WO2011161666A2

WO2011161666A2 - Enclosed liquid capsules

Info

Publication number: WO2011161666A2
Application number: PCT/IL2011/000314
Authority: WO
Inventors: Doron Marco; Shany Peled; Yariv Ziv; Shlomi Eiger
Original assignee: White Innovation Ltd.
Priority date: 2010-06-21
Filing date: 2011-04-14
Publication date: 2011-12-29
Also published as: WO2011161666A3

Abstract

A method of enclosing liquids including the steps of encapsulating a first material within a second material to produce a capsule, locating the capsule in a liquid material to which the second material is permeable, and providing a liquid-enclosing capsule by allowing the liquid material to pass through the second material and thereby to be enclosed by the second material.

Description

ENCLOSED LIQUID CAPSULES

REFERENCE TO RELATED APPLICATIONS

Reference is made to U.S. Provisional Patent Application Serial No. 61/356,929, filed June 21, 2010 and entitled "COMPOSITION FOR TREATING CONSTIPATION", the disclosure of which is hereby incorporated by reference and priority of which is hereby claimed pursuant to 37 CFR 1.78(a) (4) and (5)(i).

FIELD OF THE INVENTION The present invention relates to the formation of enclosed liquid capsules.

BACKGROUND OF THE INVENTION

The following patents and publications are believed to represent the current state of the art:

U.S. Patent No.: 5,593,697; and

Agyilirah, G. A. and Banker, G.S., "Polymers for Enteric Coating Applications" in Polymers for Controlled Drug Delivery, Tarcha, P.J., ed., CRC Press (1991) Boca Raton, pp. 39-66;

Kenyon, C.J., et al., Int. J. Pharm. 112:207-213 (1994);

Levine et al., Gastroenterology 92:1037-1044 (1987); and

Rasmussen, S.N., et al, Gastroenterology 83:1062 (1982). SUMMARY OF THE INVENTION

The present invention provides methods for the formation of enclosed liquid capsules. There is thus provided in accordance with a preferred embodiment of the present invention a method of enclosing liquids including the steps of encapsulating a first material within a second material to produce a capsule, locating the capsule in a liquid material to which the second material is permeable, and providing a liquid- enclosing capsule by allowing the liquid material to pass through the second material and thereby to be enclosed by the second material.

Preferably, the first material is soluble in the liquid. Preferably, the second material is permeable also to the first material, when dissolved in the liquid.

In accordance with a preferred embodiment of the present invention, the liquid enclosing capsule is a leaky capsule wherein the liquid leaks from the leaky capsule unless retained therein by osmotic pressure.

Alternatively, the liquid enclosing capsule is a non-leaky capsule. Preferably, the second material includes at least one expandable component which effectively seals the liquid enclosed by second material against egress of the liquid therethrough.

Preferably, the method also includes the step of placing the liquid- enclosing capsule in a different liquid which is immiscible with the liquid. Preferably, the method also includes the step of forming a coating over the second material, which coating is impermeable to the liquid.

Preferably, the first material contains an active ingredient and the amount of the liquid in which the first material is dissolved enclosed within the second material governs the concentration of the active ingredient in the liquid enclosing capsule. Alternatively, the first material contains an active ingredient and liquid contains the active ingredient in a dissolved form and the amount of the liquid enclosed within the second material governs the concentration of the active ingredient in the liquid enclosing capsule. Alternatively, the first material does not contain an active ingredient and the liquid contains an active ingredient in a dissolved form. Preferably, the second material includes at least one of ethyl cellulose, cellulose acetate, cellulose acetate phthalate, polyethylene glycol, Eudragit LI 00, methyl cellulose, polyketal, polylactic acid, starch-based polymers, aromatic aliphatic co-polyesters and polyhydroxyalkanoates (PHA).

There is also provided in accordance with another preferred embodiment of the present invention an at least partially encapsulated liquid including a liquid surrounded by an enclosing material which is permeable to the liquid, thereby providing a leaky liquid enclosing capsule.

In accordance with a preferred embodiment of the present invention, the enclosing material is coated with a material that is generally impermeable to the liquid. Additionally or alternatively, the at least partially encapsulated liquid also includes an enclosed material surrounded by the enclosing material. Preferably, the enclosed material is at least partially dissolved in the liquid surrounded by the enclosing material. Alternatively, the enclosed material is not dissolved in the liquid.

Preferably, the at least partially encapsulated liquid is located in a non- encapsulated liquid. Preferably, the non-encapsulated liquid is immiscible with the liquid surrounded by the enclosing material. Alternatively, the non-encapsulated liquid is identical to the liquid surrounded by the enclosing material.

Preferably, the enclosing material includes at least one of ethyl cellulose, cellulose acetate, cellulose acetate phthalate, polyethylene glycol, Eudragit LI 00, methyl cellulose, polyketal, polylactic acid, starch-based polymers, aromatic aliphatic co-polyesters and polyhydroxyalkanoates (PHA).

There is further provided in accordance with yet another preferred embodiment of the present invention an article of manufacture including a first liquid, and a multiplicity of leaky capsules located in the liquid, each of the multiplicity of leaky capsules including a second liquid surrounded by an enclosing material which is at least partially permeable to the first and second liquids.

In accordance with a preferred embodiment of the present invention, the first liquid and the second liquids are identical. Alternatively, the first liquid and the second liquids are identical aside from their respective concentrations. Alternatively, the first liquid and the second liquids are different. Preferably, the first liquid and the second liquid are different only in their respective concentrations. In accordance with a preferred embodiment of the present invention, the first liquid and the second liquids are mutually immiscible. Preferably, the enclosing material includes at least one of ethyl cellulose, cellulose acetate, cellulose acetate phthalate, polyethylene glycol, Eudragit LI 00, methyl cellulose, polyketal, polylactic acid, starch-based polymers, aromatic aliphatic co-polyesters and polyhydroxyalkanoates (PHA).

