CN114796140A - Good-palatability milbemycin oxime praziquantel soft chewable tablets for animals and preparation method thereof - Google Patents
Good-palatability milbemycin oxime praziquantel soft chewable tablets for animals and preparation method thereof Download PDFInfo
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- CN114796140A CN114796140A CN202210468610.9A CN202210468610A CN114796140A CN 114796140 A CN114796140 A CN 114796140A CN 202210468610 A CN202210468610 A CN 202210468610A CN 114796140 A CN114796140 A CN 114796140A
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- China
- Prior art keywords
- praziquantel
- soft chewable
- milbemycin oxime
- agent
- tablet
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- 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.)
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- FSVJFNAIGNNGKK-UHFFFAOYSA-N 2-[cyclohexyl(oxo)methyl]-3,6,7,11b-tetrahydro-1H-pyrazino[2,1-a]isoquinolin-4-one Chemical compound C1C(C2=CC=CC=C2CC2)N2C(=O)CN1C(=O)C1CCCCC1 FSVJFNAIGNNGKK-UHFFFAOYSA-N 0.000 title claims abstract description 51
- 229960002957 praziquantel Drugs 0.000 title claims abstract description 51
- 229940099245 milbemycin oxime Drugs 0.000 title claims abstract description 50
- CKVMAPHTVCTEMM-ALPQRHTBSA-N milbemycin oxime Chemical compound O1[C@H](C)[C@@H](C)CC[C@@]11O[C@H](C\C=C(C)\C[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)C(=N/O)/[C@H]3OC\2)O)C[C@H]4C1.C1C[C@H](C)[C@@H](CC)O[C@@]21O[C@H](C\C=C(C)\C[C@@H](C)\C=C\C=C/1[C@]3([C@H](C(=O)O4)C=C(C)C(=N/O)/[C@H]3OC\1)O)C[C@H]4C2 CKVMAPHTVCTEMM-ALPQRHTBSA-N 0.000 title claims abstract description 49
- 239000007910 chewable tablet Substances 0.000 title claims abstract description 40
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 241001465754 Metazoa Species 0.000 title abstract description 8
- 239000000796 flavoring agent Substances 0.000 claims abstract description 43
- 229940068682 chewable tablet Drugs 0.000 claims abstract description 23
- 235000013355 food flavoring agent Nutrition 0.000 claims abstract description 23
- 239000000843 powder Substances 0.000 claims abstract description 22
- 239000003086 colorant Substances 0.000 claims abstract description 20
- 239000000945 filler Substances 0.000 claims abstract description 18
- 235000013372 meat Nutrition 0.000 claims abstract description 14
- 235000003599 food sweetener Nutrition 0.000 claims abstract description 13
- 239000003765 sweetening agent Substances 0.000 claims abstract description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 12
- 239000004902 Softening Agent Substances 0.000 claims abstract description 10
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 9
- 239000000203 mixture Substances 0.000 claims description 26
- 239000007779 soft material Substances 0.000 claims description 22
- 239000003826 tablet Substances 0.000 claims description 14
- 241000287828 Gallus gallus Species 0.000 claims description 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 12
- 239000002245 particle Substances 0.000 claims description 12
- 238000002156 mixing Methods 0.000 claims description 10
- 235000019202 steviosides Nutrition 0.000 claims description 9
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 claims description 8
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 8
- 229920002472 Starch Polymers 0.000 claims description 8
- BGNXCDMCOKJUMV-UHFFFAOYSA-N Tert-Butylhydroquinone Chemical compound CC(C)(C)C1=CC(O)=CC=C1O BGNXCDMCOKJUMV-UHFFFAOYSA-N 0.000 claims description 8
- 235000006708 antioxidants Nutrition 0.000 claims description 8
- 235000015278 beef Nutrition 0.000 claims description 8
- 239000008101 lactose Substances 0.000 claims description 8
- 210000004185 liver Anatomy 0.000 claims description 8
- 239000008107 starch Substances 0.000 claims description 8
- 235000019698 starch Nutrition 0.000 claims description 8
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 7
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 7
- 229930195725 Mannitol Natural products 0.000 claims description 7
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 7
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 claims description 7
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 7
- 229930006000 Sucrose Natural products 0.000 claims description 7
- 239000000594 mannitol Substances 0.000 claims description 7
- 235000010355 mannitol Nutrition 0.000 claims description 7
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 7
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 7
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 7
- 229940013618 stevioside Drugs 0.000 claims description 7
- OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 claims description 7
- 239000005720 sucrose Substances 0.000 claims description 7
- 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 6
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 6
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 claims description 6
- 239000008103 glucose Substances 0.000 claims description 6
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 claims description 6
- NEGYEDYHPHMHGK-UHFFFAOYSA-N para-methoxyamphetamine Chemical compound COC1=CC=C(CC(C)N)C=C1 NEGYEDYHPHMHGK-UHFFFAOYSA-N 0.000 claims description 6
- 239000002994 raw material Substances 0.000 claims description 6
- 235000011888 snacks Nutrition 0.000 claims description 6
- 229930091371 Fructose Natural products 0.000 claims description 5
- 239000005715 Fructose Substances 0.000 claims description 5
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims description 5
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 5
- 229940067573 brown iron oxide Drugs 0.000 claims description 5
- 239000004250 tert-Butylhydroquinone Substances 0.000 claims description 4
- 235000019281 tert-butylhydroquinone Nutrition 0.000 claims description 4
- 239000004255 Butylated hydroxyanisole Substances 0.000 claims description 3
- 239000004322 Butylated hydroxytoluene Substances 0.000 claims description 3
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- 241001122767 Theaceae Species 0.000 claims description 3
- 235000010323 ascorbic acid Nutrition 0.000 claims description 3
- 229960005070 ascorbic acid Drugs 0.000 claims description 3
- 239000011668 ascorbic acid Substances 0.000 claims description 3
- 235000019282 butylated hydroxyanisole Nutrition 0.000 claims description 3
- 235000010354 butylated hydroxytoluene Nutrition 0.000 claims description 3
- 229920001223 polyethylene glycol Polymers 0.000 claims description 3
- 150000008442 polyphenolic compounds Chemical class 0.000 claims description 3
- 235000013824 polyphenols Nutrition 0.000 claims description 3
- -1 proper amount Substances 0.000 claims description 3
- 235000010388 propyl gallate Nutrition 0.000 claims description 3
- 239000000473 propyl gallate Substances 0.000 claims description 3
- 229940075579 propyl gallate Drugs 0.000 claims description 3
- 235000013616 tea Nutrition 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 2
- 238000000465 moulding Methods 0.000 claims description 2
- 229920001451 polypropylene glycol Polymers 0.000 claims description 2
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 claims 1
- 229960002737 fructose Drugs 0.000 claims 1
- 229960001031 glucose Drugs 0.000 claims 1
- FXWHFKOXMBTCMP-WMEDONTMSA-N milbemycin Natural products COC1C2OCC3=C/C=C/C(C)CC(=CCC4CC(CC5(O4)OC(C)C(C)C(OC(=O)C(C)CC(C)C)C5O)OC(=O)C(C=C1C)C23O)C FXWHFKOXMBTCMP-WMEDONTMSA-N 0.000 claims 1
- 150000002923 oximes Chemical class 0.000 claims 1
- 229940085605 saccharin sodium Drugs 0.000 claims 1
- 229960004793 sucrose Drugs 0.000 claims 1
- 235000019629 palatability Nutrition 0.000 abstract description 7
- 150000001875 compounds Chemical class 0.000 abstract description 6
- 235000019634 flavors Nutrition 0.000 description 20
- 239000003814 drug Substances 0.000 description 12
- 238000005303 weighing Methods 0.000 description 12
- 241000282472 Canis lupus familiaris Species 0.000 description 8
- 244000045947 parasite Species 0.000 description 6
- 239000004698 Polyethylene Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000001125 extrusion Methods 0.000 description 4
- 235000020993 ground meat Nutrition 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 4
- 238000007873 sieving Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 235000019640 taste Nutrition 0.000 description 4
- 239000011248 coating agent Substances 0.000 description 3
- 239000011247 coating layer Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 235000012054 meals Nutrition 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 238000007789 sealing Methods 0.000 description 3
- 241000282326 Felis catus Species 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 241000244206 Nematoda Species 0.000 description 2
- 239000004383 Steviol glycoside Substances 0.000 description 2
- 241000869417 Trematodes Species 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 235000019411 steviol glycoside Nutrition 0.000 description 2
- 229930182488 steviol glycoside Natural products 0.000 description 2
- 150000008144 steviol glycosides Chemical class 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 241001465677 Ancylostomatoidea Species 0.000 description 1
- 241000242722 Cestoda Species 0.000 description 1
