|Publication number||US3137631 A|
|Publication date||Jun 16, 1964|
|Filing date||Dec 1, 1959|
|Priority date||Dec 1, 1959|
|Publication number||US 3137631 A, US 3137631A, US-A-3137631, US3137631 A, US3137631A|
|Original Assignee||Faberge Inc|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (8), Referenced by (166), Classifications (16)|
|External Links: USPTO, USPTO Assignment, Espacenet|
3,137,631 EN CAPSULATION 1N NATURAL PRODUCTS Saul Soloway, New Rochelle, N.Y., assignor, by mesne assignments, to Faberge, Inc., Ridgefield, NJL, a corporation of Delaware No Drawing. Filed Dec. 1, 1959, Ser. No. 856,379 11 Claims. (Cl. 167-83) This invention relates to encapsulating water insoluble organic liquids and the resulting products.
Those liquids, compounds or mixtures, which have appreciable vapor pressures or which are subject to chemical change by reaction with some atmospheric constituent, may be protected from volatilization or reaction with the environment by enclosure in inert capsules. Solids, having similar properties, may be dissolved in appropriate liquids and then encapsulated as solutions. Some of the volatile essential oils of commerce which could be encapsulated to advantage for applications to be discussed later are: oils of lemon, orange, anise, pine, almond, thyme, rose, jasmine and citronella. In fact one might include all the oils used in the perfume, flavor, food and allied industries. Specific types of compounds such as aldehydes, olefins, acetylenes, mercaptans, amines, ethers and phenols are readily protected against autoxidation by encapsulation. Protection of oxygen sensitive compounds without the use of an anti oxidant is particularly desirable for the preservation of animal fats, vegetable oils and vitamins such as A, E, and C. The general use of anti oxidants in these instances is viewed as that of a necessary contaminant.
It is often desirable to envelop substances, which may or may not be stable, in capsules which are frangible. Such capsules may be integrated into a fabric, woven or non-woven, so that the application of pressure will release the material. This concept constitutes a novel Way of dispensing perfume and certain types of medication. The encapsulation of such voltile compounds as menthol, camphor, pine oil, oil of eucalyptus, etc. offers a most convenient mode of dispensing alleviants for respiratory disease.
The separate encapsulation of two or more potential reactants offers many possibilities. Carbonless Carbon Paper can be made by coating the under side of one sheet of paper with capsules containing a potential color forming reactant. The top side of a second sheet is impregnated with capsules containing the developing reagent. The application of pressure to the pair of sheets in contact causes both types of capsules to rupture, thereby releasing the contents with consequent color development.
For the reasons given above, many attempts have been made to encapsulate organic substances which are in soluble in Water and are liquid at temperatures at which water is liquid. (Such substances are hereinafter called water insoluble organic liquids.) For example, efforts have been made to encapsulate such substances in gels or encompass them in waxes. Such efforts have not been adequately successful because of rapid leakage through the gel and structural weakness of the wax. Waxes are also readily dissolved by most organic oils and hence are only limited to use for encapsulating polar liquids.
' It is a principal object of this invention to overcome, or at least abate the drawbacks heretofore associated with encapsulating water insoluble organic liquids. It is a special object of this invention to provide an encapsulating process which can be carried out at the mild temperature at which water is liquid. It is a special object of this invention to encapsulate volatile substances such as perfume coils or substances which favorably affect respiration. Other objects and features of the invention A United States Patent will become apparent from the more detailed description of the invention which follows.
In my copending application Serial No. 846,535, filed October 15, 1959, now abandoned, it was disclosed that the aforesaid objectives can be obtained by encapsulating water insoluble liquids, such as mentioned above, in solid shells of cross-linked synthetic resins. These encapsulating cross-linked synthetic resin shells, as is known, are water insoluble and are insoluble in usual organic solvents. In order to encapsulate the water insoluble organic liquids in the synthetic crosslinked resin shells, the water insoluble organic liquid was dispersed in an aqueous solution of compounds capable of forming cross-linked synthetic resins by the application of heat or catalyst or both and then the resinforming compounds were polymerized in the presence of the dispersed Water insoluble liquids to thereby encapsulate them. Urea-aldehyde prepolymers are disclosed as being especially suitable for use in such a process but Water soluble resins forming compounds capable of forming melamine, epoxy, thiourea, polyamide, dicyanodiamidealdehyde resins are likewise disclosed as being suitable.
In special embodiments of that invention, the water insoluble organic liquids were disclosed as being encapsulated in a plurality of concentric shells made of the same or different resin-forming compounds or in a composite shell composed of a plurality of resin-forming compounds. In a particular embodiment of that invention, it was disclosed that the water insoluble organic liquids could be encapsulated in a water insoluble composite shell derived conjointly from water soluble heat denaturable proteins and water soluble compounds which form cross-linked synthetic resins.
In accordance with this invention, the objectives set out above, and other valuable objectives, are obtained by encapsulating water insoluble organic liquids in water insoluble shells derived from water soluble heat denaturable proteins. In order to encapsulate the water insoluble organic liquids, they are dispersed in an aqueous solution of the water soluble proteins and the proteins are then denatured in the presence of the dispersed particles of water insoluble organic liquids to thereby encapsulate the particles in a water insoluble solid protein shell. In an important method of practicing the invention, the proteins are denatured by the application of heat but they can be denatured by use of other kinds of energy as by use of ultraviolet light or ultrasonic sound or by chemicals as by acid or alkali denaturing. Although valuable substances in capsule form may be obtained by encapsulating the Water insoluble organic liquids in shells derived from water soluble heat denaturable proteins alone, known cross-linking agents for proteins such as formaldehyde, glyoxal and the like may be used to react with the proteins during the formation of the shell, or after the shell is formed, to impart increased stability to the capsule. By following the process hereof water insoluble organic liquids are encapsulated in a substantially impermeable shell of a denatured denaturable protein.
