CN111329997A - 一种治疗猫炎症性肠道疾病的软咀嚼片剂及其制备方法 - Google Patents
一种治疗猫炎症性肠道疾病的软咀嚼片剂及其制备方法 Download PDFInfo
- Publication number
- CN111329997A CN111329997A CN202010143498.2A CN202010143498A CN111329997A CN 111329997 A CN111329997 A CN 111329997A CN 202010143498 A CN202010143498 A CN 202010143498A CN 111329997 A CN111329997 A CN 111329997A
- Authority
- CN
- China
- Prior art keywords
- soft chewable
- chewable tablet
- inflammatory bowel
- cats
- bowel disease
- 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.)
- Pending
Links
- 241000282326 Felis catus Species 0.000 title claims abstract description 61
- 239000007910 chewable tablet Substances 0.000 title claims abstract description 40
- 229940068682 chewable tablet Drugs 0.000 title claims abstract description 31
- 238000002360 preparation method Methods 0.000 title abstract description 14
- 208000028774 intestinal disease Diseases 0.000 title abstract description 10
- 230000002757 inflammatory effect Effects 0.000 title abstract description 9
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims abstract description 14
- 150000004676 glycans Chemical class 0.000 claims abstract description 14
- 229920001282 polysaccharide Polymers 0.000 claims abstract description 14
- 239000005017 polysaccharide Substances 0.000 claims abstract description 14
- 239000004366 Glucose oxidase Substances 0.000 claims abstract description 12
- 108010015776 Glucose oxidase Proteins 0.000 claims abstract description 12
- 102000016943 Muramidase Human genes 0.000 claims abstract description 12
- 108010014251 Muramidase Proteins 0.000 claims abstract description 12
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 claims abstract description 12
- 229940116332 glucose oxidase Drugs 0.000 claims abstract description 12
- 235000019420 glucose oxidase Nutrition 0.000 claims abstract description 12
- 235000010335 lysozyme Nutrition 0.000 claims abstract description 12
- 229960000274 lysozyme Drugs 0.000 claims abstract description 12
- 239000004325 lysozyme Substances 0.000 claims abstract description 12
- 229930182816 L-glutamine Natural products 0.000 claims abstract description 10
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 8
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 8
- 239000000796 flavoring agent Substances 0.000 claims abstract description 8
- 241000233866 Fungi Species 0.000 claims abstract description 7
- 239000004480 active ingredient Substances 0.000 claims abstract description 7
- 239000000945 filler Substances 0.000 claims abstract description 6
- 235000013355 food flavoring agent Nutrition 0.000 claims abstract description 6
- 239000003995 emulsifying agent Substances 0.000 claims abstract description 5
- 239000000314 lubricant Substances 0.000 claims abstract description 5
- 239000000853 adhesive Substances 0.000 claims abstract description 4
- 230000001070 adhesive effect Effects 0.000 claims abstract description 4
- 239000003906 humectant Substances 0.000 claims abstract description 4
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 3
- 239000003755 preservative agent Substances 0.000 claims abstract description 3
- 230000002335 preservative effect Effects 0.000 claims abstract description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 35
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 33
- 239000000203 mixture Substances 0.000 claims description 21
- 239000000843 powder Substances 0.000 claims description 21
- 239000008187 granular material Substances 0.000 claims description 18
- 239000007787 solid Substances 0.000 claims description 18
- 235000011187 glycerol Nutrition 0.000 claims description 13
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical group [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 12
- 229920001184 polypeptide Polymers 0.000 claims description 11
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 11
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 9
- 229930006000 Sucrose Natural products 0.000 claims description 9
- 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 9
- 239000000600 sorbitol Substances 0.000 claims description 9