- 208000003917 Dirofilariasis Diseases 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229940124277 aminobutyric acid Drugs 0.000 description 1
- 230000002141 anti-parasite Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000000828 effect on cestoda Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 235000021050 feed intake Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- QKLFOLOIKNGNCL-UHFFFAOYSA-N isoquinoline;pyridine Chemical class C1=CC=NC=C1.C1=NC=CC2=CC=CC=C21 QKLFOLOIKNGNCL-UHFFFAOYSA-N 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- VOZIAWLUULBIPN-LRBNAKOISA-N milbemycin A4 Chemical compound C1C[C@H](C)[C@@H](CC)O[C@@]21O[C@H](C\C=C(C)\C[C@@H](C)\C=C\C=C/1[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\1)O)C[C@H]4C2 VOZIAWLUULBIPN-LRBNAKOISA-N 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 230000001769 paralizing effect Effects 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000006467 substitution reaction Methods 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2068—Compounds of unknown constitution, e.g. material from plants or animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/10—Anthelmintics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/14—Ectoparasiticides, e.g. scabicides
Abstract
The invention discloses a milbemycin oxime praziquantel soft chewable tablet for animals with good palatability and a preparation method thereof. The milbemycin oxime praziquantel soft chewable tablets comprise the following components: 0.1-1 part of milbemycin oxime, 1-10 parts of praziquantel, 20-80 parts of filling agent, 20-60 parts of meat powder flavoring agent, 5-20 parts of softening agent, 0-20 parts of sweetening agent, 0-10 parts of flavoring agent, 0-2 parts of coloring agent, and a proper amount of antioxidant and water, wherein the hardness is 3.0 kg-6.0 kg. The milbemycin oxime praziquantel soft chewable tablets of the embodiment have stable quality; the hardness of the compound is moderate, and the compound has better hardness stability, so that the compound has good palatability.
Description
Technical Field
The invention belongs to the field of veterinary medicines, and particularly relates to a milbemycin oxime praziquantel soft chewable tablet for animals with good palatability and a preparation method thereof.
Background
With the improvement of living standard of people, the raising amount of pets is increased, and cats and dogs account for most of various pet species. Pet cats and dogs are very susceptible to infection by parasites such as nematodes, parasites around, trematodes, etc., and most parasites are transmissible to humans. Antiparasitic activity in pets is of paramount importance for the health of humans and pets. At present, the parasite control medicines in the market comprise tablets and external liquid, and the oral tablets are the main medicines.
Milbemycin oxime is a macrolide antibody internal and external parasite medicine, is oxime derivative of milbemycin A3 and A4, wherein A4 accounts for more than 80%. The paralytic death of the polypide is mainly caused by enhancing the release of the inhibitory neurotransmitter C-aminobutyric acid of the polypide. Is generally used for preventing heartworm disease and controlling flagellosis of dogs caused by roundworms and hookworms.
Praziquantel is a synthetic isoquinoline pyridine derivative, has an effect on most trematodes of human beings and animals, has a good parasite expelling effect on all tapeworm adults of livestock and companion animals, and has a good effect on tapeworm larvae.
The milbemycin oxime and the praziquantel have certain peculiar smell and bitter taste, and the smell and the taste of the pet are very sensitive, so that the pet is very easy to eat refusing to directly influence the curative effect if the preparation formula is improper.
CN112220769A discloses a milbemycin oxime praziquantel flavor tablet, which consists of a tablet core and a coating layer which is coated on the surface of the tablet core and does not contain medicine, wherein the coating layer can be one layer or a plurality of layers, and the coating layer contains at least one phagostimulant or flavoring agent; the tablet core consists of pellets, a glidant and a lubricant. Making the medicine into pellet, tabletting the pellet, coating the tablet core and masking taste. Therefore, the pet can well mask the taste no matter directly swallow or bite the tablet, and the feed intake rate of the pet is increased. The treatment process is relatively complex, and multiple coating treatments also have certain adverse effects on the release, absorption and the like of the medicament. Pets lick for a long time may also cause the coating to dissolve, causing the pet's unpleasant taste.