While no theory is necessary to an understanding of this invention, it is felt that the dissolved water soluble proteins normally have some aflinity for the diluted dispersion of globules of water insoluble organic'liquids and, therefore, tend to concentrate at the interface between the globules and the continuous aqueous phase. In this way, the proteins form a coating around the globules and, when denatured, form a solid water insoluble capsule therearound.
If desired, known emulsifying agents, which are usually of an oily or fatty nature, may be used to facilitate the formation of an aqueous dispersion.
Egg albumin has proven especially valuable as a source of heat denaturable protein for, among other things,
the egg albumin is a good emulsifying agent and the ta water bath. At 65 C.
water insoluble organic liquid can be easily dispersed in the aqueous body'in the presence of egg albumin by mechanical agitation with a conventional high speed mixer. Other water soluble and heat denaturable proteins I suitable for use in the process of this invention include blood, other albumins, blood plasma, globulin, myosin,
glutelin, excelsin, edestin, arachin, casein and like water soluble proteins and their mixtures which become denatured by heating. I t I In the encapsulating process disclosed above, the water soluble proteins maybe effectively and economically denatured by the application of heat tothereby form a I water insoluble solid shell around the water insoluble liquid. On the other hand, other forms of energy or chemical means may be'used to denature the proteins and render them water insoluble as by the use of ultraviolet light, ultrasonic sound or by the use of chemicals such as acid or alkali denaturants.
Thus, broadly considered, the present invention relates to a process for encapsulating, or coating, particles 'of water insoluble organic liquids'withdenatured and water a I insolubilized proteins and to. the resulting encapsulated I product. In accordance with a more limited aspect of the invention, the invention'relates to a process involving dispersing particles of a water insoluble organic compound in anaqueous solution of a water soluble heat denaturable protein-thereby applying to and absorbing on the surfaces of the dispersed particles the heat denaturable protein and denaturing the protein on the surfaces of the' particles until it'becornes substantially water insoluble, i.e., cross-linked.
If desired, the dispersion of the water insoluble organic liquid in the aqueous media may be facilitated by using I a water soluble thickening agent, or an agent imparting colloidality to the media. Compounds found very useful as thickening agents include methyl cellulose, hy-
droxyethyl cellulose and sodium carboxymethyl cellulose V and similar compounds known to improve the sus end, ing capacity of aqueous media. Although these colloids are water soluble, they also have some affinity for the Water insoluble organic liquid. ,Thus, thesefcolloids fa cilitate the formation ofv an aqueous dispersion of the organic liquid and have a tendency to concentrate at the interface between the dispersed Water insoluble organic liquid and the continuous aqueous phase. In this way,
the encapsulation is aided.
In many instances sequential coating of the dispersed water insoluble organic liquid particles gives an importantly improved encapsulated material enclosed in concentric shells. In this way, two or more concentric shells composed of water insolubilized proteins may be formed around the water insoluble organic liquid as disclosed herein or concentric shells respectively composed of water insolubilized proteins and cross-linked resins may serve as fillers for any imperfectly formed capsules containing micro cracks. I I
The meaning and significance of the invention will become even more apparent from the following illustrative examples. a
EXAMPLE I I Methyl'Benzoate Encapsulated in Egg'Albumin I Twenty-seven (27) grams of'methyl 'benzoate were added to a solution of ,ZO grams of egg'albumin in' 230 ml. of water at room temperature. The mixture was stirred at approximately 300 r.p.m. and heated on I asuspension in benzene.
ture waspoured into 800 ml. of tap water. Two solid phases formed. One was lighter and the otherhe'avier than the aqueous medium. The less dense solid was washed extensively with methanol. The heavier solid was washed with'water several times by decantation y Both washed solids were dried at 50C. with air'cir vculating through the oven; The odorless mass liberated the odor of methyl benzoate on rubbingthe solid par- 'ti cles against'one another. I
' I EXAMPLE 2 Pinene Encapsulated in Egg Albumin One hundred lOO) grams of pinene were emulsified I I in a solution of'45 grams of egg albumin dissolved in A 900 grams of water. The resulting suspension washeated on a water bath at a rateof 2 to 3 degrees O per minute;
The main batch "of solids was split into' t wo parts One was treated with '30 grams of 37%aqueous form-" aldehyde and the other with 40 grams of 30% glyoxal. Both batches were heated to C. for 15 minutes.
The separation and @drying'steps Were thesame asde scribed in the first"preparation; The resulting dried glyoxal treated material was quite hard and difficultto break by crushing with the fingers. yielded odor on the applicationof frictional forces. Q
EXAMPLIEIISI' Encapsulation of Born'yl Acetate in Bornyl acetate wassuccessfully encapsulated inegg I albumin in weight ratiosfof 1:1 and 2:1 and thereafter treated with formaldehyde by following the procedure I as disclosed in Example 2. An experiment using a3 to 1 ratio had a tendency to oil out. I I s v In these preparations the intial oil dispersion was passed through a colloid mill before theheating step. The final preparationconsisted'of particles of about 1 cm. in diameter. These were broken up in an osterizer as The separated particles were odor free on drying, but
ticle friction. a
- EXAMPLE 4 readily released the odor of bornyl acetate on inter par I V Encapsulation of:-'B 0rnyl Acetate. in Albumin and "Urea- I Formaldehyde Polymer Forty-five; (45) grams of bornyl acetatewere emulsified in a solution of 45 grams of egg albumin dissolved in 900 grams of water. The resulting dispersion was passed through a colloidal mill and the suspension was then heated on a water bath at a rate of 2 to'3 degrees C .'PI' minute. When the temperature reached C., it was held:
[phosphates were dissolved in 25 "grams of an oily-mass I consisting of a perfume oil'prepared from2 0% of each there for ten minutes. After the coagulation was completed, 10'grams of urea, 25. ml. of 35% formaldehyde,
and 1 mol of concentrated hydrochloric acid were'added I in successionand the heating was continued on the water bath until solid urea-formaldehyde resin wasno longer formed. The encapsulated solids were separated in the same .manner as in the preceding examples.
