CN115317498A - 一种治疗犬猫寄生虫和真菌皮肤病的复方滴剂及制备方法 - Google Patents
一种治疗犬猫寄生虫和真菌皮肤病的复方滴剂及制备方法 Download PDFInfo
- Publication number
- CN115317498A CN115317498A CN202211032050.9A CN202211032050A CN115317498A CN 115317498 A CN115317498 A CN 115317498A CN 202211032050 A CN202211032050 A CN 202211032050A CN 115317498 A CN115317498 A CN 115317498A
- Authority
- CN
- China
- Prior art keywords
- compound
- dogs
- selamectin
- pyriproxyfen
- skin diseases
- 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.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 81
- 241000282472 Canis lupus familiaris Species 0.000 title claims abstract description 47
- 241000282326 Felis catus Species 0.000 title claims abstract description 33
- 208000007163 Dermatomycoses Diseases 0.000 title claims abstract description 21
- 206010012504 Dermatophytosis Diseases 0.000 title claims abstract description 21
- 208000022196 parasitic skin disease Diseases 0.000 title claims description 12
- 230000003071 parasitic effect Effects 0.000 title claims description 11
- 238000002360 preparation method Methods 0.000 title abstract description 34
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims abstract description 96
- AFJYYKSVHJGXSN-KAJWKRCWSA-N selamectin Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1C(/C)=C/C[C@@H](O[C@]2(O[C@@H]([C@@H](C)CC2)C2CCCCC2)C2)C[C@@H]2OC(=O)[C@@H]([C@]23O)C=C(C)C(=N\O)/[C@H]3OC\C2=C/C=C/[C@@H]1C AFJYYKSVHJGXSN-KAJWKRCWSA-N 0.000 claims abstract description 61
- 229960002245 selamectin Drugs 0.000 claims abstract description 61
- DOMXUEMWDBAQBQ-WEVVVXLNSA-N terbinafine Chemical compound C1=CC=C2C(CN(C\C=C\C#CC(C)(C)C)C)=CC=CC2=C1 DOMXUEMWDBAQBQ-WEVVVXLNSA-N 0.000 claims abstract description 57
- 239000005927 Pyriproxyfen Substances 0.000 claims abstract description 56
- NHDHVHZZCFYRSB-UHFFFAOYSA-N pyriproxyfen Chemical compound C=1C=CC=NC=1OC(C)COC(C=C1)=CC=C1OC1=CC=CC=C1 NHDHVHZZCFYRSB-UHFFFAOYSA-N 0.000 claims abstract description 54
- 229960000699 terbinafine hydrochloride Drugs 0.000 claims abstract description 52
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 claims abstract description 38
- 229960003639 laurocapram Drugs 0.000 claims abstract description 38
- 244000045947 parasite Species 0.000 claims abstract description 21
- 238000010521 absorption reaction Methods 0.000 claims abstract description 18
- 239000003623 enhancer Substances 0.000 claims abstract description 17
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 11
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 11
- 239000006084 composite stabilizer Substances 0.000 claims abstract description 11
- 239000002131 composite material Substances 0.000 claims abstract description 10
- 238000003756 stirring Methods 0.000 claims description 62
- BGNXCDMCOKJUMV-UHFFFAOYSA-N Tert-Butylhydroquinone Chemical compound CC(C)(C)C1=CC(O)=CC=C1O BGNXCDMCOKJUMV-UHFFFAOYSA-N 0.000 claims description 39
- 239000004250 tert-Butylhydroquinone Substances 0.000 claims description 39
- 235000019281 tert-butylhydroquinone Nutrition 0.000 claims description 39
- CUDYYMUUJHLCGZ-UHFFFAOYSA-N 2-(2-methoxypropoxy)propan-1-ol Chemical compound COC(C)COC(C)CO CUDYYMUUJHLCGZ-UHFFFAOYSA-N 0.000 claims description 36
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 claims description 36
- 239000011259 mixed solution Substances 0.000 claims description 30
- 208000017520 skin disease Diseases 0.000 claims description 16
- 241000233866 Fungi Species 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 6
- -1 polyoxyethylene Polymers 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- 206010048768 Dermatosis Diseases 0.000 claims description 3
- 239000003381 stabilizer Substances 0.000 claims description 3
- XRCRJFOGPCJKPF-UHFFFAOYSA-N 2-butylbenzene-1,4-diol Chemical group CCCCC1=CC(O)=CC=C1O XRCRJFOGPCJKPF-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- 229920003171 Poly (ethylene oxide) Polymers 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
