MXPA06003647A - Methods for preparing oil bodies comprising active ingredients - Google Patents
Methods for preparing oil bodies comprising active ingredientsInfo
- Publication number
- MXPA06003647A MXPA06003647A MXPA/A/2006/003647A MXPA06003647A MXPA06003647A MX PA06003647 A MXPA06003647 A MX PA06003647A MX PA06003647 A MXPA06003647 A MX PA06003647A MX PA06003647 A MXPA06003647 A MX PA06003647A
- Authority
- MX
- Mexico
- Prior art keywords
- oil
- oil bodies
- bodies
- solvent
- active ingredient
- Prior art date
Links
- 239000004480 active ingredient Substances 0.000 title claims abstract description 78
- 239000000203 mixture Substances 0.000 claims abstract description 55
- 239000000839 emulsion Substances 0.000 claims abstract description 24
- 230000002209 hydrophobic Effects 0.000 claims abstract description 24
- 239000003921 oil Substances 0.000 claims description 326
- 235000019198 oils Nutrition 0.000 claims description 326
- 239000002904 solvent Substances 0.000 claims description 74
- -1 glycol ethers Chemical class 0.000 claims description 50
- 239000003795 chemical substances by application Substances 0.000 claims description 48
- OMPJBNCRMGITSC-UHFFFAOYSA-N Incidol Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 claims description 35
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 claims description 34
- HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 26
- 150000002632 lipids Chemical class 0.000 claims description 26
- 235000019485 Safflower oil Nutrition 0.000 claims description 23
- 235000005713 safflower oil Nutrition 0.000 claims description 23
- 239000003813 safflower oil Substances 0.000 claims description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 22
- KFZMGEQAYNKOFK-UHFFFAOYSA-N iso-propanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 20
- CBGUOGMQLZIXBE-XGQKBEPLSA-N Clobetasol propionate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CCl)(OC(=O)CC)[C@@]1(C)C[C@@H]2O CBGUOGMQLZIXBE-XGQKBEPLSA-N 0.000 claims description 19
- 229960001727 Tretinoin Drugs 0.000 claims description 19
- 229930002330 retinoic acid Natural products 0.000 claims description 19
- NUZWLKWWNNJHPT-UHFFFAOYSA-N Dithranol Chemical compound C1C2=CC=CC(O)=C2C(=O)C2=C1C=CC=C2O NUZWLKWWNNJHPT-UHFFFAOYSA-N 0.000 claims description 18
- 229960001259 diclofenac Drugs 0.000 claims description 17
- 238000005194 fractionation Methods 0.000 claims description 17
- 229960004703 Clobetasol Propionate Drugs 0.000 claims description 16
- 235000003255 Carthamus tinctorius Nutrition 0.000 claims description 15
- 240000005801 Carthamus tinctorius Species 0.000 claims description 15
- 241000196324 Embryophyta Species 0.000 claims description 15
- GKCBAIGFKIBETG-UHFFFAOYSA-N Tetracaine Chemical compound CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 GKCBAIGFKIBETG-UHFFFAOYSA-N 0.000 claims description 14
- NNJVILVZKWQKPM-UHFFFAOYSA-N Xylocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 claims description 14
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 claims description 14
- 229960002311 dithranol Drugs 0.000 claims description 14
- 241000219198 Brassica Species 0.000 claims description 13
- 229960002372 Tetracaine Drugs 0.000 claims description 13
- 210000004027 cells Anatomy 0.000 claims description 12
- 239000004615 ingredient Substances 0.000 claims description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M NaHCO3 Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 11
- 235000019400 benzoyl peroxide Nutrition 0.000 claims description 11
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 11
- 239000000194 fatty acid Substances 0.000 claims description 11
- 150000004665 fatty acids Chemical class 0.000 claims description 11
- 238000002156 mixing Methods 0.000 claims description 11
- 235000010469 Glycine max Nutrition 0.000 claims description 10
- 240000007842 Glycine max Species 0.000 claims description 10
- 240000006669 Helianthus annuus Species 0.000 claims description 9
- 235000003222 Helianthus annuus Nutrition 0.000 claims description 9
- 240000007049 Juglans regia Species 0.000 claims description 9
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- 229960003328 benzoyl peroxide Drugs 0.000 claims description 9
- 235000020234 walnut Nutrition 0.000 claims description 9
- 235000012284 Bertholletia excelsa Nutrition 0.000 claims description 8
- 240000009304 Bertholletia excelsa Species 0.000 claims description 8
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- 240000006773 Coriandrum sativum Species 0.000 claims description 8
- 235000011309 Crambe hispanica subsp abyssinica Nutrition 0.000 claims description 8
- 241000219146 Gossypium Species 0.000 claims description 8
- 235000004431 Linum usitatissimum Nutrition 0.000 claims description 8
- 240000006240 Linum usitatissimum Species 0.000 claims description 8
- 235000004443 Ricinus communis Nutrition 0.000 claims description 8
- 235000004426 flaxseed Nutrition 0.000 claims description 8
- PMATZTZNYRCHOR-CGLBZJNRSA-N (3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17 Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims description 7
- KDLRVYVGXIQJDK-AWPVFWJPSA-N Clindamycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@H](C)Cl)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 KDLRVYVGXIQJDK-AWPVFWJPSA-N 0.000 claims description 7
- 244000044822 Simmondsia californica Species 0.000 claims description 7
- 235000004433 Simmondsia californica Nutrition 0.000 claims description 7
- 229960004194 lidocaine Drugs 0.000 claims description 7
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical group [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 7
- 235000013311 vegetables Nutrition 0.000 claims description 7
- 239000004342 Benzoyl peroxide Substances 0.000 claims description 6
- 108010036949 Cyclosporine Proteins 0.000 claims description 6
- 229960000640 Dactinomycin Drugs 0.000 claims description 6
- 229960001265 ciclosporin Drugs 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 240000005781 Arachis hypogaea Species 0.000 claims description 5
- 235000003351 Brassica cretica Nutrition 0.000 claims description 5
- 240000002791 Brassica napus Species 0.000 claims description 5
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- 235000004977 Brassica sinapistrum Nutrition 0.000 claims description 5
- 235000002787 Coriandrum sativum Nutrition 0.000 claims description 5
- 240000008042 Zea mays Species 0.000 claims description 5
- 239000012062 aqueous buffer Substances 0.000 claims description 5
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 claims description 5
- 238000001704 evaporation Methods 0.000 claims description 5
- 235000010460 mustard Nutrition 0.000 claims description 5
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 claims description 5
- 235000010777 Arachis hypogaea Nutrition 0.000 claims description 4
- 235000013162 Cocos nucifera Nutrition 0.000 claims description 4
- 240000007170 Cocos nucifera Species 0.000 claims description 4
- 229920000742 Cotton Polymers 0.000 claims description 4
- 235000003901 Crambe Nutrition 0.000 claims description 4
- 241000220246 Crambe <angiosperm> Species 0.000 claims description 4
- 241000220247 Crambe hispanica subsp. abyssinica Species 0.000 claims description 4
- 235000009854 Cucurbita moschata Nutrition 0.000 claims description 4
- 108010092160 Dactinomycin Proteins 0.000 claims description 4
- 241000512897 Elaeis Species 0.000 claims description 4
- 235000001942 Elaeis Nutrition 0.000 claims description 4
- 235000001950 Elaeis guineensis Nutrition 0.000 claims description 4
- 240000003133 Elaeis guineensis Species 0.000 claims description 4
- 235000009438 Gossypium Nutrition 0.000 claims description 4
- 210000003463 Organelles Anatomy 0.000 claims description 4
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- 235000005822 corn Nutrition 0.000 claims description 4
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- 150000002170 ethers Chemical class 0.000 claims description 4
- 230000002829 reduced Effects 0.000 claims description 4
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- 244000140786 Brassica hirta Species 0.000 claims description 3
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- 241000801434 Eruca Species 0.000 claims description 3
- 241000795633 Olea <sea slug> Species 0.000 claims description 3
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- 230000002378 acidificating Effects 0.000 claims description 3
- 150000001298 alcohols Chemical class 0.000 claims description 3
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 claims description 3
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 150000002334 glycols Chemical class 0.000 claims description 3
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- 150000001242 acetic acid derivatives Chemical class 0.000 claims description 2
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- 210000004215 spores Anatomy 0.000 claims description 2
- CMXPERZAMAQXSF-UHFFFAOYSA-M sodium;1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate;1,8-dihydroxyanthracene-9,10-dione Chemical compound [Na+].O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=CC=C2O.CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC CMXPERZAMAQXSF-UHFFFAOYSA-M 0.000 claims 2
- 241000195493 Cryptophyta Species 0.000 claims 1
- SHGAZHPCJJPHSC-NWVFGJFESA-N Tretinoin Chemical compound OC(=O)/C=C(\C)/C=C/C=C(C)C=CC1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-NWVFGJFESA-N 0.000 claims 1
- 230000001172 regenerating Effects 0.000 claims 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims 1
- 235000017557 sodium bicarbonate Nutrition 0.000 claims 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 111
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- 238000000605 extraction Methods 0.000 description 32
- SHGAZHPCJJPHSC-YCNIQYBTSA-N Retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 24
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- 239000008346 aqueous phase Substances 0.000 description 22
- 239000002253 acid Substances 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- 238000002360 preparation method Methods 0.000 description 19
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Abstract
The present invention provides novel emulsions that comprise oil bodies. The invention also relates to novel methods for generating formulations comprising oil bodies and active ingredients wherein the active ingredient is partitioned into the oil body. The methods are particularly useful for generating emulsions with either hydrophobic or amphipathic biologically active agents.
Description
METHODS FOR REPAIRING ACCEPTED ACCEPTING BODIES CONTAINING ACTIVE INGREDIENTS
FIELD OF THE INVENTION The present invention provides new emulsions containing oil bodies. The invention also relates to novel methods for generating formulations having oil bodies and active agents in which the active ingredient is fractionated in the oil body. The methods are particularly useful for generating emulsions with either hydrophobic or antipathetic biologically active agents. BACKGROUND OF THE INVENTION In the seeds of oil-producing seed crops, which include economically important crops, such as soybeans, rapeseed, sunflower, safflower and palm seeds, the fraction of oil insoluble in water is stored in structures discrete subcellular ones known in the art as oil bodies, oleosomes, lipid bodies or spherosomes (Huang 1992, Ann. Rev. Plant.Mol. Biol. 43: 177-200). In addition to a mixture of oils (riacylglycerides), which are chemically defined as glycerol esters of fatty acids, the oil bodies comprise phospholipids and a number of associated proteins, collectively referred to as oil body proteins. From the structural point of view, the oil bodies are considered as a matrix of triacylglycerides encapsulated by means of a monolayer of phospholipids, in which the proteins of the oil body are included (Huang 1992, Ann.Rev. Plant.Mol. Biol. 43: 177-200). The seed oil present in the oil body fraction of the plant species is a mixture of several triacylglycerides, of which the exact composition depends on the plant species from which the oil is derived. It has become possible through the combination of classical culture and genetic engineering techniques, to manipulate the oil profile of seeds and expand into the naturally available repertoire of vegetable oil compositions. A summary of the continuing efforts in this area, see Designer Oil Crops, JBreedin, Processing and Biotechnology, D. J. Murphy Ed., 1 994, VCH Verlagsgesellschaft, Weinheim, Germany. Vegetable seed oils are used in a variety of industrial applications. In order to obtain the vegetable oils used in those applications, the seeds are crushed or compressed and subsequently subsequently using processes such as organic extraction, gum removal, neutralization, bleaching and filtering. The aqueous extraction of the vegetable oil seeds has also been documented (for example Embong and Jelen, 1977, Can.Inst. Food Sci. Technol. J. 1 0: 239-243). Since the objective of the processes shown in the prior art is to obtain pure oils, the oil bodies in the course of those production processes lose their structural integrity. Therefore emulsions of the prior art formulated with vegetable oils generally do not contain intact oil bodies. U.S. Patents 65,683,740 to Voultoury et al, and 5,613, 583 to Voultoury et al describe emulsions containing lipid vesicles that have been prepared from seeds of crushed oil plants. In the course of the grinding process described in those patents, the oil bodies lose their structural integrity. Accordingly, it is disclosed that in the grinding process, 70 to 90% of the seed oil is released as free oil. Thus, the emulsions which are the subject of these patents are prepared from crushed seeds from which a substantial amount of free oil has been released while the structural integrity of the oil bodies is lost. In addition, the emulsions described in these two patents are prepared from raw seed extracts and consist of multiple endogenous components of the seeds including glycosylated and non-glycosylated non-oily body seed proteins. It is a disadvantage of the emulsions to which those patents that contain contaminants of the seed that impart a variety of undesirable properties refer., which may include allergens and odors, favors, colors and undesirable organoleptic characteristics, to emulsions. Due to the presence of the seed contaminants, the emulsions described in these patents have limited applications. A non-destructive preparation of the oil bodies is described by Deckers et al. (US Patents 6, 183,762, 6,210,742, 6, 146,645, 6,372,234, 6, 582,710, 6,96,287, 6,761, 914, US 2002/00373036 and 6,599.51 3). According to these patents and patent applications a purified preparation of the oil bodies is collected as a natural emulsion and other emulsions can be prepared in the presence of a plurality of other substances in order to achieve a desirable balance of emulsification, viscosity, stability and appearance in order to make suitable emulsions, among other things, for cosmetic, pharmaceutical and food applications. Additional ingredients to achieve these characteristics may include water, emulsifiers, stabilizers, thickeners or slimming agents, preservatives, fragrances or other additives. Of particular interest are body oil preparations containing active ingredients, While simply mixing the active ingredient of interest with the body oil emulsion can result in an acceptable oil body preparation, it is particularly desirable to prepare body emulsions. of oil containing active ingredients that are selectively divided with the body of oil. For example, traditionally unstable active substances can be used which can be stabilized when they are fractionated in the core of an oil body. In addition, in the formulations that are used for topical application to human skin, the delivery characteristics of the active ingredient to human skin can be modulated when the active substance is fractionated in the body of oil. While the simple mixture according to the aforementioned Deckers patents can promote the fractionation of the active ingredients, fractionation is often not achieved or fractionation of the active ingredient is not optimal. To be considered fractionated, the active ingredients must be in physical contact with the body of oil for example by means of a link or some other affiliation and must be fractionated with the body of oil.
