor. Remove using a re-evaporator to form a solid foam-like material. water or other Addition of the aqueous phase to the solid produces a stable O/W emulsion.

ACAT inhibitor is dissolved in corn oil in a flask to create a concentrated solution. to be accomplished. Add PVP in a ratio of 3.5:1::PVP:oil solution. Water, Pv Add until P is dissolved to form a two-phase system.

The water is then removed using a rotary evaporator to form a solid foam-like substance. do. Adding water or another aqueous phase to the solid again produces a stable O/W emulsion. tion.

perfluorodecalin, an oil that can dissolve oxygen; lin), is completely gassed with carbon dioxide over water.

Then it was flasked with PVP (22% perfluorodecalin, 78% PVP). Mix in a pot. Cold water is added until the PvP is dissolved, resulting in a two-phase system. Next The water is removed using a rotary evaporator to form a foam-like solid. NaC 1 (0.6%), MgCh (0.02%), C1 (0.03%), sodium lactate Aqueous solution consisting of physiological saline containing thorium (0.31%) and glucose (0.1%) Add solution and allow to stabilize. /W emulsion is formed. Resulting oil-in-water emulsion Con may be used in blood substitute compositions.

L Sarako 11 U-eye Mulsion■- 70% vegetable oil, 7% Arlacel C and insulin, glycerin and A first emulsion of 23% aqueous solution containing cresol (2.5 mg/sl) was stirred. Prepare in a stirrer. PvP and 3.5:1::PYP:1st emulsion Mix in a flask at the following ratio: Add water until PvP is dissolved and form a two-phase system. do. The water is then removed using a rotary evaporator to form a solid foam-like Make it a substance. Adding water or other aqueous phase to the solid foam-like material results in stable W1 A 0/W emulsion results.

L family and 30 WOW emulsion I-1 70% soybean oil, 7% Arlacel C and 23% aqueous solution (ceftriaxose) A first emulsion containing 40% of water at pH 6,7 is prepared in a homogenizer. do. Then mix it with PvP and the ratio of 3.5:1::PVP:first emulsion. Mix in flask. Water is added until the PvP is dissolved, resulting in a two-phase system. Next The water is then removed using a rotary evaporator to form a solid foam-like substance. Ru. Addition of water or other aqueous phase to the solid results in a stable W10/W emulsion. menstruation.

``Shinshi-jo''''- WIEn emulsion 11- 70% heavy mineral oil, 7% Arlacel C and 23% aqueous solution (1,5% acetic acid) A first emulsion (containing tominophen) is prepared in a stirrer. That, PVP and 3.5:1::PVP: flask with a ratio of the first emulsion in the flask. Mix in a pot. Add water and PvP until dissolved to form a two-phase system. Then that Water is removed using a rotary evaporator to a solid foam-like material. water Alternatively, if another aqueous phase is added to the solid again, a stable W10/W emuldigon can be obtained. occurs.

70% bean oil, 7% Arlacel C and 23% aqueous solution (20+m g/ml of labetalol at pH 2 to pH 4). Prepare in modinizer. Then convert it to PVP and 3.5:1::PI/P: 1 part emulsion in a flask. Add water until PvP is dissolved. to form a two-phase system. The water is then removed using a rotary evaporator. , a solid foam-like substance. When water is added to the solid again, stable W10/W Forms an emulsion.

Support ■ Lord Yu WOW Emulsion V- 70% mineral oil, 7% Arlacel C and 23% aqueous solution (1,25% 5- The first emulsion of fluorouracil (5Fυ) at pH 8.0 was added to a homogenizer. Prepare in a neiser. Next, add it to PVP and 3.5:1::PVP:1st Emma Mix in a flask in the proportions of 1.

Water is added until the PvP is dissolved, resulting in a two-phase system. Then pour the water into the rotary Remove using a vaporizer to form a solid foam-like substance. water or other aqueous phase Addition to the solid again yields a stable W10/If emuldigon.