- 235000010354 butylated hydroxytoluene Nutrition 0.000 claims description 2
- 150000002191 fatty alcohols Chemical class 0.000 claims description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 2
- 229920000053 polysorbate 80 Polymers 0.000 claims description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 2
- 230000000749 insecticidal effect Effects 0.000 abstract description 13
- 230000000843 anti-fungal effect Effects 0.000 abstract description 6
- 229960002722 terbinafine Drugs 0.000 abstract description 5
- 239000003814 drug Substances 0.000 abstract description 4
- 229940079593 drug Drugs 0.000 abstract description 3
- 239000000273 veterinary drug Substances 0.000 abstract description 2
- 230000000052 comparative effect Effects 0.000 description 53
- 239000000243 solution Substances 0.000 description 38
- 238000012360 testing method Methods 0.000 description 23
- 210000003491 skin Anatomy 0.000 description 16
- 238000002156 mixing Methods 0.000 description 14
- 230000001502 supplementing effect Effects 0.000 description 14
- 239000000203 mixture Substances 0.000 description 10
- 230000000694 effects Effects 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 8
- 238000007789 sealing Methods 0.000 description 8
- 210000004209 hair Anatomy 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 6
- 230000002147 killing effect Effects 0.000 description 6
- 241000238876 Acari Species 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 5
- 235000013601 eggs Nutrition 0.000 description 5
- 230000002538 fungal effect Effects 0.000 description 5
- 239000004743 Polypropylene Substances 0.000 description 4
- 230000000844 anti-bacterial effect Effects 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 229920001155 polypropylene Polymers 0.000 description 4
- 241000282465 Canis Species 0.000 description 3
- 206010015150 Erythema Diseases 0.000 description 3
- 241000244206 Nematoda Species 0.000 description 3
- 241001674048 Phthiraptera Species 0.000 description 3
- 208000003251 Pruritus Diseases 0.000 description 3
- 206010000496 acne Diseases 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 231100000321 erythema Toxicity 0.000 description 3
- 230000007803 itching Effects 0.000 description 3
- 210000000282 nail Anatomy 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000010998 test method Methods 0.000 description 3
- 238000010257 thawing Methods 0.000 description 3
- 206010063409 Acarodermatitis Diseases 0.000 description 2
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 2
- 201000004384 Alopecia Diseases 0.000 description 2
- 241000238421 Arthropoda Species 0.000 description 2
- 208000015898 Bacterial Skin disease Diseases 0.000 description 2
- 108010062745 Chloride Channels Proteins 0.000 description 2
- 102000011045 Chloride Channels Human genes 0.000 description 2
- 241000282324 Felis Species 0.000 description 2
- 206010017533 Fungal infection Diseases 0.000 description 2
- 239000005906 Imidacloprid Substances 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- 208000031888 Mycoses Diseases 0.000 description 2
- 241000447727 Scabies Species 0.000 description 2
- 241000869417 Trematodes Species 0.000 description 2
- 241000223238 Trichophyton Species 0.000 description 2
- 241000607479 Yersinia pestis Species 0.000 description 2
- 210000001015 abdomen Anatomy 0.000 description 2
- 230000001133 acceleration Effects 0.000 description 2
- 244000052616 bacterial pathogen Species 0.000 description 2
- 230000003385 bacteriostatic effect Effects 0.000 description 2
- 238000003287 bathing Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 231100000517 death Toxicity 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 244000078703 ectoparasite Species 0.000 description 2