- GHKOFFNLGXMVNJ-UHFFFAOYSA-N Didodecyl thiobispropanoate Chemical compound CCCCCCCCCCCCOC(=O)CCSCCC(=O)OCCCCCCCCCCCC GHKOFFNLGXMVNJ-UHFFFAOYSA-N 0.000 claims description 8
- 239000003508 Dilauryl thiodipropionate Substances 0.000 claims description 8
- 239000002202 Polyethylene glycol Substances 0.000 claims description 8
- 244000269722 Thea sinensis Species 0.000 claims description 8
- 235000019304 dilauryl thiodipropionate Nutrition 0.000 claims description 8
- 238000002156 mixing Methods 0.000 claims description 8
- 239000002245 particle Substances 0.000 claims description 8
- 150000003904 phospholipids Chemical class 0.000 claims description 8
- 229920001223 polyethylene glycol Polymers 0.000 claims description 8
- 150000008442 polyphenolic compounds Chemical class 0.000 claims description 8
- 235000013824 polyphenols Nutrition 0.000 claims description 8
- 239000005720 sucrose Substances 0.000 claims description 8
- 229920002472 Starch Polymers 0.000 claims description 7
- 235000006708 antioxidants Nutrition 0.000 claims description 7
- 239000008107 starch Substances 0.000 claims description 7
- 235000019698 starch Nutrition 0.000 claims description 7
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 6
- 235000019359 magnesium stearate Nutrition 0.000 claims description 6
- 239000000463 material Substances 0.000 claims description 6
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 6
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 6
- 238000007873 sieving Methods 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- 235000015278 beef Nutrition 0.000 claims description 5
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 4
- HDIFHQMREAYYJW-XGXNLDPDSA-N Glyceryl Ricinoleate Chemical compound CCCCCC[C@@H](O)C\C=C/CCCCCCCC(=O)OCC(O)CO HDIFHQMREAYYJW-XGXNLDPDSA-N 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- 108010039918 Polylysine Proteins 0.000 claims description 4
- 229940116338 glyceryl ricinoleate Drugs 0.000 claims description 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 4
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 4
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 4
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 3
- NVNLLIYOARQCIX-MSHCCFNRSA-N Nisin Chemical compound N1C(=O)[C@@H](CC(C)C)NC(=O)C(=C)NC(=O)[C@@H]([C@H](C)CC)NC(=O)[C@@H](NC(=O)C(=C/C)/NC(=O)[C@H](N)[C@H](C)CC)CSC[C@@H]1C(=O)N[C@@H]1C(=O)N2CCC[C@@H]2C(=O)NCC(=O)N[C@@H](C(=O)N[C@H](CCCCN)C(=O)N[C@@H]2C(NCC(=O)N[C@H](C)C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCSC)C(=O)NCC(=O)N[C@H](CS[C@@H]2C)C(=O)N[C@H](CC(N)=O)C(=O)N[C@H](CCSC)C(=O)N[C@H](CCCCN)C(=O)N[C@@H]2C(N[C@H](C)C(=O)N[C@@H]3C(=O)N[C@@H](C(N[C@H](CC=4NC=NC=4)C(=O)N[C@H](CS[C@@H]3C)C(=O)N[C@H](CO)C(=O)N[C@H]([C@H](C)CC)C(=O)N[C@H](CC=3NC=NC=3)C(=O)N[C@H](C(C)C)C(=O)NC(=C)C(=O)N[C@H](CCCCN)C(O)=O)=O)CS[C@@H]2C)=O)=O)CS[C@@H]1C NVNLLIYOARQCIX-MSHCCFNRSA-N 0.000 claims description 3
- 108010053775 Nisin Proteins 0.000 claims description 3
- 239000004288 Sodium dehydroacetate Substances 0.000 claims description 3
- 239000004309 nisin Substances 0.000 claims description 3
- 235000010297 nisin Nutrition 0.000 claims description 3
- 235000019259 sodium dehydroacetate Nutrition 0.000 claims description 3
- 229940079839 sodium dehydroacetate Drugs 0.000 claims description 3
- DSOWAKKSGYUMTF-GZOLSCHFSA-M sodium;(1e)-1-(6-methyl-2,4-dioxopyran-3-ylidene)ethanolate Chemical compound [Na+].C\C([O-])=C1/C(=O)OC(C)=CC1=O DSOWAKKSGYUMTF-GZOLSCHFSA-M 0.000 claims description 3
- AZJQQNWSSLCLJN-UHFFFAOYSA-N 2-ethoxyquinoline Chemical compound C1=CC=CC2=NC(OCC)=CC=C21 AZJQQNWSSLCLJN-UHFFFAOYSA-N 0.000 claims description 2
- 240000004670 Glycyrrhiza echinata Species 0.000 claims description 2
- 235000001453 Glycyrrhiza echinata Nutrition 0.000 claims description 2
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 claims description 2
- 235000017382 Glycyrrhiza lepidota Nutrition 0.000 claims description 2
- 229920003081 Povidone K 30 Polymers 0.000 claims description 2
- 229930003427 Vitamin E Natural products 0.000 claims description 2
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 claims description 2
- 229960000913 crospovidone Drugs 0.000 claims description 2