There is yet further provided in accordance with still another preferred embodiment of the present invention an article of manufacture including a first material encapsulated by a second material which is water permeable, the first material being in a first inoperative state in the absence of water and transforming to a second operative state upon engagement therewith with at least a predetermined quantity of water permeating through the second material.

Preferably, the second material includes at least one of ethyl cellulose, cellulose acetate, cellulose acetate phthalate, polyethylene glycol, Eudragit LI 00, methyl cellulose, polyketal, polylactic acid, starch-based polymers, aromatic aliphatic co-polyesters and polyhydroxyalkanoates (PHA).

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will be understood and appreciated more fully from the following detailed description, taken in conjunction with the drawings in which:

Fig. 1 is a simplified illustration of an initial stage in a method of formation of enclosed liquid capsules in accordance with a preferred embodiment of the present invention;

Figs. 2A, 2B and 2C are simplified illustrations of exemplary further stages in a method of formation of enclosed liquid capsules in accordance with a preferred embodiment of the present invention;

Fig. 3 is a simplified illustration of optional coating of an enclosed liquid capsule constructed and operative in accordance with a preferred embodiment of the present invention;

Figs. 4A, 4B and 4C are simplified illustrations of liquid release from enclosed liquid capsules of the types shown in Figs. 2A, 2B and 2C respectively in a non-liquid environment;

Figs. 5A, 5B, 5C and 5D are simplified illustrations of liquid release from enclosed liquid capsules of the types shown in Figs. 2A, 2B, 2C and 3 respectively in a liquid environment;

Figs. 6A, 6B, 6C and 6D are simplified pictorial illustrations of use of the enclosed liquid capsules of the present invention administered by mouth for various types of medical applications;

Figs. 7A and 7B are simplified pictorial illustrations of use of multiple types of enclosed liquid capsules of the present invention adiiinistered by mouth for two additional types of medical application;

Fig. 8 is a simplified pictorial illustration of incorporation of the enclosed liquid capsules of the present invention in a bandage;

Figs. 9A and 9B are simplified pictorial illustrations of use of the enclosed liquid capsules of the present invention administered by mouth for two further types of medical application; Fig. 10 is a simplified pictorial illustration of incorporation of the enclosed liquids of the present invention in a low calorie chocolate product;

Figs. 11 A and 1 IB are simplified pictorial illustrations of incorporation of the enclosed liquid capsules of the present invention containing alcoholic beverages in food products;

Figs. 12A and 12B are simplified pictorial illustrations of incorporation of the enclosed liquid capsules of the present invention in slow release arinks;

Fig. 13 is a simplified pictorial illustration of incorporation of the enclosed liquids of the present invention in a timed release cosmetic product;

Fig. 14 is a simplified pictorial illustration of the use of the enclosed liquids of the present invention in a timed release horticultural spray;

Fig. 15 is a simplified pictorial illustration of the use of the enclosed liquids of the present invention in a seed strip;

Fig. 16 is a simplified pictorial illustration of the use of the enclosed liquids of the present invention in a Ph buffer strip;

Figs. 17A and 17B are simplified pictorial illustrations of the use of the enclosed liquids of the present invention in fish ponds;

Fig. 18 is a simplified pictorial illustration of the use of the enclosed liquids of the present invention in concrete;

Figs. 19A and 19B are simplified pictorial illustrations of incorporation of the enclosed liquid capsules of the present invention in narcotic-containing drugs;

Figs. 20A and 20B are simplified pictorial illustrations of an alternative method of incorporation of the enclosed liquid capsules of the present invention in narcotic-containing drugs; and

Figs. 21A and 2 IB are simplified pictorial illustrations of another alternative method of incorporation of the enclosed liquid capsules of the present invention in narcotic-containing drugs. DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

Reference is made to Fig. 1, which is a simplified illustration of an initial stage in a method of formation of enclosed liquid capsules in accordance with a preferred embodiment of the present invention, and to Figs. 2A, 2B and 2C, which are simplified illustrations of exemplary further stages in the method of formation of enclosed liquid capsules in accordance with a preferred embodiment of the present invention. The method comprises the steps of encapsulating a first material within a second material to produce a capsule, locating said capsule in a liquid material to which said second material is permeable, and providing a liquid-enclosing capsule by allowing said liquid material to pass through said second material and thereby to be enclosed by said second material.

As shown in Fig. 1, a plurality of particles 100 of a preferably soluble material, such as sugar, are initially encapsulated within a preferably semi-permeable material 102, thereby forming a plurality of capsules 104. Semi-permeable material 102 may comprise, for example, at least one of ethyl cellulose, cellulose acetate, cellulose acetate phthalate, polyethylene glycol, Eudragit LI 00, methyl cellulose, polyketal, polylactic acid, starch-based polymers, aromatic aliphatic co-polyesters and polyhydroxyalkanoates (PHA).

Capsules 104 are then preferably immersed in a liquid 106 to which material 102 is semi-permeable, thereby allowing capsules 104 to absorb liquid 106. Preferably, liquid 106 has an osmolality which is lower than the osmolality of particles 100.

Turning now to Fig. 2 A, it is shown that optionally, liquid 106, having a lower osmolality than the osmolality of particles 100, flows into capsules 104 through semi-permeable material 102, and the soluble material of particles 100 flows out of capsules 104 through semi-permeable material 102, resulting in capsules 104 containing only liquid material 106.