Thus there is a need in the art to facilitate the fractionation of the active ingredients including for example the traditionally unstable active ingredients, forming unstable oil bodies. SUMMARY OF THE INVENTION The invention herein provides one or more active hydrophobic and / or antipathetic reagents of interest that are fractionated in the inner oil core, on the lipid membrane, in the lipid membrane or bound to the outer surface of the membrane. the lipid membrane of the body of oil. Here a new system is described to improve the fractionation of the oil body. The system includes the use of two solvents and the soliloquization of an active ingredient resulting in the mixture of the active ingredients and the emulsion of the cores. The system is more complex than mixing the oil body emulsions with the active ingredients and results in greater active fractionation in and over the oil bodies. This is especially useful for dividing solid and semi-solid, hydrophobic and antipathetic molecules that are particularly difficult to solubilize, often requiring the use of organic solvents. The removal of the first solvent can be carried out in an optical step when this solvent is undesirable incompatible in the final product. Finally the active ingredients and the solvents are mixed and fractionated in the oil bodies.
The present invention relates to new methods for generating formulations containing oil bodies and active agents in which active ingredients are fractionated in the oil body. Currently, the inventors have described new methods for preparing oil bodies containing active redients, including active ingredients that are reactive and unstable in current formulations. Broadly stated, the present invention provides methods for forming emulsions containing fractionated active ingredients in oil bodies, where they are stabilized and readily available for topical or oral application. Accordingly, the present invention provides a method for fractionating an active agent in oil bodies consisting of: a) dissolving the active agent in a first solvent; b) mixing the dissolved agent with a second solvent; and c) contacting the mixture of solvents with the bodies, of oil and fractionating the active agent in the oil bodies. In a preferred embodiment of the invention, the active ingredient is not fractionated in the oily bodies upon contact with the oil bodies in the absence of a solvent or when the active ingredient is dissolved in the first solvent. In another preferred embodiment of the invention, the active agent is selected from the group of active agents consisting of hydrophobic molecules and antipathetic molecules.
In another preferred embodiment of the present invention, the first solvent is an organic solvent. Preferably the first solvent is substantially removed by means of evaporation or is substantially reduced in volume by means of the solution after mixing with the second solvent. In still another preferred embodiment of the invention, the second solvent is selected from the group of solvents consisting of water, aqueous buffers, oils, fatty acids and lipids. The methods for preparing oil bodies containing active ingredients and the emulsions resulting from the present invention can be used in a wide range of applications including in the preparation of personal care and dermatological products. Other features and advantages of the present invention will be apparent from the detailed description. It should be understood, however, that the detailed description and specific examples while indicating preferred embodiments of the invention are given by way of illustration only, since various changes and modifications may be made within the spirit and scope of the invention that are apparent to those skilled in the art from the detailed description. DETAILED DESCRIPTION OF THE INVENTION As mentioned above, the present invention relates to new methods for generating formulations containing oil bodies and active ingredients. The invention also relates to new emulsion formulations which are prepared from oil bodies. Using the present invention it is possible to fractionate the active ingredient for example 20-30% (dry weight of the active ingredient / dry weight of the oil body), in the oil bodies. The inventors have found that certain biologically active agents which are reactive and unstable in certain formulations have been stable and therefore more effective as products for personal and dermatological care. The level of charged active ingredients that can be obtained, the stabilizing properties of the oil bodies, and the ability to topically deliver novel agents make the present invention of considerable use. According to this, according to the present invention, there is provided a method for fractionating the active agents in oil bodies, which method consists of: (i) dissolving the active ingredient in a first solvent; (ii) mixing the dissolved active agent with a second solvent to obtain a mixture of the first and second solvents comprising the active ingredient; and (iii) contacting the mixture of the first and second solvents with the oil bodies to fractionate the active agent between the oil bodies. In a preferred embodiment the active agent is not fractionated in the oil bodies when it is contacted with the oil bodies in the absence of a solvent or when a solvent or when the active agent is present. dissolves directly in the first solvent. Preferably the active agent is further characterized in that it is insoluble or essentially insoluble in water. The methods of the present invention are particularly useful when the active agent is additionally insoluble or essentially insoluble in the second solvent. All meanings of the term "fractionate" as used herein means that the active ingredient is located internal oil core, on the lipid membrane, on the lipid membrane or attached to the outer surface of the lipid membrane of the oil body. . Solvents The term "first solvent" as used herein refers to the first solvent or initial solvent that is used to dissolve the active agent. Preferably the first solvent is an organic solvent. Examples of organic solvents include but are not limited to alcohols, aliphatic hydrocarbons, aromatic hydrocarbons, chlorinated hydrocarbons, glycols, glycol ethers and their acetates, esters, ethers and ketones. Examples of alcohols include but are not limited to methanol, ethanol and isopropyl alcohol (isopropanol). Examples of aliphatic hydrocarbons include but are not limited to n-hexane. Examples of aromatic hydrocarbons include but are not limited to toluene, xylene, styrene and benzene. Examples of chlorinated hydrocarbons, carbon tetrachlorides methyl chloroform, chloroform and trichlorethylene. Examples of glycols include but are not limited to propylene glycol, triethylene glycol and ethylene glycol. Examples of the flicol ethers include but are not limited to butyl cellulose (2-butoxyethanol), cellulose (2-ethoxyethanol), methylcellulose (2-methoxyethanol), and cellulose acetate (2-extoxyethyl acetate). Exemplary esters include, but are not limited to, methyl formate, ethyl acetate, isopropyl acetate, methyl acetate, secamyl acetate, and isoamyl acetate. Examples of ethers include but are not limited to ethyl ether, tetrahydrofuran. dioxane and propyl ether. Examples of ketones include, but are not limited to acetone methyl ethyl ketone (MEK), cyclohexanone and isophorone. More preferably the first solvent is an alcohol or a chlorinated hydrocarbon. More preferably the first solvent is selected from the group of solvents consisting of isopropanol, ethanol and chloroform. In addition, the first solvent could be an oil, a lipid or a fatty acid. The term "second solvent" as used herein refers to the solvent that is mixed with the active agent once it has dissolved in the first solvent. The second solvent can be any solvent that is compatible with the oil bodies. Note that the methods of the present invention are particularly useful in cases where the active agent is not directly soluble in the bodies of the oil or the second solvent. The solubility of the active agent in the second solvent can be easily determined by a person skilled in the art, for example by referring to the standard chemical indices that provide it. information on stability, include but are not limited to The CRC, Handbook of Chemistry and Physics or The Merck Index, Merck & Co., Inc. Budavari S (Ed.). The second solvent is selected from a group consisting of water, aqueous buffer, oils, fatty acids, and lipids. Examples of aqueous buffers include but are not limited to buffers containing phosphates, saline solutions buffered with phosphate, bicarbonate and HEPES (N- [2-hydroxyethyl] piperazine-N '- [2-ethanesulfonic acid]). The concentration of the salt and the pH may need to be altered to facilitate the fractionation of the active ingredient depending on the loading of active ingredients. Preferably the aqueous buffer used is a 450 mM monobasic sodium phosphate, pH 8.0 or 25 mM osdium bicarbonate, pH 8.2. Examples of oils include but are not limited to oils of the following seeds: rapeseed (Brassica spp.), Soybean (Glycine max), sunflower (Helianthus annuus), oil palm (Elaeis winkle), olive (Olea spp.), Cotton ( Gossypium spp.), Ground walnut (Arachis hypogaea), coconut (Cocus nucifera), castor (Ricinus communis), safflower (Carthamus tinctorius), mustard (Brassica spp. And Sinapis alba), cilantro (Coriandrum sativum), squash (Cucurbita max) ), linseed (Linum usitatissimum), Brazil nut (Bertholletia excelsa), jojoba (Simmondsia chinensis), corn (Zea mays), crambe (Crambe abyssinica) and eruca (Eruca sativa). Other examples of oil include but are not limited to oils, synthetics, mineral oils and silicone oils. In a preferred embodiment, the second solvent is safflower oil. The term "fatty acids" as used herein to describe a chain of long chain hydrocarbons ending in a carboxyl group. Fatty acids are the main component of lipids such as oils, fats and waxes. Examples of fatty acids include but are not limited to arachidonic acid, arachidonic acid, beic acid, brasidic acid, capric acid, carpyl acid, certotic acid, ketorolac acid, erucuco acid, gadoléic acid, lauric acid, lauroléic acid, acidicignol, linoleic acid, Acidolinolénico, margaric acid, melísico / triacontanóico acid, acidiciristoléico, acidicmonánico, acidic, acetic acid, oleic acid, palmitic acid, palmitoléic acid, steric acid, selacolaic or nervonic acid, stearic acid. The term "lipids" as used herein refers to a general group of organic substances which are insoluble in polar solvents such as water, but which readily dissolve in non-polar organic solvents, such as chloroform, ether, benzene. Many, though not all, contain fatty acids as their main structural components. Oil Bodies The term "oil bodies" as used herein means any discrete subcellular organelle of oil or wax storage. The oil bodies can be obtained from any cell that contains organelles of oil bodies or similar to bodies of oil. This includes animal, plant, fungal, yeast cells (Leber, R. et al., 1 994, Yeast 1 0: 1421-1428), bacterial cells (Pieper-Fürst et al., 1994, J. Bacteriol. 176: 4328-4337) and algal cells (Roessler, PG, 1988, J. Phycol. (London) 24: 394-400). In preferred embodiments of the invention the oil bodies are obtained from plant cells which include pollen cells, spores, seeds and organs of vegetative plants in which the organelles of oil bodies or the like are present in oil bodies (Huang , 1992, Ann. Rey, Plant Physiol. 