Support doctor 1↓ WOW Emulsion Vl- 70% safflower oil, 7% Arlacel C and 23% aqueous solution (1+eg/ +ml Methotrexate (2% bovine serum alcohol) A first emulsion (containing Bumin) is prepared in a homogenizer. Next This was mixed with PVP in a ratio of 3.5:1::PVP:first emulsion in a flask. Mix. Water is added until the PVP is dissolved, resulting in a two-phase system. Next, pour the water into -Remove using a tally evaporator to form a solid foam-like substance. water or Adding another aqueous phase to the solid again produces a stable W10/Vl emulsion. Ru.

moxibustion master WOW emulsion v:/VI117) - '70% light mineral oil, 7% Arlacel C or and 23% aqueous solution (2 mg/ra 1 mechlorethamine hydrochloride (+gech loretha + aine HCI) at pH 6), Prepared in a stirrer. Next, PvP and 3.5:1::PVP: 1st emal Mix in a flask in the following proportions: Add water until PVP is dissolved; It is a two-phase system. The water is then removed using a rotary evaporator and the solids are It is a foam-like substance. When water or another aqueous phase is added to the solid again, it becomes stable. Resulting in a W10/W emulsion.

70% vegetable oil, 7% Arlacel C and 23% aqueous solution (pH 7.1 etc.) The first emulsion of strong 10 MM zoline salt, 1% hemoglobin was mixed with a stirrer. Prepare inside. Next, add it to PvP and 3.5:1::PVP:1st Emulsico mix in a flask at the same rate. Add cold water until the PvP is dissolved and It is assumed to be a phase system. The water is then removed using a rotary evaporator and the solid A foam-like substance is formed. NaCl (C0-6%), MgCh (0.02%) , I [CI (0,03%), sodium lactate (0,31%), glucose (0 , 2%) to form a stable w1o7w emulsion. . The resulting water-in-oil-in-water emulsicon can be used in blood substitutes.

70% light mineral oil, 7% Arlacel C and 23% aqueous solution (0.06% urethane) A first emulsicon of Aze solution) is prepared in a stirrer. Next, PvP and 3.5:1::PVP:first emulsion in a flask. P Water is added until the VP is dissolved, resulting in a two-phase system. Next, pour the water into a rotary evaporator. Remove using a porator to form a solid foam-like substance. add water to the solid again This results in a stable W10/W emulsion.

Refreshing five masters WOW Emulsion X- Dissolved in 70% light mineral oil, 7% Arlacel C1 and NaCl for tonicity. 5 B/ml of 1. H-Rtl analogue and benzilua of 9 cabinets g/+*l A first emulsion of 23% aqueous solution consisting of alcohol is prepared in a homogenizer. make Next, mix it with sucrose and 3.5:f::shi*11f: of the first emulsion. Mix in a flask in proportions. Add water until the sima sugar is dissolved to form a two-phase system. Ru. The water is then removed using a rotary evaporator to form a solid foam-like substance. quality. Adding water again to the solid produces a stable W10/W emulsion. Jiru.

Actual 11 draw 1”- WOW Emulsion X! of- First emulsion of 70% light mineral oil, 7% Arlacel C and 23% 2N sulfuric acid The mixture is prepared in a stirrer. Next, add it to PvP and 3.5:1::PVP:1st Mix in a flask in proportions of emulsion. Add water until PvP is dissolved It is assumed to be a two-phase system. The water is then removed using a rotary evaporator, It is a solid foam-like substance. When water is added again, a stable W10/W emulsion , which is useful for continuous flow extraction of cationic toxic substances.

Real k WOW emulsion- 70% light mineral oil, 7% Arlacel C and 23% aqueous phase (10% EDTA). , prepared in a stirrer. Next, PvP and 3.5:1::PVP: 1st Emma Mix in a flask in the proportions of 1. Add water until the PVP is dissolved; It is a two-phase system. The water is then removed using a rotary evaporator and the solids are It is a foam-like substance. Adding water again produces a stable W10/W emulzidine. Similarly, it is useful for continuous flow extraction of toxic substances that can form complexes with chelating agents. It is for use.

Real J1 Masu 41 System with glass The self-emulsifying glass was prepared for use in sucrose and pharmaceutical applications and in the body by the method of Example 2. Prepared from a mixture with an oil suitable for administration, such as mineral oil. All preparations are , under conditions suitable for the preparation of human medicinal products. The ratio of sucrose to oil is At least about 2=1. Lipid-soluble active ingredients with pharmaceutical activity, i.e. fat-soluble The drug is dissolved in the oil phase prior to processing to form the glass. The treatment conditions are The activity of the agent should be substantially unaffected. The resulting glass is fat-soluble Contains active ingredients. The glass can be used as a solid drug substance for humans or animals. into capsules or other similar means suitable for administration. gala in capsule The amount of solids is adjusted to provide the desired dosage. Capsules are also suitable May contain fillers. Alternatively or additionally, the concentration of active ingredient in the oil phase can be adjusted to suit the desired application. May be adjusted to provide a range of amounts. The resulting capsule is then loaded with the desired dose of the pharmaceutical agent. It is administered orally to a human or animal patient.