- 210000002615 epidermis Anatomy 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 208000024963 hair loss Diseases 0.000 description 2
- 230000003676 hair loss Effects 0.000 description 2
- 230000012447 hatching Effects 0.000 description 2
- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 2
- 229940056881 imidacloprid Drugs 0.000 description 2
- YWTYJOPNNQFBPC-UHFFFAOYSA-N imidacloprid Chemical compound [O-][N+](=O)\N=C1/NCCN1CC1=CC=C(Cl)N=C1 YWTYJOPNNQFBPC-UHFFFAOYSA-N 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- 239000004540 pour-on Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 208000005687 scabies Diseases 0.000 description 2
- 210000001991 scapula Anatomy 0.000 description 2
- 230000037380 skin damage Effects 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- OILXMJHPFNGGTO-UHFFFAOYSA-N (22E)-(24xi)-24-methylcholesta-5,22-dien-3beta-ol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)C=CC(C)C(C)C)C1(C)CC2 OILXMJHPFNGGTO-UHFFFAOYSA-N 0.000 description 1
- RQOCXCFLRBRBCS-UHFFFAOYSA-N (22E)-cholesta-5,7,22-trien-3beta-ol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CCC(C)C)CCC33)C)C3=CC=C21 RQOCXCFLRBRBCS-UHFFFAOYSA-N 0.000 description 1
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 1
- OQMZNAMGEHIHNN-UHFFFAOYSA-N 7-Dehydrostigmasterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CC(CC)C(C)C)CCC33)C)C3=CC=C21 OQMZNAMGEHIHNN-UHFFFAOYSA-N 0.000 description 1
- 239000005660 Abamectin Substances 0.000 description 1
- 241001465677 Ancylostomatoidea Species 0.000 description 1
- 241001480043 Arthrodermataceae Species 0.000 description 1
- 241000228212 Aspergillus Species 0.000 description 1
- 241000335423 Blastomyces Species 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- 241000222173 Candida parapsilosis Species 0.000 description 1
- 229920002101 Chitin Polymers 0.000 description 1
- 208000003322 Coinfection Diseases 0.000 description 1
- 229920000832 Cutin Polymers 0.000 description 1
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- 241001128004 Demodex Species 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 241000255925 Diptera Species 0.000 description 1
- 208000017701 Endocrine disease Diseases 0.000 description 1
- DNVPQKQSNYMLRS-NXVQYWJNSA-N Ergosterol Natural products CC(C)[C@@H](C)C=C[C@H](C)[C@H]1CC[C@H]2C3=CC=C4C[C@@H](O)CC[C@]4(C)[C@@H]3CC[C@]12C DNVPQKQSNYMLRS-NXVQYWJNSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 241000258937 Hemiptera Species 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 241000228404 Histoplasma capsulatum Species 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 241000255777 Lepidoptera Species 0.000 description 1
- 241000555688 Malassezia furfur Species 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- 241000002163 Mesapamea fractilinea Species 0.000 description 1
- 241000243190 Microsporidia Species 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 208000030852 Parasitic disease Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 241000509427 Sarcoptes scabiei Species 0.000 description 1
- 241000258242 Siphonaptera Species 0.000 description 1
- 208000028990 Skin injury Diseases 0.000 description 1
- 241001149962 Sporothrix Species 0.000 description 1
- 102000005782 Squalene Monooxygenase Human genes 0.000 description 1
- 108020003891 Squalene monooxygenase Proteins 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 241001468227 Streptomyces avermitilis Species 0.000 description 1
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 1
- 241001414989 Thysanoptera Species 0.000 description 1
- 241001045770 Trichophyton mentagrophytes Species 0.000 description 1
- 241000223229 Trichophyton rubrum Species 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- RRZXIRBKKLTSOM-XPNPUAGNSA-N avermectin B1a Chemical compound C1=C[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 RRZXIRBKKLTSOM-XPNPUAGNSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 229940095731 candida albicans Drugs 0.000 description 1
