EP1089709A1 - Icecream-type pharmaceutical formulation and process for preparing the same - Google Patents
Icecream-type pharmaceutical formulation and process for preparing the sameInfo
- Publication number
- EP1089709A1 EP1089709A1 EP00921116A EP00921116A EP1089709A1 EP 1089709 A1 EP1089709 A1 EP 1089709A1 EP 00921116 A EP00921116 A EP 00921116A EP 00921116 A EP00921116 A EP 00921116A EP 1089709 A1 EP1089709 A1 EP 1089709A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- icecream
- type
- milk
- formulation
- egg yolk
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 22
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 7
- 239000000203 mixture Substances 0.000 claims abstract description 55
- 238000009472 formulation Methods 0.000 claims abstract description 43
- 229940079593 drug Drugs 0.000 claims abstract description 15
- 239000003814 drug Substances 0.000 claims abstract description 15
- 235000013336 milk Nutrition 0.000 claims abstract description 14
- 239000008267 milk Substances 0.000 claims abstract description 14
- 210000004080 milk Anatomy 0.000 claims abstract description 14
- 102000002322 Egg Proteins Human genes 0.000 claims abstract description 11
- 108010000912 Egg Proteins Proteins 0.000 claims abstract description 11
- 239000006071 cream Substances 0.000 claims abstract description 11
- 235000013345 egg yolk Nutrition 0.000 claims abstract description 11
- 210000002969 egg yolk Anatomy 0.000 claims abstract description 11
- 238000002156 mixing Methods 0.000 claims abstract description 10
- 235000009470 Theobroma cacao Nutrition 0.000 claims abstract description 8
- 244000299461 Theobroma cacao Species 0.000 claims abstract description 8
- 235000015243 ice cream Nutrition 0.000 claims abstract description 4
- 238000003756 stirring Methods 0.000 claims abstract description 4
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims description 43
- 229960005489 paracetamol Drugs 0.000 claims description 21
- 229940088594 vitamin Drugs 0.000 claims description 17
- 239000011782 vitamin Substances 0.000 claims description 17
- 230000001754 anti-pyretic effect Effects 0.000 claims description 16
- 239000002221 antipyretic Substances 0.000 claims description 16
- 229930003231 vitamin Natural products 0.000 claims description 15
- 235000013343 vitamin Nutrition 0.000 claims description 15
- 229960003022 amoxicillin Drugs 0.000 claims description 14
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 claims description 14
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 11
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 10
- 230000003115 biocidal effect Effects 0.000 claims description 10
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 6
- 235000000346 sugar Nutrition 0.000 claims description 6
- -1 - ibuprofen Chemical compound 0.000 claims description 5
- 235000010323 ascorbic acid Nutrition 0.000 claims description 5
- 229960005070 ascorbic acid Drugs 0.000 claims description 5
- 239000011668 ascorbic acid Substances 0.000 claims description 5
- 229960000342 retinol acetate Drugs 0.000 claims description 5
- QGNJRVVDBSJHIZ-QHLGVNSISA-N retinyl acetate Chemical compound CC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C QGNJRVVDBSJHIZ-QHLGVNSISA-N 0.000 claims description 5
- 235000019173 retinyl acetate Nutrition 0.000 claims description 5
- 239000011770 retinyl acetate Substances 0.000 claims description 5
- 150000003722 vitamin derivatives Chemical class 0.000 claims description 5
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 claims description 4
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 claims description 4
- RMRCNWBMXRMIRW-BYFNXCQMSA-M cyanocobalamin Chemical compound N#C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O RMRCNWBMXRMIRW-BYFNXCQMSA-M 0.000 claims description 4
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 claims description 4
- 235000005282 vitamin D3 Nutrition 0.000 claims description 4
- 239000011647 vitamin D3 Substances 0.000 claims description 4
- 229940021056 vitamin d3 Drugs 0.000 claims description 4
- 239000000839 emulsion Substances 0.000 claims description 3
- 229960003966 nicotinamide Drugs 0.000 claims description 3
- 235000005152 nicotinamide Nutrition 0.000 claims description 3
- 239000011570 nicotinamide Substances 0.000 claims description 3
- ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 claims description 3
- 239000011764 pyridoxine hydrochloride Substances 0.000 claims description 3