For pets, the soft chewable tablets are more acceptable for pets and can improve the palatability of pets. However, soft chewable tablets have an inadequate formulation and become hard during storage
Disclosure of Invention
The invention aims to overcome at least one defect of the prior art and provides a milbemycin oxime praziquantel soft chewable tablet for animals with good palatability and a preparation method thereof.
The technical scheme adopted by the invention is as follows:
in a first aspect of the present invention, there is provided:
the soft chewable tablet of milbemycin oxime praziquantel comprises the following components in parts by weight:
wherein the softener is at least one selected from polyethylene glycol, glycerol and polypropylene glycol, and the hardness is preferably 3.0 kg-6.0 kg.
In some examples of the milbemycin oxime praziquantel soft chewable tablets, the mass composition is as follows:
| components | The dosage is% |
| Milbemycin oxime | 0.1～1 |
| Praziquantel | 1～10 |
| Filler | 30～50 |
| Meat powder flavoring agent | 25～35 |
| Softening agent | 5～20 |
| Sweetening agent | 0～20 |
| Flavouring agent | 0～10 |
| Coloring agent | 0～2 |
| Antioxidant agent | Proper amount of |
| Water (W) | Proper amount of |
。
In some examples of the milbemycin oxime praziquantel soft chewable tablets, the mass composition is as follows:
in some examples of the milbemycin oxime praziquantel soft chewable tablet, the filler is selected from at least one of starch, lactose, mannitol, and microcrystalline cellulose.
In some examples of the milbemycin oxime praziquantel soft chewable tablet, the meat powder flavoring agent is selected from at least one of beef powder and chicken powder.
In some examples of the milbemycin oxime soft chewable tablet, the flavoring agent is at least one selected from chicken liver powder, a powder flavoring agent for dogs and a flavor special for snacks.
In some examples of the milbemycin oxime praziquantel soft chewable tablet, the sweetener is selected from at least one of glucose, fructose, sucrose, sodium saccharin, stevioside, and steviol glycosides.
In some examples of the milbemycin oxime soft chewable tablet, the colorant is selected from at least one of red iron oxide 3651, yellow iron oxide 1651, and brown iron oxide 7651.
In some examples of the milbemycin oxime praziquantel soft chewable tablet, the antioxidant is selected from at least one of BHA, BHT, TBHQ, ascorbic acid, tea polyphenol, and propyl gallate.
In some examples of the milbemycin oxime praziquantel soft chewable tablet, the filler is selected from at least one of starch, lactose, mannitol, and microcrystalline cellulose, and the meat meal flavoring agent is selected from at least one of beef meal and chicken meal.
In some examples of the milbemycin oxime soft chewable tablets, the filler is selected from at least one of starch, lactose, mannitol, and microcrystalline cellulose, the ground meat flavor is selected from at least one of powdered beef and powdered chicken, and the flavor is selected from at least one of powdered chicken liver, powdered dog flavor, and special snack flavor.
In some examples of the milbemycin oxime soft chewable tablets, the filler is selected from at least one of starch, lactose, mannitol, and microcrystalline cellulose, the ground meat flavor is selected from at least one of powdered beef and powdered chicken, the flavor is selected from at least one of powdered chicken liver, powdered dog flavor, and snack-specific flavor, and the sweetener is selected from at least one of glucose, fructose, sucrose, sodium saccharin, stevioside, and stevioside.
In some examples of the milbemycin oxime soft chewable tablet, the filler is selected from at least one of starch, lactose, mannitol, and microcrystalline cellulose, the ground meat flavor is selected from at least one of powdered beef and powdered chicken, the flavor is selected from at least one of powdered chicken liver, powdered dog flavor, and snack-specific flavor, the sweetener is selected from at least one of glucose, fructose, sucrose, sodium saccharin, stevioside, and the colorant is selected from at least one of red iron oxide 3651, yellow iron oxide 1651, and brown iron oxide 7651.
In some examples of the milbemycin oxime praziquantel soft chewable tablet, the filler is selected from at least one of starch, lactose, mannitol, and microcrystalline cellulose, the ground meat flavor is selected from at least one of powdered beef and powdered chicken, the flavor is selected from at least one of powdered chicken liver, powdered dog flavor, and snack-specific flavor, the sweetener is selected from at least one of glucose, fructose, sucrose, sodium saccharin, stevioside, and steviol glycoside, the colorant is selected from at least one of red iron oxide 3651, yellow iron oxide 1651, and brown iron oxide 7651, and the antioxidant is selected from at least one of BHA, BHT, TBHQ, ascorbic acid, tea polyphenol, and propyl gallate.