' EXAMPLE .5
Encapsulation of a Mixture of Essential Oils l Formaldehyde and Albumin Two (2) grams. of 'a mixture of mono: and' 'dilauryl Ureaof the following natural oils and synthetic compounds} B-phenyl ethylalcohol, 'geraniol, linalool, altarof 'Rose coagulation beganto set in. r After the temperature reached C;, thereaction mix I When the temperature reached 75 C., it was held there for ten minutes.
A small portion of theformed solids Wcresep'arated by decantation and washed with water and, acetone. This, prod'uct'yielded no pinene odor on crushing.
Both preparations I j 8 and oil of Neroli. This solution was added to a solution of 20 grams of urea in 300 ml. of water, followed by an addition of 50 ml. of 37% formaldehyde. While the above dispersion was being stirred, a solution of 10 grams of alubumin in 100 ml. of water was added dropwise over a period of 2 minutes. The albumin caused the oil to become more finely dispersed and seemed to coagulate around the droplets at room temperature. The preparation was heated in the manner as described in the preceding examples, filtered, Washed with water and isopropanol and dried. Stable capsules of the perfume oil were obtained.
EXAMPLE 6 Encapsulation a Mixture of Essential Oils in Urea- F ormaldelzyde, Albumin and Barium Sulfate Fifty (50) ml. of water was used to dissolve grams of urea, 12.5 grams of 37% aqueous formaldehyde, and 2.5 grams of sodium sulfate. Ten grams of the perfume oil of Example 5 and 1 gram of a mixture of mono and dilauryl phosphates were stirred into the aqueous solution while stirring with a stirrer rotating at 200-300 r.p.m. Then 5 grams of egg albumin in 25 ml. of water was added, and the stirring at 200-300 r.p.m. continued for a half hour. After reaction period induced by heating the reaction mass, the urea formaldehyde resin and the denatured egg albumin were formed into a shell around the oil. A dilute barium chloride solution was then added to form a final coat of barium sulfate with the aqueous sulfate ion present. A very stable encapsulated perfume oil was obtained encased in the cross-linked resins and the coating of barium sulfate.
Colloidal silica or powdered titanium dioxide could be added, at this point in the procedure, in lieu of barium chloride.
EXAMPLE 7 Encapsulation of Normally Solid Volatile Compounds A liquid mixture of 30 grams'of menthol, 10 grams of camphor, and 10 grams of bornyl acetate was stirred and dispersed in 50 grams of 10% methyl cellulose c.p.s.) in water. Fifty grams of an aqueous acidic colloidal solution containing 10% of an urea-formaldehyde prepolymer was added to this dispersion. After stirring, at room temperature, for a half hour, 50 grams of a 10% aqueous egg albumin solution was added and the stirring continued for an equal period. The resulting suspension of capsules may be washed free of mother liquid or used as such for spray-drying, brush or blade application to the surface of paper or other nonwoven or woven fibrous materials.
This preparation can be made odor free by air-drying the filtered, or centrifuged, capsules overnight in an oven kept at 50 to 60 C.
Also, where it is desired to obtain an intimate admixture of the encapsulated material and the carrier, such as in the production of paper for producing a paper handkerchief it is possible to introduce the capsules into the carrier during its manufacture such as by mixing together an aqueous paper pulp and the aqueous suspension of capsules during the processing of the pulp to paper.
A very satisfactory product for the alleviation of colds has been obtained by incorporating the capsules of this example in non-woven paper tissue. Other types of nonwoven fibrous tissue may be used in the same way.
While the preceding examples have related to encapsulating volatile water insoluble organic liquids, especially perfume oils and aromatics, it will be understood that other types of water insoluble liquids, mentioned herein, may be encapsulated by following the same procedure. Also, water soluble heat hardenable proteins may be dissolved in the aqueous medium in place of the egg albumin in equivalent proportions, to encapsulate the water insoluble organic liquids in the other types of denatured proteins derived from the other proteins disclosed above. Likewise, other resins typified by those disclosed hereinbefore, may be substituted for the urea-formaldehyde resins of the examples to modify the denatured protein capsules.
It is apparent from the foregoing discussion that encapsulation and encapsulate has reference to the formation of solid shells or capsules around the dispersed globules of water insoluble organic liquids. As pointed out in the body of the specification and in the specific examples, a dilute suspension of the organic liquid is first formed in an aqueous solution of the heat denaturable protein. These water soluble heat denaturable proteins can concentrate at the oil-water interface where they are insolubilized and formed into a denatured protein shell encapsulating the water insoluble oil by the action of heat or by other methods set out above.
It will be understood the foregoing general description as complemented by the specific examples has served to illustrate the invention and its principles. However, many modifications and variations in the details of the disclosure will occur to those skilled in the art to which the invention appertains and still remain within the principles of the invention and its scope. For instance, the illustrative embodiments of the invention have been concerned primarily with encapsulating water insoluble organic compounds which are liquid at temperatures at which water is liquid and with encapsulating such compounds containing dissolved, or otherwise dispersed therein, additional ingredients which are readily dispersed in the water insoluble organic compounds. It will be apparent, however, that the principles of the invention can be applied to encapsulating ingredients which are more difiicult to disperse in the water insoluble organic liquids. Broadly considered, the principles of this invention can be applied to the encapsulation of any ingredient which has a greater affinity for the water insoluble organic liquid than it has for Water. For example, when the water insoluble organic compound is an oil any ingredient may be kept in dispersion in the dispersed oil phase which is more lipophilic than hydrophilic. Predominantly lipophilic emulsifiers could be used to assist in the dispersion of the substances in the oil phase. The same principle may be used to encapsulate solids which are insoluble both in the oil phase and in the water. For example, the absorption, or coating, of a substance onto the solid particles being dispersed in the oil phase which has an amnity for oil and then dispersing the solid in the oil before it is, in turn, dispersed in the water for encapsulation. This latter principle can be used even to disperse and then encapsulate water soluble solids.
Thus, it will be seen the invention is capable of many modifications as to details and still remain within the scope of the invention as defined in the claims.