- 229940055022 candida parapsilosis Drugs 0.000 description 1
- 210000001736 capillary Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229940121657 clinical drug Drugs 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 230000035617 depilation Effects 0.000 description 1
- 230000037304 dermatophytes Effects 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000036267 drug metabolism Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 210000000613 ear canal Anatomy 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- DNVPQKQSNYMLRS-SOWFXMKYSA-N ergosterol Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H](CC[C@]3([C@H]([C@H](C)/C=C/[C@@H](C)C(C)C)CC[C@H]33)C)C3=CC=C21 DNVPQKQSNYMLRS-SOWFXMKYSA-N 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000002816 gill Anatomy 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000029052 metamorphosis Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000002232 neuromuscular Effects 0.000 description 1
- 235000018343 nutrient deficiency Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003151 ovacidal effect Effects 0.000 description 1
- 230000017448 oviposition Effects 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 235000019629 palatability Nutrition 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 229960000490 permethrin Drugs 0.000 description 1
- RLLPVAHGXHCWKJ-UHFFFAOYSA-N permethrin Chemical compound CC1(C)C(C=C(Cl)Cl)C1C(=O)OCC1=CC=CC(OC=2C=CC=CC=2)=C1 RLLPVAHGXHCWKJ-UHFFFAOYSA-N 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 210000004994 reproductive system Anatomy 0.000 description 1
- 210000001732 sebaceous gland Anatomy 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 229940031439 squalene Drugs 0.000 description 1
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 210000004003 subcutaneous fat Anatomy 0.000 description 1
- 210000004304 subcutaneous tissue Anatomy 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- 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
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- 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
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
- A61K9/0017—Non-human animal skin, e.g. pour-on, spot-on
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Dermatology (AREA)
- Zoology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Emergency Medicine (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
本发明属于兽药制剂技术领域,具体涉及一种治疗犬猫寄生虫和真菌皮肤病的复方滴剂及制备方法,包括以下组分:按质量份计,赛拉菌素5.5‑13份,吡丙醚2‑6.5份,盐酸特比萘芬2‑6份,复合稳定剂17‑40份,抗氧化剂0.05‑0.14份和复合透皮吸收促进剂34.36‑73.45份。本发明提供的复方滴剂,通过将具有杀虫效果的赛拉菌素和吡丙醚与具有抗真菌效果的特比萘芬复配使用,因而使得本发明滴剂具有良好的杀虫和抗真菌效果;同时,本发明中以异丙醇、月桂氮卓酮为透皮吸收促进剂,复合透皮吸收促进剂的使用能够有效提高本发明中主药的渗透量,进而提高本发明的杀虫和抗真菌效果。
Description
技术领域
本发明属于兽药制剂技术领域,具体涉及一种治疗犬猫寄生虫和真菌皮肤病的复方滴剂及制备方法。
背景技术
在犬猫的临床疾病中,皮肤病是一种比较常见的疾病。按照病因的不同,犬猫皮肤病大致可以分为真菌性皮肤病、细菌性皮肤病、寄生虫性皮肤病、过敏性皮肤病、内分泌障碍及营养缺乏性皮肤病。外源性因素如细菌、真菌、寄生虫等引起的皮肤病具有一定的传染性,甚至可以通过接触由犬猫传染给人。真菌性皮肤病主要是由真菌感染引起,寄生和腐生在表皮、毛发和甲板的角质组织中,主要侵害动物的毛发、指甲和皮肤等,其中最常见的病原菌有微孢子虫和毛癣菌属。细菌性皮肤病往往不局限于动物表皮,它常涉及到真皮甚至更深处的组织。致病菌种主要是化脓性细菌,如葡萄球菌等。病因主要是其他因素比如真菌感染、免疫缺陷、内分泌功能障碍等引起动物体表皮肤生态系统平衡被打破,使机体在接触化脓性细菌时不能有效地抑制其生长,从而引起其大量繁殖,故多为继发性感染。引起犬猫寄生虫性皮肤病的主要是跳蚤、虱子、蜱虫、疥螨、蠕形螨、耳痒螨、姬鳖螨等寄生虫,他们具有一定的传染性。不同寄生虫寄生部位有所不同,疥螨一般先发于耳部,并且可以向眼、颈部蔓延,耳痒螨一般寄生在耳道内,但是重度感染可以在头部、背部、尾部发生,蠕形螨通常寄生于皮脂腺和皮囊中,多见于面部、四肢及腋下,跳蚤多寄生于背部、尾部、根部、腹后部及四肢内侧。
赛拉菌素是美国辉瑞公司由基因重组的阿维链霉菌新菌株发酵而成的一种阿维菌素类抗生素,是最先研制的抗动物体内、体外寄生虫药,其对很多寄生虫都有广泛的抑制和杀灭作用,包括蚤类、疥螨、蜱、钩虫、虱、线虫和犬恶丝虫等,由于使用方便、疗效较好、毒性小等优点。它通过干扰虫体谷氨酸控制的氯离子通道使虫体发生快速、致死性和非痉挛性的神经肌肉麻痹。对体内(线虫)和体外(节肢昆虫)寄生虫有杀灭活性。由于吸虫、绦虫不含有受谷氨酸控制的氯离子通道,故赛拉菌素对吸虫和绦虫无效,只对部分线虫和节肢动物类体表寄生虫有杀灭作用。
吡丙醚是一种保幼激素类型的几丁质合成抑制剂,具有强烈的杀卵作用。除螨类外,对绝大多数害虫卵有效;吡丙醚被昆虫体表接触吸收后,进入生殖系统,对产下的卵起到杀灭作用,使产下的卵为无效卵;阻碍幼虫的蜕变和抑制蛹的孵化;能降低雌成虫的产卵数量,且使所产生的卵孵化率降低;它具有高效、用药量少、持效期长、对生态环境影响小等特点,是一种有发展潜力的第三代杀虫剂。可用于防治同翅目、缨翅目、双翅目、鳞翅目的害虫。