The self-emulsifying glass prepared as described above containing a lipophilic drug can be used to prepare oral drugs. It can be used to prepare tablets for administration.

Bloody Solitary Land 1 ■Dan L 1 glass ゛ Self-emulsifying glass was mixed with sucrose for pharmaceutical use and internal administration by the method of Example 2. Prepared from a water-in-oil mixture suitable for All preparations are human drug preparations under appropriate conditions. The ratio of sucrose to oil in a water-in-oil emulsion is small. water-soluble active ingredients with pharmaceutical activity, i.e. water-soluble The sexual drug is dissolved in the aqueous phase prior to formation of the water-in-oil emulsion. The processing conditions are The activity of the drug should be substantially unaffected. The resulting glass is soluble in water. Contains sexually active ingredients. The glass can be used to deliver solid drugs to humans or animals. Incorporate into capsules or other similar means suitable for administration. glass in capsule The amount of solids is adjusted to provide the desired dosage. Capsules are also suitable may contain fillers. or in addition, the activity within the aqueous phase of the water-in-oil emulsion. The concentration of sexual components can be adjusted to achieve the desired dosage range. The resulting capsule , orally administered to a human or animal patient to provide a desired dose of a pharmaceutical agent. .

The self-emulsifying glass prepared as above containing water-soluble drugs can be used as tablets for oral drug administration. It can be used in the preparation of pharmaceutical agents.

Tribe medicine land There was glass 0- Mix the sucrose with enough aqueous solution to dissolve it. The aqueous solution is Contains water-soluble ingredients suitable for food preparation, including flavoring agents such as vanilla extract. Vegetable oil Added to this is an oil suitable for use in food preparation, such as: like perfume Fat-soluble ingredients are dissolved in oil before mixing with the sucrose solution.

The ratio of sucrose to oil is at least about 2=1. Remove water from the mixture In order to do this, it is subjected to evaporation to form a glass solid. Powder the glass solid , as well as other foods containing added sugar, soy sauce, spices, and leavening powder. Mix with ingredients. This mixture is then processed until required for preparation into the final food product. save. If desired, mix the mixture with water and make a cake or similar preparation. Make butter suitable for baking things. No eggs or other emulsifiers are necessary.

All documents cited above in the specification and examples are herein incorporated by reference in their entirety. It is used.

Those skilled in the art of emulsicone technology and drug delivery will appreciate the clarity set forth in the preceding examples. (i.e. glasses, emulsions, multiphase emulsions and drug delivery products of the invention) Alternative techniques, procedures, methods, and reagents other than It is recognized that these materials can be obtained or substituted. Alternative but functionally equivalent The reagents, solvents and methods are readily apparent to those skilled in the art and require no undue experimentation. It can be applied to the present invention without carrying out. All substitutes, modified products, equivalent products, etc. are included in the present invention. is considered to be within the spirit and scope of.

(Margin below) Bottle A (1/cm) -2,fLAr,'lf-person 79 *: a thin -3,51 FIG. 4B First move to beg (W/g) international search report -11-1-^ Marshal ni 11-? ! f/US91103F16&

Claims (1)