What is claimed is:
1. A liquid phase process for encapsulating a water insoluble organic liquid, which comprises dispersing finely divided particles of said liquid and a solution of a water soluble heat denaturable albumin in a body of water, denaturing said albumin by the application of heat until it forms a substantially water insoluble denatured protein coating around said particles while said particles are dispersed in said body of Water thereby encapsulating the particles in a solid shell and separating the encapsulated particles from the body of water.
2. A liquid phase process for encapsulating a water insoluble organic liquid, which comprises dispersing finely divided particles of said liquid and a solution of egg albumin in a body of water, heat denaturing said albumin until it forms a substantially water insoluble denatured egg albumin coating around said particles while said particles are dispersed in said body of water thereby encapsulating the particles in a solid shell and separating the encapsulated particles from the body of water.
'3. A liquid phase process for encapsulating a water insoluble organic liquid, which comprises dispersing finely divided particles of said liquid and a solution of a plurality ofwater soluble cross-linking resin-forming compounds in a' body ofwater, at least one of said resin-forming compounds being a heat denaturable albumin, denaturing said albumin by the application of heat and polymerizing any remaining resin-forming compounds until they deposit solution of a water soluble heat denaturable albumin in v a body of Water, applying heat to said body of water untilsaid albumin deposits a substantially water insoluble heat denatured albumin coating around said particles while said particles are dispersed in said body of Water thereby encapsulating particles in' a solid shell and separating the encapsulated particles from the body Of'WZlIGI". 5. A plurality of small discrete particles of a Water insoluble organic liquid encapsulated in a Water insoluble and substantially impermeable solid shell of a heat denatured albumin. 6. Finely divided particles of a water insoluble aromatic liquid encapsulated in a solid shell of a heat denatured albumin.
7. Finely divided particles of a liquid odoriferous substance encapsulated in a solid shell of a heat denatured egg albumin. g i V V,
8. Finely divided particlesof a perfume oil encapsulated in a solid shell of'a heat denatured egg albumin.
9.' A fibrous tissue having incorporated therein finely divided particles of a Water insoluble but Volatile liquid encapsulated in a heat denatured alb umin shell derived from, a Water soluble albumin.
10'. A plurality of small'discrete, particles ofa water insoluble organic liquid encapsulated in a water insoluble and substantially impermeable composite solid shell coma prising a heat denatured" albumin, "and across-linked imino synthetic resin.
7 11. l A paperltissue having incorporated therein a Water. insoluble but volatile decongestant encapsulatedin. a solid shell of aheat denatured water soluble albumin.
References Cited the file of this patent I IE sT riss PATENTS 2,491,475 Bogin Dec. 20, 1949 2,656,298 Loewe Oct. 20, 1953 2,797,201 Ve'atch et a1. June 25; 1957- 2,80Q,457 Green July 23; 1957 2,800,458 Green July 23,1957 2,870,062 Stanley, et a1. Jan. 20,- 1960 a 2,969,330 Brynko -i Ian, 24, 1961" Katchen et a1. June 2 6, 1962
|Cited Patent||Filing date||Publication date||Applicant||Title|
|US2491475 *||Mar 25, 1946||Dec 20, 1949||Parke Davis & Co||Enteric capsule|
|US2656298 *||Nov 10, 1948||Oct 20, 1953||Jacques Loewe Res Foundation||Therapeutic product|
|US2797201 *||Oct 2, 1953||Jun 25, 1957||Standard Oil Co||Process of producing hollow particles and resulting product|
|US2800457 *||Jun 30, 1953||Jul 23, 1957||Ncr Co||Oil-containing microscopic capsules and method of making them|
|US2800458 *||Jun 30, 1953||Jul 23, 1957||Ncr Co||Oil-containing microscopic capsules and method of making them|
|US2870062 *||Apr 27, 1956||Jan 20, 1959||Scherer Corp R P||Gelatin composition for capsules|
|US2969330 *||Jun 4, 1958||Jan 24, 1961||Ncr Co||Oil containing capsules and method of making them|
|US3041289 *||Jan 2, 1959||Jun 26, 1962||Ncr Co||Method of making walled clusters of capsules|
|Citing Patent||Filing date||Publication date||Applicant||Title|
|US3257267 *||May 19, 1965||Jun 21, 1966||Hay Harold R||Retarding liberation of an additament in forming a fibrous web by embedding the additament in a gel matrix prior to addition to the fibers|
|US3293114 *||Apr 3, 1964||Dec 20, 1966||Dow Chemical Co||Method of forming paper containing gaseous filled spheres of thermoplastic resins and paper thereof|
|US3384536 *||Mar 24, 1965||May 21, 1968||Ncr Co||Process for forming fibrous sheets containing limited penetration of additaments within the sheet and sheets thereof|
|US3406119 *||Mar 5, 1965||Oct 15, 1968||Keuffel & Esser Co||Encapsulation|
|US3490454 *||Oct 21, 1966||Jan 20, 1970||United Merchants & Mfg||Catamenial products having a coating of rupturable microcapsules containing medicants|
|US3515070 *||May 15, 1968||Jun 2, 1970||Us Army||Chemiluminescent peraminoethylene positioned within a brittle capsule|
|US3516846 *||Nov 18, 1969||Jun 23, 1970||Minnesota Mining & Mfg||Microcapsule-containing paper|
|US3516941 *||Jul 25, 1966||Jun 23, 1970||Minnesota Mining & Mfg||Microcapsules and process of making|
|US3521637 *||Nov 28, 1967||Jul 28, 1970||Haskett Barry F||Tampon or similar sanitary napkin containing vitamin a|
|US3623659 *||Dec 29, 1969||Nov 30, 1971||Ncr Co||Articles of manufacture containing encapsulated, vaporizable core material|
|US3663685 *||Apr 1, 1968||May 16, 1972||Minnesota Mining & Mfg||Biodegradable radioactive particles|
|US3669899 *||Apr 29, 1969||Jun 13, 1972||Us Plywood Champ Papers Inc||Microcapsular opacifier system|
|US3720579 *||Mar 16, 1971||Mar 13, 1973||Champion Int Corp||Fibrous substrates with microcapsular opacifiers|
|US3816169 *||Apr 20, 1972||Jun 11, 1974||Champion Int Corp||Fibrous and non-fibrous substrates coated with microcapsular pacifier system and the production of such coated substrates|
|US3886084 *||Aug 23, 1971||May 27, 1975||Champion Int Corp||Microencapsulation system|
|US3911099 *||Jan 23, 1974||Oct 7, 1975||Defoney Brenman Mayes & Baron||Long-acting articles for oral delivery and process|
|US3937668 *||Nov 6, 1972||Feb 10, 1976||Ilse Zolle||Method for incorporating substances into protein microspheres|
|US3957964 *||Jun 3, 1975||May 18, 1976||Colgate-Palmolive Company||Dentifrice containing encapsulated flavoring|
|US3978204 *||Dec 12, 1974||Aug 31, 1976||L'oreal||Cosmetic composition containing microencapsulated solvents for nail enamel|
|US4001480 *||Aug 16, 1974||Jan 4, 1977||Swift & Company||Encapsulation process utilizing microorganisms and products produced thereby|
|US4039653 *||Jul 21, 1975||Aug 2, 1977||Defoney, Brenman, Mayes & Baron||Long-acting articles for oral delivery and process|
|US4105823 *||Nov 15, 1976||Aug 8, 1978||Wiggins Teape Limited||Microcapsules, method for their preparation, and sheet material carrying microcapsules|
|US4115534 *||Jun 20, 1977||Sep 19, 1978||Minnesota Mining And Manufacturing Company||In vitro diagnostic test|
|US4138362 *||Jan 18, 1977||Feb 6, 1979||Champion International Corporation||Formation of microcapsules by interfacial cross-linking, microcapsules produced, and microcapsular dispersion|
|US4138505 *||Oct 28, 1976||Feb 6, 1979||Blue Wing Corporation||Nutrient compositions derived from animal blood solids and process for producing same|
|US4145184 *||Nov 28, 1975||Mar 20, 1979||The Procter & Gamble Company||Detergent composition containing encapsulated perfume|
|US4152272 *||Oct 25, 1977||May 1, 1979||The Procter & Gamble Company||Fabric conditioning composition|
|US4169804 *||Jun 20, 1977||Oct 2, 1979||Minnesota Mining And Manufacturing Company||Magnetically responsive composite microparticle|
|US4184495 *||Jun 29, 1978||Jan 22, 1980||Philip Morris, Inc.||Process for incorporating flavorant into cellulosic substrates and products produced thereby|
|US4217369 *||Aug 9, 1976||Aug 12, 1980||The Pillsbury Company||Moisture resistant nut-like food composition|
|US4217370 *||Sep 29, 1978||Aug 12, 1980||Blue Wing Corporation||Lipid-containing feed supplements and foodstuffs|
|US4225620 *||Aug 26, 1977||Sep 30, 1980||Blue Wing Corporation||Method for feeding ruminant animals|
|US4248899 *||Feb 26, 1979||Feb 3, 1981||The United States Of America As Represented By The Secretary Of Agriculture||Protected feeds for ruminants|
|US4273672 *||Mar 6, 1974||Jun 16, 1981||Champion International Corporation||Microencapsulation process|
|US4331654 *||Jun 13, 1980||May 25, 1982||Eli Lilly And Company||Magnetically-localizable, biodegradable lipid microspheres|
|US4349530 *||Dec 11, 1980||Sep 14, 1982||The Ohio State University||Implants, microbeads, microcapsules, preparation thereof and method of administering a biologically-active substance to an animal|
|US4357259 *||Dec 12, 1977||Nov 2, 1982||Northwestern University||Method of incorporating water-soluble heat-sensitive therapeutic agents in albumin microspheres|
|US4388352 *||Aug 3, 1981||Jun 14, 1983||Board Of Regents, University Of Washington||Method for preparing a controlled release composition|
|US4396670 *||Mar 24, 1981||Aug 2, 1983||The Wiggins Teape Group Limited||Process for the production of microcapsules|
|US4514461 *||Aug 10, 1981||Apr 30, 1985||Woo Yen Kong||Fragrance impregnated fabric|
|US4608263 *||Sep 11, 1984||Aug 26, 1986||The Quaker Oats Company||Method for making flavored dipeptide sweetened comestible|
|US4660763 *||Sep 11, 1985||Apr 28, 1987||S. C. Johnson & Son, Inc.||Vapor-dispensing device|
|US4666641 *||Jun 4, 1985||May 19, 1987||Universite Paris-Sud (Paris Xi)||Preparation of biodegradable microcapsules based on serum albumin|
|US4715390 *||Nov 19, 1985||Dec 29, 1987||Philip Morris Incorporated||Matrix entrapment of flavorings for smoking articles|
|US4729792 *||May 22, 1986||Mar 8, 1988||The Standard Register Company||Microcapsules, printing inks and their production|
|US4798786 *||May 6, 1982||Jan 17, 1989||Stolle Research And Development Corporation||Living cells encapsulated in crosslinked protein|
|US4898780 *||Jan 7, 1988||Feb 6, 1990||The Standard Register Company||Production of microcapsules|
|US4956129 *||Feb 1, 1988||Sep 11, 1990||Ici Americas Inc.||Microencapsulation process|
|US5023080 *||Jun 17, 1988||Jun 11, 1991||Basic Bio Systems, Inc.||Time release protein|
|US5055300 *||Jun 5, 1989||Oct 8, 1991||Basic Bio Systems, Inc.||Time release protein|
|US5074902 *||Jul 30, 1990||Dec 24, 1991||Connick Jr William J||Granular products containing fungi encapsulated in a wheat gluten matrix for biological control of weeds|
|US5132117 *||Jan 11, 1990||Jul 21, 1992||Temple University||Aqueous core microcapsules and method for their preparation|
|US5143737 *||Oct 15, 1990||Sep 1, 1992||The Regents Of The University Of California||Method to produce unsaturated milk fat and meat from ruminant animals|
|US5332584 *||Dec 9, 1991||Jul 26, 1994||Zeneca Inc.||Microcapsules|
|US5383862 *||Dec 14, 1993||Jan 24, 1995||Telemedysis Inc||Method and device for enveloping and disinfecting of sharp instruments|
|US5418010 *||Oct 5, 1990||May 23, 1995||Griffith Laboratories Worldwide, Inc.||Microencapsulation process|
|US5549903 *||Jul 28, 1994||Aug 27, 1996||Ben Gurion University Of Negev Research & Development Aurthority||Microencapsulated composition containing chlorpyrifos or endosulfsan|
|US5578709 *||Mar 4, 1994||Nov 26, 1996||Middlesex Sciences, Inc.||Macromolecular microparticles and methods of production|
|US5607754 *||Jun 1, 1995||Mar 4, 1997||Kimberly-Clark Corporation||Paper web product and method for manufacturing same|
|US5686113 *||Mar 21, 1995||Nov 11, 1997||Temple University Of The Commonwealth System Of Higher Education||Microcapsules of predetermined peptide(s) specificity (ies), their preparation and uses|
|US6090925 *||Aug 19, 1996||Jul 18, 2000||Epic Therapeutics, Inc.||Macromolecular microparticles and methods of production and use|
|US6174514 *||Apr 12, 1999||Jan 16, 2001||Fuisz Technologies Ltd.||Breath Freshening chewing gum with encapsulations|
|US6268053||Jan 14, 2000||Jul 31, 2001||Epic Therapeutics, Inc.||Macromolecular microparticles and methods of production and use|
|US6500662||Dec 22, 1999||Dec 31, 2002||Pfizer Inc.||Infectious cDNA clone of North American porcine reproductive and respiratory syndrome (PRRS) virus and uses thereof|
|US6531156||Jul 12, 1999||Mar 11, 2003||Temple University||Aqueous solven encapsulation method, apparatus and microcapsules|
|US6555110||May 4, 1995||Apr 29, 2003||The Corporation Of Mercer University||Microencapsulated compounds and method of preparing same|
|US6576264||Oct 17, 1996||Jun 10, 2003||Skyepharma Canada Inc.||Insoluble drug delivery|
|US6610348||Nov 14, 2001||Aug 26, 2003||Fonterra Tech Limited||Gelling agents and gels containing them|
|US6634576||Aug 29, 2001||Oct 21, 2003||Rtp Pharma Inc.||Milled particles|
|US6682761||Apr 20, 2001||Jan 27, 2004||Rtp Pharma, Inc.||Water-insoluble drug particle process|
|US6890888||Jul 2, 2001||May 10, 2005||Nft Industries, Llc||Controlled release agricultural products and processes for making same|
|US6911206||Feb 16, 2000||Jun 28, 2005||Pfizer Inc.||Fusion proteins comprising carriers that can induce a dual immune response|
|US6974593||Jun 9, 2003||Dec 13, 2005||Jagotec Ag||Insoluble drug delivery|
|US6979456||Mar 30, 1999||Dec 27, 2005||Jagotec Ag||Anticancer compositions|
|US7041705||Mar 26, 2001||May 9, 2006||Jagotec Ag||Injectable aqueous dispersions of propofol|
|US7097849||Aug 18, 1999||Aug 29, 2006||Jagotec Ag||Injectable aqueous dispersions of propofol|
|US7132106||Sep 11, 2002||Nov 7, 2006||Pfizer Inc.||Infectious cDNA clone of North American porcine reproductive and respiratory syndrome (PRRS) virus and uses thereof|
|US7232680||Apr 22, 2002||Jun 19, 2007||Pfizer Inc.||Infectious cDNA clone of North American porcine reproductive and respiratory syndrome (PRRS) virus and uses thereof|
|US7255877||Mar 31, 1999||Aug 14, 2007||Jagotec Ag||Fenofibrate microparticles|
|US7425543||Aug 29, 2002||Sep 16, 2008||The Corporation Of Mercer University||Microencapsulated materials and method of making same|
|US7618797||Oct 25, 2006||Nov 17, 2009||Pfizer Inc|
|US7691389||Mar 1, 2006||Apr 6, 2010||Pfizer Inc||Infectious cDNA clone of north american porcine reproductive and respiratory syndrome (PRRS) virus and uses thereof|
|US7763238 *||Jan 15, 2003||Jul 27, 2010||Monell Chemical Senses Center||Olfactory adaptation and cross-adapting agents to reduce the perception of body odors|
|US7939105||Nov 19, 1999||May 10, 2011||Jagotec Ag||Process for preparing a rapidly dispersing solid drug dosage form|
|US7939106||May 23, 2003||May 10, 2011||Jagotec Ag||Process for preparing a rapidly dispersing solid drug dosage form|
|US8147896 *||Mar 14, 2007||Apr 3, 2012||Nestec S.A.||Solid product comprising oil-droplets|
|US8206746||Sep 30, 2002||Jun 26, 2012||Jagotec Ag||Microparticles of water-insoluble substances|
|US8383131||Apr 13, 2011||Feb 26, 2013||Boehringer Ingelheim Vetmedica, Inc.||Porcine reproductive and respiratory syndrome isolates and methods of use|
|US8399187||Oct 8, 2009||Mar 19, 2013||Regents Of The University Of Minnesota||Identifying virally infected and vaccinated organisms|
|US8415329||May 28, 1999||Apr 9, 2013||Jagotec Ag||Thermoprotected compositions and process for terminal steam sterilization of microparticle preparations|
|US8481705||Nov 17, 2009||Jul 9, 2013||Zoetis Llc|
|US8492132||Oct 28, 2009||Jul 23, 2013||Zoetis Llc||Infectious cDNA clone of north american porcine reproductive and respiratory syndrome (PPRS) virus and uses thereof|
|US8546124||Sep 29, 2005||Oct 1, 2013||Boehringer Ingelheim Vetmedica Gmbh||Infectious clones of RNA viruses and vaccines and diagnostic assays derived thereof|
|US8586094||May 2, 2003||Nov 19, 2013||Jagotec Ag||Coated tablets|
|US8609827||Nov 10, 2009||Dec 17, 2013||Zoetis Llc|
|US8668930||Mar 29, 2006||Mar 11, 2014||Mycone Dental Supply Co., Ltd.||Durable film coating compositions having sustained slow-release capability, and methods of use therefor|
|US8684739||Mar 14, 2003||Apr 1, 2014||Mycone Dental Supply Co., Inc.||Durable film coating compositions having sustained slow-release capability, and methods of use therefor|
|US8703202||Jul 24, 2006||Apr 22, 2014||Jagotec Ag||Coated tablets|
|US8741309||Jul 24, 2006||Jun 3, 2014||The United States Of America As Represented By The Secretary Of Agriculture||Porcine reproductive and respiratory syndrome vaccine based on isolate JA-142|
|US8747859||Feb 20, 2009||Jun 10, 2014||The United States Of America, As Represented By The Secretary Of Agriculture||Porcine reproductive and respiratory syndrome vaccine based on isolate JA-142|
|US8765142||Feb 14, 2012||Jul 1, 2014||Boehringer Ingelheim Vetmedica Gmbh||European PRRSV strain|
|US8790656||Jun 8, 2006||Jul 29, 2014||Boehringer Ingelheim Vetmedica Gmbh||PRRSV vaccines|
|US8846388||Apr 16, 2010||Sep 30, 2014||Zoetis Llc||Infectious clones of torque teno virus|
|US8895025||Oct 29, 2009||Nov 25, 2014||Zoetis Llc||Infectious cDNA of north american porcine reproductive and respiratory syndrome (PRRS) virus and uses thereof|
|US8921535||Apr 16, 2010||Dec 30, 2014||Zoetis Llc||Infectious clones of torque teno virus|
|US8969536||Oct 16, 2009||Mar 3, 2015||Zoetis Llc||Torque teno virus (TTV) isolates and compositions|
|US9080143||Oct 19, 2011||Jul 14, 2015||University Of Minnesota||PRRS viruses, infectious clones, mutants thereof, and method of use|
|US9149441||Sep 29, 2009||Oct 6, 2015||The Corporation Of Mercer University||Nanospheres encapsulating bioactive material and method for formulation of nanospheres|
|US9187731||Jul 26, 2012||Nov 17, 2015||Boehringer Ingelheim Vetmedica Gmbh||PRRS virus inducing type I interferon in susceptible cells|
|US9315781||Jul 30, 2012||Apr 19, 2016||Boehringer Ingelheim Vetmedica Gmbh||Infectious CDNA clone of european PRRS virus and uses thereof|
|US9561270||Sep 2, 2010||Feb 7, 2017||Boehringer Ingelheim Vetmedica, Inc.||Methods of reducing virucidal activity in PCV-2 compositions and PCV-2 compositions with an improved immunogenicity|
|US9566324||Nov 9, 2011||Feb 14, 2017||Zoetis Services Llc||North American porcine reproductive and respiratory syndrome (PRRS) virus and uses thereof|
|US9579373||Mar 12, 2014||Feb 28, 2017||Boehringer Ingelheim Vetmedica, Inc.||Porcine reproductive and respiratory syndrome virus, compositions, vaccine and methods of use|
|US20020098573 *||Jun 5, 2001||Jul 25, 2002||Meulenberg Johanna Jacoba Maria||Infectious clones of RNA viruses and vaccines and diagnostic assays derived thereof|
|US20020119199 *||Mar 31, 1999||Aug 29, 2002||Indu Parikh||Fenofibrate microparticles|
|US20020172690 *||Apr 22, 2002||Nov 21, 2002||Calvert Jay G.||Infectious cDNA clone of north american porcine reproductive and respiratory syndrome (PRRS) virus and uses thereof|
|US20030013693 *||Apr 22, 2002||Jan 16, 2003||Rtp Pharma Inc.||Method and composition for treatment of inflammatory conditions|
|US20030049274 *||Sep 7, 2001||Mar 13, 2003||Janneke Meulenberg||PRRSV vaccines|
|US20030152538 *||Jan 15, 2003||Aug 14, 2003||George Preti||Olfactory adaptation and cross-adapting agents to reduce the perception of body odors|
|US20030157689 *||Sep 11, 2002||Aug 21, 2003||Calvert Jay G.|
|US20030175347 *||Mar 14, 2003||Sep 18, 2003||Steffier Larry W.||Durable film coating compositions having sustained slow-release capability, and methods of use therefor|
|US20030194442 *||May 19, 2003||Oct 16, 2003||Skyepharma Canada Inc||Insoluble drug particle compositions with improved fasted-fed effects|
|US20040018229 *||Jun 9, 2003||Jan 29, 2004||Henriksen Inge B.||Insoluble drug delivery|
|US20040043079 *||Aug 29, 2002||Mar 4, 2004||D'souza Martin J.||Microencapsulated materials and method of making same|
|US20040086571 *||Mar 17, 2003||May 6, 2004||Skyepharma Canada Inc.||Fibrate-statin combinations with reduced fed-fasted effects|
|US20040091535 *||May 2, 2003||May 13, 2004||Skyepharma Canada Inc.||Coated tablets|
|US20040197872 *||Dec 30, 2003||Oct 7, 2004||Meulenberg Johanna Jacoba Maria||Infectious clones of RNA viruses and vaccines and diagnostic assays derived thereof|
|US20040224327 *||Dec 30, 2003||Nov 11, 2004||Meulenberg Johanna Jacoba Maria||Infectious clones of RNA viruses and vaccines and diagnostic assays derived thereof|
|US20050095258 *||Nov 29, 2004||May 5, 2005||Manuel Campos||Fusion proteins comprising carriers that can induce a dual immune response|
|US20050107259 *||Dec 22, 2004||May 19, 2005||Taylor Pursell||Controlled release agricultural products and processes for making same|
|US20060183113 *||Mar 1, 2006||Aug 17, 2006||Calvert Jay G||Infectious cDNA clone of north american porcine reproductive and respiratory syndrome (PRRS) virus and uses thereof|
|US20060198890 *||Mar 29, 2006||Sep 7, 2006||Keystone Industries|
|US20060205033 *||Sep 29, 2005||Sep 14, 2006||Boehringer Ingelheim Vetmedica Gmbh||Infectious clones of RNA viruses and vaccines and diagnostic assays derived thereof|
|US20060210622 *||Nov 14, 2005||Sep 21, 2006||Skyepharma Canada Inc.||Surface modified particulate compositions of biologically active substances|
|US20060240041 *||Jun 8, 2006||Oct 26, 2006||Meulenberg Johanna J M||PRRSV Vaccines|
|US20060257494 *||Jul 24, 2006||Nov 16, 2006||Michael Vachon||Coated tablets|
|US20070042000 *||Jul 24, 2006||Feb 22, 2007||Mengeling William L||Porcine reproductive and respiratory syndrome vaccine based on isolate ja-142|
|US20070116720 *||Oct 25, 2006||May 24, 2007||Calvert Jay G|
|US20070197670 *||Feb 23, 2006||Aug 23, 2007||International Business Machines Corporation||Rigidized compliant foam and method for implementing a rigidized compliant foam|
|US20080233219 *||Feb 27, 2008||Sep 25, 2008||Nature Technology Inc.||Composition for diet comprising plant essential oil as active ingredient, sheet type composition for diet comprising thereof, percutaneous pharmaceutical agent for diet comprising thereof, and method for producing thereof|
|US20090078918 *||Sep 25, 2007||Mar 26, 2009||Cary Michael Huettner||Methods and Structures With Fire Retardant Spheres for Implementing Enhanced Fire Protection|
|US20090081306 *||Sep 8, 2008||Mar 26, 2009||The Corporation Of Mercer University||Microencapsulated materials and method of making same|
|US20090258786 *||Apr 3, 2009||Oct 15, 2009||Taylor Pursell||Controlled release agricultural products and processes for making the same|
|US20090304896 *||Mar 14, 2007||Dec 10, 2009||Nestec S.A.||Solid product comprising oil-droplets|
|US20100035276 *||Oct 8, 2009||Feb 11, 2010||Regents of of the University of Minnesota||Identifying virally infected and vaccinated organisms|
|US20100111984 *||Sep 29, 2009||May 6, 2010||The Corporation Of Mercer University||Nanospheres encapsulating bioactive material and method for formulation of nanospheres|
|US20110059126 *||Sep 2, 2010||Mar 10, 2011||Boehringer Ingelheim Vetmedica, Inc.||Methods of reducing virucidal activity in pcv-2 compositions and pcv-2 compositions with an improved immunogenicity|
|US20110064758 *||Apr 16, 2010||Mar 17, 2011||Pfizer Inc.||Infectious clones of torque teno virus|
|US20110104201 *||Feb 20, 2009||May 5, 2011||Mengeling William L||Porcine Reproductive and Respiratory Syndrome Vaccine Based on Isolate JA-142|
|US20110117129 *||Aug 24, 2009||May 19, 2011||Boehringer Ingelheim Vetmedica, Inc.||Vaccine Against Highly Pathogenic Porcine Reproductive and Respiratory Syndrome (HP PRRS)|
|US20110150913 *||Oct 16, 2009||Jun 23, 2011||Pfizer Inc.||Torque teno virus (ttv) isolates and compositions|
|US20110195088 *||Apr 13, 2011||Aug 11, 2011||Boehringer Ingelheim Vetmedica, Inc.||Porcine Reproductive and Respiratory Syndrome Isolates and Methods of Use|
|US20120034337 *||Dec 29, 2009||Feb 9, 2012||Friesland Brands B.V.||Protein particles and their use in food|
|USB498208 *||Aug 16, 1974||Apr 13, 1976||Title not available|
|USRE29066 *||Mar 15, 1974||Dec 7, 1976||Minnesota Mining And Manufacturing Company||Biodegradable radioactive particles|
|USRE32713 *||Mar 3, 1986||Jul 12, 1988||Capsule impregnated fabric|
|EP0093668A1 *||Apr 29, 1983||Nov 9, 1983||Etablissement Public dit: CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS)||Microcapsules having a wall of reticulately bound milk proteins, and method for their preparation|
|EP0349428A1 *||Jun 28, 1989||Jan 3, 1990||Centre National De La Recherche Scientifique (Cnrs)||Process for preparing colloidal dispersive protein systems in the shape of nanoparticles|
|EP1627919A1||Nov 25, 1999||Feb 22, 2006||Pfizer Products Inc.||An infectious cDNA clone of North American porcine reproductive and respiratory syndrome (PRRS) virus and uses thereof|
|WO1979000111A1 *||Aug 24, 1978||Mar 8, 1979||Blue Wing Corp||Improved lipid-containing feed supplements and foodstuffs|
|WO1982001994A1 *||Dec 9, 1981||Jun 24, 1982||Univ Ohio||Implants,microbeads,microcapsules,and method for their preparation|
|WO1984000304A1 *||Jul 8, 1982||Feb 2, 1984||Mitchell Harman||Injectible sustained release dosage cylinders|
|WO1985000011A1 *||Jun 14, 1984||Jan 3, 1985||Univ Miami||Microdroplets of water-insoluble drugs|
|WO1991005482A1 *||Oct 15, 1990||May 2, 1991||The Regents Of The University Of California||Method to produce unsaturated milk fat and meat from ruminant animals|
|WO2010044889A2||Oct 16, 2009||Apr 22, 2010||Pfizer Inc.||Torque teno virus (ttv) isolates and compositions|
|WO2012168818A1||May 24, 2012||Dec 13, 2012||Ah Usa 42 Llc||Infectious clones of torque teno virus|
|U.S. Classification||424/491, 131/337, 426/98, 264/4.1, 428/402.2, 264/4, 512/4, 162/158, 264/4.7|
|International Classification||A61K9/50, B01J13/08, B01J13/06|
|Cooperative Classification||B01J13/08, A61K9/50|
|European Classification||A61K9/50, B01J13/08|