特比萘芬为烯丙胺类抗真菌药,抑制真菌细胞麦角甾醇合成过程中的鲨烯环氧化酶,并使鲨烯在细胞中蓄积而起杀菌作用。动物体细胞对特比萘芬的敏感性为真菌的万分之一,不影响细胞色素P450酶系统,故不影响体内激素和相关药物代谢。特比萘芬具有亲脂性和亲角质性,因此皮肤、毛发和甲板中的浓度较高,而且停药后在皮肤角质层中还能保持有效抑菌浓1个月,在甲板中保持有效浓度约2~3个月。特比萘芬具有广谱抗真菌活性,尤其对皮肤癣菌(红色毛发癣菌、须癣毛癣菌等)有较强的杀菌或抑菌作用。对丝状体、暗色孢科真菌、酵母菌、曲霉菌、皮炎芽生菌、荚膜组织胞浆菌等有杀菌作用。对申克孢子丝菌、白色念珠菌、近平滑念珠菌和卵圆糠秕孢子菌等也有较强的抑菌作用。
现有技术中有关动物皮肤病的剂型有浇泼剂、喷剂、香波剂、注射剂、膏剂、片剂、滴剂等。由于猫舔自己的毛或者多猫在一起生活时,它们通过梳理舔和吞咽对方的毛,会出现中毒和副作用的情况,因此浇泼剂和喷剂的使用受到一定的限制。很多宠物都比较抗拒洗澡,或洗澡时动作比较大,依从性比较差,使得香波剂的使用也受到一定的限制。注射剂对宠物的应激比较大,依从性也是比较差,使得使用推广也受到一定的限制。片剂和膏剂都需要考虑犬猫适口性的问题,犬猫对不同的诱食剂的喜爱程度不同,往往犬喜欢的猫不喜欢,反之亦然,使得企业需要设计两套配方,造成成本的增加。
综上所述,以上剂型的应用受到一定的局限,滴剂有剂量准确、使用简单方便的优点,可以在与宠物互动的时候给药于宠物舔不到的部位,安全性高,依从性好。但现有滴剂技术中,如专利文献CN106727552在2017年5月31日公开了复方吡虫啉滴剂及其制备方法和应用,其配方中二氯苯醚菊酯含量高,对使用者的眼睛有一定的刺激性。如专利文献CN106806369在2017年6月9日公开了含天然植物精油的宠物外用杀虫滴剂及其制备方法和应用,其配方中的α-吡咯烷酮会对皮肤有轻度刺激作用;CN106692171在2017年5月24日公开了宠物用复方赛拉菌素外用滴剂及其方法和应用,通过将赛拉菌素等具有杀虫效果的成分复配使用,因而具有良好的杀虫效果,但上述专利滴剂无法解决犬猫真菌皮肤病的问题。鉴于此,有必要研究出一种既能治疗犬猫寄生虫皮肤病,又能治疗真菌皮肤病,同时使用方便和安全的复方滴剂。
发明内容
针对上述问题,本发明旨在发明一种治疗犬猫寄生虫和真菌皮肤病的复方滴剂,包括以下组分:按质量份计,赛拉菌素5.5-13份,吡丙醚2-6.5份,盐酸特比萘芬2-6份,复合稳定剂17-40份,抗氧化剂0.05-0.14份和复合透皮吸收促进剂34.36-73.45份。
进一步的,所述的复合稳定剂由聚氧乙烯脂肪醇、吐温-80、二丙二醇甲醚和乙二醇单甲醚中的两种或多种组成。
进一步的,所述的复合稳定剂由二丙二醇甲醚和乙二醇单甲醚组成。
更进一步的,所述的二丙二醇甲醚与乙二醇单甲醚的体积比为(0.5-4)/1。
进一步的,所述的抗氧化剂为2,6-二叔丁基对甲酚、丁基羟基茴香醚和特丁基对苯二酚中的至少一种。
更进一步的,所述的抗氧化剂为丁基对苯二酚。
进一步的,所述的复合透皮吸收促进剂由乙醇、丙醇、异丙醇和月桂氮卓酮中的两种或多种组成。
进一步的,所述的复合透皮吸收促进剂由异丙醇和月桂氮卓酮组成。
更进一步的,所述的月桂氮卓酮的重量份数为12-20份。
本发明还提供一种治疗犬猫寄生虫和真菌皮肤病的复方滴剂的制备方法,包括以下步骤:
S1:在搅拌容器中加入复合稳定剂、复合透皮吸收促进剂并搅拌均匀,然后加入赛拉菌素,搅拌直至溶解;
S2:在步骤S1中得到的混合溶液中分别加入吡丙醚、盐酸特比萘芬和抗氧化剂,搅拌直至溶解后加入吸收促进剂即制得复方滴剂。
与现有技术相比,本发明的有益效果是:
1、本发明使用二丙二醇甲醚、乙二醇单甲醚作为复合溶剂和稳定剂,解决了滴剂因加入盐酸特比萘芬后而使赛拉菌素容易析出沉淀的问题,使得本发明制备的复方滴剂具有良好的稳定性;
2、本发明使用异丙醇、月桂氮卓酮作为复合透皮吸收促进剂,复合透皮吸收促进剂的使用能够有效提高本发明制备的复方滴剂的主药的渗透量,进而提高本发明复方滴剂的杀虫和抗真菌效果;
3、本发明制备的滴剂将赛拉菌素、吡丙醚、盐酸特比萘芬三种成分联用,不仅扩大了杀虫谱,同时达到有效预防和治疗常见的犬猫体外寄生虫和真菌皮肤病的目的。
具体实施方式
下面将结合实施例对本发明的实施方案进行详细描述,但是本领域技术人员将会理解,下列实施例仅用于说明本发明,而不应视为限制本发明的范围。实施例中未注明具体条件者,按照常规条件或制造商建议的条件进行。所用试剂或仪器未注明生产厂商者,均为可以通过市售购买获得的常规产品。
实施例1、本发明治疗犬猫寄生虫和真菌皮肤病的复方滴剂及其制备
本实施例提供100ml治疗犬猫寄生虫和真菌皮肤病的复方滴剂,由以下占比的各组分组成:按质量分数计,
赛拉菌素6%,吡丙醚3%,盐酸特比萘芬2.5%,二丙二醇甲醚12%,乙二醇单甲醚6%,月桂氮卓酮13%,特丁基对苯二酚0.08%,异丙醇57.42%;
制备方法:
S1:在搅拌容器中加入二丙二醇甲醚、乙二醇单甲醚、月桂氮卓酮和部分异丙醇,把四种溶液混合在一起搅拌直到均匀,然后加入赛拉菌素,搅拌直至溶解,得混合液;
S2:在混合液中分别加入吡丙醚、盐酸特比萘芬和特丁基对苯二酚,搅拌直至溶解,异丙醇补齐即得。
实施例2、本发明治疗犬猫寄生虫和真菌皮肤病的复方滴剂及其制备
本实施例提供100ml治疗犬猫寄生虫和真菌皮肤病的复方滴剂,由以下占比的各组分组成:按质量份数计,
赛拉菌素6%,吡丙醚6%,盐酸特比萘芬5%,二丙二醇甲醚12%,乙二醇单甲醚6%,月桂氮卓酮17%,特丁基对苯二酚0.08%,异丙醇47.92%;
制备方法:
S1:在搅拌容器中加入二丙二醇甲醚、乙二醇单甲醚、月桂氮卓酮和部分异丙醇,把四种溶液混合在一起搅拌直到均匀,然后加入赛拉菌素,搅拌直至溶解,得混合液;
S2:在混合液中分别加入吡丙醚、盐酸特比萘芬和特丁基对苯二酚,搅拌直至溶解,异丙醇补齐即得。
实施例3、本发明治疗犬猫寄生虫和真菌皮肤病的复方滴剂及其制备
本实施例提供100ml治疗犬猫寄生虫和真菌皮肤病的复方滴剂,由以下占比的各组分组成:按质量份数计,
赛拉菌素9%,吡丙醚5%,盐酸特比萘芬4%,二丙二醇甲醚18%,乙二醇单甲醚9%,月桂氮卓酮15%,特丁基对苯二酚0.08%,异丙醇39.92%;
制备方法:
S1:在搅拌容器中加入二丙二醇甲醚18%、乙二醇单甲醚9%、月桂氮卓酮15%和部分异丙醇,把四种溶液混合在一起搅拌直到均匀,然后加入赛拉菌素9%,搅拌直至溶解,得混合液;
S2:在混合液中分别加入吡丙醚5%、盐酸特比萘芬4%和特丁基对苯二酚0.08%,搅拌直至溶解,异丙醇补齐即得。
实施例4、本发明治疗犬猫寄生虫和真菌皮肤病的复方滴剂及其制备
本实施例提供100ml治疗犬猫寄生虫和真菌皮肤病的复方滴剂,由以下占比的各组分组成:按质量份数计,
赛拉菌素12%,吡丙醚6%,盐酸特比萘芬5%,二丙二醇甲醚24%,乙二醇单甲醚12%,月桂氮卓酮17%,特丁基对苯二酚0.08%,异丙醇23.92%;
制备方法:
S1:在搅拌容器中加入二丙二醇甲醚、乙二醇单甲醚、月桂氮卓酮和部分异丙醇,把四种溶液混合在一起搅拌直到均匀,然后加入赛拉菌素,搅拌直至溶解,得混合液;
S2:在混合液中分别加入吡丙醚、盐酸特比萘芬和特丁基对苯二酚,搅拌直至溶解,异丙醇补齐即。
实施例5、本发明治疗犬猫寄生虫和真菌皮肤病的复方滴剂及其制备
本实施例提供100ml治疗犬猫寄生虫和真菌皮肤病的复方滴剂,由以下占比的各组分组成:按质量份数计,
赛拉菌素12%,吡丙醚3%,盐酸特比萘芬2.5%,二丙二醇甲醚24%,乙二醇单甲醚12%,月桂氮卓酮13%,特丁基对苯二酚0.08%,异丙醇33.42%;
制备方法:
S1:在搅拌容器中加入二丙二醇甲醚、乙二醇单甲醚、月桂氮卓酮和部分异丙醇,把四种溶液混合在一起搅拌直到均匀,然后加入赛拉菌素,搅拌直至溶解,得混合液;
S2:在混合液中加入吡丙醚、盐酸特比萘芬和特丁基对苯二酚,搅拌直至溶解,异丙醇补齐即得。
对比例1
本实施例提供100ml复方滴剂,由以下占比的各组分组成:按质量份数计,
赛拉菌素6%,吡丙醚3%,二丙二醇甲醚12%,乙二醇单甲醚6%,月桂氮卓酮13%,特丁基对苯二酚0.08%,异丙醇59.92%;
制备方法:
S1:在搅拌容器中加入二丙二醇甲醚、乙二醇单甲醚、月桂氮卓酮和部分异丙醇,把四种溶液混合在一起搅拌直到均匀,然后加入赛拉菌素,搅拌直至溶解,得混合液;
S2:在混合液中加入吡丙醚和特丁基对苯二酚,搅拌直至溶解,异丙醇补齐即得。
本对比例与实施例1类似,区别在于:本对比例中未添加盐酸特比萘芬。
对比例2
本实施例提供100ml复方滴剂,由以下占比的各组分组成:按质量份数计
赛拉菌素12%,吡丙醚6%,二丙二醇甲醚24%,乙二醇单甲醚12%,月桂氮卓酮17%,特丁基对苯二酚0.08%,异丙醇28.92%;
制备方法:
S1:在搅拌容器中加入二丙二醇甲醚24%、乙二醇单甲醚12%、月桂氮卓酮17%和部分异丙醇,把四种溶液混合在一起搅拌直到均匀,然后加入赛拉菌素12%,搅拌直至溶解,得混合液;