- 229960004172 pyridoxine hydrochloride Drugs 0.000 claims description 3
- 235000019171 pyridoxine hydrochloride Nutrition 0.000 claims description 3
- 235000020183 skimmed milk Nutrition 0.000 claims description 3
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 2
- 235000013162 Cocos nucifera Nutrition 0.000 claims description 2
- 244000060011 Cocos nucifera Species 0.000 claims description 2
- 235000010469 Glycine max Nutrition 0.000 claims description 2
- 244000068988 Glycine max Species 0.000 claims description 2
- OJMMVQQUTAEWLP-UHFFFAOYSA-N Lincomycin Natural products CN1CC(CCC)CC1C(=O)NC(C(C)O)C1C(O)C(O)C(O)C(SC)O1 OJMMVQQUTAEWLP-UHFFFAOYSA-N 0.000 claims description 2
- 241001465754 Metazoa Species 0.000 claims description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 2
- 229960000723 ampicillin Drugs 0.000 claims description 2
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 claims description 2
- 239000010775 animal oil Substances 0.000 claims description 2
- 229940106164 cephalexin Drugs 0.000 claims description 2
- ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 claims description 2
- 239000011666 cyanocobalamin Substances 0.000 claims description 2
- 229960002104 cyanocobalamin Drugs 0.000 claims description 2
- 235000000639 cyanocobalamin Nutrition 0.000 claims description 2
- 229960003276 erythromycin Drugs 0.000 claims description 2
- 229960001680 ibuprofen Drugs 0.000 claims description 2
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 claims description 2
- 229960000991 ketoprofen Drugs 0.000 claims description 2
- 229960005287 lincomycin Drugs 0.000 claims description 2
- OJMMVQQUTAEWLP-KIDUDLJLSA-N lincomycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@@H](C)O)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 OJMMVQQUTAEWLP-KIDUDLJLSA-N 0.000 claims description 2
- PXWLVJLKJGVOKE-UHFFFAOYSA-N propyphenazone Chemical compound O=C1C(C(C)C)=C(C)N(C)N1C1=CC=CC=C1 PXWLVJLKJGVOKE-UHFFFAOYSA-N 0.000 claims description 2
- 229960002189 propyphenazone Drugs 0.000 claims description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 claims description 2
- 239000008158 vegetable oil Substances 0.000 claims description 2
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 claims 2
- UIERGBJEBXXIGO-UHFFFAOYSA-N thiamine mononitrate Chemical compound [O-][N+]([O-])=O.CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N UIERGBJEBXXIGO-UHFFFAOYSA-N 0.000 claims 2
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 claims 1
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 claims 1
- 229940022663 acetate Drugs 0.000 claims 1
- 239000002151 riboflavin Substances 0.000 claims 1
- 229960002477 riboflavin Drugs 0.000 claims 1
- 235000019192 riboflavin Nutrition 0.000 claims 1
- 230000036765 blood level Effects 0.000 description 12
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 8
- 241000700159 Rattus Species 0.000 description 7
- 239000003242 anti bacterial agent Substances 0.000 description 7
- 239000004615 ingredient Substances 0.000 description 7
- 229940088710 antibiotic agent Drugs 0.000 description 6
- 229940125716 antipyretic agent Drugs 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 210000000214 mouth Anatomy 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 3
- 229910002651 NO3 Inorganic materials 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- LDXJRKWFNNFDSA-UHFFFAOYSA-N 2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound C1CN(CC2=NNN=C21)CC(=O)N3CCN(CC3)C4=CN=C(N=C4)NCC5=CC(=CC=C5)OC(F)(F)F LDXJRKWFNNFDSA-UHFFFAOYSA-N 0.000 description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000007059 acute toxicity Effects 0.000 description 2
- 231100000403 acute toxicity Toxicity 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- HMUNWXXNJPVALC-UHFFFAOYSA-N 1-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C(CN1CC2=C(CC1)NN=N2)=O HMUNWXXNJPVALC-UHFFFAOYSA-N 0.000 description 1
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 1
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 229940068682 chewable tablet Drugs 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229940116364 hard fat Drugs 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000001459 mortal effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229940042585 tocopherol acetate Drugs 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
Definitions
- the present invention relates to a soft icecream-type pharmaceutical formulation and a process for preparing the same .