Alternatively, as shown in Fig. 2B, semi-permeable material 102 is capable of absorbing liquid 106. Absorption of liquid material 106 in material 102 results in capsules 104 containing particles 100 which are encapsulated in a layer of semi-permeable material 102 that is saturated with liquid 106.

Alternatively, as shown in Fig. 2C, liquid material 106, having a lower osmolality than the osmolality of particles 100, flows into capsules 104 through semipermeable material 102, and the soluble material of particles 100 flows out of capsules 104 through semi-permeable material 102, resulting in capsules 104 containing only liquid material 106. Additionally, absorption of liquid material 106 causes pores in semi-permeable material 102 to close, thereby sealing semi-permeable material 102.

Reference is now made to Fig. 3, which is a simplified illustration of optional coating of an enclosed liquid capsule constructed and operative in accordance with a preferred embodiment of the present invention. As shown in Fig. 3, after absorbing liquid material 106, capsules 104 of either of Figs. 2A, 2B and 2C are optionally coated with an additional non-permeable sealing layer 110. It is appreciated that sealing layer 110 may be sensitive to pH levels in its immediate surroundings, and that relatively low pH levels may cause disintegration of sealing layer 110.

Reference is now made to Figs. 4A, 4B and 4C, which are simplified illustrations of liquid release from enclosed liquid capsules of the types shown in Figs. 2A, 2B and 2C respectively in a non-liquid environment. As shown in Fig. 4A, when capsules 104 of Fig. 2A are placed in a non-liquid environment, the osmolality of liquid 106 encapsulated in capsules 104 is higher than the osmolality of the non-liquid environment. Therefore, as shown in Fig. 4A, liquid 106 gradually leaks out of capsules 104 through semi-permeable material 102, until capsules 104 are totally void of liquid 106.

Alternatively, as shown in Fig. 4B, when capsules 104 of Fig. 2B are placed in a non-liquid environment, the osmolality of liquid 106 absorbed within the semi-permeable material 102 of capsules 104 is higher than the osmolality of the non- liquid environment. Therefore, as shown in Fig. 4B, liquid 106 gradually leaks out of the semi-permeable material 102 of capsules 104, until the semi-permeable material 102 is totally void of liquid 106, and particles 100 remain coated in a thin layer of semipermeable material 102. Alternatively, as shown in Fig. 4C, when capsules 104 of Fig. 2C are placed in a non-liquid environment, material 102 gradually disintegrates, thereby allowing liquid 106 to escape from capsules 104 into the non-liquid environment.

Reference is now made to Figs. 5A, 5B, 5C and 5D, which are simplified illustrations of liquid release from enclosed liquid capsules of the types shown in Figs. 2A, 2B, 2C and 3 respectively, in a liquid environment. As shown in Fig. 5A, when capsules 104 of Fig. 2 A are placed in a liquid environment 120 having an osmolality which is lower than the osmolality of liquid 106 within capsules 104, liquid 106 gradually leaks out of capsules 104 through semi-permeable material 102 into liquid environment 120, until capsules 104 are totally void of liquid 106.

Alternatively, as shown in Fig. 5B, when capsules 104 of Fig. 2B are placed in liquid environment 120 having an osmolality which is lower than the osmolality of liquid 106 absorbed within semi-permeable material 102, liquid 106 gradually leaks out of the semi-permeable material 102 of capsules 104, until semipermeable material 102 is totally void of liquid 106, and particles 100 remain coated in a thin layer of semi-permeable material 102.

Alternatively, as shown in Fig. 5C, when capsules 104 of Fig. 2C are placed in a liquid environment 120 having a relatively low pH level, material 102 gradually disintegrates, thereby allowing liquid 106 to escape from capsules 104 into liquid environment 120.

Alternatively, as shown in Fig. 5D, when capsules 104 which are optionally coated with an additional non-permeable sealing layer 110 as shown in Fig. 3 are placed in a liquid environment 120 having a relatively low pH level, the additional non-permeable sealing layers 110 of capsules 104 gradually disintegrate, thereby exposing capsules 104 to the liquid environment. Liquid 106 encapsulated in capsules 104 is then released into the liquid environment as shown in Figs. 5A - 5C.

Reference is now made to Figs. 6A, 6B, 6C and 6D, which are simplified pictorial illustrations of use of the enclosed liquid capsules of the present invention administered by mouth for various types of medical applications. As shown in Fig. 6A, at 8:00 AM, a patient suffering from constipation ingests a solution 130 containing a multiplicity of capsules 132, each of capsules 132 containing a liquid 134 encapsulated merewithin. After several hours, such as at 4:00 PM, capsules 132 enter the patient's large intestine 136 which, due the patient's condition, is relatively void of liquids. At a later time, such as at 8:00 PM, liquid 134 encapsulated in capsules 132 begins to flow out of capsules 132 into large intestine 136 due to the relatively lower osmolality of large intestine 136. After several additional hours, such as at 8:00 AM the next morning, it is seen that all of liquid 134 encapsulated in capsules 132 has flowed out of capsules 132 into large intestine 136. At a later time, such as at 9:00 AM, intestine 136 has absorbed all of liquid 134, and the remaining portions of capsules 132 have been excreted.

Turning now to Fig. 6B, it is shown that at 8:00 AM a patient ingests a solution 140 containing a multiplicity of capsules 142, each of capsules 142 containing a liquid drug 144 encapsulated therewithin. After several hours, such as at 4:00 PM, capsules 142 enter the patient's large intestine 146. At a later time, such as at 8:00 PM, drug 144 encapsulated in capsules 142 begins to flow out of capsules 142 into large intestine 146 due to the relatively lower osmolality of large intestine 146. After several additional hours, such as at 8:00 AM the next morning, it is seen that all of drug 144 encapsulated in capsules 142 has flowed out of capsules 142 into large intestine 146. At a later time, such as at 8:00 PM, intestine 146 has absorbed all of drug 144, and the remaining portions of capsules 142 have been excreted.