S2:在混合液中分别加入吡丙醚6%和特丁基对苯二酚0.08%,搅拌直至溶解,异丙醇补齐即得;
本对比例与实施例4类似,区别在于,本对比例中未添加盐酸特比萘芬。
对比例3
本实施例提供100ml复方滴剂,由以下占比的各组分组成:按质量份数计,
赛拉菌素6%,吡丙醚3%,盐酸特比萘芬2.5%,二丙二醇甲醚12%,乙二醇单甲醚6%,特丁基对苯二酚0.08%,异丙醇70.42%;
制备方法:
S1:在搅拌容器中加入二丙二醇甲醚、乙二醇单甲醚和部分异丙醇,把三种溶液混合在一起搅拌直到均匀,然后加入赛拉菌素,搅拌直至溶解,得混合液;
S2:在混合液中分别加入吡丙醚、盐酸特比萘芬和特丁基对苯二酚,搅拌直至溶解,异丙醇补齐即得。
本对比例与实施例1类似,区别在于:本对比例中未添加月桂氮卓酮。
对比例4
本实施例提供100ml复方滴剂,由以下占比的各组分组成:按质量份数计,
赛拉菌素6%,吡丙醚3%,盐酸特比萘芬2.5%,二丙二醇甲醚12%,乙二醇单甲醚6%,特丁基对苯二酚0.08%,月桂氮卓酮70.42%;
制备方法:
S1:在搅拌容器中加入二丙二醇甲醚、乙二醇单甲醚和部分月桂氮卓酮,把三种溶液混合在一起搅拌直到均匀,然后加入赛拉菌素,搅拌直至溶解,得混合液;
S2:在混合液中加入吡丙醚、盐酸特比萘芬和特丁基对苯二酚,搅拌直至溶解,月桂氮卓酮补齐即得。
本对比例与实施例1类似,区别在于:本对比例中未添加异丙醇。
对比例5
本实施例提供100ml复方滴剂,由以下占比的各组分组成:按质量份数计,
赛拉菌素6%,吡丙醚3%,盐酸特比萘芬2.5%,月桂氮卓酮13%,特丁基对苯二酚0.08%,异丙醇75.42%;
制备方法:
S1:在搅拌容器中加入月桂氮卓酮和部分异丙醇,把两种溶液混合在一起搅拌直到均匀,然后加入赛拉菌素,搅拌直至溶解,得混合液;
S2:在混合液中分别加入吡丙醚、盐酸特比萘芬和特丁基对苯二酚,搅拌直至溶解,异丙醇补齐即得。
本对比例与实施例1类似,区别在于:本对比例中未添加二丙二醇甲醚、乙二醇单甲醚。
对比例6
本实施例提供100ml复方滴剂,由以下占比的各组分组成:按质量份数计
赛拉菌素6%,吡丙醚3%,盐酸特比萘芬2.5%,乙二醇单甲醚18%,月桂氮卓酮13%,特丁基对苯二酚0.08%,异丙醇57.42%;
制备方法:
S1:在搅拌容器中加入二丙二醇甲醚、乙二醇单甲醚、月桂氮卓酮和部分异丙醇,把四种溶液混合在一起搅拌直到均匀,然后加入赛拉菌素,搅拌直至溶解,得混合液;
S2:在混合液中分别加入吡丙醚、盐酸特比萘芬和特丁基对苯二酚,搅拌直至溶解,异丙醇补齐即得。
本对比例与实施例1类似,区别在于:本对比例中未添加二丙二醇甲醚。
对比例7
本实施例提供100ml复方滴剂,由以下占比的各组分组成:按质量份数计
赛拉菌素6%,吡丙醚3%,盐酸特比萘芬2.5%,二丙二醇甲醚18%,月桂氮卓酮13%,特丁基对苯二酚0.08%,异丙醇57.42%;
制备方法:
S1:在搅拌容器中加入二丙二醇甲醚、乙二醇单甲醚、月桂氮卓酮和部分异丙醇,把四种溶液混合在一起搅拌直到均匀,然后加入赛拉菌素,搅拌直至溶解,得混合液;
S2:在混合液中分别加入吡丙醚、盐酸特比萘芬和特丁基对苯二酚,搅拌直至溶解,异丙醇补齐即得。
本对比例与实施例1类似,区别在于:本对比例中未添加乙二醇单甲醚。
对比例8
本实施例提供100ml复方滴剂,由以下占比的各组分组成:按质量份数计,
盐酸特比萘芬2.5%,二丙二醇甲醚12%,乙二醇单甲醚6%,月桂氮卓酮13%,特丁基对苯二酚0.08%,异丙醇66.42%;
制备方法:
S1:在搅拌容器中加入二丙二醇甲醚、乙二醇单甲醚、月桂氮卓酮和部分异丙醇,把四种溶液混合在一起搅拌直到均匀,得混合液;
S2:在混合液中分别加入盐酸特比萘芬和特丁基对苯二酚,搅拌直至溶解,异丙醇补齐即得。
本对比例与实施例1类似,区别在于:本对比例中未添加赛拉菌素、吡丙醚。
对比例9
本实施例提供100ml复方滴剂,由以下占比的各组分组成:按质量份数计,
吡丙醚3%,盐酸特比萘芬2.5%,二丙二醇甲醚12%,乙二醇单甲醚6%,月桂氮卓酮13%,特丁基对苯二酚0.08%,异丙醇63.42%;
制备方法:
S1:在搅拌容器中加入二丙二醇甲醚、乙二醇单甲醚、月桂氮卓酮和部分异丙醇,把四种溶液混合在一起搅拌直到均匀,得混合液;
S2:在混合液中加入吡丙醚、盐酸特比萘芬和特丁基对苯二酚,搅拌直至溶解,异丙醇补齐即得。
本对比例与实施例1类似,区别在于,本对比例中未添加赛拉菌素。
试验例一、稳定性试验
1、高温加速试验
(1)试验样品:按对比例5-7配制滴剂,用聚丙烯管分装,用红外线封口机封口;按实施例1-5配制滴剂,用聚丙烯管分装,用红外线封口机封口;放置于40℃、75%RH的恒温恒湿稳定箱中1、3、6个月,考察滴剂体系的性状及含量变化;
(2)考察指标及检测方法:
赛拉菌素含量:高效液相色谱法
吡丙醚含量;高效液相色谱—质谱法
盐酸特比萘芬含量:高效液相色谱法
性状:肉眼观察
(3)试验结果:
表1实施例1-5与对比例5-7复方滴剂的高温加速试验结果
从表1试验结果可知,本发明实施例1-5制备的复方滴剂由于使用二丙二醇甲醚、乙二醇单甲醚作为复合稳定剂,所以具有很好的稳定性,高温加速6个月后的赛拉菌素、吡丙醚、盐酸特比萘芬的含量还维持在95%以上,滴剂的颜色也没有发生变化;其中实施例2制备的复方滴剂,在高温加速6个月后的赛拉菌素、吡丙醚、盐酸特比萘芬的含量维持最高,为本发明的最佳实施例;而对比例5-7制备的复方滴剂由于没有二丙二醇甲醚或乙二醇单甲醚作为复合稳定剂,高温加速1个月就开始不稳定,其原因可能是在高温加速过程中,有机溶剂容易通过包材挥发,所以在高温加速6个月后,赛拉菌素、吡丙醚、盐酸特比萘芬的含量不足87%,并且析出较多沉淀,使得滴剂的颜色由无色澄明变成了深黄澄明。
2、反复冻融试验
(1)试验样品:按对比例5-7配制滴剂,用聚丙烯管分装,用红外线封口机封口;按实施例1-5配制滴剂,用聚丙烯管分装,用红外线封口机封口;一起放置于-20℃条件下2天,再取出于40℃加速条件下放置2d,如此循环四次,考察每次循环的滴剂体系性状及含量变化。
(2)考察指标及检测方法:
赛拉菌素含量:高效液相色谱法
吡丙醚含量;高效液相色谱—质谱法
盐酸特比萘芬含量:高效液相色谱法
性状:肉眼观察
析出:肉眼观察
(3)试验结果
表2实施例1-5与对比例5-7滴剂的反复冻融试验结果
从表2的数据可以看出,本发明实施例1-5制备的复方滴剂具有很好的稳定性,反复冻融4次后的赛拉菌素、吡丙醚、盐酸特比萘芬的含量还维持在94%以上,其中实施例2制备的复方滴剂在反复冻融4次后的赛拉菌素、吡丙醚、盐酸特比萘芬的含量均最高,为本发明的最佳实施例;而对比例5-7制备的复方滴剂由于没有二丙二醇甲醚或乙二醇单甲醚作为复合稳定剂,其原因可能是反复冻融4次后,溶解度下降,溶剂结构被破坏,导致赛拉菌素、吡丙醚、盐酸特比萘芬的含量下降到90%以下,稳定性明显下降。
试验例二、透皮试验
1、试验样品:实施例1-5、对比例3-4制备的复方滴剂配制样品;
2、试验方法:取乳猪腹部已剃毛的皮肤,并除去皮下脂肪、组织和毛细血管,然后用生理盐水反复冲洗,擦干;在室温下,进行皮肤体外透皮吸收实验,释放剂用量为2ml,接受剂为7ml,实验温度为37℃,在第1、2、4、6、8、10、12h时间点分别取5.0ml接受液,同时补充等量接受液,以赛拉菌素为参照物,检测实施例1-5和对比例3-4接受液中赛拉菌素的含量,并计算出不同时间点赛拉菌素单位面积渗透量;
3、试验结果:
表3实施例1-5与对比例3-4复方滴剂在透皮试验接受液中赛拉菌素单位面积渗透量(μg/cm2)
实施例1 | 实施例2 | 实施例3 | 实施例4 | 实施例5 | 对比例3 | 对比例4 | |
1h | 107.54 | 119.33 | 110.47 | 108.65 | 106.01 | 87.55 | 90.32 |
2h | 189.57 | 197.81 | 191.53 | 193.31 | 188.75 | 150.57 | 151.41 |
4h | 268.43 | 280.67 | 283.81 | 284.37 | 279.76 | 218.39 | 226.32 |
6h | 359.59 | 368.88 | 360.93 | 362.42 | 366.56 | 289.75 | 296.46 |
8h | 486.88 | 493.10 | 488.78 | 490.06 | 485.58 | 310.13 | 309.27 |
10h | 624.81 | 640.03 | 657.51 | 651.15 | 630.06 | 421.37 | 415.85 |
12h | 798.90 | 800.31 | 790.10 | 787.39 | 788.82 | 537.45 | 530.05 |