[Claims] 1. a self-emulsifying glass containing a mixture of an oil-based substance and a non-surface-active water-soluble matrix compound, the glass being from about 10% to about 60% microcrystalline as measured by a differential scanning calorimeter; , the glass is in contact with a sufficient amount of the aqueous phase A self-emulsifying glass that can form stable emulsions with. 2. The glass of claim 1, wherein the matrix compound is selected from the group consisting of sucrose, trehalose, fructose, cyclamate, saccharin, and mixtures thereof. 3. The matrix compound is selected from the group consisting of monosaccharides, disaccharides, and sweeteners. 2. The glass of claim 1, wherein the matrix compound is at least about as sweet as sucrose. 4. 4. The glass of claim 3, wherein the matrix compound is sucrose. 5. The glass according to claim 4, wherein the mixture further contains maltodextrin. vinegar. 6. The glass according to claim 1, further comprising a fat-soluble active ingredient in the oily substance. vinegar. 7. 7. The glass of claim 6, wherein the fat-soluble active ingredient is a temperature-sensitive active ingredient. 8. The glass of claim 1, wherein the oily substance is a water-in-oil emulsion. 9. 9. The glass of claim 8, wherein the aqueous phase of the water-in-oil emulsion contains a water-soluble active ingredient. 10. the weight ratio of the matrix compound to the oily substance is at least about 2; The glass according to claim 1, wherein: :1. 11. the weight ratio of the matrix compound to the oily substance is at least about 2; 3. The glass of claim 2, wherein the glass is between about 20:1 and about 20:1. 12. The glass according to claim 1 in powder form. 13. The glass according to claim 1 in solid form. 14. The oily substance may be fluorodecalin, mineral oil, peanut oil, vegetable oil, or 2. The glass of claim 1, wherein the glass is selected from the group consisting of corn oil, soybean oil, safflower oil, and olive oil. 15. A self-emulsifying glass containing a mixture of an oily substance and a non-surface-active water-soluble matrix compound, the non-surface-active water-soluble matrix compound forming a self-emulsifying glass. Compounds include polyvinylpyrrolidone, cellulose derivatives, maltodextrin, and less A self-emulsifying glass selected from the group consisting of sweeteners that are about as sweet as sucrose, and mixtures thereof, wherein the glass is capable of forming a stable emulsion when contacted with an aqueous phase. 16. 16. The matrix compound according to claim 15, wherein the matrix compound is polyvinylpyrrolidone. glass on top. 17. 16. The glass according to claim 15 in powder form. 18. 16. Glass according to claim 15 in solid form. 19. 16. Glass according to claim 15, containing a fat-soluble active ingredient in the oily substance. 20. 20. The glass of claim 19, wherein the lipophilic active ingredient is temperature sensitive. 21. 16. The gas according to claim 15, wherein the oily substance contains a water-in-oil emulsion. Russ. 22. 22. The glass of claim 21, wherein the aqueous phase of the water-in-oil emulsion contains a water-soluble active ingredient. 23. the weight ratio of the matrix compound to the oily substance is at least about 2; 16. The glass according to claim 15, wherein: 1. 24. The oily substance may be fluorodecalin, mineral oil, peanut oil, vegetable oil, or 16. The glass of claim 15, wherein the glass is selected from the group consisting of corn oil, soybean oil, safflower oil, and olive oil. 25. containing a mixture of oily substances and non-surface active water-soluble matrix compounds. A self-emulsifying glass, wherein the structure of the non-surface-active water-soluble matrix compound includes a tripartite group having electronegative atoms, polar bonds, and a hydrophobic region. A self-emulsifying glass containing tripartite glucophores that can form a stable emulsion when the glass is contacted with a sufficient amount of an aqueous phase. Russ. 26. 26. The glass of claim 25, which is about 10% (w/w) to about 60% (w/w) microcrystalline. 27. 26. The matrix compound according to claim 25, wherein the matrix compound is selected from the group consisting of sucrose, trehalose, fructose, cyclamate, saccharin, and mixtures thereof. glass on top. 28. 26. The glass of claim 25, wherein the matrix compound is selected from the group consisting of monosaccharides, disaccharides, and sweeteners, and the sweetener is at least about as sweet as sucrose. 29. 28. The gas of claim 27, wherein the mixture further contains maltodextrin. Russ. 30. 26. The gas according to claim 25, further comprising a fat-soluble active ingredient in the oily substance. Russ. 31. 31. The glass of claim 30, wherein the lipophilic substance is a temperature sensitive active ingredient. 32. The glass of claim 25, wherein the oily substance is a water-in-oil emulsion. 33. 33. The glass of claim 32, wherein the aqueous phase of the water-in-oil emulsion contains a water-soluble active substance. 34. 26. The glass of claim 25, wherein the weight ratio of the compound to the oily substance is at least about 2:1. 35. 26. The glass according to claim 25, which is in powder form. 36. The glass according to claim 25, which is in a solid state. 