- 239000007884 disintegrant Substances 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 2
- 229940010454 licorice Drugs 0.000 claims description 2
- 238000003825 pressing Methods 0.000 claims description 2
- 235000019165 vitamin E Nutrition 0.000 claims description 2
- 229940046009 vitamin E Drugs 0.000 claims description 2
- 239000011709 vitamin E Substances 0.000 claims description 2
- 229940057917 medium chain triglycerides Drugs 0.000 claims 2
- 239000004909 Moisturizer Substances 0.000 claims 1
- 239000011230 binding agent Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000001333 moisturizer Effects 0.000 claims 1
- 238000000465 moulding Methods 0.000 claims 1
- 208000024891 symptom Diseases 0.000 abstract description 12
- 230000000694 effects Effects 0.000 abstract description 11
- 239000003814 drug Substances 0.000 abstract description 8
- 235000019629 palatability Nutrition 0.000 abstract description 8
- 239000002552 dosage form Substances 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 5
- 230000007774 longterm Effects 0.000 abstract description 5
- 239000000126 substance Substances 0.000 abstract description 4
- 238000000034 method Methods 0.000 abstract description 3
- 230000008569 process Effects 0.000 abstract description 2
- 230000003750 conditioning effect Effects 0.000 abstract 1
- 230000000968 intestinal effect Effects 0.000 description 22
- 238000012360 testing method Methods 0.000 description 19
- 239000003826 tablet Substances 0.000 description 17
- 210000001035 gastrointestinal tract Anatomy 0.000 description 16
- 229960002743 glutamine Drugs 0.000 description 11
- 206010012735 Diarrhoea Diseases 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 210000004347 intestinal mucosa Anatomy 0.000 description 7
- 229960004793 sucrose Drugs 0.000 description 7
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 7
- FDJOLVPMNUYSCM-WZHZPDAFSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+3].N#[C-].N([C@@H]([C@]1(C)[N-]\C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C(\C)/C1=N/C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C\C1=N\C([C@H](C1(C)C)CCC(N)=O)=C/1C)[C@@H]2CC(N)=O)=C\1[C@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]1[C@@H](O)[C@@H](N2C3=CC(C)=C(C)C=C3N=C2)O[C@@H]1CO FDJOLVPMNUYSCM-WZHZPDAFSA-L 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 206010061218 Inflammation Diseases 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 235000013305 food Nutrition 0.000 description 5
- 230000002496 gastric effect Effects 0.000 description 5
- 229920001491 Lentinan Polymers 0.000 description 4
- 206010047700 Vomiting Diseases 0.000 description 4
- 239000003242 anti bacterial agent Substances 0.000 description 4
- 229940088710 antibiotic agent Drugs 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000003745 diagnosis Methods 0.000 description 4
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 4
- 210000003767 ileocecal valve Anatomy 0.000 description 4
- 210000003405 ileum Anatomy 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 229940115286 lentinan Drugs 0.000 description 4
- 210000001165 lymph node Anatomy 0.000 description 4
- 239000001253 polyvinylpolypyrrolidone Substances 0.000 description 4
- WBHHMMIMDMUBKC-QJWNTBNXSA-M ricinoleate Chemical compound CCCCCC[C@@H](O)C\C=C/CCCCCCCC([O-])=O WBHHMMIMDMUBKC-QJWNTBNXSA-M 0.000 description 4
- 229940066675 ricinoleate Drugs 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 229940126585 therapeutic drug Drugs 0.000 description 4
- 238000012795 verification Methods 0.000 description 4
- 230000008673 vomiting Effects 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 241000282324 Felis Species 0.000 description 3
- 240000001080 Grifola frondosa Species 0.000 description 3
- 235000007710 Grifola frondosa Nutrition 0.000 description 3
- 230000005856 abnormality Effects 0.000 description 3
- 208000022531 anorexia Diseases 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 210000001072 colon Anatomy 0.000 description 3
- 206010061428 decreased appetite Diseases 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 210000003608 fece Anatomy 0.000 description 3
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 3