43: 177-200). More preferably, the oil body preparation of the present invention is obtained from a vegetable seed. Among the useful vegetable seeds, those seeds obtainable from vegetable species selected from the group of vegetable species consisting of almonds (Prunus dulcís) are preferred.; anis (Pimpinella anisum); avocado (Persea spp.); walnut of the beach (Fagus sylvatica); borage (also known as spring noctura) (Boragio officinalis); Brazil nut (Bertholletia excelsa); wax nut (Aleuritis tiglium); Carapa (Carapa guineensis); walnut paper husk (Ancardium occidentale); Castor (Ricinus communis); coconut (Cocus nucifera); cilantro (Coriandrum sativum); cottonseed (Gossypium spp.); crambe (Crambe abyssinica); Alpine crepis; croton (Croton tiglium); Cuphea spp.; dill (Anethum gravealis); Euphorbia lagascae; Dimorphoteca pluyialis; false flax (Camolina sativa); Fennel (Foeniculum vulgaris); nutmeg (Arachis hypogaea); hazelnut (coryllus avellana); marijuana (Cannabis sativa); lunaria (Lunnaria annua); jojoba (Simmondsia chinensis); kapok fruit (Ceiba pentandra); walnut kukui (Aleuritis moluccana); Lesquerella spp. , linseed (Linum usitatissimum); lupine (Lupinus spp.); macademia nut (Macademia spp.); corn (Zea mays); field foam (Limnanthes alba); mustard (Brassica spp. and Sinapís alba); olive (Olea spp.); oil palm (Elaeis guiñeéis); oiticia (rigid Licania); paw paw (Assimina triloba); walnut (Juglandaceae spp.); knob (Perilla frutescens); Castilian walnut (Gatropha curcas); Dwarf walnut (Canarium ovatum); pine nut (pine spp.); pistachio (Pistachia vera); ponem (Bongamin glabra); poppy seed (Papaver soniferum); rapeseed (Brassica spp.); safflower (Carthamus tinctorius); sesame (Sesamum indicum); soybean (Glycine max); pumpkin (Cucurbit maximum); saline (Shorea rubusha); Stokes aster (Stokesia laevis); sunflower (Helianthus annuus); tukuma (Astocarya spp.); walnut tung (Aleuritis cordatta); Vernonia (Vernonia galamensis) and its mixtures. More preferably vegetable seeds of the species that include: rapeseed (Brassica spp.), Soybean (Glycine max), sunflower (Helianthus annuus), oil palm (Elaeis winkle), cotton (Gossypium spp.), Nutmeg (Arachis hypogaea) , coct (Cocus nucifera), castor (Ricinus communis), safflower (Carthamus tínctorius), mustard. { Brassica spp. and Sinapis alba), coriander (Coriandrum sativum), squash (Cucúrbita na), linseed (Linum usitatissimum), Brazil nut (Bertholletia excelsa), jojoba nondsia chinensis), corn (Zea mays), crambe (Crambe abyssinica) and eruca ( Eurca sativa). More preferably, bodies of fat prepared from safflower are used. { Carthamus tinctorius). In order to prepare plant oil bodies, the plants are grown and allowed to produce seeds using agricultural cultivation practices well known to those skilled in the art. After harvesting the seeds, if the removal of the material such as stones and pods (husking) is desired, by means of for example sifting or rinsing, and optionally drying the seed, the seeds are subsequently processed by means of seed grinding. This is known as dry milling. Preferably the liquid is water, although organic solvents such as ethanol can also be used. Wet milling in oil extraction processes has been reported for seeds of a variety of plant species including: mustard (Aquilar et al., 1991, Journal of Texture studies 22: 59-84), soybean (North American patent 3,971, 856; Cárter et al, 1 974, J. Am. Oil, Chem Soc. 51: 137-141), peanuts (US Pat. Nos. 4,025,658, 4,362,759), cotton sachets (Lawhon et al, 1977, H. Am. Chem. Soc. 54: 75-80) and coconut (Kumar et al., 1995 (INFORM 6 (11): 1217-1240) It may also be advantageous to immerse the seeds for a period of time of about fifteen minutes to approximately two days in a liquid phase before being ground in. Immersion can soften cell walls and facilitate the grinding process.Dipping for longer periods of time can mimic germination processes and result in certain advantageous alterations in the composition of the constituents of the seed The seeds are preferably ground using a colloid millIn addition to colloid mills, other milling and crushing equipment capable of processing industrial scale quantities of seeds may also be employed in the invention including: disk mills, colloid mills, pin mills, orbital mills, 1KA mills, and industrial scale homogenizers. The selection of the mill may depend on the seed processing requirements as well as the seed source being used. It is of critical importance that the seed oil bodies remain intact during the grinding process. Therefore, any operative condition commonly employed in the processing of seeds, which tend to break the bodies are unsuitable for use in the process of the present invention. The milling temperatures are preferably between 10 ° C and 90 ° C and more preferably between 25 C and 50 ° C and most preferably between 30 ° C and 40 ° C, while the pH is preferably maintained between 2.0 and 1 1 , more preferably between 6.0 and 9.0, and more preferably between 7.0 and 8.5. Solid contaminants, such as sheaths, fibrous material, undissolved carbohydrates and proteins "and other insoluble contaminants are removed from the fraction of ground seeds.The separation of solid contaminants can be achieved using a centrifuge with decantation.Depending on the processing requirements of seeds, the capacity of the decanting centrifuge can be varied using other models of decanting centrifuges such as 3 phase decanters.The operating conditions may vary depending on the particular centrifuge that is being used and must be adjusted in such a way that the contaminating materials settle and remain sedimented after decanting.A separation of the oil body phase and the liquid phase can be observed under these conditions.After removing the insoluble contaminants, the oil body phase is separated from the the aqueous phase In one embodiment of the invention and it uses a centrifuge with a tubular container. In one embodiment, a centrifuge with disc stacking is used. In other modalities hydrocyclones or settlement of the phases are used under natural gravity or any other separation method based on gravity. It is also possible to separate the factions from the oil body of the aqueous phase using size exclusion methods, such as filtration, for example membrane ultrafiltration and cross-flow microfiltration. An important parameter is the size of the annular dam used to operate the centrifuge. Annular dikes are removable rings with a central circular orifice that vary in size and regulate the separation of the phase accused of the oil body phase thus managing the purity of the fraction of oil that is obtained. The exact amount of the annular dam used depends on the type of centrifuge used, the type of oil seeds used and the final desired consistency of oil body preparation. Accordingly, in one embodiment the safflower oil bodies can be obtained using a disc stacking centrifuge SA-7 (Westphalia) in conjunction with a 73 mm annular dam. The efficiency of the separation is also affected by the flow rate. In this mode the flow rates are typically maintained between 2.0 and 7.0 l / min and the temperatures are preferably maintained between 26 ° C and 40 ° C. Depending on the model of centrifuge used, the flow rates and sizes of annular dikes can be adapted in such a way that an optimum separation of the oil body fraction of the aqueous phase is achieved. Those adjustments will be readily apparent to those skilled in the art. The separation of the solids and the separation of the aqueous phase from the oil body fraction can also be carried out concomitantly using a gravity-based separation method such as a three-stage tubular vessel centrifuge or a decanter or a hydrocyclone or a separation method based on size exclusion. The compositions obtained in this stage in the process are generally relatively crude and present numerous seed proteins, which include glycosylated and non-glycosylated proteins and other contaminants such as glucosinilates or their decomposition products. In preferred embodiments of the present invention, a significant amount of seed contaminants is removed. To achieve removal of the contaminants from the seed material, the oil body preparation obtained after the separation of the aqueous phase is washed at least once by resuspending the oil fraction and centrifuging the resuspended fraction. This process produces what for the purposes of this application is referred to as washed preparation of body oil. The number of washings will generally depend on the desired purity of the oil body fraction. Depending on the washing conditions that are employed, an essentially pure oil body preparation can be obtained. In that preparation the only proteins present would be the body's oil proteins. In order to wash the oil fraction, tubular container centrifuges and other centrifuges can be used. The washing of the oil bodies can be carried out using ag ua, buffer systems, for example, sodium chloride in concentrations between 0.01 M and at least 2M, 0.1 M sodium carbonate at a pH (1 1 -12), salt buffer lower, such as 50 mM Tris-HCl pH 7.5, organic solvents, detergents or any other liquid phase. In embodiments in which a high purity oil body fraction is considered desirable, the washes are preferably carried out at a high pH (11 1 -12). The liquid phase used for washing as well as the washing conditions, such as pH and temperature, can be varied depending on the type of seed used. Washing at a number of different pH levels between pH 2 and pH 1 1 -12 can be beneficial as this will allow stepwise removal of contaminants, particularly proteins. The washing conditions are selected in such a way that the washing step results in the removal of a significant amount of contaminants without compromising the structural integrity of the oil bodies. In embodiments in which more than one washing step is performed, the washing conditions may vary for the different washing steps. SDS gel electrophoresis or other analytical techniques can be conveniently used to monitor the removal of seed proteins and other contaminants after washing the oil bodies. If it is not necessary to remove the aqueous phases between the washing steps and the final preparation of the washed oil body, a buffer system, for example 50 mM Tris-HCl pH 7.5, or any liquid phase and, if desired, can be suspended in water. the pH can be adjusted to any pH between a pH of 2.0 and 1 1, more preferably between 6.0 and 9.0 and more preferably between 7.0 and 8.5. The process for manufacturing the oil body preparation can be done in batch operations or in a continuous flow process. Particularly when disk stacking is used, a pump system is conveniently adjusted to generate a continuous flow. The pumps can be for example a double diaphragm pump operated by air, or a positive displacement or peristaltic hydraulic pump. In order to maintain a homogeneous consistency supply to the decanting centrifuge and to the tubular container centrifuge, homogenizers, such as an I KA homogenizer may be added between the separation stages. Online homogenizers can also be added among various centrifuges or separation equipment based on the size exclusion employed to wash the body oil preparations. The annular dike sizes, the buffer compositions, the temperature and the pH may differ in each washing step from the size of the annular die used in the first separation stage. Active Ingredients According to the present invention, a wide variety of formulations may be formulated. variety of biologically active ingredients with the oil bodies of the present invention. The terms "biologically active agent""active", "active agent" and "active ingredient" as used herein means any agent that when administered to a living organism have a detectable biological effect, including any physiological, diagnostic, prophylactic or pharmacological effect. The terms are intended to include but not be limited to any pharmaceutical, therapeutic, nutraceutical, dermatological or cosmetic-pharmaceutical agent. In addition the terms "biologically active agent", "active", "active agent" and "active ingredient" as used herein are preferably referred to a compound that is not soluble in a body of oil, water, aqueous solution, oil, acid fatty or lipid directly, while the active ingredient is soluble in organic solvents. The active ingredients may be able to improve or promote the physical appearance, health, agility or performance of the surface area of the human body, including the skin, hair, scalp, teeth and nails. The acíivos ingredients can be loaded in levels clinically significant with an excess capable of loads (20-30% in dry weight of the active ingredient / dry weight of the body of oil). The amount of active ingredient formulated will depend on the desired effect and the active ingredient that is selected. In general, the amount of active will be in the range of 0.0001% (w / w) to approximately 50% (w / w). More preferably, however, the amount of the active ingredient in the final composition will be in the range of about 0.01% to about 10% (w / w). Depending on the chemical nature of the active ingredient, the active ingredient can be incorporated into the final formulation in a variety of forms, for example an aliphatic active ingredient can be fractionated in the phosphine membrane of the oil body, while a hydrophobic active ingredient can be fractionated into the lipid core of the oil body. The active ingredient is dissolved in the first solvent in an amount of the first solvent that is sufficient to dissolve the active agent. The amount will vary depending on the active ingredient and the solvent. The amount can be easily determined by someone skilled in the art. For example, when referring to standard chemical indices that provide information on stability including but not limited to The CRC, Handbook of Chemistry and Physics or The Merck Index, Merck &; Co., Inc. Budavari S (Ed.). Once the active ingredient is dissolved in the first solvent, the active disaest is mixed with the second solvent. Preferably the first solvent is substantially removed after mixing with the second solvent. In a specific embodiment the first solvent is substantially removed by means of evaporation or substantially reduced in volume