37. The oily substance may be mineral oil, peanut oil, vegetable oil, corn oil, soybean oil, safflower oil, etc. 26. The glass of claim 25 selected from the group consisting of banana oil and olive oil. 38. A self-emulsifying glass containing a mixture of an oily substance and a non-surface-active water-soluble matrix compound, the non-surface-active water-soluble matrix compound being selected from the group consisting of monosaccharides, disaccharides, and sweeteners; is at least about as sweet as sucrose, and the oily substance contains a temperature-sensitive, fat-soluble active ingredient, and is capable of forming an emulsion when the glass is contacted with a sufficient amount of an aqueous phase. . 39. 39. The glass of claim 38, wherein the temperature sensitive active ingredient is a drug. 40. 39. The glass of claim 38, which is about 10% to about 60% microcrystalline. 41. 39. The glass of claim 38, wherein the temperature sensitive active ingredient decomposes at a temperature greater than about 140<0>C. 42. A self-emulsifying glass containing a mixture of an oily substance and a non-surface-active water-soluble matrix compound, wherein the non-surface-active water-soluble matrix compound is polymers selected from the group consisting of nylpyrrolidone, cellulose derivatives, and maltodextrins, the oily material containing a lipophilic material that is a temperature sensitive active material, and when the glass is contacted with a sufficient amount of the aqueous phase, it forms an emulsion. self-breast that can form Molded glass. 43. Mixing water-in-oil emulsions and non-surface active water-soluble matrix compounds a self-emulsifying glass containing a non-surface-active water-soluble matrix compound; The structure of the object includes a tripartite glucophore with electronegative atoms, polar bonds and a hydrophobic region, forming a stable W/O/W glass when the glass is in contact with a sufficient amount of aqueous phase. A self-emulsifying glass that can form emulsions. 44. 44. The glass of claim 43, wherein the matrix compound is selected from the group consisting of sucrose, fructose, trehalose, cyclamate and saccharin. 45. 44. The sugar of claim 43, wherein the matrix compound is selected from the group consisting of monosaccharides, disaccharides, and sweeteners, each of which is at least as sweet as sucrose. Russ. 46. 44. The glass of claim 43 further comprising maltodextrin. 47. 44. The method of claim 43, wherein the aqueous phase of the water-in-oil emulsion contains an active ingredient. glass on top. 48. containing a water-in-oil emulsion and a mixture of non-surface-active water-soluble polymers. a self-emulsifying glass, wherein the non-surface active water-soluble polymer is polyvinyl pyrolyte. A self-emulsifying glass selected from the group consisting of lydones, cellulose derivatives, and maltodextrins, which is capable of forming a stable W/O/W emulsion when the glass is contacted with a sufficient amount of an aqueous phase. 49. 49. The aqueous phase of the water-in-oil emulsion contains an active ingredient. glass on top. 50. Able to form stable oil-in-water emulsions when contacted with a sufficient amount of aqueous phase. A method of producing a self-emulsifying glass comprising the steps of: (a) combining an oily substance and a non-surface active water-soluble matrix compound and a solvent; forming a non-stable emulsion combination in which the non-surface-active water-soluble matrix compound has electronegative atoms, polar bonds, and hydrophobic regions in its structure; Contains glucophores and (b) removing the solvent from the combination such that a glass remains. 51. 51. The method of claim 50, wherein the non-surface active water soluble matrix compound is selected from the group consisting of sucrose, trehalose, fructose, cyclamate and sugars. 52. The non-surface active water-soluble matrix compound is selected from the group consisting of monosaccharides, disaccharides and sweeteners, each of which is at least about as sweet as sucrose. The method according to claim 50. 53. 51. The method of claim 50, wherein the solvent is aqueous. 54. 51. The method of claim 50, wherein the solvent is removed from the combination at a rate faster than the rate of crystallization of the non-surface active water-soluble matrix compound. 55. 51. The method of claim 50, wherein the solvent is removed using a rotary evaporator. 56. 51. The method of claim 50, wherein the weight ratio of the non-surface-active water-soluble matrix compound to the oily substance is at least about 2:1. 57. 51. The method of claim 50, wherein a fat-soluble active ingredient is added to the oily substance. 58. 58. The method of claim 57, wherein the fat-soluble active ingredient is temperature sensitive. 59. 51. The method of claim 50, wherein the solvent removal step is performed at a temperature below about 50<0>C. How to put it on. 60. carried out at a temperature below the melting point of the non-surface-active water-soluble matrix compound. 51. The method of claim 50. 61. A self-emulsifying glass produced by the method of claim 50. 62. A method of preparing a stable oil-in-water emulsion comprising contacting a self-emulsifying glass produced by the method of claim 50 with a sufficient amount of an aqueous phase. 63. 51. The method of claim 50, wherein the oily substance contains an aqueous phase and an emulsifier. 64. A method of making a self-emulsifying glass capable of forming a stable emulsion upon contact with a sufficient amount of an aqueous phase, the method comprising the steps of: (a) an oil-based substance and a non-surface-active water-soluble polymer; and a solvent to form a non-stable emulsion combination, wherein the non-surface-active water-soluble polymer contains polyvinylpyrrolidone, a cellulose derivative, and a todextrin, wherein the amount of the solvent is substantially all of the polymer. (b) removing the solvent from the combination such that the self-emulsifying glass remains. The process of leaving. 65. 65. The method of claim 64, wherein the solvent is aqueous. 66. 65. The method of claim 64, wherein the solvent is removed using a rotary evaporator. 67. the non-surface-active water-soluble polymer is polyvinylpyrrolidone; 65. The method of claim 64, wherein the solvent is chloroform. 68. The weight ratio of the non-surface-active water-soluble polymer to the oily substance is at least 65. The method of claim 64, wherein the ratio is also about 2:1. 69. 65. The method of claim 64, wherein a fat-soluble active ingredient is added to the oily substance. 70. 65. The method of claim 64, wherein the solvent removal step is performed at a temperature below about 50<0>C. How to put it on. 71. 65. The method of claim 64, wherein the method is carried out at a temperature below the melting point of the non-surface-active water-soluble polymer. 72. 65. The method of claim 64, wherein the oily substance contains an aqueous phase and an emulsifier. 73. 65. A self-emulsifying glass produced by the method of claim 64. 74. 65. A method of preparing a stable oil-in-water emulsion comprising contacting a self-emulsifying glass produced by the method of claim 64 with a sufficient amount of an aqueous phase. 75. 75. An emulsion prepared by the method of claim 74. 76. A method of making a self-emulsifying glass capable of forming a stable water-in-oil-in-water emulsion upon contact with a sufficient amount of an aqueous phase, the method comprising the steps of: (a) a non-surface-active water-soluble matrix; A process in which a water-in-oil emulsion having a compound is combined with a solvent to obtain a combination, the non-surface-active water-soluble matrices The structure of the Rix compound contains a tripartite glucophore with an electronegative atom, a polar backbone, and a hydrophobic region, and the amount of solvent is sufficient to dissolve substantially all of the compound. and (b) removing the solvent from the combination to leave the glass. 77. The non-surface-active water-soluble matrix compound may include sucrose, trehalose, fruit, etc. 77. The method of claim 76, wherein the method is selected from the group consisting of sugars, cyclamates, and saccharins. 78. 77. The method of claim 76, wherein the non-surface active water soluble matrix compound is selected from the group consisting of monosaccharides, disaccharides and sweeteners, each of which is at least about as sweet as sucrose. 79. 77. The method of claim 76, wherein the solvent is water. 80. 77. The method of claim 76, wherein a fat-soluble active ingredient is added to the water-in-oil emulsion. 81. 77. The method of claim 76, wherein a water-soluble active ingredient is added to the water-in-oil emulsion. 82. 77. The method of claim 76, wherein the solvent removal step is performed at a temperature below about 50<0>C. 83. carried out at a temperature below the melting point of the non-surface-active water-soluble matrix compound. 77. The method of claim 76. 84. 77. The method of claim 76, wherein the solvent is removed using a rotary evaporator. 85. A self-emulsifying glass produced by the method of claim 76. 86. 77. A water-in-oil-in-water emulsion produced by the method of claim 76. 87. When contacted with a sufficient amount of aqueous phase, a stable water-in-oil-in-water emulsion can be formed. A method for producing a self-emulsifying glass comprising: (a) polyvinylpyrrolidone, a cellulose derivative and maltodextrin; A water-in-oil emulsion having a non-surface-active, water-soluble polymer selected from the group consisting of: and (b) removing the solvent from the combination leaving behind the glass. 88. 88. The method of claim 87, wherein the solvent is removed using a rotary evaporator. 89. The weight ratio of the non-surface-active water-soluble polymer to the oily substance is at least 88. The method of claim 87, wherein the ratio is also about 2:1. 90. 90. The method of claim 87, wherein a fat-soluble active ingredient is added to the water-in-oil emulsion material. 91. A water-soluble active ingredient is added to the aqueous phase of the water-in-oil emulsion of step (a). 88. The method of claim 87. 92. 88. The method of claim 87, wherein the solvent removal step is performed at a temperature below about 50<0>C. How to put it on. 93. 88. The method of claim 87, wherein the method is carried out at a temperature below the melting point of the non-surface active water soluble polymer. 94. A self-emulsifying glass produced by the method of claim 87. 95. 88. A water-in-oil-in-water emulsion produced by the method of claim 87.