- 230000036737 immune function Effects 0.000 description 3
- 230000008944 intestinal immunity Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 235000013372 meat Nutrition 0.000 description 3
- 244000045947 parasite Species 0.000 description 3
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 3
- 229960005205 prednisolone Drugs 0.000 description 3
- 208000016261 weight loss Diseases 0.000 description 3
- 208000004998 Abdominal Pain Diseases 0.000 description 2
- 208000002881 Colic Diseases 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 235000019733 Fish meal Nutrition 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 210000004534 cecum Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000001143 conditioned effect Effects 0.000 description 2
- 230000006866 deterioration Effects 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000004467 fishmeal Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 235000019152 folic acid Nutrition 0.000 description 2
- 239000011724 folic acid Substances 0.000 description 2
- 239000013568 food allergen Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 208000026278 immune system disease Diseases 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 230000036046 immunoreaction Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 235000012054 meals Nutrition 0.000 description 2
- 210000000214 mouth Anatomy 0.000 description 2
- 210000004877 mucosa Anatomy 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 210000000813 small intestine Anatomy 0.000 description 2
- 235000015424 sodium Nutrition 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
- 235000013616 tea Nutrition 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000008719 thickening Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 238000002604 ultrasonography Methods 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- 241000251468 Actinopterygii Species 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 238000012935 Averaging Methods 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000711573 Coronaviridae Species 0.000 description 1
- 241001480079 Corymbia calophylla Species 0.000 description 1
- 241000223935 Cryptosporidium Species 0.000 description 1
- 208000006558 Dental Calculus Diseases 0.000 description 1
- 208000036649 Dysbacteriosis Diseases 0.000 description 1
- 208000027244 Dysbiosis Diseases 0.000 description 1
- 101710146739 Enterotoxin Proteins 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 241000224466 Giardia Species 0.000 description 1
- 102000006395 Globulins Human genes 0.000 description 1
- 108010044091 Globulins Proteins 0.000 description 1
- 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 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 206010022678 Intestinal infections Diseases 0.000 description 1
- 235000006552 Liquidambar styraciflua Nutrition 0.000 description 1
- 206010025476 Malabsorption Diseases 0.000 description 1
- 208000004155 Malabsorption Syndromes Diseases 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- 102000019280 Pancreatic lipases Human genes 0.000 description 1
- 108050006759 Pancreatic lipases Proteins 0.000 description 1
- 208000037581 Persistent Infection Diseases 0.000 description 1
- 241000125945 Protoparvovirus Species 0.000 description 1
- 208000037656 Respiratory Sounds Diseases 0.000 description 1
- 241001591005 Siga Species 0.000 description 1
- 206010044029 Tooth deposit Diseases 0.000 description 1
- 241000224526 Trichomonas Species 0.000 description 1
- 241001489151 Trichuris Species 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000002052 anaphylactic effect Effects 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 238000002555 auscultation Methods 0.000 description 1
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
- 229960002170 azathioprine Drugs 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 208000019902 chronic diarrheal disease Diseases 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 230000007140 dysbiosis Effects 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 230000037149 energy metabolism Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000000147 enterotoxin Substances 0.000 description 1