- Antipyretics, antibiotics and vitamins have been conventionally formulated in the forms of tablet, capsule, liquid, injection solution and syrup.
- the conventional dosage forms are, however, proven to be less satisfactory in the sense that they are not convenient for administering to children. Accordingly, particular attention should be paid in choosing the dosage forms, especially, orally administrable pharmaceutical formulations are selected under a careful consideration of taste and mouth feel in oral cavity.
- many medicines and active ingredients are bitter in taste or else hold uncomfortable taste, rough or chalky feeling.
- the pharmaceutical formulations of relatively easy administration for children such as chewable tablet, jelly-like tablet, granules, etc., have been developed. They are commercially available though these pharmaceutical formulations are not ideal in terms of children's affinity. Under the circumstances, there are strong reasons for exploring and developing new type of pharmaceutical formulation for children.
- the present inventors have made efforts to develop an icecream-type pharmaceutical formulation which can be applied in drugs such as antipyretics, antibiotics and vitamins, and found that it provides excellent drug absorption with improved patient's drug compliance in light of easy oral application and high affinity.
- the primary object of the present invention is, therefore, to provide an icecream-type pharmaceutical formulation.
- the other object of the invention is to provide a process for preparing the icecream-type pharmaceutical formulation.
- Another object of the invention is to provide icecream-type formulations of antipyretic, antibiotic and vitamin.
- Figure 1 is a high performance liquid chromatography chromatogram of acetaminophen in blood.
- Figure 2 is a graph showing blood level of tablet- type and icecream-type acetaminophen after oral administration.
- Icecream-type pharmaceutical formulation of the present invention is prepared by the steps of: mixing egg yolk and milk with stirring until they are completely mixed; whipping cream until it is reduced to pulp and mixing it with the said mixture in a volume ratio of 9:1 to 5:5, more preferably 8:2 to 6:4, most preferably 7:3; adding drugs into the said mixture in a ratio of 0.1 to 20wt% and blending them; and, finally putting them into an icecream maker and formulating into a pharmaceutical formula by subjecting at the temperature range of 0°C to -10°C.
- sugar and/or cocoa may be further added to the mixture of egg yolk and milk according to the patient's preference, and coconut hard fat may substitute for the egg yolk.
- the milk includes soy bean milk, processed skim milk (containing 7.2% skimmed milk powder) and plain milk.
- the cream includes: commercially available emulsion cream which can be obtained by the centrifuge of animal/vegetable oil; and, carboxymethylcellulose (CMC) solution.
- CMC carboxymethylcellulose
- the antipyretics include acetaminophen, aspirin, ibuprofen, ketoprofen and isopropyl-antipyrin, preferably acetaminophen and/or mixture thereofs
- the antibiotics include amoxicillin, ampicillin, erythromycin, lincomycin, and cefalexin, most preferably amoxicillin
- the vitamins include retinol acetate, cholecalciferol, tocopherol acetate, ascorbic acid, thiamme nitrate, riboflamin, pyridoxine hydrochloride, ⁇ icotinamide and cyanocobalamin.
- Example 1 Preparation of icecream-type formulation containing an antipyretic of acetaminophen Example 1-1
- An icecream-type antipyretic formulation was prepared in an analogous manner as in Example 1-1, except for employing the ingredients shown in Table 2 below.
- An icecream-type antipyretic formulation was prepared in an analogous manner as in Example 1-1, except for employing the ingredients shown m Table 3 below.
- An icecream-type antibiotic formulation was prepared m an analogous manner as in Example 1-1, except for employing the ingredients shown in Table 4 below.