从表3的数据可以看出,本发明实施例1-5制备的复方滴剂由于使用了异丙醇、月桂氮卓酮作为复合透皮吸收促进剂,透皮效果随着时间的流逝效果显著,12h后的赛拉菌素单位面积渗透量能达到787μg/cm2以上,其中实施例2制备的复方滴剂在12h后的赛拉菌素单位面积渗透量最高,为本发明的最佳实施例;而对比例3-4制备的复方滴剂由于没有添加异丙醇或月桂氮卓酮,透皮效果则明显有差距,12h后的赛拉菌素单位面积渗透量只有530μg/cm2左右。
试验例三、杀寄生虫试验
1.试验样品:按实施例1-5、对比例8-9制备的复方滴剂配制样品;
2.试验方法:从犬猫养殖场选取56只贵宾犬,对贵宾犬体表进行清洗杀死体表寄生虫。将犬平均分为7组,每组8只,Ⅰ组为实施例1组,Ⅱ组为实施例2组,Ⅲ组为实施例3组,Ⅳ组为实施例4组,Ⅴ组为实施例5组,Ⅵ组为对比例8组,Ⅶ组为对比例9组。分别对每组的每只犬称重,并在每只贵宾犬前胸部接入约100只啮毛虱,在接入2d后,将每只贵宾犬颈背后肩胛骨前部的毛发分开,暴露皮肤,将7种样品分别依次按组别挤到7组贵宾犬的一处皮肤上,不需要按摩用药部位,勿用于破损皮肤,每1kg体重用量为0.1ml。Ⅰ组每只贵宾犬使用实施例1样品,Ⅱ组每只贵宾犬使用实施例2样品,Ⅲ组每只贵宾犬使用实施例3样品,Ⅳ组每只贵宾犬使用实施例4样品,Ⅴ组每只贵宾犬使用实施例5样品,Ⅵ组每只贵宾犬使用对比例6样品,Ⅶ组每只贵宾犬使用对比例7样品,分别统计在给药24和48h后,在每个时间点分别从每组中选取4只贵宾犬统计各组贵宾犬的啮毛虱的死亡数,计算死亡率;
3.试验结果:
表4实施例1-5、对比例8-9复方滴剂的杀啮毛虱效果比较
组别 | 24h死亡率(%) | 48h死亡率(%) |
实施例1 | 95 | 100 |
实施例2 | 97 | 100 |
实施例3 | 96 | 100 |
实施例4 | 96 | 100 |
实施例5 | 95 | 100 |
对比例8 | 0 | 0 |
对比例9 | 52 | 75 |
从表4的数据可以看出,本发明实施例1-5制备的复方滴剂由于添加了赛拉菌素、吡丙醚,杀寄生虫的效果显著,杀虫效果更好,24h的死亡率即达到95%以上,48h的死亡率更是达到了100%;其中实施例2制备的复方滴剂杀寄生虫的24h死亡率和48h死亡率均最高,为本发明的最佳实施例;而对比例9制备的复方滴剂由于没有添加赛拉菌素,杀虫效果较差,对比例8制备的复方滴剂的没有添加吡丙醚,24h和48h的杀虫死亡率均为0,没有杀虫的功效。
试验例四、抗真菌皮肤病试验
1、试验样品:按实施例1-5、对比例1-2制备的复方滴剂配制样品;
2、试验方法:从犬猫养殖场收集有典型临床症状并刮取患处的皮屑做真菌镜检为全部阳性毛癣菌的犬77只作为临床用药研究对象,将犬平均分为7组,每组11只,Ⅰ组为实施例1组,Ⅱ组为实施例2组,Ⅲ组为实施例3组,Ⅳ组为实施例4组,Ⅴ组为实施例5组,Ⅵ组为对比例1组,Ⅶ组为对比例2组。分别对每只犬称重,将犬颈背后肩胛骨前部的毛发分开,暴露皮肤,将样品挤到一处皮肤上,不需要按摩用药部位,勿用于破损皮肤,每1kg体重用量为0.1ml,每周2次,连用4周。从犬的体征、皮肤的情况等方面,按照“痊愈、显效、有效、无效”4个等级来评定用药的效果;
备注:
痊愈:患犬的体征都恢复正常,皮肤损伤如碎屑、瘙痒、脱毛、红斑、丘疹等症状消失,仅留下色斑。伍德氏灯镜检为阴性。
显效:患犬的体征几乎正常,皮肤损伤如碎屑、瘙痒、脱毛、红斑、丘疹等症状明显减轻。伍德氏灯镜检为阴性。
有效:患犬的体征有明显好转,瘙痒程度减轻,偶有脱毛、皮肤碎屑的现象,红斑、丘疹程度减轻,伍德氏灯镜检为阳性,真菌镜检及培养均为阳性。
无效:患犬的体征无好转,皮肤损伤无好转甚至会加剧,伍德氏灯镜检为阳性,真菌镜检及培养均为阳性
3、试验结果:
表5实施例1-5、对比例1-2疗效比较
从表5的数据可以看出,本发明实施例1-5制备的复方滴剂由于添加了盐酸特比萘芬,对于治疗真菌皮肤病有很好的疗效,其中实施例2制备的复方滴剂的治愈和显效的犬只数量最多,是本发明的最佳实施例;而对比例1-2制备的复方滴剂由于缺乏盐酸特比萘芬,治疗真菌皮肤病疗效较差,治愈和显效的犬数量为0。
上述实施例仅例示性说明本发明的原理及功效,而并非限制本发明。本领域任何熟悉此技术的认识皆不可在违背本发明的精神及范畴下,对上述实施例进行修改。因此,举凡所属技术领域中具有通常知识者在未脱离本发明所提供的技术思想下完成的一切等效修饰或改变,仍由本发明的权利要求所涵盖。
Claims (10)
1.一种治疗犬猫寄生虫和真菌皮肤病的复方滴剂,其特征在于,包括以下组分:按质量份数计,赛拉菌素5.5-13份,吡丙醚2-6.5份,盐酸特比萘芬2-6份,复合稳定剂17-40份,抗氧化剂0.05-0.14份和复合透皮吸收促进剂34.36-73.45份。
2.根据权利要求1所述的治疗犬猫寄生虫和真菌皮肤病的复方滴剂,其特征在于,所述复合稳定剂由聚氧乙烯脂肪醇、吐温-80、二丙二醇甲醚和乙二醇单甲醚中的两种或多种组成。
3.根据权利要求2所述的复合稳定剂,其特征在于,所述复合稳定剂由二丙二醇甲醚和乙二醇单甲醚组成。
4.根据权利要求3所述的复合稳定剂,其特征在于,所述二丙二醇甲醚与乙二醇单甲醚的体积比为(0.5-4):1。
5.根据权利要求1所述的治疗犬猫寄生虫和真菌皮肤病的复方滴剂,其特征在于,所述抗氧化剂为2,6-二叔丁基对甲酚、丁基羟基茴香醚和特丁基对苯二酚中的至少一种。
6.根据权利要求5所述的治疗犬猫寄生虫和真菌皮肤病的复方滴剂,其特征在于,所述抗氧化剂为丁基对苯二酚。
7.根据权利要求1所述的治疗犬猫寄生虫和真菌皮肤病的复方滴剂,其特征在于,所述复合透皮吸收促进剂由乙醇、丙醇、异丙醇和月桂氮卓酮中的两种或多种组成。
8.根据权利要求7所述的治疗犬猫寄生虫和真菌皮肤病的复方滴剂,其特征在于,所述的复合透皮吸收促进剂由异丙醇和月桂氮卓酮组成。
9.根据权利要求8所述的复合透皮吸收促进剂,其特征在于,所述月桂氮卓酮的重量份数为12-20份。
10.一种如权利要求1-9任一项所述的治疗犬猫寄生虫和真菌皮肤病的复方滴剂的制备方法,其特征在于,包括以下步骤:
S1:在搅拌容器中加入复合稳定剂、复合透皮吸收促进剂并搅拌均匀,然后加入赛拉菌素,搅拌直至溶解;
S2:在步骤S1中得到的混合溶液中分别加入吡丙醚、盐酸特比萘芬和抗氧化剂,搅拌直至溶解后加入吸收促进剂即制得复方滴剂。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202211032050.9A CN115317498B (zh) | 2022-08-26 | 2022-08-26 | 一种治疗犬猫寄生虫和真菌皮肤病的复方滴剂及制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202211032050.9A CN115317498B (zh) | 2022-08-26 | 2022-08-26 | 一种治疗犬猫寄生虫和真菌皮肤病的复方滴剂及制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN115317498A true CN115317498A (zh) | 2022-11-11 |
CN115317498B CN115317498B (zh) | 2023-12-19 |
Family
ID=83927548
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202211032050.9A Active CN115317498B (zh) | 2022-08-26 | 2022-08-26 | 一种治疗犬猫寄生虫和真菌皮肤病的复方滴剂及制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN115317498B (zh) |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101401783A (zh) * | 2007-09-16 | 2009-04-08 | 杨喜鸿 | 含有艾拉莫德的透皮吸收剂及其制备方法和它的药物应用 |
WO2010026370A1 (en) * | 2008-09-05 | 2010-03-11 | Norbrook Laboratories Limited | A topical ectoparasiticide composition |
CN105395484A (zh) * | 2015-12-25 | 2016-03-16 | 武汉回盛生物科技有限公司 | 一种复方特比萘芬喷剂及其制备方法 |
CN106692171A (zh) * | 2017-01-18 | 2017-05-24 | 佛山市南海东方澳龙制药有限公司 | 宠物用复方赛拉菌素外用滴剂及其方法和应用 |
CN108743946A (zh) * | 2018-07-02 | 2018-11-06 | 佛山市南海东方澳龙制药有限公司 | 复方非泼罗尼宠物外用驱虫滴剂及其制备方法和应用 |
JP2020015765A (ja) * | 2019-10-31 | 2020-01-30 | 住友化学株式会社 | 農薬組成物および有害生物防除方法 |