In a second aspect of the present invention, there is provided:
the preparation method of the milbemycin oxime soft chewable tablet comprises the following steps:
s1) uniformly mixing the colorant, the softener and water to obtain a mixture B;
s2) mixing the rest raw materials uniformly to obtain a mixture A;
s3) mixing the mixture A and the mixture B to prepare soft materials and granulating to obtain soft material particles;
s4) extruding and molding the soft material particles, drying and curing to set hardness to obtain the milbemycin oxime soft chewable tablets.
The invention has the beneficial effects that:
the milbemycin oxime praziquantel soft chewable tablets of the embodiment have stable quality; the hardness of the compound is moderate, and the compound has better hardness stability, so that the compound has good palatability.
Detailed Description
The technical scheme of the invention is further explained by combining the examples. In the following examples, the composition percentages are by mass unless otherwise specified. Hardness was determined using an intelligent tablet hardness tester: the sampling piece is placed in the vertical direction for determination.
Example 1
The milbemycin oxime praziquantel soft chewable tablets comprise the following components:
preparation process
1) Weighing milbemycin oxime, praziquantel, a filling agent and a meat powder flavoring agent which are required by the prescription amount, mixing in a PE sealing bag, and sieving by a 30-mesh sieve to obtain a mixture A for later use;
2) weighing the softening agent and the water with the formula ratio into a container, and stirring until the coloring agent is completely dissolved; then adding the mixture into the mixture A to prepare a soft material;
3) after the soft material is sieved by a 10-mesh sieve and wet-sized, weighing soft material particles with corresponding weight according to the specification, and putting the soft material particles into a manual extruder for extrusion molding;
4) the resulting soft chewable tablet samples were left to cure for 24h at 25 ℃ in a 30% RH environment.
Example 2
The milbemycin oxime praziquantel soft chewable tablets comprise the following components:
| function of | Raw and auxiliary materials | Amount (%) |
| Raw material medicine | Milbemycin oxime | 0.3 |
| Raw material medicine | Praziquantel | 3 |
| Filler | Starch | 44.3 |
| Meat powder flavoring agent | Beef powder | 30 |
| Softening agent | Polyethylene glycol | 12 |
| Sweetening agent | Glucose | 5 |
| Coloring agent | Red iron oxide 3651 | 0.4 |
| Wetting agent | Water (W) | 5 |
Preparation process
1) Weighing milbemycin oxime, praziquantel, a filling agent, a meat powder flavoring agent and a sweetening agent which are required by the prescription amount, mixing in a PE sealing bag, and sieving by a 30-mesh sieve to obtain a mixture A for later use;
2) weighing the softening agent, the water and the coloring agent according to the formula ratio in a container, and stirring until the coloring agent is completely dissolved; then adding the mixture into the mixture A to prepare a soft material;
3) after the soft material is sieved by a 10-mesh sieve and wet-sized, weighing soft material particles with corresponding weight according to the specification, and putting the soft material particles into a manual extruder for extrusion molding;
4) the resulting soft chewable tablet samples were left to cure for 24h at 25 ℃ in a 30% RH environment.
Example 3
The milbemycin oxime praziquantel soft chewable tablets comprise the following components:
| function of | Raw and auxiliary materials | Amount (%) |
| Raw material medicine | Mier's riceBeethime | 0.3 |
| Raw material medicine | Praziquantel | 3 |
| Filler | Lactose | 45.25 |
| Meat powder flavoring agent | Chicken powder | 30 |
| Softening agent | Glycerol | 12 |
| Sweetening agent | Sucrose | 5 |
| Coloring agent | Red iron oxide 3651 | 0.4 |
| Antioxidant agent | TBHQ | 0.05 |
| Wetting agent | Water (W) | 4 |
Preparation process
1) Weighing milbemycin oxime, praziquantel, a filling agent, a meat powder flavoring agent and a sweetening agent which are required by the prescription amount, mixing in a PE sealing bag, and sieving by a 30-mesh sieve to obtain a mixture A for later use;
2) weighing the softening agent, the water, the antioxidant and the colorant according to the formula ratio in a container, and stirring until the colorant is completely dissolved; then adding the mixture into the mixture A to prepare a soft material;
3) after the soft material is sieved by a 10-mesh sieve and wet-sized, weighing soft material particles with corresponding weight according to the specification, and putting the soft material particles into a manual extruder for extrusion molding;
4) the resulting soft chewable tablet samples were left to cure for 24h at 25 ℃ in a 30% RH environment.
Example 4
The milbemycin oxime praziquantel soft chewable tablets comprise the following components:
preparation process
1) Weighing milbemycin oxime, praziquantel, a filling agent, a meat powder flavoring agent, a sweetening agent and a flavoring agent which are required by the prescription amount, mixing in a PE (polyethylene) sealed bag, and sieving by a 30-mesh sieve to obtain a mixture A for later use;
2) weighing the softening agent, the water, the antioxidant and the colorant according to the formula ratio in a container, and stirring until the colorant is completely dissolved; then adding the mixture into the mixture A to prepare a soft material;
3) after the soft material is sieved by a 10-mesh sieve and wet-sized, weighing soft material particles with corresponding weight according to the specification, and putting the soft material particles into a manual extruder for extrusion molding;
4) the resulting soft chewable tablet samples were left to cure for 24h at 25 ℃ in a 30% RH environment.
Examples 1-4 prescription high temperature 60 ℃ stability 30 days survey data results are as follows:
the data result of 30-day high-temperature 60 ℃ stability shows that:
the contents of milbemycin oxime and praziquantel in the examples 1 and 2 are slightly reduced, the total impurities are increased, and the hardness is stable;
the contents of milbemycin oxime and praziquantel in the examples 3 and 4 are not obviously changed, and the hardness is stable;
in both the example 3 and the example 4 (compared with the example 1 and the example 2), the antioxidant is added, and the product stability can be improved by adding the antioxidant according to the content and the total impurity data.
In summary, the colorant is added in the example 2 more than in the example 1, and the experimental data result shows that the two prescriptions have no obvious difference, and the colorant is added to facilitate the medication distinction; example 4 the flavor chicken liver powder was added more than in example 3 to improve palatability due to the common addition of flavors to commercial animal feeds. According to the experimental data, the content, the total impurities and the hardness of the two prescriptions have no obvious difference, so that the stability of the prescriptions is not influenced by adding the flavoring agent.
Because the auxiliary materials of the product are the filler and the meat powder in a large proportion, the following different addition proportions of the filler and the meat powder (chicken powder) are selected for prescription optimization and 30-day investigation of high-temperature 60 ℃ stability.
| Material prescription | EXAMPLE 5 | EXAMPLE 6 | EXAMPLE 7 |
| Milbemycin oxime% | 0.395 | 0.395 | 0.395 |
| Praziquantel% | 3.8 | 3.8 | 3.8 |
| Pregelatinized starch% | 43.705 | 38.705 | 33.705 |
| Chicken powder% | 25 | 30 | 35 |
| Chicken liver powder% | 4 | 4 | 4 |
| Sucrose% | 5 | 5 | 5 |
| Brown iron oxide% | 0.1 | 0.1 | 0.1 |
| Purified water% | 4 | 4 | 4 |
| Glycerol content% | 14 | 14 | 14 |
The data of 30-day high-temperature 60 ℃ stability examination are as follows:
the data result of 30-day high-temperature 60 ℃ stability inspection shows that the content of 5-milbemycin oxime is reduced, praziquantel has no obvious change trend, the hardness is increased to 9.63kg in 30 days, and the hardness is too high; the content of 6 milbemycin oxime and praziquantel is not obviously changed, and the hardness is slightly increased but still more stable; in the implementation, the content of 7 milbemycin oxime and praziquantel both have small descending trend, and the total impurity is greatly increased in 30 days. In conclusion, the adding amount of the chicken powder selected to be implemented in 6 percent is 30 percent finally.
The foregoing is a more detailed description of the invention and is not to be taken in a limiting sense. It will be apparent to those skilled in the art that simple deductions or substitutions without departing from the spirit of the invention are within the scope of the invention.
Claims (10)
1. The soft chewable tablet of milbemycin oxime praziquantel comprises the following components in parts by weight:
antioxidant, proper amount, water and proper amount;
wherein the softener is at least one selected from polyethylene glycol, glycerol and polypropylene glycol, and the hardness is preferably 3.0 kg-6.0 kg.