- An icecream-type antibiotic formulation was prepared in an analogous manner as in Example 1-1, except for employing tne ingredients shown in Table 5 below.
- An icecream-type antibiotic formulation was prepared in an analogous manner as in Example 1-1, except for employing the ingredients shown in Table 6 below.
- An icecream-type multi-vitamin formulation was prepared in an analogous manner as in Example 1-1, except for employing the ingredients of retinol acetate, cholecalciferol, tocopheroi acetate, ascorbic acid, th amine nitrate, ⁇ boflavm, py ⁇ doxine hydrochlo ⁇ de, nicotinamide and cyanocobalamm as shown in Table 7 below.
- Table 7 The contents of icecream-type formulation containing vitamins
- An icecream-type multi-vitamin formulation was prepared m an analogous manner as m Example 1-1, except for employing the ingredients of retinol acetate, cholecalci erol, tocopheroi acetate, ascorbic acid, nitrate, nooflavm, py ⁇ oxine hydrochlo ⁇ de, nicotinamide and cyanocobalamm as snown in Table 8 below.
- Table 8 The contents o-i icecream-type formulation containing vitamins
- Acute toxicities of icecream-type formulations of antipyretics, antibiotics, and vitamins prepared m Examples 1, 2 and 3 were investigated by employing 5 sets of male and female rats, which revealed that no mortal rat was detected up to the level of 5g/kg/day which is 500 times of antipyretics, 5000 times of antibiotics and 50000 times of vitamins m terms of their effective amounts.
- the icecream-type formulation of present invention which comprises antipyretic, antibiotic, or vitamin as an active ingredient is formulated for orally applicable purpose, accordance with the conventional formulating method by containing surfactants, excipients, t ctorials, stabilizers, buffers, suspensions, lsotomc solution, and other additives, organic or inorganic carriers.
- the icecream-type formulation may be administered to children in an oral dosage in an amount of 2 to 20mg/kg(20kg as a standard weight), while it may be varied depending on the type o drugs, medical treatments, diseases, patient's age and duration of medication.
- the present invention provides an icecream-type pharmaceutical formulation and a process for preparing the same. Icecream-type pharmaceutical formulations prepared by the invention have higher drug compliance to children with easy administration and good absorption and thus may substitute for troches .
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Zoology (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The present invention relates to a soft icecream-type pharmaceutical formulation and a process for preparing the same. The icecream-type pharmaceutical formulation of present invention is prepared by the steps of mixing egg yolk, milk, and cocoa with stirring until the cocoa is completely dissolved in the mixture; whipping a cream until it is reduced to pulp and mixing it with the said mixture in a volume ratio of 9:1 to 5:5; adding drugs into the said mixture and blending them; and, putting them into an ice cream maker and formulating into a pharmaceutical formula. Since a soft ice cream-type-formulation of the invention has merits over conventional formulas in terms of taking preference and absorbtion efficacy in oral application, it can be used as an improved pharmaceutical formula for children and infants, while substituting for troches.
Description
ICECREAM-TYPE PHARMACEUTICAL FORMULATION AND PROCESS FOR PREPARING THE SAME
BACKGROUND OF THE INVENTION
field of the invention
The present invention relates to a soft icecream-type pharmaceutical formulation and a process for preparing the same .
Description of the Prior Art
Antipyretics, antibiotics and vitamins have been conventionally formulated in the forms of tablet, capsule, liquid, injection solution and syrup. The conventional dosage forms are, however, proven to be less satisfactory in the sense that they are not convenient for administering to children. Accordingly, particular attention should be paid in choosing the dosage forms, especially, orally administrable pharmaceutical formulations are selected under a careful consideration of taste and mouth feel in oral cavity. Unfortunately, many medicines and active ingredients are bitter in taste or else hold uncomfortable taste, rough or chalky feeling. With the recent development in pharmaceutical technology, to improve taste and/or mouth feel in oral cavity, the pharmaceutical formulations of relatively easy administration for children such as chewable tablet, jelly-like tablet, granules, etc., have been developed. They are commercially available though these pharmaceutical formulations are not ideal in terms of children's affinity. Under the circumstances, there are strong reasons for exploring and developing new type of pharmaceutical formulation for children.
SUMMARY OF THE INVENTION
The present inventors have made efforts to develop an icecream-type pharmaceutical formulation which can be applied in drugs such as antipyretics, antibiotics and vitamins, and found that it provides excellent drug absorption with improved patient's drug compliance in light of easy oral application and high affinity.
The primary object of the present invention is, therefore, to provide an icecream-type pharmaceutical formulation.
The other object of the invention is to provide a process for preparing the icecream-type pharmaceutical formulation.
Another object of the invention is to provide icecream-type formulations of antipyretic, antibiotic and vitamin.
BRIEF DESCRIPTION OF THE DRAWINGS
The above and the other objects and features of the present invention will become apparent from the following descriptions given in conjunction with the accompanying drawings, in which:
Figure 1 is a high performance liquid chromatography chromatogram of acetaminophen in blood.
Figure 2 is a graph showing blood level of tablet- type and icecream-type acetaminophen after oral administration.
DETAILED DESCRIPTION OF THE INVENTION
Icecream-type pharmaceutical formulation of the present invention is prepared by the steps of: mixing egg
yolk and milk with stirring until they are completely mixed; whipping cream until it is reduced to pulp and mixing it with the said mixture in a volume ratio of 9:1 to 5:5, more preferably 8:2 to 6:4, most preferably 7:3; adding drugs into the said mixture in a ratio of 0.1 to 20wt% and blending them; and, finally putting them into an icecream maker and formulating into a pharmaceutical formula by subjecting at the temperature range of 0°C to -10°C. In the preparation of the icecream-type formulation, sugar and/or cocoa may be further added to the mixture of egg yolk and milk according to the patient's preference, and coconut hard fat may substitute for the egg yolk. Further, the milk includes soy bean milk, processed skim milk (containing 7.2% skimmed milk powder) and plain milk. And, the cream includes: commercially available emulsion cream which can be obtained by the centrifuge of animal/vegetable oil; and, carboxymethylcellulose (CMC) solution. Though several pharmaceutical formulations of antipyretics, antibiotics or vitamins are illustrated in the Examples below, they do not specifically limit the drugs contained in the formulation. The antipyretics include acetaminophen, aspirin, ibuprofen, ketoprofen and isopropyl-antipyrin, preferably acetaminophen and/or mixture thereofs, the antibiotics include amoxicillin, ampicillin, erythromycin, lincomycin, and cefalexin, most preferably amoxicillin, and the vitamins include retinol acetate, cholecalciferol, tocopherol acetate, ascorbic acid, thiamme nitrate, riboflamin, pyridoxine hydrochloride, πicotinamide and cyanocobalamin.
The present invention is further illustrated in the following examples, which should not be taken to limit the scooe of the invention.
Example 1: Preparation of icecream-type formulation containing an antipyretic of acetaminophen
Example 1-1
Sugar, cocoa, egg yolk and milk were weighed in the ratios shown in Table 1 below, and mixed with stirring until they were completely dissolved. Then, commercially available emulsion cream was whipped until it was reduced to pulp and mixed with the said mixture. And then, acetaminophen, an antipyretic, was added to the mixture, blended, and put in an icecream maker (Philips, HR2034) and subjected at a temperature of 0°C to -10°C, to give an icecream-type formula.
Table 1. The contents of icecream-type formulation containing acetaminophen
Example 1-2
An icecream-type antipyretic formulation was prepared in an analogous manner as in Example 1-1, except for employing the ingredients shown in Table 2 below.
Table 2. The contents of icecream-type formulation containing acetaminophen
Example 1-3
An icecream-type antipyretic formulation was prepared in an analogous manner as in Example 1-1, except for employing the ingredients shown m Table 3 below.
Table 3. The contents of icecream-type formulation containing acetaminophen
Example Preparation of icecream-type formulation containing an antibiotic of amoxicillin
Example 2-1
An icecream-type antibiotic formulation was prepared m an analogous manner as in Example 1-1, except for employing the ingredients shown in Table 4 below.
Table 4: The contents of icecream-type formulation containing amoxicillin
Example 2-2
An icecream-type antibiotic formulation was prepared in an analogous manner as in Example 1-1, except for employing tne ingredients shown in Table 5 below.
Table 5: The contents of icecream-type formulation containing amoxicillin
Example 2-3
An icecream-type antibiotic formulation was prepared in an analogous manner as in Example 1-1, except for employing the ingredients shown in Table 6 below.
Table 6: The contents of icecream-type formulation containing amoxicillin
Example Preparation of icecream-type formulation containing vitamins
Example 3 - 1 :
An icecream-type multi-vitamin formulation was prepared in an analogous manner as in Example 1-1, except for employing the ingredients of retinol acetate, cholecalciferol, tocopheroi acetate, ascorbic acid, th amine nitrate, πboflavm, pyπdoxine hydrochloπde, nicotinamide and cyanocobalamm as shown in Table 7 below.
Table 7 : The contents of icecream-type formulation containing vitamins
example 3-2:
An icecream-type multi-vitamin formulation was prepared m an analogous manner as m Example 1-1, except for employing the ingredients of retinol acetate, cholecalci erol, tocopheroi acetate, ascorbic acid, nitrate, nooflavm, pyπαoxine hydrochloπde, nicotinamide and cyanocobalamm as snown in Table 8 below.
Table 8 : The contents o-i icecream-type formulation containing vitamins
Example 4 : Measurement of Blood Level of Drugs
To measure the blood level of acetaminophen, male SD rats were cannulized in arteriae femoralis after the ether treatment. When the rats were come out of the ether, comm.ercially available acetaminophen tablet and icecream- type formulation were orally administered with an equal amount of lOOmg/kgBW as acetaminophen per each. Blood was collected in an equal interval and injected to high performance liquid chromatography (HPLC) working under the analysis condition below. The HPLC chromatogram of acetaminophen in blood is shown in Figure 1.
Condition for HPLC Analysis:
Column: Bonaapak C18 (Waters, U.S.A.)
Mobile phase: acetcnitrile : 1% acetate (1:9, v:v' flow rate - lml/min Detector: UV spectrophotometer (λ=254nm)
Example 5: Changes in Blood Level of Acetaminophen
Changes in blood level of acetaminophen were monitored by the method illustrated in Example 4, after oral administration of 50g icecream-type formulation prepared in Example 2-2 (containing 500mg acetaminophen) and commercially available acetaminophen tablet (containing 500mg acetaminophen) in an amount of lOOmg/kg to experimental rats (s≤e.: Figure 2) . As shown in Figure 2, C^., for the icecream-type formulation containing acetaminophen (o) was shown- at 20min while tablet form(*) was at 30min, and the blood level of drug in the icecream- type formulation was 3 times as high as the tablet-type formulation .
Example 6: Changes in Blood Level of Amoxicillin
Changes in blood level of amoxicillin were monitored by the method illustrated in Example 4, after oral administration of 50g icecream-type formulation prepared in Example 2-2 (containing 500mg amoxicillin) and commercially available amoxicillin capsule (containing 500mg amoxicillin) in an amount of lOmg/kg to experimental rats.
As a result, it was clearly determined that both of the icecream-type formulation and capsule-type formulation of amoxicillin showed similar blood level curve.
Example 7 : Changes in Blood Level of Tocopheroi Acetate
Changes in blood level of tocopheroi acetate were monitored by the method illustrated in Example 4, after oral administration of 50g icecream-type formulation prepared in Example 3-2 ( containing 500mg tocopheroi acetate) and commercially available tocopheroi acetate tablet (containing 500mg tocopheroi acetate) in an amount of lmg/kg to experimental rats.
As a result, ooth of the icecream-type formulation and tablet-type formulation of tocopheroi acetate showed similar blood level curve.
Acute Toxicity
Acute toxicities of icecream-type formulations of antipyretics, antibiotics, and vitamins prepared m Examples 1, 2 and 3 were investigated by employing 5 sets of male and female rats, which revealed that no mortal rat was detected up to the level of 5g/kg/day which is 500 times of antipyretics, 5000 times of antibiotics and 50000 times of vitamins m terms of their effective amounts.
The icecream-type formulation of present invention which comprises antipyretic, antibiotic, or vitamin as an active ingredient is formulated for orally applicable purpose, accordance with the conventional formulating method by containing surfactants, excipients, t ctorials, stabilizers, buffers, suspensions, lsotomc solution, and other additives, organic or inorganic carriers.
The icecream-type formulation may be administered to children in an oral dosage in an amount of 2 to 20mg/kg(20kg as a standard weight), while it may be varied depending on the type o drugs, medical treatments, diseases, patient's age and duration of medication.
As clearly illustrated and demonstrated as above, the present invention provides an icecream-type pharmaceutical formulation and a process for preparing the same. Icecream-type pharmaceutical formulations prepared by the invention have higher drug compliance to children with easy administration and good absorption and thus may substitute for troches .
Although the preferred embodiments of the present invention have been disclosed for illustrative purpose, those who are skilled in the art will appreciate that various modifications, additions and substitutions are possible, without departing from the scope and spirit of the invention as disclosed in the accompanying claims.
Claims
1. An icecream-type pharmaceutical formulation.
2. The icecream-type formulation of claim 1, wherein the drug is antipyretic, antibiotic or vitamin.
3. The icecream-type formulation of claim 2, wherein the antipyretic is selected from the group consisting of acetaminophen, aspirin, - ibuprofen, ketoprofen and isopropylantipyrin .
4. The icecream-type formulation of claim 2, wherein the antibiotic is selected from the group consisting of amoxicillin, ampicillin, erythromycin, lincomycin and cefalexin.
5. The icecream-type formulation of claim 2, wherein the vitamin is retinol acetate, cholecalciferol, tocopheroi acetate, ascorbic acid, thiamine nitrate, riboflavin, pyridoxine hydrochloride, nicotinamide, cyanocobalamin or mixture thereofs .
6. A process for preparing icecream-type pharmaceutical formulation, which comprises the steps of: mixing egg yolk and milk with stirring until they are completely mixed; whipping cream and mixing it with the mixture in a volume ratio of 9:1 to 5:5; adding drugs into the said mixture in a ratio of 0.1 to 20wt% and blending them; and, putting them into an icecream maker and formulating into a pharmaceutical formula.
7. The process of claim 6, further comprising a step of mixing sugar and/or cocoa with the egg yolk and the milk.
8. The process of claim 6, wherein the egg yolk is suostituted with coconut harα fat.
9. The process of claim 6, wherein the milk is substituted with soy bean milk or processed skim milk.
10. The process of claim 6, wherein the cream is carboxymethylcellulose (CMC) solution or emulsion cream which is obtained by the centrifuge of animal/vegetable oil.
11. The process of "claim 6, wherein the drug is antipyretic, antibiotic or vitamin.
12. An icecream-type formulation containing antipyretic prepared by the process of claim 6, which comprises 3.0 to 18.0wt of sugar, cocoa, egg yolk, and cream per each; 0.2 to 10.0wt% acetaminophen; and, milk.
13. An icecream-type formulation containing antibiotic prepared by the process of claim 6, which comprises 3.0 to 18.0 wt% of sugar, cocoa, egg yolk, and cream per each; 0.2 to 10.0w% amoxicillin; and, milk.
14. An icecream-type formulation containing multi- vitamin prepared by the process of claim 6 which comprises
3.0 to 18.0wt% of sugar, cocoa, egg yolk, and cream per each; 0.002 to 0.1wt% retinol acetate; 0.0004 to 0.02wt% cholecalciferol; 0.02 to 1.0wt% tocopheroi acetate; 0.04 to 2.0wt% ascorbic acid; 0.0008 to 0.04wt% thiamine nitrate; 0.0008 to 0.04wt% riboflavm; 0.0012 to 0.06wt% pyridoxine hydrochloride; 0.008 to 0.4wt% nicotinamide; 0.000004 to 0.0002 cyanocobalamm; and, milk.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR9912520 | 1999-04-09 | ||
| KR1019990012520A KR20000065822A (en) | 1999-04-09 | 1999-04-09 | Icecream-type Pharmaceutical Formulation and Process for Preparing the Same |
| PCT/KR2000/000321 WO2000061110A1 (en) | 1999-04-09 | 2000-04-07 | Icecream-type pharmaceutical formulation and process for preparing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EP1089709A1 true EP1089709A1 (en) | 2001-04-11 |
| EP1089709A4 EP1089709A4 (en) | 2002-01-23 |
Family
ID=19579240
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP00921116A Withdrawn EP1089709A4 (en) | 1999-04-09 | 2000-04-07 | ICE CREAM-LIKE PHARMACEUTICAL FORMULATION AND METHOD FOR PRODUCING THE SAME |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP1089709A4 (en) |
| JP (1) | JP2002541184A (en) |
| KR (1) | KR20000065822A (en) |
| CN (1) | CN1300208A (en) |
| AU (1) | AU4146500A (en) |
| WO (1) | WO2000061110A1 (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030049304A1 (en) * | 2001-08-29 | 2003-03-13 | Somani Jitendra Krishan | Quiescently frozen ice products |
| WO2003026625A1 (en) | 2001-09-28 | 2003-04-03 | Mcneil-Ppc, Inc. | Modified release dosage forms |
| US6896923B2 (en) | 2002-11-07 | 2005-05-24 | Good Humor-Breyers Ice Cream | Frozen confection |
| CN100402030C (en) * | 2006-01-05 | 2008-07-16 | 珠海联邦制药股份有限公司 | Pharmaceutical composition containing amoxicillin and preparation method thereof |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1071017A (en) * | 1965-07-07 | 1967-06-07 | Georg Hipp | Process for producing biologically active compositions |
| US4218482A (en) * | 1979-02-05 | 1980-08-19 | Detyzco, Inc. | Frozen, nutritious pet food |
| US5290605A (en) * | 1989-06-29 | 1994-03-01 | Niva Shapira | Sun-exposure nutritional supporting composition |
| GR1001437B (en) * | 1992-11-05 | 1993-12-30 | Aggelos Kontos | Pastry system for the administration of pharmacologically active substances. |
| WO1997006697A1 (en) * | 1995-08-21 | 1997-02-27 | Unilever N.V. | Antioxidant comprising food products |
| BG61964B1 (en) * | 1996-03-05 | 1998-11-30 | Георги Г. Попов | Dietetic ice-cream having high protein content |
| GR1002668B (en) * | 1996-03-15 | 1997-04-14 | N | Process for addition of sterile gaseous nitrogen and pharmaceutically active substances to solid yoghurt. |
| KR100291142B1 (en) * | 1998-09-15 | 2001-07-12 | 박호군 | Composition for preventing and treating atherosclerosis, hyperlipidemia, hepatic diseases and glycosemia, comprising neohesperidin dihydrochalcone |
-
1999
- 1999-04-09 KR KR1019990012520A patent/KR20000065822A/en not_active Ceased
-
2000
- 2000-04-07 AU AU41465/00A patent/AU4146500A/en not_active Abandoned
- 2000-04-07 CN CN00800535A patent/CN1300208A/en active Pending
- 2000-04-07 EP EP00921116A patent/EP1089709A4/en not_active Withdrawn
- 2000-04-07 WO PCT/KR2000/000321 patent/WO2000061110A1/en not_active Application Discontinuation
- 2000-04-07 JP JP2000610443A patent/JP2002541184A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CN1300208A (en) | 2001-06-20 |
| AU4146500A (en) | 2000-11-14 |
| JP2002541184A (en) | 2002-12-03 |
| WO2000061110A1 (en) | 2000-10-19 |
| KR20000065822A (en) | 2000-11-15 |
| EP1089709A4 (en) | 2002-01-23 |
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