- 231100000655 enterotoxin Toxicity 0.000 description 1
- 201000001564 eosinophilic gastroenteritis Diseases 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 230000008378 epithelial damage Effects 0.000 description 1
- 230000004887 epithelial permeability Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 229940014144 folate Drugs 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 210000005026 intestinal epithelial barrier Anatomy 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000008141 laxative Substances 0.000 description 1
- 229940125722 laxative agent Drugs 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 210000003563 lymphoid tissue Anatomy 0.000 description 1
- 230000007257 malfunction Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000006996 mental state Effects 0.000 description 1
- 210000002200 mouth mucosa Anatomy 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 229940116369 pancreatic lipase Drugs 0.000 description 1
- 230000003071 parasitic effect Effects 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 239000006041 probiotic Substances 0.000 description 1
- 235000018291 probiotics Nutrition 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000028070 sporulation Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000013517 stratification Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 230000001810 trypsinlike Effects 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 210000004916 vomit Anatomy 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 239000013585 weight reducing agent Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/44—Oxidoreductases (1)
- A61K38/443—Oxidoreductases (1) acting on CH-OH groups as donors, e.g. glucose oxidase, lactate dehydrogenase (1.1)
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2063—Proteins, e.g. gelatin
-
- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y101/00—Oxidoreductases acting on the CH-OH group of donors (1.1)
- C12Y101/03—Oxidoreductases acting on the CH-OH group of donors (1.1) with a oxygen as acceptor (1.1.3)
- C12Y101/03004—Glucose oxidase (1.1.3.4)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y302/01017—Lysozyme (3.2.1.17)
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Biochemistry (AREA)
- Botany (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Molecular Biology (AREA)
- Physiology (AREA)
- Nutrition Science (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明公开了一种治疗猫炎症性肠道疾病的软咀嚼片剂及其制备方法，按质量分数计，由活性成分35‑45％，粘合剂1.8‑2.4％，保湿剂6‑8％，乳化剂4‑6％，风味剂8‑10％，抗氧化剂3‑4％，防腐剂0.5‑1％，崩解剂4‑5％，润滑剂0.3‑0.5％，填充剂组成。所述活性成分由葡萄糖氧化酶、溶菌酶、食用菌多糖、L‑谷氨酰胺组成，且添加比例为2:2:3:3。本发明解决了常规化学治疗药物存在的只改善表症、不能从根本上调理、副作用大、不适合长期使用、适口性差等问题，本品是经过科学组方及特殊的软咀嚼片剂工艺制备而成的一种效果显著、高效安全、标本兼治、剂型独特、适口性佳、性状及性能稳定的治疗型药物，可长期服用，针对猫的炎症性肠道疾病的治疗有显著效果。
Description
技术领域
本发明涉及宠物用药技术领域，具体涉及一种治疗猫炎症性肠道疾病的软咀嚼片剂及其制备方法。
背景技术
炎症性肠道疾病(Inflammatory Bowel Disease，IBD)是猫最常见的肠道疾病，也是造成猫慢性体重减轻的“五大原因”之一。IBD不具有诊断特异性，它并不是单指一种病，而是由胃、小肠和/或结肠的慢性炎症相关的一系列胃肠紊乱所引起的综合症。
猫的IBD与狗IBD或人IBD在临床上和组织学上几乎没有相似性。虽然炎症性肠道疾病在犬常造成慢性腹泻症状，但猫却是最常出现慢性间歇性呕吐，其他可能症状包括腹泻、失重、厌食，但在临床的检查上通常都不会出现任何异常。炎症性肠道疾病通常发生于中年至较老的猫咪，平均约8岁(5月龄--20岁)，并没有品种或性别好发性。
IBD被定义为一种原发性综合症，是累及消化道的一种与免疫相关的疾病，其发病机制尚不明确，目前流行的假说认为猫的IBD都是因为局部胃肠道黏膜免疫机能紊乱，伴随着对共生菌群或食物类抗原等的不耐受，最终导致出现慢性肠道炎症。IBD的发病与肠道菌群失调、肠黏膜免疫紊乱有关,近年来大量研究显示其可能的机制如下：(1)抗生素不规范使用、肠道内pH改变、感染等因素的影响使肠道内发生菌群紊乱、内环境失调，直接损伤肠上皮屏障；(2)肠道菌群紊乱，条件致病菌可分泌肠毒素使上皮通透性增加，使外源性致病菌侵入肠道，还可分泌免疫球蛋白，导致肠道黏膜免疫失调；(3)某些致病菌可影响肠上皮能量代谢，导致上皮损伤，诱发肠道炎症。
IBD的诊断与治疗复杂，严重影响患病猫的生活质量，其诊治集合了困难、风险及高昂的花费等问题，许多猫只能用“尝试性治疗”一步步来。最常用的用于猫IBD消炎的药物是泼尼松龙，使用泼尼松龙能有效缓解症状。其他如硫唑嘌呤这种压制免疫系统，防止过敏反应的药物也被视情况使用。然而像泼尼松龙这样的激素类消炎药会增加猫患上糖尿病和消化道溃疡的几率，长期使用也增加了肾脏负担。许多兽医不顾长期风险，持续给猫用泼尼松龙，这不可取。另外猫对治疗产品的适口性要求很高，尤其是猫更加挑剔，猫对味道特别敏感，对粉剂、硬片剂、胶囊等剂型都会抵抗，虽然宠物产品都会添加调味剂、娇味剂、诱食剂，但这不足以完全吸引其自主采食和吞咽。
因此，现有技术需要进一步改进。
发明内容
本发明提供了一种治疗猫炎症性肠道疾病的软咀嚼片剂及其制备方法，解决了常规化学治疗药物存在的只改善表症、不能从根本上调理、副作用大、不适合长期使用、适口性差等问题。
为解决上述技术问题，本发明采用的技术方案为：
一种治疗猫炎症性肠道疾病的软咀嚼片剂，按质量分数计，由以下组分组成：
进一步地，所述的活性成分由葡萄糖氧化酶、溶菌酶、食用菌多糖和L-谷氨酰胺组成，所述葡萄糖氧化酶、溶菌酶、食用菌多糖及L-谷氨酰胺的添加比例为2:2:3:3，其中，所述的葡萄糖氧化酶酶活为10000U/g，所述的溶菌酶酶活为200000U/mg，所述的食用菌多糖为香菇多糖、木耳多糖、或舞茸多糖中的任一种，所述香菇多糖含量为40％，所述木耳多糖含量为30％，所述舞茸多糖含量为30％，所述L-谷氨酰胺含量为95％。
进一步地，所述的粘合剂为淀粉、羟丙基甲基纤维素、聚维酮K30中的一种，将所述粘合剂用纯化水配制成3％-4％的溶液。