WO2020217701A1 (ja) * | 2019-04-25 | 2020-10-29 | クミアイ化学工業株式会社 | 粒状農薬組成物およびこれの散布方法 |
-
2022
- 2022-08-26 CN CN202211032050.9A patent/CN115317498B/zh active Active
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101401783A (zh) * | 2007-09-16 | 2009-04-08 | 杨喜鸿 | 含有艾拉莫德的透皮吸收剂及其制备方法和它的药物应用 |
WO2010026370A1 (en) * | 2008-09-05 | 2010-03-11 | Norbrook Laboratories Limited | A topical ectoparasiticide composition |
CN105395484A (zh) * | 2015-12-25 | 2016-03-16 | 武汉回盛生物科技有限公司 | 一种复方特比萘芬喷剂及其制备方法 |
CN106692171A (zh) * | 2017-01-18 | 2017-05-24 | 佛山市南海东方澳龙制药有限公司 | 宠物用复方赛拉菌素外用滴剂及其方法和应用 |
CN108743946A (zh) * | 2018-07-02 | 2018-11-06 | 佛山市南海东方澳龙制药有限公司 | 复方非泼罗尼宠物外用驱虫滴剂及其制备方法和应用 |
WO2020217701A1 (ja) * | 2019-04-25 | 2020-10-29 | クミアイ化学工業株式会社 | 粒状農薬組成物およびこれの散布方法 |
JP2020015765A (ja) * | 2019-10-31 | 2020-01-30 | 住友化学株式会社 | 農薬組成物および有害生物防除方法 |
Non-Patent Citations (1)
Title |
---|
崔一民,等: "《特殊释药系统的临床药代动力学试验设计》", 中国协和医科大学出版社, pages: 76 - 77 * |
Also Published As
Publication number | Publication date |
---|---|
CN115317498B (zh) | 2023-12-19 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Seddiek et al. | The acaricidal efficacy of aqueous neem extract and ivermectin against Sarcoptes scabiei var. cuniculi in experimentally infested rabbits | |
EP1252820B1 (en) | Pediculicidal and ovicidal treatment compositions and methods for killing head lice and their eggs | |
US7064108B2 (en) | Topical ivermectin composition | |
Shanks et al. | The efficacy of selamectin in the treatment of naturally acquired aural infestations of Otodectes cynotis on dogs and cats | |
BRPI0117119B1 (pt) | composição oral sistemicamente ativa para o controle e a erradicação de pestes phthiaptera, siphonaptera e acarina, bem como o uso da dita composição ativa | |
Hamel et al. | Treatment and control of bovine sarcoptic and psoroptic mange infestation with ivermectin long-acting injectable (IVOMEC® GOLD) | |
Cutolo et al. | Efficacy of afoxolaner (NexGard®) on the treatment of myiasis caused by the New World screwworm fly Cochliomyia hominivorax (Diptera: Calliphoridae) in naturally infested dogs | |
AU2009260140B2 (en) | Topical use composition for combatting ectoparasites in dogs and cats | |
RU2732965C1 (ru) | Комбинация неоникотиноидного и пиретроидного соединений для контроля распространения дирофиляриоза собак сердечной формы | |
Page et al. | Observations on topical ivermectin in the treatment of otoacariosis, cheyletiellosis, and toxocariosis in cats. | |
CN115317498B (zh) | 一种治疗犬猫寄生虫和真菌皮肤病的复方滴剂及制备方法 | |
Sobhy et al. | Clinical Studies on The Efficacy of Different Topical Drugs With Ivermectin Injection in The Treatment of Egyptian Water Buffalo Calves Infested with Psoroptes Spp. Mites. | |
Maynard et al. | Field efficacy of a 10 per cent pyriproxyfen spot‐on for the prevention of flea infestations on cats | |
RU2340181C1 (ru) | Инсектоакарицидное средство "инсектал-плюс" | |
Kotb et al. | Epidemiological studies of equine mange with special reference to different therapeutic protocols for effective treatment of Chorioptic mange | |
CN112972437B (zh) | 一种包含碘硝酚的长效外用制剂及其制备方法和用途 | |
CN112294831B (zh) | 一种用于动物驱虫的透皮滴剂及其制备方法 | |
CN118078746B (zh) | 一种牛羊驱虫用苦参碱浇背溶液剂及其制备方法与应用 | |
CN107960419A (zh) | 含乙基多杀菌素和灭幼脲的杀虫组合物 | |
TW201102000A (en) | Ectoparasiticidal methods and formulations | |
CN114681479A (zh) | 一种驱虫药剂及其使用方法 | |
AU2016336658B2 (en) | Veterinary compositions for sandfly control | |
CN113925919A (zh) | 用于动物杀虫、灭菌和修复的外用防治剂及其制备方法 | |
Singh et al. | Chemotherapeutics for control and treatment of ectoparasites in companion animals | |
M ALI et al. | In Vitro efficacy of aqueous neem extract and deltamethrin against Sarcoptes scabiei var. Cuniculi and in vivo using experimentally infested rabbits |
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 | ||
GR01 | Patent grant | ||
GR01 | Patent grant |