Turning now to Fig. 6C, it is shown that at 8:00 AM a patient ingests a solution 150 containing a multiphcity of capsules 152, each of capsules 152 containing a liquid drug 154 encapsulated therewithin. After several hours, such as at 4:00 PM, capsules 152 enter the patient's small intestine 156. At a later time, such as at 8:00 PM, drug 154 encapsulated in capsules 152 begins to flow out of capsules 152 into small intestine 156 due to the relatively lower osmolality of small intestine 156. After several additional hours, such as at 8:00 AM the next morning, it is seen that all of drug 154 encapsulated in capsules 152 has flowed out of capsules 152 into small intestine 156. At a later time, such as at 8:00 PM, intestine 156 has absorbed all of drug 154, and the remaining portions of capsules 152 have been excreted.

Turning now to Fig. 6D, it is shown that at 8:00 AM a patient ingests a solution 160 containing a multiplicity of capsules 162, each of capsules 162 containing a liquid drug 164 encapsulated Iherewithin. After several hours, such as at 4:00 PM, capsules 162 enter the patient's stomach 166. At a later time, such as at 8:00 PM, drug 164 encapsulated in capsules 162 begins to flow out of capsules 162 into stomach 166 due to the relatively lower osmolarity of stomach 166. After several additional hours, such as at 8:00 AM the next morning, it is seen that all of drug 164 encapsulated in capsules 162 has flowed out of capsules 162 into stomach 166. At a later time, such as at 9:00 AM, stomach 166 has absorbed all of drug 164, and the remaining portions of capsules 162 have been excreted.

Reference is now made to Figs. 7A and 7B, which are simplified pictorial illustrations of use of multiple types of enclosed liquid capsules of the present invention administered by mouth for two additional types of medical application. As shown in Fig. 7A, at 8:00 AM a patient ingests a solution 170 containing a multiplicity of capsules of various types, such as capsules 172 of the type of capsule of Fig. 2A, capsules 174 of the type of capsule of Fig. 2B and capsules 176 of the type of capsule of Fig. 2C. Each of capsules 172, 174 and 176 may contain a different liquid or drug. It is appreciated that different types capsules may release the liquid encapsulated merewithin at different time rates. Therefore, the use of multiple types of capsules preferably provides for a longer time release mechanism than the use of a single type of capsule as shown in Figs. 6A - 6D.

As seen in Fig. 7A, several hours after ingesting solution 170, such as at 4:00 PM, capsules 172, 174 and 176 enter the patient's small intestine 178. After several additional hours, such as at 8:00 PM, capsules 176 begin to disintegrate, due to the relatively low pH level of small intestine 178, thereby releasing liquid 179 enclosed therewithin into small intestine 178. Liquid 180 encapsulated in capsules 172 also begins to flow out of capsules 172 into small intestine 178 due to the relatively lower osmolarity of small intestine 178. After several additional hours, such as at 8:00 AM the next morning, capsules 176 are completely disintegrated, and all of liquid 180 has flowed out of capsules 172 into small intestine 178. Additionally, liquid absorbed in the semi-permeable material 182 encapsulating capsule 174 begins to leak out of semipermeable material 182. After several additional hours, such as at 4:00 PM, semipermeable material 182 encapsulating capsule 174 is totally void of liquid, and encapsulated particles 184 remain coated in a thin layer of the semi-permeable material 182. After several additional hours, such as at 8:00 PM, it is shown that all remaining portions of capsules 172, 174 and 176 have been excreted. Turning now to Fig. 7B, it is shown that at 8:00 AM a patient ingests a solution 190 containing a multiplicity of capsules of various types, such as capsules 192 of the type of capsule of Fig. 2A, capsules 194 of the type of capsule of Fig. 2B and capsules 196 of the type of capsule of Fig. 2C. Each of capsules 192, 194 and 196 may contain a different liquid or drug. It is appreciated that different types capsules may release the liquid encapsulated merewithin at different time rates. Therefore, the use of multiple types of capsules preferably provides for a longer time release mechanism than the use of a single type of capsule as shown in Figs. 6A - 6D.

As seen in Fig. 7B, several hours after ingesting solution 170, such as at 4:00 PM, capsules 192, 194 and 196 enter the patient's stomach 198, and capsules 196 disintegrate due to the relatively low pH level of stomach 198, thereby releasing liquid 199 enclosed merewithin into stomach 198. After several additional hours, such as at 8:00 PM, capsules 192 and 194 reach the patient's small intestine 200, where liquid absorbed in the semi-permeable material 202 encapsulating capsule 194 begins to leak out of semi-permeable material 202. After several additional hours, such as at 8:00 AM the next morning, capsules 192 and 194 reach the patient's large intestine 206 where liquid 208 encapsulated in capsules 192 begins to flow out of capsules 192 into large intestine 206 due to the relatively lower osmolarity of large intestine 206. Additionally, the remainder of the liquid absorbed in semi-permeable material 202 encapsulating capsules 194 leaks out of semi-permeable material 202 into large intestine 206. After several additional hours, such as at 8:00 PM, it is shown that all remaining portions of capsules 192, 194 and 196 have been excreted.

Reference is now made to Fig. 8, which is a simplified pictorial illustration of incorporation of the enclosed liquid capsules of the present invention in a bandage. As shown in Fig. 8, at 8:00 AM on December 10, a burn victim wishing to bandage a burn on his forearm applies a bandage 210 which includes a multiplicity of capsules 220 of various types, such as capsules 222 of the type of capsule of Fig. 2A, capsules 224 of the type of capsule of Fig. 2B and capsules 226 of the type of capsule of Fig. 2C, each of which capsules 222, 224 and 226 may contain a different liquid or drug. It is appreciated that different types capsules may release the liquid encapsulated merewithin at different time rates. Therefore, the use of multiple types of capsules preferably provides for a longer time release mechanism than the use of a single type of capsule.

As seen in Fig. 8, several hours after applying bandage 210 to the patient's forearm such as at 10:00 PM, liquid 228 encapsulated in capsules 222 begins to flow out of capsules 222 into the patient's burn. Additionally, liquid absorbed in semi-permeable material 230 encapsulating capsules 224 leaks out of semi-permeable material 230 into the patient's burn, and capsules 226 begin to disintegrate. Several days later, such as by December 12, it is shown that all of liquid 228 encapsulated in capsules 222 has flowed out of capsules 222 into the patient's burn, and some of the liquid absorbed in semi-permeable material 230 encapsulating capsules 224 has flowed out of semi-permeable material 230 into the patient's bum.

As also shown in Fig 8., several days later, such as by December 14, all of the liquid absorbed in semi-permeable material 230 encapsulating capsules 224 has flowed out of semi-permeable material 230 into the patient's burn, and liquid 232 which was encapsulated in capsules 226 which have totally disintegrated has flowed out of capsules 226 into the patient's burn.

Reference is now made to Figs. 9A and 9B, which are simplified pictorial illustrations of use of the enclosed liquid capsules of the present invention adrninistered by mouth for two further types of medical application. As shown in Fig. 9A, at 8:00 AM, a patient ingests a solution 250 containing a multiplicity of capsules 252, each of capsules 252 containing a liquid 254 encapsulated merewithin. At a later time, such as at 9:00 AM, capsules 252 enter the patient's stomach 256. As shown in Fig. 9A, liquid 254 encapsulated in capsules 252 gradually flows out of capsules 252 into stomach 256 and a liquid 258 contained in patient's stomach 256 gradually flows into capsules 252 due to the osmolality of liquid 254 being lower than the osmolality of liquid 258.

As seen in Fig. 9A, by a later time, such as by 10:00 AM, liquid 258 has totally replaced liquid 254 in capsules 252. As further shown in Fig. 9A, by a later time, such as by 12:00 PM, capsules 252 exit the patient's stomach 256 and enter the patient's duodenum 260. It is appreciated that liquid 258 may comprise a substance which is harmful to the patient and therefore is preferably removed from the patient's stomach by the mechanism described hereinabove. Turning now to Fig. 9B, it is shown that at 8:00 AM, a patient ingests a solution 270 containing a multiplicity of capsules 272, each of capsules 272 containing a liquid 274 encapsulated therewithin. At a later time, such as at 12:00 PM, capsules 272 enter the patient's small intestine 276. As shown in Fig. 9B, liquid 274 encapsulated in capsules 272 gradually flows out of capsules 272 into small intestine 276 and liquid 278 contained in patient's small intestine 278 gradually flows into capsules 272 due to the osmolarity of liquid 274 being lower than the osmolarity of liquid 278.

As seen in Fig. 9B, by a later time, such as by 4:00 PM, liquid 278 has totally replaced liquid 274 in capsules 272. As further shown in Fig. 9B, by a later time, such as by 8:00 PM, small intestine 278 is totally void of capsules 272 which have been excreted. It is appreciated that liquid 278 may comprise a substance which is harmful to the patient and therefore is preferably removed from the patient's small intestine 278 by the mechanism described hereinabove.

Reference is now made to Fig. 10, which is a simplified pictorial illustration of incorporation of the enclosed liquids of the present invention in a low calorie chocolate product. As shown in Fig. 10, a plurality of capsules 300 enclosing a low calorie liquid 302 are introduced into a tank 304 of liquid chocolate 306. Liquid chocolate 306 is poured from tank 304 into molds 308 and is allowed to solidify into tablets of low calorie chocolate 310. It is appreciated that tablets 310 include less chocolate than a standard tablet of chocolate of the same volume, and therefore includes less calories than does a standard tablet of chocolate.

Reference is now made to Figs. 11A and 11B, which are simplified pictorial illustrations of incorporation of the enclosed liquid capsules of the present invention containing alcoholic beverages in food products. As shown in Fig. 11 A, doughnuts 320 are filled with a jelly filling 322. Filling 322 includes a plurality of capsules 324 each enclosing an alcoholic beverage 326. It is appreciated that the enclosing of alcoholic beverage 326 within capsules 324 is operative to prevent evaporation of alcoholic beverage 326 and to retain at least most of beverage 326 within doughnuts 320 until consumption thereof.

Turning now to Fig. 11B, capsules 330 each enclosing an alcoholic beverage 332 are embedded within ice cream popsicles 334. It is appreciated that the enclosing of alcoholic beverage 332 within capsules 330 is operative to prevent evaporation of alcoholic beverage 332 and to retain at least most of beverage 332 within ice cream popsicles 334 until consumption thereof.

Reference is now made to Figs. 12A and 12B, which are simplified pictorial illustrations of incorporation of the enclosed liquid capsules of the present invention in slow release drinks. As shown in Fig. 12A, at 8:00 AM, an individual ingests an energy drink 340 which includes a plurality of capsules 342 encapsulating particles 344, each of capsules 342 having a liquid 345 absorbed in the encapsulating semi-permeable material 346. Liquid 345 may be, for example, and alcoholic beverage or a caffeine-based substance.

After several hours, such as at 10:00 AM, capsules 342 enter the patient's small intestine 346. At a short time later, such as at 11:00 AM, liquid 345 begins to leak out of semi-permeable material 346 into the patient's small intestine 348. At a short time later, such as at 11 :40 AM, semi-permeable material 346 encapsulating each of capsules 342 is totally void of liquid 345, and encapsulated particles 344 remain coated in a thin layer of semi-permeable material 346.

Turning now to Fig. 12B, it is shown that a plurality of capsules 360 enclosing a liquid 362 are introduced into a mug of coffee 364 by a coffee machine 366. Liquid 362 may be, for example, a sweetener or an alcoholic beverage. It is appreciated that the enclosing of alcoholic liquid 362 within capsules 360 is preferably operative to prevent evaporation or dilution of liquid 362 and to retain at least most of liquid 362 within coffee 364 until consumption thereof.

As shown in Fig. 12B, at 8:00 AM, coffee 364 including capsules 360 which have retained most of liquid 362 is served to an individual for consumption. As seen in Fig. 12B, at a later time, such as at 11:00PM, capsules 360 reach the small intestine 368 of the individual in a decomposed state, after being decomposed in the digestive tract of the individual and after releasing hquid 362 therein.

Reference is now made to Fig. 13, which is a simplified pictorial illustration of incorporation of the enclosed liquids of the present invention in a timed release cosmetic product. As shown in Fig. 13, a plurality of capsules 380 each encapsulating a hquid 382 are disposed within a container of face cream 384. Liquid 382 may be, for example, a drug or an ointment. It is appreciated that the enclosing of liquid 382 within capsules 380 is preferably operative to prevent evaporation or dilution of liquid 382 and to retain at least most of liquid 382 within face cream 384 until use thereof.

As seen in Fig. 13, face cream 384 including capsules 380 which have retained most of liquid 382 is applied to the facial skin of an individual. Face cream 384 is then absorbed into the individual's facial skin where capsules 380 decompose and release liquid 382.

Reference is now made to Fig. 14, which is a simplified pictorial illustration of the use of the enclosed liquids of the present invention in a timed release horticultural spray. As shown in Fig. 14, at 10:00 AM on December 10, an aircraft 390 sprays a newly planted field 391 with a horticultural spray comprising capsules 392 each encapsulating a liquid 394. Liquid 394 may be, for example, a pesticide. It is appreciated that the enclosing of pesticide 394 within capsules 392 is operative to provide a slow release mechanism for pesticide 394.

As seen in Fig. 14, by a later date, such as by December 12 at 8:00 AM, some of pesticide 394 has been released from capsules 392 into the soil of field 391 and is effective is exterminating vermin from field 391. By a later date, such as by December 25, all of pesticide 394 has been released from capsules 392 into field 391 and crops 396 have commenced growth.

Reference is now made to Fig. 15, which is a simplified pictorial illustration of the use of the enclosed liquids of the present invention in a seed strip. As seen in Fig. 15, on December 10, multiple seed strips 400, each comprising a plurality of seeds 402 adhered thereon, and including a plurality of capsules 404 embedded therewithin are disposed in the ground of a greenhouse 406. Each of capsules 404 preferably encloses a liquid 408, such as water or nutrients needed by germinating seeds for growth. It is appreciated that the enclosing of liquid 408 within capsules 404 is operative to provide a slow release mechanism for liquid 408.

As seen in Fig. 15, by a later date, such as by December 15, at least some of liquid 408 has been released from capsules 404 into the ground of greenhouse 406, and seeds 402 have germinated into plants 410. By a later date, such as by December 25, all of liquid 408 has been released into the ground of greenhouse 406, further contributing to the growth of plants 410. Reference is now made to Fig. 16, which is a simplified pictorial illustration of the use of the enclosed liquids of the present invention in a pH buffer strip. As seen in Fig. 16, on December 10, multiple pH strips 420 each comprising a plurality of capsules 422 embedded therewithin are disposed in the ground of a greenhouse 426. Each of capsules 422 preferably encloses a liquid 428, such as a buffer operative to lower the pH of the ground of a greenhouse 426. It is appreciated that the enclosing of liquid 428 within capsules 422 is operative to provide a slow release mechanism for liquid 428.

As shown in Fig. 16, by a later date, such as by December 15, at least some of liquid 428 has been released from capsules 422 into the ground of greenhouse 426. By a later date, such as by December 25, all of liquid 428 has been released into the ground of greenhouse 426.

Reference is now made to Figs. 17A and 17B, which are simplified pictorial illustrations of the use of the enclosed liquids of the present invention in fish ponds. As seen in Fig. 17A, a plurality of capsules 440 each encapsulating a liquid 442 are introduced into a fish tank 444 containing fish 446. Liquid 442 may be, for example, a nutrient or a drug to be ingested by fish 446. It is appreciated that the enclosing of liquid 442 within capsules 440 is operative to provide a slow release mechanism for liquid 442. As seen in Fig. 17A, liquid 442 is gradually released into tank 444 and is gradually consumed by fish 446.

Turning now to Fig. 17B, it is shown that a plurality of capsules 450 each encapsulating a liquid 452 are introduced into a fish tank 454 containing fish 456. As shown in Fig. 17B, liquid 452 encapsulated in capsules 450 gradually flows out of capsules 450 into fish tank 454 and a liquid 458 contained in fish tank 454 gradually flows into capsules 450 due to the osmolality of liquid 452 being lower than the osmolality of liquid 458. It is appreciated that liquid 458 may comprise a substance which is harmful to the fish and therefore is preferably removed from fish tank 454 by the mechanism described hereinabove.

Reference is now made to Fig. 18, which is a simplified pictorial illustration of the use of the enclosed liquids of the present invention in concrete. As seen in Fig. 18, a cement mixture 460 comprising a plurality of capsules 462 is poured as part of the construction of a cement frame of a building 464. Each of capsules 462 preferably encloses water 466. It is appreciated that the enclosing of water 466 within capsules 462 is operative to provide a slow release mechanism for water 466, and that the introduction of water into a concrete mixture while in a drying phase after being poured is operative to increase the quality of the resulting hardened concrete.

As shown in Fig. 18, after concrete mixture 460 is poured, water 466 is slowly released from capsules 462 until capsules 462 are totally void of water 466.

Reference is now made to Figs. 19A and 19B, which are simplified pictorial illustrations of incorporation of the enclosed liquid capsules of the present invention in narcotic-containing drugs. As shown in Fig. 19A, at 9:00 AM, an individual ingests a drug tablet 500 containing a multiplicity of capsules 502 embedded therewithin. Preferably, each of capsules 502 is formed with a non-permeable sealing layer 504, such as the sealing layer of capsules 104 in Figs. 2C & 3. Preferably, each of capsules 502 contains a liquid 506 encapsulated merewithin. Preferably, liquid 506 is an antidote to the drug of tablet 500, whereby mixing of liquid 506 with the drug of tablet 500 results in nullification of the narcotic contained in the drag of tablet 500. As shown in Fig. 19A, drug tablet 500 is preferably digested in patient's stomach 510, while sealing layer 504 of capsules 502 remains intact and liquid 506 is not mixed with the drug of tablet 500.

At a later time, such as at 11:00 AM, intact capsules 502 enter the patient's small intestine 512. By a later time, such as by 3:00 PM, intact capsules 502 have been excreted from the patient's body.

Turning now to Fig. 19B it is shown that an individual attempts to obtain a concentrate of the narcotic contained in drug tablets 500 by grinding drug tablets 500 and extracting the narcotic substance contained therewithin. While grinding drug tablets 500, capsules 502 are ruptured and liquid 506 is mixed with the narcotic substance contained in drug tablets 500 thereby nullifying the narcotic and preventing the individual from obtaining a concentrate of the narcotic contained in drug tablets 500.

Reference is now made to Figs. 20A and 20B, which are simplified pictorial illustrations of an alternative method of incorporation of the enclosed liquid capsules of the present invention in narcotic-containing drugs. As shown in Fig. 20A, at 9:00 AM, an individual ingests a drug tablet 520 containing a multiplicity of first capsules 522 and second capsules 524 embedded within drug tablet 520. Preferably, each of capsules 522 and each of capsules 524 are formed with non-permeable sealing layers 526 and 528 respectively, such as the sealing layer of capsules 104 in Figs. 2C & 3. Each of capsules 522 preferably contains water 530 encapsulated therewithin, and each of capsules 524 preferably contains a gel 532 encapsulated therewithin. It is appreciated that mixing of water 530 and gel 532 results in a highly viscous mixture. As shown in Fig. 20A, drug tablet 520 is preferably digested in patient's stomach 540, while sealing layers 526 and 528 of capsules 522 and 524 remain intact and water 530 is not mixed with gel 532.

At a later time, such as at 11 :00 AM, intact capsules 522 and 524 enter the patient's small intestine 542. By a later time, such as by 3.00 PM, intact capsules 522 and 524 have been excreted from the patient's body.

Turning now to Fig. 20B it is shown that an individual attempts to obtain a concentrate of the narcotic contained in drug tablets 520 by grinding drug tablets 520 and extracting the narcotic substance contained merewithrn. While grinding drug tablets 520, capsules 522 and 524 are ruptured and water 530 previously encapsulated in capsules 522 is mixed with gel 532 previously encapsulated in capsules 524, forming a highly viscous mixture 544. Mixture 544 absorbs the narcotic substance contained in drug tablets 520 thereby preventing the individual from obtaining a concentrate of the narcotic contained in drug tablets 520.

Reference is now made to Figs. 21A and 21B, which are simplified pictorial illustrations of an alternative method of incorporation of the enclosed liquid capsules of the present invention in narcotic-containing drugs. As shown in Fig. 21 A, at 9:00 AM, an individual ingests a drug tablet 560 containing a multiplicity of capsules 562 embedded therewithin. Preferably, each of capsules 562 is formed with a non- permeable sealing layer 566, such as the sealing layer of capsules 104 in Figs. 2C & 3. Each of capsules 562 preferably contains water 570 encapsulated merewithrn. As shown in Fig. 21 A, drug tablet 560 is preferably digested in patient's stomach 580, while sealing layers 566 of capsules 562 remain intact.

At a later time, such as at 11:00 AM, intact capsules 562 enter the patient's small intestine 582. By a later time, such as by 3:00 PM, intact capsules 562 have been excreted from the patient's body. Turning now to Fig. 2 IB it is shown that an individual attempts to obtain a concentrate of the narcotic contained in drug tablets 560 by grinding drug tablets 560 and extracting the narcotic substance contained therewithin. While grinding drug tablets 560, capsules 562 are ruptured and water 570 previously encapsulated in capsules 562 absorbs the narcotic substance contained in drug tablets 560 thereby preventing the individual from obtaining a concentrate of the narcotic contained in drug tablets 560.

It will be appreciated by persons skilled in the art that the present invention is not limited by what has been particularly shown and described hereinabove. Rather the scope of the present invention includes both combinations and subcombinations of the various features described hereinabove as well as modifications thereof which would occur to persons skilled in the art upon reading the foregoing description and which are not in the prior art.

Claims

C L A I M S

1. A method of enclosing liquids comprising the steps of:

encapsulating a first material within a second material to produce a capsule;

locating said capsule in a liquid material to which said second material is permeable; and

providing a liquid-enclosing capsule by allowing said liquid material to pass through said second material and thereby to be enclosed by said second material.

2. A method of enclosing liquids according to claim 1 and wherein said first material is soluble in said liquid.

3. A method of enclosing liquids according to claim 2 and wherein said second material is permeable also to said first material, when dissolved in said liquid.

4. A method of enclosing liquids according to any of the preceding claims and wherein said liquid enclosing capsule is a leaky capsule wherein said liquid leaks from said leaky capsule unless retained therein by osmotic pressure.

5. A method of enclosing liquids according to any of claims 1- 3 and wherein said liquid enclosing capsule is a non-leaky capsule.

6. A method of enclosing liquids according to claim 5 and wherein said second material includes at least one expandable component which effectively seals said liquid enclosed by second material against egress of said liquid therethrough.

7. A method of enclosing liquids according to any of the preceding claims and also comprising the step of placing said liquid-enclosing capsule in a different liquid which is immiscible with said liquid.

8. A method of enclosing liquids according to any of the preceding claims and also comprising the step of forming a coating over said second material, which coating is impermeable to said liquid.

9. A method of enclosing liquids according to any of the preceding claims and wherein said first material contains an active ingredient and the amount of said liquid in which said first material is dissolved enclosed within said second material governs the concentration of said active ingredient in said liquid enclosing capsule.

10. A method of enclosing liquids according to any of the preceding claims 1

- 8 and wherein said first material contains an active ingredient and liquid contains said active ingredient in a dissolved form and the amount of said liquid enclosed within said second material governs the concentration of said active ingredient in said liquid enclosing capsule.

11. A method of enclosing liquids according to any of the preceding claims 1

- 8 and wherein said first material does not contain an active ingredient and said liquid contains an active ingredient in a dissolved form.

12. A method of enclosing liquids according to any of the preceding claims and wherein said second material comprises at least one of ethyl cellulose, cellulose acetate, cellulose acetate phthalate, polyethylene glycol, Eudragit LI 00, methyl cellulose, polyketal, polylactic acid, starch-based polymers, aromatic aliphatic co- polyesters and polyhydroxyalkanoates (PHA).

13. An at least partially encapsulated liquid comprising:

a liquid surrounded by an enclosing material which is permeable to said liquid, thereby providing a leaky liquid enclosing capsule.

14. An at least partially encapsulated liquid according to claim 13 and wherein said enclosing material is coated with a material that is generally impermeable to said liquid.

15. An at least partially encapsulated liquid according to claim 13 and also comprising an enclosed material surrounded by said enclosing material.

16. An at least partially encapsulated liquid according to claim 15 and wherein said enclosed material is at least partially dissolved in said liquid surrounded by said enclosing material.

17. An at least partially encapsulated liquid according to claim 15 and wherein said enclosed material is not dissolved in said liquid.

18. An at least partially encapsulated liquid according to any of claims 13 - 17 and wherein said at least partially encapsulated liquid is located in a non- encapsulated liquid.

19. An at least partially encapsulated liquid according to claim 18 and wherein said non-encapsulated liquid is immiscible with said liquid surrounded by said enclosing material.

20. An at least partially encapsulated liquid according to claim 18 and wherein said non-encapsulated liquid is identical to said hquid surrounded by said enclosing material.

21. A method of enclosing liquids according to any of the preceding claims 13 - 20 and wherein said enclosing material comprises at least one of ethyl cellulose, cellulose acetate, cellulose acetate phthalate, polyethylene glycol, Eudragit LI 00, methyl cellulose, polyketal, polylactic acid, starch-based polymers, aromatic aliphatic co-polyesters and polyhydroxyalkanoates (PHA).

22. An article of manufacture comprising:

a first hquid; and a multiplicity of leaky capsules located in said liquid, each of said multiplicity of leaky capsules comprising a second liquid surrounded by an enclosing material which is at least partially permeable to said first and second liquids.

23. An article of manufacture according to claim 22 and wherein said first liquid and said second liquids are identical.

24. An article of manufacture according to claim 22 and wherein said first liquid and said second liquids are identical aside from their respective concentrations.

25. An article of manufacture according to claim 22 and wherein said first liquid and said second liquids are different.

26. An article of manufacture according to claim 25 and wherein said first liquid and said second liquid are different only in their respective concentrations.

27. An article of manufacture according to claim 22 and wherein said first liquid and said second liquids are mutually immiscible.

28. A method of enclosing liquids according to any of the preceding claims 22 - 27 and wherein said enclosing material comprises at least one of ethyl cellulose, cellulose acetate, cellulose acetate phthalate, polyethylene glycol, Eudragit LI 00, methyl cellulose, polyketal, polylactic acid, starch-based polymers, aromatic aliphatic co-polyesters and polyhydroxyalkanoates (PHA).

29. An article of manufacture comprising:

a first material encapsulated by a second material which is water permeable, said first material being in a first inoperative state in the absence of water and transforming to a second operative state upon engagement therewith with at least a predetermined quantity of water permeating through said second material.

30. A method of enclosing liquids according to claim 29 and wherein said second material comprises at least one of ethyl cellulose, cellulose acetate, cellulose acetate phthaiate, polyethylene glycol, Eudragit LI 00, methyl cellulose, polyketal, polylactic acid, starch-based polymers, aromatic aliphatic co-polyesters and polyhydroxyalkanoates (PHA).