进一步地，所述的保湿剂由甘油和中链甘油三酯组成，所述甘油和中链甘油三酯添加比例为2：3或1:2。
优选的，所述所述甘油和中链甘油三酯添加比例为2：3。
进一步地，所述的乳化剂由磷脂和聚乙二醇甘油蓖麻酸酯组成，所述磷脂和聚乙二醇甘油蓖麻酸酯添加比例为1:2。
进一步地，所述的风味剂为多肽牛肉粉、多肽金枪鱼粉中的一种。
进一步地，所述的抗氧化剂为甘草抗氧化物、硫代二丙酸二月桂酯、乙氧基喹啉、丁基羟基茴香醚、茶多酚、维生素E中的任意两种。
优选的，所述抗氧化剂采用硫代二丙酸二月桂酯和茶多酚，且二者添加比例为1:1。
进一步地，所述的崩解剂为羧甲基淀粉钠或交联聚维酮中的一种。
进一步地，所述的防腐剂为乳酸链球菌素、ε-聚赖氨酸盐酸盐或脱氢乙酸钠中的一种；所述的润滑剂为硬脂酸镁；所述的填充剂由山梨醇和蔗糖组成，其中所述山梨醇和蔗糖添加比例为1:1或2:1。
优选的，所述山梨醇和蔗糖的添加比例为1：1。
一种治疗猫炎症性肠道疾病的软咀嚼片剂的制备方法，包括以下步骤：
步骤1，将粘合剂用60％的100℃热水制成浓度为3-4％的溶液A，并晾凉至室温待用；
步骤2，将保湿剂及乳化剂顺序倒入溶液A中并搅拌均匀，制得溶液B；
步骤3，将活性成分、风味剂、抗氧化剂、崩解剂、填充剂固体原辅料混合均匀，并过40目筛网，获得固体粉末混合物C；
步骤4，将溶液B分多次加入固体粉末混合物C中制成湿颗粒并进行整粒；
步骤5，将步骤4中制备的湿颗粒放入40度烘箱中干燥50-60分钟，使颗粒水分维持在8-10％之间；
步骤6，将润滑剂加入步骤5制得的颗粒中混合均匀，然后在旋转压片机上使用15mm*15mm的原型冲头进行压制。
本发明的治疗猫炎症性肠道疾病的软咀嚼片剂的片重为0.95±0.05g时，其的用法用量如下：口服，每天两次，每次按照1片/2kg体重的用量，连用10天为一个疗程。
本发明的有益效果
1、多种成分协同作用，从消炎、调节肠道菌群平衡、提升肠道免疫、修复胃肠黏膜等几方面多管齐下，从而从根本上解决猫的炎症性肠道疾病：其中葡萄糖氧化酶在动物肠道内以葡萄糖为底物发生一系列的催化反应，改变肠道内酸性环境及氧气浓度，同时具有抗氧化作用及类抗生素的作用，能够有效平衡猫的肠道微生态系统，具有保护肠道结构完整性、提高机体免疫力等功效。溶菌酶是一种具有杀菌作用的天然抗感染物质，它对革兰阳性菌、好氧性孢子形成菌、枯草杆菌、地衣型芽孢杆菌等都有抗菌作用。葡萄糖氧化酶与溶菌酶协同作用，消炎效果显著。植物多糖一方面通过促进益生菌的增殖，调整肠道菌群，活化肠黏膜内的相关淋巴组织，使sIgA抗体分泌增强，从而间接增强机体肠道黏膜免疫功能，另一方面通过调节机体的整体免疫机能，防止机体免疫系统过度反应产生过敏效应。谷氨酰胺是肠道粘膜细胞代谢必需的营养物质，对维持肠道粘膜上皮结构的完整性起着十分重要的作用，尤其是在猫患上肠道感染等严重应激状态下，肠道粘膜上皮细胞内谷氨酰胺很快耗竭，当肠道缺乏食物、消化液等刺激或缺乏谷氨酰胺时，肠道粘膜萎缩、绒毛变稀、变短甚至脱落，隐窝变浅，肠粘膜通透性增加，肠道免疫功能受损。肠外途径提供谷氨酰胺均可有效地防止肠道粘膜萎缩，保持正常肠道粘膜重量、结构及蛋白质含量，增强肠道细胞活性，改善肠道免疫功能，减少肠道细菌及内毒素的易位。
2、安全高效，标本兼治：本产品主要由生物酶和食用菌提取物组成，属于绿色、安全的治疗型药物，与常规化学类抗生素或激素等治疗药物相比，更加安全，适合长期使用，不仅能改善猫炎症性肠道疾病的腹泻、呕吐、厌食等多种临床症状，还能从根本上调理猫的胃肠道菌群平衡、修复胃肠黏膜、提升肠道免疫，呵护猫的胃肠健康。
3、剂型独特，方便饲喂，适口性好：猫这种动物本身对食物、药品、保健品就很挑剔，而患上IBD的猫因其具有呕吐、厌食等表现，故饲喂治疗药物更加困难，所以对药物的适口性要求更为严格和苛刻。本品采用软咀嚼片剂，与常规硬片剂、胶囊等剂型相比，因其具有更低的硬度和更高的含水量，因而更受宠物猫的喜爱，更方便饲喂。与膏剂、粉剂、液体等剂型相比，喂食剂量更好控制，保存更方便，方便饲喂。另外本品中添加的多肽肉粉或多肽鱼粉等风味剂均以新鲜畜禽或海洋鱼为原料制成，为低敏性原料，同时富含小分子蛋白、多肽、游离氨基酸、牛磺酸、EPA、DHA等功能性成分，与常规用的肉类香精等诱食剂相比，风味更加浓郁醇厚，具有良好的适口性和耐口性，同时在新鲜度和抗氧化性等方面都有显著优势。
4、产品性状及性能稳定：经加速试验验证，本软咀嚼片剂性状及性能稳定，无发霉变质现象发生，同时水分、片重、多种有效成分含量等指标都稳定。
附图说明
图1是本发明实施例6中病猫肠道回盲瓣部位的两幅超声影像图；
图2是本发明实施例6中另一角度拍摄病猫肠道回盲瓣板部位的两幅超声影像图。
具体实施方式
下面将结合本发明具体实施例，对本发明的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
本发明的软咀嚼片剂是以葡萄糖氧化酶、溶菌酶、食用菌多糖、L-谷氨酰胺为主要活性物质，辅以粘合剂、保湿剂、乳化剂、风味剂、抗氧化剂、防腐剂、崩解剂、润滑剂、填充剂等非活性成分，本品是经过科学组方及特殊的软咀嚼片剂工艺制备而成的一种效果显著、高效安全、标本兼治、剂型独特、适口性佳、性状及性能稳定的治疗型药物，可长期服用，针对猫的炎症性肠道疾病的治疗有显著效果。
实施例1
一种治疗猫炎症性肠道疾病的软咀嚼片剂及其制备方法，含有的组分及各自的质量分数分别为：
其制备方法，包括以下步骤：
(1)将羟丙基甲基纤维素用60ml 100℃热水制成浓度为3.33％的溶液A，并晾凉至室温待用；
(2)将甘油、中链甘油三酯、磷脂、聚乙二醇甘油蓖麻酸酯顺序倒入溶液A中并搅拌均匀，制得溶液B；
(3)将葡萄糖氧化酶、溶菌酶、香菇多糖、L-谷氨酰胺、多肽牛肉粉、硫代二丙酸二月桂酯、茶多酚、乳酸链球菌素、羧甲基淀粉钠、山梨醇、蔗糖等固体原辅料混合均匀，并过40目筛网，获得固体粉末混合物C；
(4)将溶液B少量多次加入固体粉末混合物C中制成湿颗粒，并用摇摆式颗粒机14目筛网进行整粒；
(5)将上述湿颗粒放入40度烘箱中进行干燥60分钟，使颗粒水分降至8％。
(6)将硬脂酸镁加入步骤5制得的颗粒中混合均匀，然后在旋转压片机上使用15mm*15mm的原型冲头进行压制，片重控制在0.95±0.05g。
实施例2
一种治疗猫炎症性肠道疾病的软咀嚼片剂及其制备方法，含有的组分及各自的质量分数分别为：
其制备方法，包括以下步骤：
(1)将淀粉用60ml 100℃热水制成浓度为3％的溶液A，并晾凉至室温待用；
(2)将甘油、中链甘油三酯、磷脂、聚乙二醇甘油蓖麻酸酯顺序倒入溶液A中并搅拌均匀，制得溶液B；
(3)将葡萄糖氧化酶、溶菌酶、木耳多糖、L-谷氨酰胺、多肽金枪鱼粉、硫代二丙酸二月桂酯、茶多酚、ε-聚赖氨酸盐酸盐、交联聚维酮(PVPP)、山梨醇、蔗糖等固体原辅料混合均匀，并过40目筛网，获得固体粉末混合物C；
(4)将溶液B少量多次加入固体粉末混合物C中制成湿颗粒，并用摇摆式颗粒机14目筛网进行整粒；
(5)将上述湿颗粒放入40度烘箱中进行干燥55分钟，使颗粒水分降至9％。
(6)将硬脂酸镁加入步骤5制得的颗粒中混合均匀，然后在旋转压片机上使用15mm*15mm的原型冲头进行压制，片重控制在0.95±0.05g。
实施例3
一种治疗猫炎症性肠道疾病的软咀嚼片剂及其制备方法，含有的组分及各自的质量分数分别为：
其制备方法，包括以下步骤：
(1)将聚维酮(PVP)K30用60ml 100℃热水制成浓度为3.33％的溶液A，并晾凉至室温待用；
(2)将甘油、中链甘油三酯、磷脂、聚乙二醇甘油蓖麻酸酯顺序倒入溶液A中并搅拌均匀，制得溶液B；
(3)将葡萄糖氧化酶、溶菌酶、舞茸多糖、L-谷氨酰胺、多肽牛肉粉、硫代二丙酸二月桂酯、茶多酚、脱氢乙酸钠、羧甲基淀粉钠、山梨醇、蔗糖等固体原辅料混合均匀，并过40目筛网，获得固体粉末混合物C；
(4)将溶液B少量多次加入固体粉末混合物C中制成湿颗粒，并用摇摆式颗粒机14目筛网进行整粒；
(5)将上述湿颗粒放入40度烘箱中进行干燥50分钟，使颗粒水分降至10％。
(6)将硬脂酸镁加入步骤5制得的颗粒中混合均匀，然后在旋转压片机上使用15mm*15mm的原型冲头进行压制，片重控制在0.95±0.05g。
实施例4
一种治疗猫炎症性肠道疾病的软咀嚼片剂及其制备方法，含有的组分及各自的质量分数分别为：
其制备方法，包括以下步骤：
(1)将羟丙基甲基纤维素用60ml 100℃热水制成浓度为4％的溶液A，并晾凉至室温待用；
(2)将甘油、中链甘油三酯、磷脂、聚乙二醇甘油蓖麻酸酯顺序倒入溶液A中并搅拌均匀，制得溶液B；
(3)将葡萄糖氧化酶、溶菌酶、香菇多糖、L-谷氨酰胺、多肽金枪鱼粉、硫代二丙酸二月桂酯、茶多酚、ε-聚赖氨酸盐酸盐、交联聚维酮(PVPP)、山梨醇、蔗糖等固体原辅料混合均匀，并过40目筛网，获得固体粉末混合物C；
(4)将溶液B少量多次加入固体粉末混合物C中制成湿颗粒，并用摇摆式颗粒机14目筛网进行整粒；
(5)将上述湿颗粒放入40度烘箱中进行干燥50分钟，使颗粒水分降至10％。
(6)将硬脂酸镁加入步骤5制得的颗粒中混合均匀，然后在旋转压片机上使用15mm*15mm的原型冲头进行压制，片重控制在0.95±0.05g。
实施例5实施例1-4配方软咀嚼片剂的稳定性评价试验
1)试验方法
将四个实施例配方的软咀嚼片用铝塑包装(每组60片)并放置加速条件下6个月(40℃±2℃，相对湿度75％±5％)，观察并检测软咀嚼片剂的稳定性，主要有以下四个指标(外观、水分含量、有效成分含量、平均片重)，结果见表1-表4。
表1：实施例1配方的软咀嚼片的稳定性验证试验
表2：实施例2配方的软咀嚼片的稳定性验证试验
表3：实施例3配方的软咀嚼片的稳定性验证试验
表4：实施例4配方的软咀嚼片的稳定性验证试验
2)试验结果：
从表1-表4的结果来看，实施例1-实施例4这四个配方的软咀嚼片在加速条件下质量稳定，与试验之初各指标无差异：外观性状稳定，无发霉变质现象、另外含水量、有效成分含量、平均片重等指标都变化不显著。