2. The milbemycin oxime praziquantel soft chewable tablet of claim 1, wherein: the mass composition is as follows:
。
3. The milbemycin oxime praziquantel soft chewable tablet of claim 1, wherein: the mass composition is as follows:
4. the soft chewable milbeoxime praziquantel tablet of any one of claims 1 to 3, wherein: the filler is selected from at least one of starch, lactose, mannitol and microcrystalline cellulose.
5. The soft chewable milbeoxime praziquantel tablet of any one of claims 1 to 3, wherein: the meat powder flavoring agent is at least one of beef powder and chicken powder.
6. The soft chewable milbeoxime praziquantel tablet of any one of claims 1 to 3, wherein: the flavoring agent is selected from at least one of chicken liver powder, dog powder flavoring agent and snack special flavoring agent.
7. The soft chewable milbeoxime praziquantel tablet of any one of claims 1 to 3, wherein: the sweetener is at least one selected from glucose, fructose, sucrose, saccharin sodium, stevioside and stevioside.
8. The soft chewable milbeoxime praziquantel tablet of any one of claims 1 to 3, wherein: the colorant is at least one selected from the group consisting of red iron oxide 3651, yellow iron oxide 1651, and brown iron oxide 7651.
9. The soft chewable milbeoxime praziquantel tablet of any one of claims 1 to 3, wherein: the antioxidant is selected from at least one of BHA, BHT, TBHQ, ascorbic acid, tea polyphenols and propyl gallate.
10. A preparation method of the soft chewable tablet of milbemycin oxime praziquantel is characterized in that: the soft chewable tablet of milbemycin oxime praziquantel as claimed in any one of claims 1 to 9, comprising:
uniformly mixing a coloring agent, a softening agent and water to obtain a mixture B;
uniformly mixing the rest raw materials to obtain a mixture A;
mixing the mixture A and the mixture B to prepare a soft material, and granulating to obtain soft material particles;
and extruding and molding the soft material particles, drying and curing to set hardness to obtain the milbemycin oxime praziquantel soft chewable tablets.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN116585278A (en) * | 2023-07-17 | 2023-08-15 | 济南广盛源生物科技有限公司 | Milbezoxime praziquantel chewable tablet as well as preparation method and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104127389A (en) * | 2014-08-04 | 2014-11-05 | 青岛科技大学 | Praziquantel chewing tablet for pets and preparation method thereof |
| CN108926540A (en) * | 2017-05-25 | 2018-12-04 | 北京欧博方医药科技有限公司 | A method of for manufacturing the soft chewable dosage forms of drug delivery |
| CN112220769A (en) * | 2020-08-13 | 2021-01-15 | 浙江海正动物保健品有限公司 | Milbemycin oxime praziquantel flavored tablet and preparation method thereof |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104127389A (en) * | 2014-08-04 | 2014-11-05 | 青岛科技大学 | Praziquantel chewing tablet for pets and preparation method thereof |
| CN108926540A (en) * | 2017-05-25 | 2018-12-04 | 北京欧博方医药科技有限公司 | A method of for manufacturing the soft chewable dosage forms of drug delivery |
| CN112220769A (en) * | 2020-08-13 | 2021-01-15 | 浙江海正动物保健品有限公司 | Milbemycin oxime praziquantel flavored tablet and preparation method thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116585278A (en) * | 2023-07-17 | 2023-08-15 | 济南广盛源生物科技有限公司 | Milbezoxime praziquantel chewable tablet as well as preparation method and application thereof |
| CN116585278B (en) * | 2023-07-17 | 2023-09-22 | 济南广盛源生物科技有限公司 | Milbezoxime praziquantel chewable tablet as well as preparation method and application thereof |
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Effective date of registration: 20240402 Address after: No. 8 Shilong Avenue, Xinji Village Committee, Shijiao Town, Qingcheng District, Qingyuan City, Guangdong Province 511545. Lizhu Group Xinbeijiang Pharmaceutical Co., Ltd. has built Workshop 201 (third floor) and Workshop 202 (fourth floor) for animal protection Patentee after: Lijian (Guangdong) Animal Health Co.,Ltd. Country or region after: China Address before: 511518 Renmin 1st Road, Qingyuan City, Guangdong Province Patentee before: LIVZON NEW NORTH RIVER PHARMACEUTICAL Co.,Ltd. Country or region before: China |