by means of dissolution. Examples of methods for evaporating the first solvent include but are not limited to exposing the dead one either to a stream of compressed air, oxygen or nitrogen. Preferably the sample is exposed to a stream of nitrogen. The term substantially removed as used herein means that preferably between about 90 to 99.9% of the first solvent is removed, more preferably about 95 to 99.9% of the first solvent is removed and more preferably between about 99 to 99.9% of the first solvent is removed. . The oil bodies are incubated with the solvent / acive ingredient mixture to facilitate the fractionation of the active ingredient in the oil bodies. Incubation is preferably carried out overnight or longer, for example at a temperature of 34-37 ° C to ensure optimal fractionation. Haxane extraction can be used to remove the amount of the active ingredient present in the free oil (the free oil is defined as oil not contained within the oil bodies.) Note that the inlaid oil bodies are extensively resistant to extraction with hexane only. ). (Tzen et al (1997) J. Biochem 121: 762-768). Once the free oil has been removed from the active ingredient / body oil fraction, a total reagent oil analysis can be performed using for example hexane solution extraction: isopropanol, chloroform or cyoroform: methanol. The amount of active ingredient present in the free oil fraction and the total oil fraction can be determined by several methods including but not limited to high performance liquid chromatography (CLAP), spectrophotometry, fluorescence, or acid assays depending on the ingredient active. By comparing the amount of active ingredient in the free oil fraction and the total oil fraction, the average amount of active ingredient in the iniacid oil bodies can be determined. In general the efficiency of the fractionation of the active ingredient in the oil bodies may be in the range of approximately 1 to 99.9% more typical, however the efficiency of the fractionation of the active ingredient in the intact oil bodies will be found in the range of about 50 to about 99 and more typically of about 99 to 99. The term "hydrophobic" used herein refers to a substance that does not readily dissolve in polar solvents such as water. In general, the greater the hydrophobicity, the greater the phenotype of the subsidence to be fractionated in solvent are polar. The hydrophobic nature of the molecule can be measured by the fractionation coefficient of the molecules. Simply put, the fractionation coefficient is the proportion of the equilibrium concentrations between two immiscible phases that are found in contact. For example, the octanol / water fractionation coefficient (K0w, Pow, or P value) is the proportion of a chemical / active ingredient in the octanol phase
(not polar) at its concentration in the aqueous (polar) phase of a two-phase octanol / water system. A compound with a high P value is considered relatively hydrophobic. Since the measured values are in the range of < 10"4 to <10 + 8 (at least 12 orders of magnitude), the logarithm (log P) is commonly used to characterize its value.The log P value can be determined experimentally, for example using reverse phase CLAP (Yamagami and H araguchi, 2000. Chem pharm. Bull. (Tokyo) 47 (12): 1 973-7) or using computer programs such as KowWin developed by Syracuse Research Corporation and using a connibution method such as fragment. preferred embodiment the log P value of the active compound is between about 0 and 8. In a more preferred embodiment, the log P value is in the range of about 2 to about 7. In a more preferred embodiment, the log P value is is found in the range of about 3 to 7. A particularly preferred active ingredient, which may be used according to the present invention is clobetasol propionate Other synonyms and derivatives of ciobetasol propionate include but are not limited to Clobetasol, clobetadoi 1 7-propionate, (1 1 ß, 16ß) -21-chloro-9-fluoro-1 1 -hydroxy-1 6-methyl-17- (1-oxopropoxy) -pregna-1,4-diene -3,20-dione, Dermoval, Dermovate, Dermoxin, Dermocinale, Temovate and its derivatives. Conditions that can be brought using clobetasol propionate include inflammatory and pruritus manifestations of moderate to severe dermatoses that are responsive to corticosteroids. Examples of such indications include but are not limited to allergic reactions, aptopic dermatitis, contact dermatitis, eczema, lichen planus, lichen sclerosus, phimosis, pruritis, psoriasis, scalp dermatosis, seborrhoeic dermatitis, and skin irritations. Other particularly preferred acive ingredients that can be used according to the present invention is diclofenac. Other synonyms and derivatives of diclofenac include but are not limited to 2 - [(2,6-dichlorophenyl-amino] -benzene-acetic acid, [o-2,6-dichloroaniolin] phenyl] -acetic acid, Volibar, Caiafram (diclofenac potassium), Voltaren (diclofenac sodium), Voltaren-XR, Solaraze, Allvoran, Benfofen, Dealgic, Deflamat, Del phinac, Diclomax, Miclometin, Diclofl ogont, Diclo-Puren, Dicloreum, Diclo-Spondylol, Delobasan, Duravolten, Ecofenac, Effekton, Lexobene, Moifene , Neriodin, Novapirin, Primofenac, Profenafina, Rewodina, Rumalgan, Trabona, Tsudohmin, Valetan, Voldal, Xenid and its derivatives. Diclofenac is a non-spheroidal anti-inflammatory pain reliever that is effective in curbing fever, pain and inflammation in the body. The conditions for which diclofenac can be used include but are not limited to pain relief, sensitivity, inflammation (swelling) and stiffness caused by arthritis and gout, to relieve menstrual pain and pain after surgeries or deliveries , rheumatoid arthritis, osteoarthritis, spondyliris, post-operative inflammation after surgery of cafaraías or cornea and actinic keratinosis. Yet another particularly preferred hydrophobic active ingredient which can be used according to the present invention is dithranol. Other synonyms and derivatives of diiranol include but are not limited to 1, 8-Dihydroxy-9 (1 OH) -antracenone, 1,8-dihydroxyanthron, anthralin, anthraphor, Aniranol, Anfrascalp, Antraderm, Cignolin, Dithrocream®, Drithrocreme, Dirihro -Scalp, Micanol, Psoradrate, Prosiderm, Psorin® and its derivatives. Indications for which dithranol can be used include but are limited to subacute and chronic psoriasis.
A particularly preferred active ingredient that can be used according to the present invention is retinoic acid. Other synonyms and derivatives of retinoic acid include but are not limited to acid (al! -E) -3,7-Dimethyl-9 (2,6,6-ylmethyl-1-cyclohexen-1-yl) -2,4 , 6, 8- nonaieiraenoic, vine A acid, Finoin, Aberel, Airol, Aviia, Epi- Aberel, Eudyna, Kerlocal, Renova ™, Retin-A ™, retinol, Vesanoic, and their derivatives. The conditions for which treatment with retinoic acid can be used include but are not limited to mild to moderate acne and the rash of sun damaged skin (aging). This is to reduce fine wrinkles, hyperpigmenism of freckles and harshness. associated with over-exposure to the sun). Other particularly preferred hydrophobic active reagents which are used according to the present invention is lidocaine. Other synonyms and derivatives of lidocaine include but are not limited to 2-dieylamino-2 ', 6'-acetyloxy, 2- (dieylamino) -N- (2,6-dimethylphenyl) acetamide, Anestacon, Cuivasal, Duncaine, EMLA (R), Gravocaine , Isicaine, Leostesin, Lidocaine, UDOCAI NE BASE AND UDOCAINE HCl USP, Lidotesin, Lignocaine, Rucaine, Silestesian, omega-diethylamino-2 ', 6'-dimethylacetanilide, Xilestesin, Xylocaine, Xylocyan, Xylotox, and their derivatives. The conditions for which lidocaine treatment can be used include, but are not limited to, ventricular arrhythmias, premature ventricular contractions (PVC), tachycardia, and fibrillation. Another particularly preferred hydrophobic acid ingredient which can be used according to the present invention is clindamycin. Other synonyms and derivatives of lidocaine include but are not limited to 7- deoxy-7 (S) chlorolincomycin, 7 (S) -C lo ro-7-deoxy lincomycin, Anirole, Cleocin, Clindane icin, Clindatec, Dalacin, Dalacin C, Dalactine , Hydrochloride monohydrate (Dalactine), Klimycin, Klimicin C, Klimicin methyl xamido) -1-phio-L-urea-alpha-D-galanooctopylopyranoside, L-urea-alpha-D-galacfo-Ocíopranoside, methyl 7-cioro -6,7,8-trideoxy-6 - (((1-methyl-4-propyl-2-pyrrolidinyl) carbonyl) amino) -1-io- (2S-rans) -, hydrochloride monohydrate, Meilyl-7-chloro-6 , 7, 8-trideoxy-6- (1-methyl-frans-4-propyl-L- 2-pyrrolidinecarboxamido) -1-Iio-L-urea-alpha-D-galacto-octopyranoside, Methyl-7-chloro-6,7 , io-L-freo-alpha-D-galacium-p-oxypyranoside, Sobelin, U-21251, and its derivatives. Conditions that may be rare include but are not limited to bacillary infections fragilis in young children. The most preferred hydrophobic active ingredient active ingredient which is used according to the present invention is benzoyl peroxide.
Other synonyms and derivatives of benzoyl peroxide include but are not limited to 2,3,6-TBA, Acetoxil, incidol, loroxida, LucidoI uperco, luperox fl, naiper b and bo, Nericur, norox bzp250, norox bzp-c-35, Novadelox, Oxi-10, OXI-5, Oxi-5, Oxi 10, oxiliye, oxy-was, PanOxyl, Peroxidex, Persadox,
Persian-gel, compound quinolor, sanoxií, superox, TCBA, Teraderm, Topex,
Tribac, vanoxide, Xerac, Xerac BP 1 0, Xerac BP 5, Acnegel, aztec bpo, Benoxyl, Benzac, Benzagel l O, Benzaknen, benzaknew, benzoic acid, peroxide, benzoperoxide, benzoyl peroxide, astringent water, benzoyl superoxide, dibenzoyl peroxide, dipenilglioxal peroxide,
BPO, BZF-60, Cadet, cadox bs, Disande, Debroxide, dry and clear, epi-clear, fostex, Garox. Conditions that can be treated with benzoyl peroxide include but are not limited to weak to moderate acne.
Another preferred preferred hydrophobic acrylic ingredient used in accordance with the present invention is cyclosporin A. Other synonyms and derivatives of cyclosporin A include, but are not limited to, the amphiboids 7481 f1, cyclosporin (cyclosporin A, cyclosporin A, vol 27-400, Ramiinfin A, s7481 f, and its derivatives Conditions that can be fratás with ciclosporin A include, but are not limited to reducing the natural immunity of the body in patients who receive transplanies of organs (for example kidney, liver, and heart), psoriasis and rheumatoid arthritis According to another example, the anti-cancer drug doxoubicin (also known as Adriamycin) can be used and formulated as an oil body emulsion.The term "amphiphilic" or "amphiphilic" as used herein refers to a molecule with two different components that differ in their affinity for solutes and Solvenis. No affinity for polar solvents, such as water, is said to be hydrophilic. A second part of the molecule has affinity for non-polar solvents, such as hydrocarbons, and is said to be hydrophobic. The antipatic molecules display a different behavior when they interact with water in which the polar or hydrophilic part seeks to interact with water while the non-polar or hydrophobic part avoids interaction with water. The balance between the hydrophilic and lipophilic portions in an antipathetic molecule is used as a classification method (hydrophilic-lipophilic balance, HLB). The HLB values for commonly used antipathetic molecules will be available in the literature (eg Handbook of Pharmaceufical Excipienís, The Pharmaceuíical Press, London, 1994). The HLB system was originally conceived by Griffin (J .Soc Cosmetic Chem., 1, 31 1, 1949). Griffin defined the H LB value as an amphipalic molecule as the mole% of the hydrophilic groups fractionated by 5, where a hydrophilic molecule (without non-polar groups) has an H LVB value of 20. It is simple approximation to calculate the HLB value only It is applicable to polyoxyethylene. Consequently, for other amphipathic molecules, hLB values have been derived from various properties such as water solubility, dielectric constancy, inferfacial tension, and nebulization puncture. These dispersant agents preferably have a hydrophilic-lipophilic balance between 1 and 20 (HLB number, as defined in Griffin, W CJ Soc. Cos. Chem. 1, 1 949, 31 1: J. Soc. Cos. Chem. 5 , 1 954, 249). Davis went to. Proc. 2ns. I ní. Cong. Surface Act. > vol. 1, Butterworíhs, 10959, London, proposed a more general empirical equation that associates a consynia with two different hydrophobic and hydrophobic groups: HLB = [(nH x H) - nLxL] + 7 in which H and L are consignments assigned to groups hydrophilic and hydrophobic respectively, and nH and nL the number of these groups per molecule. For the purposes of the present invention, HLB is an empirical amount on an arbitrary scale, which is a measure of the polarity of an antipathetic molecule or mixture of antipathetic molecules. See P. Becher et al. , "Nonionic Surfactant, Physical Chemistry", Marcel Dekker, N.Y. (91 87) pages 439-456. preferably according to the present invention the HLB value of the amphipathic active ingredient is.
is in the range of about 1 to 14, more preferably the HLB of the active ingredient is in the range of about 4 to 10, and most preferably, the HLB value of the active ingredient is in the range of about 6 to 10. 8. A particularly preferred antipathic active ingredient that may be used in accordance with the present invention is amphotericin B. Synonymous moles and derivatives of amphocyterin B, include but are not limited to deoxycholamide of amphocyterin B, Fungizone ™ and its derivatives. The conditions in which amphotericin B can be used include but are not limited to mycotic infections. A particularly preferred amphipic acidic ingredient, which may be used according to the present invention, is phosphatidyl choline. Other synonyms for phosphatidyl choline include but are not limited to leciin and its derivatives. Dosfaiidil choline is a membrane phospholipid. Phosphacidyl choline is found in many skin care products and has been used in cosmetic surgery (this is injected into the fat deposits under the eyes to minimize swelling). An amphiphilic acive ingredient that can be used according to the present invention is tetracaine. Other synonyms and derivatives of tetracaine, include but are not limited to amethocaine, 2-dimethylaminoethyl, 2- (dimethylamine) 2- (dimethylamine) 4- (buanylamino) benzoic acid monohydrochloride, 4- (buylamino) benzoic acid, aneiaine, butetanol, tonexol, 2- (dimethylamino) ethyl ester of 4- (butylamino) -benzoic acid, diaine, decicaine, pontocaine and its derivatives. Iatrazine is an effective local anesthetic for topical applications. Examples of such topical applications include but are not limited to anesthesia prior to venipuncture or venous cannulation, and minor ocular operations. Another preferred parficularly antipathetic active ingredient, which may be used according to the present invention is acyinomycin. Other synonyms and derivatives of actinomycin, include but are not limited to 3H-phenoxazine-1, 9-di-carboxamide, 2-amino-N, N'-bis [hexadecahydro-2,5,9-irimethyl-6,1-bis. (1 -methylethyl) -1, 4.7, 1 1, 14-pentaoxo-1 H -pyrrolo [2, 1-i]. [1, 4,7, 1 0, 1 3] oxaieirazazacyclohexadecin-1-yl] -4,6-dimetyl-3-oxo, CT, hbf 386, Luovac cosmegen, Meracfinomycin, Oncosiain K, X 97, acycicyomycin A IV , Actinomycin 7, Actinomycin AIV, Actinomyindioic acid D, dilactone, actinomycin C1, acyinomycin d, acyinomycin D, (-) - actinomycin d, actinomycin I, actinomycin 11, actinomycin IV, actinomycin - [treo-val-pro-sar-meval ], Acphinomycin X 1, actinomycin xi, actinomycein-teo-val-pro-sar-meval, ACTO-D, AD, acycinomicindioic acid dilactone D, actinomycin D dilactone acid, Cosmegen, Dactinomycin, Dactinomycin D; dacíinomierina d, and its derivatives. Conditions for which actinomycin D may be used include but are not limited to cancer and used as an antibiotic. Other active ingredients contemplated for use in the compositions described herein include the following categories and examples of alternative forms of those ingredients such as alternative salt forms, free acid forms, free base forms and hydrates:
• analgesics / antipyretics (eg aspirin, aceiaminophen, ibuporfen, naproxen, sodium, buprenorphine, propoxyphene hydrochloride, propoxygen napsylate, meperidine hydrochloride, hydroforphone hydrochloride, morphine, oxycodone, codeine, hydrocodein birtartrate, peniazocine, biotreated idrocodone , levorphanol, diflusinal, folamin salicylate, nalcurin hydrochloride, mefenamic acid, butorphanol, choline salicylate, butalbiil, phenyltoloxamine citrate, diphenhydramine citrate, methotrimeprazine, cinamedrin hydrochloride and meprobamate), • antiasthmatics (eg ketoifen and fraxanox) (; • antibiotics (eg, neomycin, strepomycin, chloramphenicol, cephalosporin, ampicillin, penicillin, tetracycline, and ciprofloxacin);• antidepressants (eg, nefopan, oxypertine, doxepin, amoxapine, trazodone, amitriptyline, maproylline, phenelzine, deispamine, nortriptyline, tranylcypromine, fluoxetine, doxepin, imipramine, imipramine pamoate, isocarboxazide, irimipramine, and proyripyline); • antidiabetics (for example bifuanides and sulfonylurea derivatives);
• antifungal agents (for example, griseofulvin, ketoconazole, itraconizol, amphocyterin B, nystatin and candicidin); • antimicrobial agents (eg propanol, propafenone, oxyprenolol, nifedipine, reserpine, trimetaffan, phenoxybenzamine, pargyline hydrochloride, dserpidine, diazoxide, guanethidine monosulfate, moinoxidil, rescinamine, sodium nifroproduda, rauwolfia serpenine, alseroxyl, and phenolamine); • amphi-inflammatory (eg indomethacin (non-spheroid), ketoprofen, flurbiprofen, naproxen, ibuporfen, ramifenazone, poroxicam, biphenylcarboxylic acid derivatives, acetominafen, hydroxortisone (spheroid), cortisone, dexamethasone, fluazcort, celecoxib, rofecoxib, hydrocortisone, prednisolone and prednisone); • antineoplastic agents (for example iclofosfaminsa, acyinomycin, bleomycin, daunoruicine, doxorubicin, epirubicin, micomycin, metrotrexate, fluorouracil, carboplaine, carmustine (BCNU), methyl-CCN U, cisplatin, etoposide, confethercin and its derivatives, phenesterin, pacliaxel and its derivatives, doceíaxel and its derivatives vinblasíina, vincrisíina, íamoxifeno and piposulfaío); • Anxiolytic agents (eg, lorazepam, buspirone, prazepam, chlordiazepoxide, oxazepam, diposphasic clorazepamide, d azepam, hydroxyzine pamoxide, hydroxyzine hydrochloride, aiproazolam, droperidol, halazepam, chlormezanone and danirolene); • immunosuppressant agents (for example cyclosporine, azaiioprine, mizoribine and FK506 (tacrolimus)); • antimigraine agents (for example ergotamine, propanolol, mute and dicloralfenanzone): • sedatives / hypnitics (for example barbiturates such as pentobarbital, pentobarbital and secobarbital), and benzodiazapines such as flurazepam hydrochloride, iozozolam, and midazolam); • Agents of ani-angina (eg, beta-and-adrenergic blockers, calcium channel blockers, such as nifedipine, and nitrates, and nitrates such as nitroglycerin, isosorbide dinitrate, tetranitrate, pentaerythritol, tert-anhydride); • antipsychotic agents (for example, haloperidol, loxapine succinate, loxapine hydrochloride, ioridazine, ioridazine hydrochloride, iiophexene, flufenzine, fluphenazine decanoane, fluphenazine enanphafo, ureaifluoperazine, chlorpromazine, perphenazine, lithium cifrate, and prochlorperazine); • antimalarial agents (for example, pneumonia of liio); • Anhydrolyamics (eg, beyridium iosylate, esmolol, verapamil, amiodarone, encainide, digoxin, digiioxin, mexiletine, disopyramide phosphate, procainamide, quinidine sulfate, quinidine gluconate, quinidine polylacyuronate, flexinide acetyl, tocainide, and lidocaine. ); • pharmaceutical agents (for example phenylbutazone, sulindac, penicillamine, salsalate, piroxicam, azafioprine, indomeiacin, meclonamate, sodium sodium malonate, keioprofen, auranofin, aurothioglucose, and sodium solmetin); • aníigoíosos ageníes (for example cloquicina and allopurinol); • anticoagulants (for example heparin, sodium heparin and warfarin sodium); • thrombolytic agents (for example urokinase, streptokinase, and alteplase); • anti-fibrinolysis agent (for example aminocaproic acid); • hemorheological agents (for example pentoxifylline); • antiplatelet agents (for example, spirine);
• anticonvulsants (eg valproic acid, sivalproex sodium, phenytoin, phenytoin sodium, clonazepam, primidone, phenobarbital, carbamazepine, amobarbifal sodium, metosuximide, metarbital, meforitobital, mefenitoin, fensuximide, parametadione, ethotoin, phenacemide, secobarbitol sodium, diphtheria clorazepate, and trimethadione); • Agencies aníiparkinson (eg eiosuximide); • antihistamines / antipruritics (eg, hydroxyzine, diphenylhydramine, chlorpheniramine, debrompheniramine maleate, cyproheptadine hydrochloride, lerfenadine, clemastine fumarate, triprolidine, carbinoxamine, diphenylarthine, fenindamine, azatadine, tripelenamine, dexchlorpheniramine maleate, methadilazine, and); • agents useful for the regulation of calcium (eg calcitonin, and parathyroid hormone); • antibacterial agents (eg, amikacin sulfate, aztreonam, chloramphenicol, chloramphenyl palmitate, ciprofloxacin, clindmacycin, clindamycin palmitate, clindamycin phosphate, metrolnazole, metroindazole hydrochloride, gentmamycin sulfate, lincomycin hydrochloride, tobramycin sulfate, hydrochloride vancomycin, polymyxin B sulfate, sodium colysmetate and colistin sulfate); • antiviral agents for example interferon alpha, beta or gamma, zidovudine, amantadine hydrochloride, ribavirin and acyclovir); • antimicrobials (eg cephalosporins such as cefazolin sodium, cefradna, cefaclor, cefrapyrin sodium, cefizoxime sodium, cefoperazone sodium, cefoiedan disodium, cefuroima and azotil, cefotazime sodium, cefadroxil monohydrafide, cephalexin, cephalocine sodium, hydrochloride cephalexin monohydrate, cefamandola naphthalate , cefoxitin sodium, cefonicide sodium, ceforanide, ceftriazone sodium, ceftazidime, cefadrozil, cephradine, and cefurozim sodium, penicillins such as ampicillin, amoxicillin, penicillin G, benzaine, cyclacillin, sodium ampicillin, polycyclic penicillin G, potassium penicillin V, piperacillin sodium, oxacillin sodium, benjampicillin corhydrate, sodium cioxacillin, disodium ticarcillin, sodium azlocycline, indanyl sodium carbenicillin, penicillin G procaine, sodium methicillin, and sodium nacillin, erythromycins such as erithromycin, erithromycin, erythromycin, erythromycin, lacfobionium erythromycin cina, erythromycin and erythromycin etiisuccinate; and tetracyclines such as idiocycline hydrochloride, doxycycline hyclate, and minocycline hydrochloride, azithromycin, clarithomycin, íriclosan, tolnafat, chlorhexidine, benzoyl peroxide). • anti-infectious (for example CM-CSF); • bronchodilators (eg, sympaomimimetics such as epinephrine hydrochloride, meiaproterenol sulfate, terbutaline sulfate, isoetharine, isoetharine mesylate, esoketarin hydrochloride, albuterol sulfate, bitolterol mesylate, isoproterenol hydrochloride, sulfuric acid, epinephrine biomarine, emtraprprenrenol sulfate, epinephrine and epinephrine biracylate; anticholinergic agents such as ipratropium bromide; iale xaninins scomoaminofilin, diphilin, metaproterenol sulfate and aminophylline; stabilizers of medullary cells such as cromolyn sodium; choriceroserosols for inhalation such as beclomethasone dipropionate (BDP = , and monochirate dipropionate of beclomeiasone, salbuiamol, deipraimio bormuro, budesonide, keioiifeno, salmeiol, xinafoaio, sulfaio deerboalina, triamcinolone, theophylline, nedocromil sodium, sulfate meiaproferenol, albuterol, flunisolide, propionaio de fluíicaso spheroids compounds and hormones (for example, androgens such as danazol, iosioserone cepionate, fluximesyerone, eyelosphoserone, inesia); fluximesyerone, mesylystosterone, fluoximeerone and cytosine of testosterone; estrogens such as estradiol. esipromy and conjugated estrogens; progestins such as acetylation of methoxyprogesterone and acetylation of norindrone; chorioicosteroids such as triamcinolone, betameiasone, sodium phosphamide of beiramethasone, dexamethasone, sodium dexamethasone phosphate, dexamethasone acetate prednisone, meiilprednidolone acetamide suspension, rhipidium ammoniumidene, meilyprednisolone, prednisolone sodium phosphate, methylpredinsolone sodium succinate, sodium succinate hydrocortisone, triamcinolone hexacetonide, hydrocortisone, hydrocortisone cypionate, predinisolone, fludrocortisone acetamide, paramehiasone acetamide, prednisolone tebuia, prednisolone acetyl, prednisolone sodium phosphate, and sodium hydrocortisone succinate; and thyroid hormones such as levothyroxine sodium); • hypoglycemic agents (for example human insulin, purified beef insulin, purified pork insulin, gluburide, chlorpropanide, glipizide, tolbumamide and iolazamide); • hypolipidemic agents (for example, cofibraio, sodium desiroyroxine, probucol, pravasilaine, atovasiaine, lovasiaine, and niacin);
• proteins (eg DNase, alginase, superoxide dismuyase and lipase); nucleic acids (eg, sense or anti-sense nuclides encoding any therapeutically useful proiein, including any of the proteins described herein); • agents useful for the stimulation of erythropoiesis (for example, erythropoiein); • Aniululous agents / amphirereflux (for example famotidine, cimetidine and ranitidine hydrochloride); • ani-nausea / anii-heméic agents (for example meclizine hydrochloride, nabilone, prochlorperazine, dimenhydrinate, promethazine hydrochloride, thiethylperazine and scopoamine); • soluble vitamins are oil (for example vitamins A, D, E K and s imilar) as well as other drugs such as miioíano, halonitrosoureas, anthrocyclines and elipticina. • active substances such as solar panicles (for example, para-amino benzoic acid (PABA), salicylate of octyl, octyl meioxy cinnamate (Parasol MCX, fifanium dioxide) • active agents such as anti-wrinkle and anti-aging (for example retinal acid) ) • whitening and whitening agents (for example, ascorbyl palmiyate and anise root) • active anti-acne agents (eg hydrocortisone and benzoyl peroxide) • vitamins (eg vitamin A and its derivatives including retinal acid, aldehyde of retinyl, retin A, refinyl palmiiapho, adalpene, and beia-caroine, viiamine D including calciproiriene (an analogue of vine D3), and viiamine including its individual constituents alpha-beta-gamma-delta-iocopol and co-rhenols and their mixtures and derivatives of vitamin E including palm itaio of vine E, linolaio of viiamina E and aceiaío of viíamina E, viíamina K and its derivatives) • lipids (for Icyril example glycerides; fatty acids such as gamma-linoleic acid; waxes, cholesterol, sphingolipids, ceramides, phospholipids and their mixtures. Pigmeniums (for example, lithium dioxide, zinc oxide, zirconium dioxide, metozsalen, trioxsaen, carotenoids (alpha carotene, beta carotene, lutein, lycopene), chlorophylls (zyb), xynophils. • anti-oxidants (for example, vine E and the like) , alpha-lipoic acid, coenzyme Q (CoQ, Q, Ubiquinone), vine A, caroienes, lycopene, lipoic acid, meiafonin, some polyphenols, some flavonoids) • antimycoics (eg riloprirox, lanoconazole, benzylamine derivatives, im idazole, amphotericin B) • fragrances (for example, aceanisole, aceophenone, cedric, acetyl, nonyl acetaldehyde, heliopropion, sandela, methoxycintranelal, hydroxycitrile, geraniol, benzaldehyde, linalool, cyclohexyl mercaptoacetic acid, cinnamyl acetamide, 1-methylol, vanillin , sandalwood oil, angelica root oil, bergamot oil, buchu oil, acacia oil, chamomile oil, lemon oil, lava oil nda, Yla oil ng-Ylang) • Insect repellents (for example N, N-diethyl-3 methyl benzamide,
N, N-diethylamutamide (DEET), dimethyl phthalate (DMP), oil of cyanone or eucalyptus, pyreirins, pyrethroids). A description of that and other classes of active agents and a species list in each class can be found in Martindale, The Extra Pharmacopoeia, 30a. edition (The Pharmaceutical Press, London, 1993), whose description is incorporated. The following are illustrative non-limiting examples of the present invention: EXAMPLES Example 1 Obtaining preparations of oil bodies washed from safflower. This example describes the recovery of safflower oil bodies. The resulting preparation contains iniacious washed oil bodies. Decontamination of the seeds. A total of 45 kg of dried safflower seeds. { Carthamus tinctorius) were washed twice using approximately 120 I of tap water at 65 ° C and once using approximately 10 ° C of current water at approximately 15 ° C. The washing was carried out in a barrel with a mesh panialla. Separate the waste water. Ground of the semi l. The washed seeds were seen through a hopper of a colloid mill (Colloid mill, MZ-130 (Fryma); capacity: 350 kg / hr), which was equipped with a MZ-1 20 cross-spraying / defaced grinding equipment and an upper one, while approximately 2500 M of 25 mM NaH2PO amorphorator were added at a pH of 7.0 through a hose exile before grinding. The operation of the mill was with a separation adjustment of 1 R, selected to give a particle size smaller than 100 microns at 18 ° C and 30 ° C. All 45 kg of seeds were milled in 10 minutes. Homogenization and removal of solids. The resulting mixture was pumped with a line knife homogenizer (Dispx Reaclor® DR-3-6 / a, I KA® Works, Inc.) at a rate of approximately 7L / min. The exit mixture is fed directly into a decanting centrifuge (NX-314B-31, Alfa-Laval) after bringing the centrifuge to an operating speed of 3250 rpm. In about 25 minutes approximately 160 kg of the milled seed mixture was decanted. A Watson-Marlow peristaltic pump (model 704) was used for the transfer of the slurry in this efapa.
Oil body separation. Separation of the oil body fraction is achieved using a centrifugal disk stacking separator (SA 7, Westphalia) equipped with a self-cleaning three-phase separator vessel and series of removable annular dikes; maximum capacity 83 I / minute; annular dam: 69 mm. The operating speed was approx. 8520 rpm. A Waisson-Marlow perisialis pump (model 704) was used to pump the decanised liquid (DL) phase into the centrifuge after bringing it to the operating speed. This results in the separation of the liquid phase decaníada in a heavy phase (H PPI) consisting of water and soluble proieins of the seeds and a light phase (LPI) consisting of oil bodies. The oil body fraction from which it was obtained after a passage through the centrifuge, is referred to as a body preparation of unwashed oil. The unwashed oil body fraction was then passed through a static in-line mixer, mixing it with 25 mM NaH2PO4 buffer at a pH of 7.0, (35 ° C, 4L / min) in a second centrifugal separator. disk stacking (SA 7, Westfalia); maximum capacity: 83L / min; annular dam: 73 mm. The operating speed was approx. 8520 rpm. The separated light phase (LP2) which connected the oil bodies then was passed through another static line mixer with pH 8, 50 mM NaH2PO4 (35 ° C, 4L / min) to the third centrifugal disk stacking separator ( SA 7, Westphalia); maximum capacity: 83L / min; annular dam: 75 mm. The operating speed was approx. 8520 rpm. All the procedure was carried out at room temperature. The preparations obtained after the second separation are called preparations of washed oil bodies. After washing, a great quantity of the seed of soluble seeds was removed. If only the oil bodies are used in a cosmetic formulation, then 0.1% Neolone 950 and 0.1% glycacyl L can be added as preservatives. Example 2 Division of clobetasol propionate in washed safflower oil bodies. The washed safflower aceifever bodies were prepared as described in example 1. The oil bodies were preserved with
0. 1% Neolone 950 and 0.1% glycacyl L. Clobetasol propionate (CP)
(Sigma supplier) is weighed (1 2-30 mg) in a clean and dry Pyrex test tube 1 6 x 1 00 μm with screw cap and mixed with 300 μl isopropanol and then with 200 mg of chakra oil. The combined sample was vortexed and subsequently incubated at 34 ° C for 20 minutes to rinse the isopropanol. One ml of washed high dry weight oil bodies were added to the CP / safflower oil mixture at ambient temperature, centrifuged briefly to pellet the contents to allow deep mixing, vortexed and re-incubated. at 34-42 ° C overnight in an airtight tube to allow the incorporation of CP and safflower oil into the oil bodies. The extraction of hexane was used to determine the amount of CP present in the free oil (free oil is defined as that which is not contained in the oil bodies) Note that the iniactic oil bodies are extensively resistant to extraction with hexane only but all hexane exoractions of the charged oil bodies should be corrected for the damage done to the oil bodies by the hexane, by means of corrections using free oil values obtained from the uncharged oil bodies). Three ml of hexane are added to the tubes and the tubes are shaken to mix 32 times. The samples are centrifuged in a clinical oscillatory bucket at 3220 x g for one minute to separate the hexane from the aqueous phase of the oil body. Noir that the free oil will remain in the hexane layer (top). The hexane layer is removed to another tube and the hexane extraction is repeated in the CP mixture / oil body resiante. Once the majority of the solvent from the second extraction is added to the tube containing the first extrac, the tube that contains hexane is transferred to a heating block. The hexane is evaporated by subjecting the tubes to a light stream of high purity N2 gas while heating the block at 40-45 ° C for at least 1.5 hours. Once the free oil is removed from the CP fraction / oil body, an analysis of the total remaining oil is performed. The total oil remaining in the oil bodies was determined by adding 4 ml of a 3: 2 solution of hexane: isopropanol (HIP) and stirring to mix vigorously until all the oil is dissolved in the HIP solvent (approximately 10-20 seconds). This was followed by the addition of 2.5 ml of 6.67% Na2SO4 (w / v) to the tube and the tube was stirred for another 10 seconds. Phase separation is facilitated by centrifugation for 2 minutes at 3220 xg in an oscillatory bucket clinical centrifuge. The organic phase or higher is removed to a second test tube using a Pasieur pipette while preventing the transfer of the aqueous phase. Three ml of a 7.2 H I P solution was added to the original tube containing the aqueous phase and the tube was stirred for 10 seconds. The tube was centrifuged for 2 minutes at 2330 x g and the upper phase was combined with the organic phase recovered in the first exiration H I P. The exirative layer 7.2 H I P was repeated. The solvent was evaporated from the lipid exudate by submitting the tube containing the combined organic phases to a gentle stream of N2 gas while heating (40-45 ° C) in a dry block calender. The tube is weighed after an hour and then every 1 5 minutes after that. When two successive weighings are equal (+ 0.0001 g), then it is assumed that all the volatile components have evaporated and that only the extracted lipids remain. The amount of CP present in both the free oil fraction and the total oil fraction is determined by means of high performance liquid chromatography (CLAP) at a wavelength of 240 nm and then compared with a standard CLAP curve. prepared with known quantities of CP. When comparing the amount of CP in both the free oil fraction and the total oil fraction, it was determined that an average of 94.7% of the added clobetasol propionate was incorporated into the intact oil bodies. The level of clobetasol propionate incorporated in the oil bodies as a percentage of dry weight is 0.316%. When large volumes of oil bodies are loaded, it was found that the Ciio-unguator laboratory mixer (Gako Konietzko) is particularly efficient to mix the oil with the oil bodies thus promoting their efficient loading.
Example 3 Division of the retinoic acid in washed safflower oil bodies. The washed caryoidal oil bodies were prepared as described in example 1. The oil bodies were preserved with 0.1% Neolone 950 and 0.1% glycacyl L. The retinoic acid (RA) (Sigma supplier) was weighed (1 -8 mg) in a clean and dry Pyrex test tube 16 x 1 00 mm with screw cap and mixed with 3 ml isopropanol. Safflower oil is added in such a way that there is no more than 5 mg of RA per gram of safflower oil. The combined sample was subjected to a vortex and placed in a heating block at 40-45 ° C, then dried under a constant stream of nihologen until the isopropanol was removed (approximately 0.5-1 hour). Subsequently, 4 to 5 ml of dry-weight alioled oil bodies were added to the RA / safflower oil mixture per gram of safflower oil used to solubilize RA. Note that the RA / oil mixture of safflower was kept in the heating block until just before the addition of the oil bodies. This mixture of oil bodies was centrifuged briefly to make pellets with the content to allow deep mixing, vortexed and re-incubated at 34-37 ° C overnight in an air-tight tube to allow incorporation of the RA and the safflower oil in the oil bodies. The extraction of hexane was used to determine the amount of RA present in the free oil (free oil is defined as that which is not contained in the oil bodies.) Note that intact oil bodies are extensively resistant to hexane extraction. only but all extractions with hexane from the charged oil bodies should be corrected for the damage done to the oil bodies by the hexane, by means of corrections using values of free oil obtained from the uncharged oil bodies). After 3 ml of hexane was added to the tubes and the tubes are shaken to mix 32 times. The samples are centrifuged in a clinical oscillatory bucket centrifuge at 3220 x g for one minute to separate the hexane from the aqueous phase of the oil body. Noir that the free oil will remain in the hexane layer (top). The hexane layer will be redirected to hexane and the hexane exiration will be repeated in the resin of the RA / oil body mixture. Once the majority of the solvent from the second extraction is added to the tube containing the first extrac- tion, the tube containing hexane is transferred to a heating block. The hexane is evaporated by subjecting the tubes to a slight stream of alia purity of N2 gas while the block is heated to 40-45 ° C for at least 1.5 hours. Once the free oil is removed from the RA fraction / oil body, an analysis of the total oil is carried out. Residual oil in the oil bodies was determined by adding 4 ml of a 3: 2 solution of hexane: isopropanol (HIP) and stirring to mix vigorously until all the oil is dissolved in the HI P solution (approximately 10-20 seconds). This was followed by the addition of 2.5 ml of 6.67% Na2SO4 (w / v) to the tube and the tube was shaken for another 10 seconds. Phase separation is facilitated by centrifugation for 2 minutes at 3220 xg in an oscillatory bucket clinical centrifuge. The organic phase or higher is removed to a second test tube using a Pasieur pipette while preventing the transfer of the aqueous phase. Three ml of a 7.2 H I P solution was added to the original tube which conenred the aqueous phase and the tube was stirred for 10 seconds. The tube was centrifuged for 2 minutes at 2330 x g and the upper phase was combined with the organic phase recovered in the first exiration H I P. The exfiltration stage 7.2 H I P was repeated. The solvent is evaporated from the liquid extract by subjecting the tube containing the combined organic phases to a gentle stream of N2 gas while heating (40-45 ° C) in a dry block heater. The tube is weighed after one hour and then every 15 minutes after that. When two successive weighings are equal (+ 0.0001 g), then it is assumed that all the volatile components have evaporated and that only the extracted lipids remain. The amount of RA present in the free oil fraction and the total oil fraction is determined by measuring the absorbance by means of spectrometry at a wavelength of 380 nm and then comparing it with a standard curve prepared with known amounts of RA . When comparing the amount of RA in both the free oil fraction and the total oil fraction, it was determined that an average of 94.7% of the added RA was incorporated in the intact oil bodies. The level of RA incorporated in the bodies of oil as a percentage of dry weight is 0.195%. When large volumes of oil bodies are loaded, it was found that the Ciio-unguator laboratory mixer (Gako Konietzko) is particularly efficient to mix the oil with the oil bodies thus promoting their efficient loading. Example 4 Division of dithranol in washed safflower oil bodies. The washed caryoidal oil bodies were prepared as described in example 1. The oil bodies were preserved with 0.1% Neolone 950 and 0.1% glycacyl L. Diyranol (supplier Specirum) was weighed (1-30 mg) in a clean and dry Pyrex test tube 16 x 100 mm with screw cap and it was mixed with 500 μl of chloroform. Safflower oil is added in such a way that there is no more than 9 mg of dithranol per gram of safflower oil. The combined sample was submitted to a voorice and placed in a heating block at 40-45 ° C, then dried under a stream of nihologen until the chloroform was removed (approximately 1-2 hours). Subsequently, 4 to 5 ml of washed high-weight dry-weight oil bodies, which contain 0.2% L-ascorbic acid (supplier Sigma), were added to the ambient temperature of the diurethane / caryoamine oil mixture per gram of oil. carfamo used to solubilize diiranol. This mixture of oil bodies was centrifuged briefly to make pellets with the content to allow deep mixing, was subjected to vórice and re-incubated at 34-37 ° C overnight in a hermetic air tube to allow the incorporation of dithranol and the safflower oil in the oil bodies. The oil bodies are washed once with an equal volume of 50 mM phosphate, pH 8.0, containing 0.2% L-ascorbic acid (Note: unincorporated dithranol can form pellets in the wash.) Ditranol is not soluble in hexane, in such a way that the exíracción with hexane will not reíirara the dithranol not incorporated) and the bodies of oil are removed of the parfe superior and they are placed in a new tube. The extraction of hexane was used to defer the nature of free oil that indicates the efficiency of the loading of an aceifera portion (free oil is defined as that which is not contained in the oil bodies. However, all extractions with hexane from the charged oil bodies should be corrected for the damage done to the oil bodies by the hexane, by means of corrections using values of free oil obtained from hexane. the bodies of oil not loaded). After 3 ml of hexane was added to the tubes and the tubes were agitated to mix 32 times. The samples are centrifuged in an oscillatory bucket clinical centrifuge at 3220 x g for one minute to separate the hexane from the aqueous phase of the oil body. Note that the free oil will remain in the hexane layer (top). The hexane layer will be re fl ected at the top of the bitumen and the hexane exiration is repeated in the remaining dithranol / oil body mixture. Once the majority of the solvency of the second extrusion is added to the tube containing the first extract, the tube containing hexane is transferred to a heating block. The hexane is evaporated by subjecting the tubes to a light stream of high purity N2 gas while heating the block at 40-45 ° C for at least 1.5 hours. Once the free oil is removed from the fraction dithranol / body of oil, an analysis of the total remaining oil is made. The total oil remaining in the oil bodies was determined by adding 3 ml of chloroform and stirring to mix vigorously until all the oil dissolved in the solvent (approximately 10-20 seconds). Phase separation is facilitated by centrifugation for 1 minute at 3220 x g in an oscillatory bucket clinical centrifuge. The organic phase or higher is withdrawn to a second test tube using a Pasieur pipette while the transfer of the aqueous phase is avoided and 3 ml of chloroform are added to the original tube which conies the aqueous phase and the tube is shaken for the duration of the test. 10 seconds. The tube was centrifuged for 1 minute at 2330 x g and the upper phase combined with the organic phase recovered in the first extraction with chloroform. To the original tube containing the aqueous phase, 3 ml of a 7: 2 hexane: isopropanol HI P addition was added and the tube was stirred for 10 seconds. The tube was then centrifuged for 3 minutes at 3220 x g and the upper phase was combined with the lower phase of chloroform obtained in the first 2 stages. The extraction stage 7.2 H I P was repeated. The solvent is evaporated from the lipid exfracto by submitting the tube containing the combined organic phases to a gentle stream of N2 gas while heating (40-45 ° C) in a dry block heater. The tube is weighed after one hour and then every 1 5 minutes after that. When two successive weighings are equal (+ 0.0001 g), then it is assumed that all the volatile components have evaporated and that only the extracted lipids remain. The amount of difranol present in both the free oil fraction and the total oil fraction is determined by measuring the absorbance by means of spectrometry at a wavelength of 376 nm and then comparing it with a standard curve prepared with known quantities of dithranol . When comparing the amount of dithranol in both the free oil fraction and the total oil fraction, it was determined that an average of 97.3% of the added dithranol was incorporated in the iniactic oil bodies. The level of diol anol incorporated in the bodies of oil as a percentage of the dry weight is 0.253%. When large volumes of oil bodies are loaded, it was found that the Cifo-unguaua (Gako Konietzko) laboratory mixer is particularly efficient to mix the oil with the bodies of aceifera thus promoting its efficient load. Example 5 Division of diclofenac into washed safflower oil bodies. The washed caryoidal oil bodies were prepared as described in example 1. Aceifera bodies were preserved with 0.1% Neolone 950 and 0.1% glycacyl L. Diclofenac (Sigma supplier) was weighed (1 -300 mg) in a clean and dry Pyrex test tube 16 x 100 mm with screw-in plate and was mixed with 10 ml of ethanol and 3 volumes of phosphate buffer (50 MM monobasic sodium phosphate, pH 8.0 with 0. 1% neolone 950) is added to the ethanol / diclofenac mixture. One g of the oil bodies is added to the buffered ethanol mixture at room temperature and the sample is mixed well and incubated overnight at 34-37 ° C in an airtight tube to allow the incorporation of diclofenac into the bodies of oil. The oil bodies are centrifuged for the incorporation of diclofenac into the oil bodies. The oil bodies are centrifuged for 10 minutes at 23220 x g to separate them from the buffer containing the ethanol and presumably the unincorporated diclofenac. The buffer portion is removed and the oil bodies are washed twice in 2 volumes of 20 mM fe phosphate, pH 8.0 containing 0.1% Neolone 950. An exorption with chloroform: methanol (2: 1) is used to remove the oil. the amount of diclofenac contained within the oil extracted from the oil bodies. Then 3 ml of chloroform:: methanol are added to the tubes and these they stir vigorously to mix. The samples were then centrifuged in a clinical oscillatory bucket centrifuge at 3220 x g for a minute to separate the solvency from the aqueous phase of the oil body. The solvenite layer will be redirected to an iron layer and the extrusion will be repeated twice more in the mixture of diclofenac / oil body. The second and third extractions are added to the tube that contains the first extract and the tube containing the exfractos is transferred to the heating block. The solvents are evaporated when the tubes are subjected to a light stream of high purity of N2 gas while the block is heated to 40-45 ° C for at least 1.5 hours. The tube is weighed after one hour and then every 15 minutes after that. When two successive weighings are equal (+ 0.0001 g), then it is assumed that all the volatile components have evaporated and that only exíraídos lipids remain. The amount of diclofenac present in both the free oil fraction and the oil tofal fraction is determined by measuring the absorbance by spectrometry at a wavelength of 320 nm and then comparing it with a standard curve prepared with known quantities of diclofenac . When comparing the amount of diclofenac in both the free oil fraction and the total oil fraction, it was determined that an average of 43.9% of the added diclofenac was incorporated into the intact oil bodies. The level of diclofenac incorporated in the bodies of oil as a percentage of the dry weight is 1.36%. Example 6 Division of tetracaine in washed safflower oil bodies. The washed safflower oil bodies were prepared as described in example 1. The oil bodies were preserved with 0.1% Neolone 950 and 0.1% gicacil L. The tratraciana free base (Sigma supplier) was weighed (1-200 mg) in a clean and dry Pyrex test tube 16 x 100 mm with screw cap and mixed with 1 ml of isopropanol then 1 g of caryoam oil. Subsequently, 3 to 5 g of washed high-weight dry-weight oil bodies were added at room temperature to the tetracaine / safflower oil mixture and the sample mixed well and incubated at 34-37 ° C overnight in an hermeneic tube to the air to allow the incorporation of tetracaine in the oil bodies. An extraction of hexane was used to determine the amount of free oil that indicates the efficiency of the loading of an oil carrier (free oil is defined as that which is not contained in the oil bodies.) Note that the oil bodies are intact. they are widely absent from hexane extraction but all hexane extractions from the charged oil bodies must be corrected for the damage done to the oil bodies by hexane, by means of corrections using values of free oil obtained from the bodies of oil not loaded). After 3 μl of hexane was added to the tubes and the tubes were shaken to mix 32 times. The samples are centrifuged in a clinical oscillatory bucket at 3220 x g for one minute to separate the hexane from the aqueous phase of the oil body. Note that the free oil will remain in the hexane layer (top). The hexane layer will be re fl ected at the other end and the hexane exiration is repeated in the remaining tetracaine / acelline body mixture. Once the majority of the solvent from the second extraction is added to the tube containing the first extrac- tion, the tube containing hexane is transferred to a block of heating. The hexane is evaporated by subjecting the tubes to a light stream of high purity N2 gas while the block is heated at 40-45 ° C for at least 1.5 hours. Once the free oil is removed from the tetracaine / body of oil fraction, an analysis of the residual oil is performed. Residual oil in the oil bodies was determined by adding 4 ml of a 3: 2 solution of hexane: isopropanol (HIP) and stirring to mix vigorously until all the oil dissolved in the HIP solvent (approximately 10-20 seconds ). This was followed by the addition of 2.5 ml of 6.67% Na2SO4 (w / v) to the tube and the tube was stirred for a further 10 seconds. Phase separation is facilitated by centrifugation for 2 min. At 3220 xg in a clinical oscillatory bucket centrifuge. The organic phase or higher is removed to a second test tube using a Pasteur pipette while transferring the aqueous phase. Three ml of a 7.2 HIP solution was added to the original tube containing the aqueous phase and the tube was shaken for 10 seconds. The tube was centrifuged for 2 minutes at 2330 x g and the upper phase was combined with the organic phase recovered in the first HI P extraction. The extraction step 7.2 H I P was repeated. The solvents were evacuated by subjecting the tube to a gentle stream of N2 gas while heating (40-45 ° C) in a dry block heater for at least 1.5 hours. The tube is weighed after one hour and then every 1 5 minutes after that. When two successive weighings are equal (+ 0.0001 g), then it is assumed that all the volatile components have evaporated and that only the extracted lipids remain. The amount of tetracaine present in both the free oil fraction and the total oil fraction was determined by measuring the absorbance by means of spectrometry at a wavelength of 338 nm and then comparing it with a standard curve prepared with known amounts of tetracaine When comparing the amount of tetracaine tanium in the free oil fraction and the total oil fraction it was determined that an average of 90.8% of the aggregated tetracaipa was incorporated in the intact oil bodies. The level of tetracaine incorporated in the bodies of oil as a percentage of dry weight is 2.43%. When large volumes of oil bodies are loaded, it was found that the laboratory mixer Cito-unguaor (Gako Koniefzko) is particularly efficient to mix the oil with the oil bodies thus promoting their efficient loading. Example 7 Division of phosphatidylcholine in washed safflower oil bodies. The washed safflower oil bodies were prepared as described in example 1. The oil bodies were preserved with 0.1% Neolone 950 and 0.1% glycacyl L. Phosphatidylcholine (PC, Sigma supplier) were weighed (1 -300 mg) in a clean and dry Pyrex test tube 16 x 100 mm with screw cap. A fluorescent marker (phosphatidic acid, supplier - Molecular Porbes) is recycled to the PC. The amount fused was 0.'05 -0.25% the weight of the Pe of 1 mg / ml labeling solution (resuspended following the manufacturer's instructions). 200 μl of isopropanol was added for each 10 mg of OC to dissolve the PC / irradiation mixture. Amorigner (50 mM NaH2PO4 pH 8.0) was added to the isopropanol mixture using the amorphous mysis (50 mM NaH2PO4 pH 8.0) as the oil bodies were formed. The volume was equivalent to the volume of charged oil bodies. The PC / marker / isopropanol / buffer mixture was subjected to ally sound for 15 to 30 seconds. Solvent was evaporated using a coniferous stream of nihologen with a slight heat (42 ° C) of the sample for 15 minutes. The oil bodies were added and the mixture was incubated at 37 ° C for several hours to several days in an air-tight container. The oil bodies were washed twice with buffer to remove the unincorporated PC. Both the washing fractions and the fractions of the oil body were subjected to de-polymerization of the fluorescence amounts after extraction with hexane using a crude oil extraction procedure. The total oil extraction was carried out by the addition of 4 ml of a 3: 2 solution of hexane: isopropanol (HIP) and stirring to mix vigorously until all the oil dissolved in the HIP solvent (approximately 10-20 seconds. ). This was followed by the addition of 2.5 ml of 6.67% Na2SO4 (w / v) to the tube and the tube was shaken for another 10 seconds. Phase separation is facilitated by centrifugation for 2 minutes at 3220 x g in an oscillatory bucket clinical centrifuge. The organic phase or higher is removed to a second test tube using a Pasteur pipette while preventing the transfer of the aqueous phase. 3 ml of a 7.2 HIP solution was added to the original tube containing the aqueous phase and the tube was shaken for 10 seconds. The tube was centrifuged for 2 minutes at 2330 x g and the upper phase was combined with the organic phase recovered in the first H I P extraction. The extraction step 7.2 H I P was repeated. Solvenites were evaporated by subjecting the tube to a gentle stream of N2 gas while heating (40-45 ° C) in a dry block heater for at least 1.5 hours. The tube is weighed after one hour and then every 15 minutes after that. When two successive weighings are equal (+ 0.0001 g), then it is assumed that all the volatile components have evaporated and that only the exíraídos lipids remain. A known amount of isopropanol was added to the extracted fractions and the sample quantified using a fluorescence spectrometer. By comparing the amount of fluorescence recovered from the oil body and the washing fractions to which they were added to the oil bodies as a marker, it was determined that an amount of PC equivalent to an average of 0.12% oil body in dry weight could be loaded into the oil body membrane. Esyarylamine is derived from stearic acid (derived from beef bait) and ammonia. It is a positively charged inducer agent that has been used to modify the charge of PC liposomes (Moncelli et al. (1994) Biophys J. 66: 1969-1980). If stearylamine (Sigma) is included in the PC / label mixture in an amount of about 30% of the amount of PC used for loading, then the PC amount was equivalent to an average of 1.25% of the body weight of oil dry It could be charged on the membrane of the body of oil. Although the present invention has been described with reference to what are currently considered the preferred examples, it should be understood that the invention was not limited to the described examples. By the convention, the invention is intended to cover several modifications and equivalent arrangements included within the spirit and scope of the appended claims. All publications, patents, and country applications are hereby incorporated by reference in the grade in which it is indicated that each publication, patent or country request was specifically and individually incorporated as a reference.
Claims (34)
- CLAIMS 1. A method for fractionating an active agent in oil bodies, the method comprises the steps of: a) dissolving the active agent in a first solvent; b) mixing the dissolved agent with a second solvent; and c) to put the Solvenite mixture in contact with the oil bodies and fractionate the active agent in the oil bodies.
- 2. A method according to claim 1 in which the acidic agent is not fractionated in the oil bodies when placed in vacuum with the oil bodies in the absence of a solvency or when the aqueous ingredient dissolves in the first solvent. .
- 3. A method according to claim 2 in which the active ingredient is insoluble in water.
- 4. A method according to claim 2 in which the active ingredient is insoluble in the second solvency.
- 5 A method according to claim 1 in which the The amount of the fractionated active ingredient in the oil bodies is in the range of about 0.0001% to 50% (w / v) 6. A method according to claim 1 in which the amount of the fractionated aqueous ingredient in the bodies of oil is in the range of about 0.1% to 20% (w / v) 7. A method according to claim 1 in which the amount of the fractionated active ingredient in the oil bodies is in the range of about 0.1% to 10% (w / v) 8 A method according to claim 1 wherein the fractionation efficiency of the active ingredient in the intact oil bodies is in the range of about 10-99%. A method according to claim 1 in which the fractionation efficiency of the active regenerative ing in the iniactic oil bodies is in the range of about 50-99%. 1 0 A method according to the claim 1 in which the efficiency of fractionation of the active ingredient in the infamous oil bodies is found in the range of approximately 90-99%. eleven . A method according to claim 1 in which the active agent is selected from the group of active agents consisting of hydrophobic molecules and antipathetic molecules. 12. A method according to claim 1 wherein the hydrophobic molecule is selected from the group consisting of clobetasol propionate, diclofenac, dithranol, retinoic acid, lidocaine, clindamycin, benzoyl peroxide and cyclosporin A. 1 3. A method according to claim 1 wherein the hydrophobic molecule has a log P value in the range of about 0 to 8. 14. A method according to claim 1 wherein the hydrophobic molecule has a log P value. in the range of approximately 2 to 7. 15. A method according to claim 1 wherein the hydrophobic molecule has a log P value in the range of about 3 to 7. 1 6. A method according to claim 1 wherein the antipathetic molecule is selected of the group consisting of anforericino B, phosphatidyl choline, tetracaine and actinomycin D. 17. A method according to claim 1 wherein the antipathetic molecule has an HLB value in the range of about 1 to 14. 1 8. A method according to claim 1. 1 1 in which the antipathetic molecule has an H LB value in the range of about 4 to 1 0. 1 9. A method according to claim 1 wherein the amphiphilic molecule has an H LB value in the range of about 6 to 8. 20. A method according to claim 1 wherein the first solvency is not compatible with the oil bodies or is undesirable in the final product. twenty-one . A method according to claim 1 in which the first solven is an organic solven. 22. A method according to claim 1 wherein the first solvent is selected from the group of solvents consisting of alcohols, aliphatic hydrocarbons, aromatic hydrocarbons, chlorinated hydrocarbons, glycols, glycol ethers and their acetates, esters, ethers, ketones. oils, lipids and fatty acids. 23. A method according to claim 22 in which the first solvent is an alcohol or a chlorinated hydrocarbon. 24. A method according to claim 1 in which the first solvent is selected from the group consisting of isopropanol, efanol and chloroform. 25. A method according to claim 1 wherein the second solvenience is selected from the group consisting of water, aqueous amorphous, oils, fatty acids and lipids. 26. A method according to claim 25 in which the aqueous buffer is selected from the group consisting of the 50 mM monobasic sodium phosphate group, pH 8.0 and 25 mM sodium bicarbonate pH 8.3. 27. A method according to claim 25 wherein the oil is safflower oil. 28. A method according to claim 1 in which the first solvency is removed sub- sequentially after it has been mixed with the second solvenfe. 29. A method according to claim 26, wherein the first solvency is substantially reduced by evaporation or is reduced sub-volumewise by dissolution. 30. A method according to claim 27, in which the evaporation method is exposed to the sample of a nitrogen stream. 31 A method according to claim 1 in which the oil bodies are obtained from a cell containing oil bodies or organelles similar to oil bodies. 32. A method according to claim 29 in which the cells include animal, plant, fungal, yeast, bacterial and algae cells. 33. A method according to claim 30 in which the plant cells include pollen cells, spores, seeds and vegetative plant organs. 34. A method according to claim 31 wherein the vegetable seeds are obtained from groups of plant species consisting of rapeseed (Brassica spp.), Soybean (Glycine max), sunflower (Helianthus annuus), oil palm (Elaeis winkle) , olive (Olea spp.), cotton (Gossypium spp.), ground walnut (Arachis hypogaea), coconut (Cocus nucifera), castor (Ricinus communis), safflower (Carthamus tinctorius), mustard (Brassica spp. and Sinapis alba), cilantro (Coriandrum sativum), pumpkin (maximum Cucurbit), linseed (Linum usitatissimum), Brazil nut (Bertholletia excelsa), - jojoba (Simmondsia chinensis), corn (Zea mays), crambe (Crambe abyssinica) and eruca (Eruca sativa) . RES U MEN The present invention provides new emulsions having oil bodies. The invention also relates to novel methods for generating formulations containing oil bodies of active ingredients in which the active ingredient is fractionated in the oil body. The methods are particularly useful for generating emulsions with hydrophobic or antipathetic biologically active agents.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US60/507,505 | 2003-10-02 |
Publications (1)
Publication Number | Publication Date |
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MXPA06003647A true MXPA06003647A (en) | 2006-12-13 |
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