实施例6一例猫炎症性肠道疾病临床治疗效果的评价试验
1)病猫基本信息：
主述病猫精神不佳，不喜运动，有时呕吐，间断性腹泻有近半年之久，有时粪便味道较大伴随少量血液与粘稠样液体。有过它院就诊经历，进行对症治疗，口服抗生素、缓泻剂、驱虫、更换过食物。治疗后粪便好转，停药后复发，腹泻得不到长久控制，近三四个月内体重有明显下降。
家养短毛猫，雄性，8岁，已经去势，免疫驱虫完全。体重3.0kg，体温38.5℃，心率/脉搏148次/min，CRT＜2s，BCS 3/9，脱水状态5％-8％之间，口腔黏膜颜色粉红，口腔少量牙结石，牙龈线发红，处于紧张状态。听诊心音、肺音、肠鸣音无明显异常。触诊体表淋巴结、腹部未见明显异常。
2)实验室检查：
1.血常规：检查结果显示，病猫出现白细胞总数升高，嗜中性粒细胞数量升高，其他未见异常。生化检查结果显示病猫球蛋白出现轻度升高，可能与长期感染有关，其他指标均在正常范围内。
2.血清T4检查：见表5
表5病猫的血清T4检测结果
| 项目 | 测试值 | 参考值 |
| 血清总体T4 | 16nmol/L | 15-48nmol/L |
通过上表显示血清T4检测结果正常。
3.影像学检查：
图1为病猫肠道回盲瓣部位的两幅超声影像图，如图1所示，盲肠淋巴结约1.8cm*1.2cm，实质内可见一直径约0.5cm圆形液性暗区，周围血流信号丰富。
图2为另一拍摄角度拍摄病猫肠道回盲瓣部位的两幅超声影像图，如图2所示，可见回肠后段、盲肠部分肠壁厚度约0.58cm，分成不清晰；结肠前段肠壁厚度约0.6cm，可见一约2.0cm，厚度约0.4cm中等低回声团块在肠壁肌层与浆膜层。盲肠淋巴结肿胀、回盲口处(回肠、盲肠、前段结肠部分)肠壁增厚。
4.腹泻测试组合PCR检测：
冠状病毒、猫胎儿三鞭毛虫、贾弟鞭毛虫、细小病毒、滴虫、隐孢子虫均为阴性，多次镜下便检未见寄生虫。
5.病毒检测(SNAPshol Dx)：
FeLV/FIV阴性
6.食物过敏原与扩展测试(IgE/IgG)-ELISA，反应等级1-5)：
针对24项目食物过敏原进行测试排查，其中牛肉、鱼粉、马肉、鹿肉IgG反应等级为1级，鸡肉IgG反应等级为3级。
结果指出其相关性一定要同临床症状，既往病史和反应的严重程度，一同进行判读，反应的严重程度并不一定与临床症状的严重程度相关。
胰蛋白酶样免疫反应(TLI)-ELISA/胰脏脂肪酶免疫活性反应/钴胺素、叶酸浓度检测见表6。
表6胰脏相关检测结果
| 项目 | 测试值/结果 | 参考值 |
| TLI | 16nmol/L | 12-82 |
| 钴胺素 | 275pg/ml | 300-800 |
| 叶酸浓度-CLA | 10.16ng/ml | 3.0(4.0)-10.0 |
| fPL | 阴性 | - |
由表6可见检测项目中钴胺素浓度为275pg/ml明显出现了降低，其他指标均正常，钴胺素与内因子结合在小肠和回肠段被吸收利用，出现降低可能为肠细菌繁殖过多所消耗，也可能为肠道疾病引起吸收不良。
8.病理组织送检：
回肠段全层组织/盲肠淋巴结与肠道涂片
1)诊断分析：
通过该猫近半年间歇性腹泻伴随有粘液，偶尔呕吐，同时体重近半年也出现下降，患猫变得消瘦等临床症状可以判定：患猫存在大肠性腹泻可能同时出现小肠性腹泻。通过血常规、生化、寄生虫、胰脏等排除性检查。超声显示肠道分层不清晰、肠壁增厚及患猫对一些食物不耐受，胃肠道可能存在炎症反应。钴胺素的降低提示回肠部分可能出现钴胺素吸收功能障碍。根据以上相关化验及异常指标结果怀疑患猫患有炎性肠病。
2)诊断结果：
慢性中度浆细胞性与嗜酸性肠炎
3)治疗：
治疗的主要目标是降低抗原对胃肠道的刺激，调节局部胃肠道的免疫反应。采用免疫调节治疗并配合饮食，给病猫喂服实施例1配方的软咀嚼片，每天两次，每次两片，连用4个疗程(10天为一个疗程)。
4)预后：
患猫在治疗后一周症状明显好转，粪便逐渐成型，精神状态有好转。治疗40天后体重有出现明显增重，定期复查，体况好转至今稳定。
可以理解的是，对本领域普通技术人员来说，可以根据本发明的技术方案及本发明构思加以等同替换或改变，而所有这些改变或替换都应属于本发明所附的权利要求的保护范围。
Claims (10)
1.一种治疗猫炎症性肠道疾病的软咀嚼片剂，其特征在于，按质量分数计，由以下组分组成：
其余为填充剂。
2.根据权利要求1所述的治疗猫炎症性肠道疾病的软咀嚼片剂，其特征在于，所述的活性成分由葡萄糖氧化酶、溶菌酶、食用菌多糖和L-谷氨酰胺组成，所述葡萄糖氧化酶、溶菌酶、食用菌多糖及L-谷氨酰胺的添加比例为2:2:3:3。
3.根据权利要求1所述的治疗猫炎症性肠道疾病的软咀嚼片剂，其特征在于，所述的粘合剂为淀粉、羟丙基甲基纤维素、聚维酮K30中的一种。
4.根据权利要求1所述的治疗猫炎症性肠道疾病的软咀嚼片剂，其特征在于，所述的保湿剂由甘油和中链甘油三酯组成，所述甘油和中链甘油三酯添加比例为2：3或1:2。
5.根据权利要求1所述的治疗猫炎症性肠道疾病的软咀嚼片剂，其特征在于，所述的乳化剂由磷脂和聚乙二醇甘油蓖麻酸酯组成，所述磷脂和聚乙二醇甘油蓖麻酸酯添加比例为1:2。
6.根据权利要求1所述的治疗猫炎症性肠道疾病的软咀嚼片剂，其特征在于，所述的风味剂为多肽牛肉粉、多肽金枪鱼粉中的一种。
7.根据权利要求1所述的治疗猫炎症性肠道疾病的软咀嚼片剂，其特征在于，所述的抗氧化剂为甘草抗氧化物、硫代二丙酸二月桂酯、乙氧基喹啉、丁基羟基茴香醚、茶多酚、维生素E中的任意两种。
8.根据权利要求1所述的治疗猫炎症性肠道疾病的软咀嚼片剂，其特征在于，所述的崩解剂为羧甲基淀粉钠或交联聚维酮中的一种。
9.根据权利要求1所述的治疗猫炎症性肠道疾病的软咀嚼片剂，其特征在于，所述的防腐剂为乳酸链球菌素、ε-聚赖氨酸盐酸盐或脱氢乙酸钠中的一种；所述的润滑剂为硬脂酸镁；所述的填充剂由山梨醇和蔗糖组成，其中所述山梨醇和蔗糖添加比例为1:1或2:1。
10.一种如权利要求1～9任一项所述的治疗猫炎症性肠道疾病的软咀嚼片剂的制备方法，其特征在于，包括以下步骤：
步骤1，将粘合剂用60％的100℃热水制成浓度为3-4％的溶液A，并晾凉至室温待用；
步骤2，将保湿剂及乳化剂顺序倒入溶液A中并搅拌均匀，制得溶液B；
步骤3，将活性成分、风味剂、抗氧化剂、崩解剂、填充剂固体原辅料混合均匀，并过40目筛网，获得固体粉末混合物C；
步骤4，将溶液B分多次加入固体粉末混合物C中制成湿颗粒并进行整粒；
步骤5，将步骤4中制备的湿颗粒放入40度烘箱中干燥50-60分钟，使颗粒水分维持在8-10％之间；
步骤6，将润滑剂加入步骤5制得的颗粒中混合均匀后压制成型。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010143498.2A CN111329997A (zh) | 2020-03-04 | 2020-03-04 | 一种治疗猫炎症性肠道疾病的软咀嚼片剂及其制备方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010143498.2A CN111329997A (zh) | 2020-03-04 | 2020-03-04 | 一种治疗猫炎症性肠道疾病的软咀嚼片剂及其制备方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111329997A true CN111329997A (zh) | 2020-06-26 |
Family
ID=71176042
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010143498.2A Pending CN111329997A (zh) | 2020-03-04 | 2020-03-04 | 一种治疗猫炎症性肠道疾病的软咀嚼片剂及其制备方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111329997A (zh) |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1889853A (zh) * | 2003-12-05 | 2007-01-03 | 希尔氏宠物营养品公司 | 包含谷氨酰胺的抗腹泻组合物 |
| CN101370490A (zh) * | 2005-12-29 | 2009-02-18 | 希尔氏宠物营养品公司 | 用于预防或治疗炎症性肠病的组合物及其制备方法 |
| CN104207151A (zh) * | 2014-09-05 | 2014-12-17 | 浙江汇能动物药品有限公司 | 促进犬猫肠道功能恢复的营养剂及其制备方法和应用 |
| CN105535011A (zh) * | 2014-10-28 | 2016-05-04 | 天津国际生物医药联合研究院 | 香菇菌多糖的应用 |
| CN106551913A (zh) * | 2015-09-30 | 2017-04-05 | 瑞普（天津）生物药业有限公司 | 一种宠物用盐酸特比萘芬速溶咀嚼片组方及其制备方法 |
| CN106999421A (zh) * | 2014-11-03 | 2017-08-01 | 硕腾服务有限责任公司 | 适口的可咀嚼兽用组合物 |
| CN110354085A (zh) * | 2019-06-13 | 2019-10-22 | 中国农业科学院兰州畜牧与兽药研究所 | 一种宠物用阿司匹林丁香酚酯咀嚼片剂及其制备方法 |
-
2020
- 2020-03-04 CN CN202010143498.2A patent/CN111329997A/zh active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1889853A (zh) * | 2003-12-05 | 2007-01-03 | 希尔氏宠物营养品公司 | 包含谷氨酰胺的抗腹泻组合物 |
| CN101370490A (zh) * | 2005-12-29 | 2009-02-18 | 希尔氏宠物营养品公司 | 用于预防或治疗炎症性肠病的组合物及其制备方法 |
| CN104207151A (zh) * | 2014-09-05 | 2014-12-17 | 浙江汇能动物药品有限公司 | 促进犬猫肠道功能恢复的营养剂及其制备方法和应用 |
| CN105535011A (zh) * | 2014-10-28 | 2016-05-04 | 天津国际生物医药联合研究院 | 香菇菌多糖的应用 |
| CN106999421A (zh) * | 2014-11-03 | 2017-08-01 | 硕腾服务有限责任公司 | 适口的可咀嚼兽用组合物 |
| CN106551913A (zh) * | 2015-09-30 | 2017-04-05 | 瑞普（天津）生物药业有限公司 | 一种宠物用盐酸特比萘芬速溶咀嚼片组方及其制备方法 |
| CN110354085A (zh) * | 2019-06-13 | 2019-10-22 | 中国农业科学院兰州畜牧与兽药研究所 | 一种宠物用阿司匹林丁香酚酯咀嚼片剂及其制备方法 |
Non-Patent Citations (5)
| Title |
|---|
| 师海波等: "《最新临床药物手册》", 31 October 2016, 辽宁科学技术出版社 * |
| 庄司泉: "《吃对蔬菜 排毒保健》", 30 June 2013, 河北科学技术出版社 * |
| 潘道东等: "《功能性食品添加剂》", 31 January 2006, 中国轻工业出版社 * |
| 聂芙蓉等: "《饲料添加剂安全应用关键技术》", 30 September 2016, 中原农民出版社 * |
| 詹益兴: "《绿色精细化工 天然产品制造法》", 31 January 2008, 科学技术文献出版社 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Videla et al. | New perspectives in equine gastric ulcer syndrome | |
| Spaeth et al. | Bulk prevents bacterial translocation induced by the oral administration of total parenteral nutrition solution | |
| Johnson-Delaney | Anatomy and physiology of the rabbit and rodent gastrointestinal system | |
| Reese et al. | Nutrition and dietary management of equine gastric ulcer syndrome | |
| Frank et al. | Effects of dietary oils on the development of gastric ulcers in mares | |
| EP0800394A1 (en) | Prevention of adverse behaviour, diarrhoea, skin disorders and infections of the hind gut associated with acidic conditions in humans and animals | |
| US11439676B2 (en) | Method for prevention or treating gastrointestinal distress in humans using mastic gum compositions | |
| US20190046559A1 (en) | Gel formulation for the prevention and treatment of gastrointestinal distress in horses and other species | |
| US9993498B2 (en) | Method for the prevention and treatment of gastrointestinal distress in horses and other species | |
| Nowroozinia et al. | Feeding fennel (Foeniculum vulgare) seed as a potential appetite stimulant for Holstein dairy calves: Effects on growth performance and health | |
| US5556625A (en) | Pharmaceutical composition comprising Rosa roxburghii, Artemisiae argyi folium and Brassica oleracea var. capitata L. used to reduce the symptoms of diarrhea | |
| US20060257375A1 (en) | Compositions and Methods Improving Renal Function | |
| US20040197352A1 (en) | Methods of improving or augmenting kidney function | |
| US20170100429A1 (en) | Methods of Treating Diarrhea in Neonatal and Young Non-Human Animals | |
| JP2019076007A (ja) | ペット用サプリメント、ペット用飲料水、ペットフード、ペット用食品添加物、ペット用血中尿素窒素上昇抑制剤およびペット用医薬組成物、ならびにペットの血中尿素窒素上昇を抑制する方法 | |
| EP0820306B1 (en) | Pharmaceutical composition containing pectin and a phospholipid, used as an antidiarrheal and antiulcer agent | |
| CN111329997A (zh) | 一种治疗猫炎症性肠道疾病的软咀嚼片剂及其制备方法 | |
| US20040106185A1 (en) | Oral bacteriotherapy compositions and methods | |
| Lopes et al. | Effects of feeding on equine gastrointestinal function or physiology | |
| US8927565B2 (en) | Compositions for veterinary and medical applications | |
| RU2415684C2 (ru) | Фармацевтическая композиция для лечения и/или профилактики дисбиозов кишечника в процессе проведения антибактериальной терапии у теплокровных животных: крупного рогатого скота, свиней, домашних животных, в частности собак, кошек, и сельскохозяйственных птиц и способ лечения и/или профилактики дисбиозов кишечника в процессе проведения антибактериальной терапии у теплокровных животных: крупного рогатого скота, свиней, домашних животных, в частности собак, кошек, и сельскохозяйственных птиц | |
| AU698600B2 (en) | Prevention of adverse behaviour, diarrhoea, skin disorders and infections of the hindgut associated with acidic conditions in humans and animals | |
| Young | Yeast cell wall supplementation alters the performance and health of newly received crossbred heifers | |
| Abdalla et al. | Clinicopathological studies of dietary supplementation of Saccharomyces cerevisiae in calves | |
| CN113244220A (zh) | 穿琥宁在制备治疗奶牛乳房炎的兽用药物中的应用及穿琥宁兽用药剂 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |