CN114762690A - Compound preparation - Google Patents
Compound preparation Download PDFInfo
- Publication number
- CN114762690A CN114762690A CN202111655096.1A CN202111655096A CN114762690A CN 114762690 A CN114762690 A CN 114762690A CN 202111655096 A CN202111655096 A CN 202111655096A CN 114762690 A CN114762690 A CN 114762690A
- Authority
- CN
- China
- Prior art keywords
- compound preparation
- active ingredient
- preparation
- praziquantel
- release
- 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
- 238000002360 preparation method Methods 0.000 title claims abstract description 132
- 150000001875 compounds Chemical class 0.000 title claims abstract description 118
- FSVJFNAIGNNGKK-UHFFFAOYSA-N 2-[cyclohexyl(oxo)methyl]-3,6,7,11b-tetrahydro-1H-pyrazino[2,1-a]isoquinolin-4-one Chemical compound C1C(C2=CC=CC=C2CC2)N2C(=O)CN1C(=O)C1CCCCC1 FSVJFNAIGNNGKK-UHFFFAOYSA-N 0.000 claims abstract description 38
- 229960002957 praziquantel Drugs 0.000 claims abstract description 38
- 239000004480 active ingredient Substances 0.000 claims abstract description 26
- 229960001920 niclosamide Drugs 0.000 claims abstract description 22
- RJMUSRYZPJIFPJ-UHFFFAOYSA-N niclosamide Chemical group OC1=CC=C(Cl)C=C1C(=O)NC1=CC=C([N+]([O-])=O)C=C1Cl RJMUSRYZPJIFPJ-UHFFFAOYSA-N 0.000 claims abstract description 22
- BEZZFPOZAYTVHN-UHFFFAOYSA-N oxfendazole Chemical compound C=1C=C2NC(NC(=O)OC)=NC2=CC=1S(=O)C1=CC=CC=C1 BEZZFPOZAYTVHN-UHFFFAOYSA-N 0.000 claims abstract description 20
- 229960004454 oxfendazole Drugs 0.000 claims abstract description 20
- 239000003096 antiparasitic agent Substances 0.000 claims abstract description 5
- 230000002141 anti-parasite Effects 0.000 claims abstract description 3
- 239000003814 drug Substances 0.000 claims description 25
- 239000002904 solvent Substances 0.000 claims description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical group CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 13
- 239000008367 deionised water Substances 0.000 claims description 12
- 229910021641 deionized water Inorganic materials 0.000 claims description 12
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 11
- 229920001992 poloxamer 407 Polymers 0.000 claims description 11
- 229940044476 poloxamer 407 Drugs 0.000 claims description 11
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 11
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 11
- 239000000463 material Substances 0.000 claims description 10
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical group C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 8
- 244000045947 parasite Species 0.000 claims description 8
- 239000002612 dispersion medium Substances 0.000 claims description 7
- 229940068918 polyethylene glycol 400 Drugs 0.000 claims description 7
- 229940093429 polyethylene glycol 6000 Drugs 0.000 claims description 7
- 229920002988 biodegradable polymer Polymers 0.000 claims description 6
- 239000004621 biodegradable polymer Substances 0.000 claims description 6
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 6
- 229920000053 polysorbate 80 Polymers 0.000 claims description 6
- 229920001610 polycaprolactone Polymers 0.000 claims description 5
- 239000004632 polycaprolactone Substances 0.000 claims description 5
- 229940069328 povidone Drugs 0.000 claims description 5
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 claims description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000000843 powder Substances 0.000 description 24
- 230000000694 effects Effects 0.000 description 22
- 208000031513 cyst Diseases 0.000 description 15
- 238000002156 mixing Methods 0.000 description 15
- 206010011732 Cyst Diseases 0.000 description 13
- 208000015181 infectious disease Diseases 0.000 description 13
- 229940079593 drug Drugs 0.000 description 12
- 208000009366 Echinococcosis Diseases 0.000 description 11
- 238000000338 in vitro Methods 0.000 description 11
- 239000002609 medium Substances 0.000 description 11
- 239000000203 mixture Substances 0.000 description 11
- 201000004409 schistosomiasis Diseases 0.000 description 11
- 206010014096 Echinococciasis Diseases 0.000 description 10
- 241000244163 Echinococcus multilocularis Species 0.000 description 10
- 230000001186 cumulative effect Effects 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 9
- 238000001035 drying Methods 0.000 description 8
- 239000004570 mortar (masonry) Substances 0.000 description 8
- 238000001816 cooling Methods 0.000 description 7
- 238000007873 sieving Methods 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 238000013268 sustained release Methods 0.000 description 7
- 239000012730 sustained-release form Substances 0.000 description 7
- 241000282472 Canis lupus familiaris Species 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 229920001577 copolymer Polymers 0.000 description 6
- 239000002861 polymer material Substances 0.000 description 6
- 241000283690 Bos taurus Species 0.000 description 5
- 241001260012 Bursa Species 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 244000144972 livestock Species 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 239000008363 phosphate buffer Substances 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 239000007962 solid dispersion Substances 0.000 description 5
- 201000003808 Cystic echinococcosis Diseases 0.000 description 4
- 208000009434 Schistosomiasis japonica Diseases 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 201000006675 intestinal schistosomiasis Diseases 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 239000012982 microporous membrane Substances 0.000 description 4
- 239000011259 mixed solution Substances 0.000 description 4
- 229920000136 polysorbate Polymers 0.000 description 4
- 238000005070 sampling Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 241000244170 Echinococcus granulosus Species 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 208000030852 Parasitic disease Diseases 0.000 description 3
- 210000000683 abdominal cavity Anatomy 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000011081 inoculation Methods 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 239000008055 phosphate buffer solution Substances 0.000 description 3
- 241000244160 Echinococcus Species 0.000 description 2
- 239000012981 Hank's balanced salt solution Substances 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 241000242678 Schistosoma Species 0.000 description 2
- 229960002669 albendazole Drugs 0.000 description 2
- HXHWSAZORRCQMX-UHFFFAOYSA-N albendazole Chemical compound CCCSC1=CC=C2NC(NC(=O)OC)=NC2=C1 HXHWSAZORRCQMX-UHFFFAOYSA-N 0.000 description 2
- 230000000507 anthelmentic effect Effects 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000000227 grinding Methods 0.000 description 2
- 230000002458 infectious effect Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- OOSZCNKVJAVHJI-UHFFFAOYSA-N 1-[(4-fluorophenyl)methyl]piperazine Chemical compound C1=CC(F)=CC=C1CN1CCNCC1 OOSZCNKVJAVHJI-UHFFFAOYSA-N 0.000 description 1
- BHFLSZOGGDDWQM-UHFFFAOYSA-N 1h-benzimidazole;carbamic acid Chemical compound NC(O)=O.C1=CC=C2NC=NC2=C1 BHFLSZOGGDDWQM-UHFFFAOYSA-N 0.000 description 1
- 229930183010 Amphotericin Natural products 0.000 description 1
- QGGFZZLFKABGNL-UHFFFAOYSA-N Amphotericin A Natural products OC1C(N)C(O)C(C)OC1OC1C=CC=CC=CC=CCCC=CC=CC(C)C(O)C(C)C(C)OC(=O)CC(O)CC(O)CCC(O)C(O)CC(O)CC(O)(CC(O)C2C(O)=O)OC2C1 QGGFZZLFKABGNL-UHFFFAOYSA-N 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 241000754688 Cercaria Species 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 241000601180 Clematis villosa Species 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 206010019659 Hepatic echinococciasis Diseases 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 238000012449 Kunming mouse Methods 0.000 description 1
- 241000699684 Meriones unguiculatus Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 229920000331 Polyhydroxybutyrate Polymers 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 241000869417 Trematodes Species 0.000 description 1
- 201000003894 alveolar echinococcosis Diseases 0.000 description 1
- 229940009444 amphotericin Drugs 0.000 description 1
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001136 anti-cestodal effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007727 cost benefit analysis Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- DMBHHRLKUKUOEG-UHFFFAOYSA-N diphenylamine Chemical compound C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000007877 drug screening Methods 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000005015 poly(hydroxybutyrate) Substances 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 239000002745 poly(ortho ester) Substances 0.000 description 1
- 229940113115 polyethylene glycol 200 Drugs 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- -1 polytrimethylene carbonate Polymers 0.000 description 1
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- LWIHDJKSTIGBAC-UHFFFAOYSA-K potassium phosphate Substances [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 229940074545 sodium dihydrogen phosphate dihydrate Drugs 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 206010048282 zoonosis Diseases 0.000 description 1
Images
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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/10—Anthelmintics
- A61P33/12—Schistosomicides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Tropical Medicine & Parasitology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A compound preparation comprises a first active ingredient and a second active ingredient, wherein the weight component of the antiparasitic compound preparation is 100, the weight component of the first active ingredient in the compound preparation is 5-95, and the weight component of the second active ingredient in the compound preparation is 5-95. The first active ingredient in the compound preparation is the antiparasitic drug praziquantel, and the second active ingredient is niclosamide or oxfendazole. The preparation method of the compound preparation is simple, has good stability and is easy to popularize.
Description
Technical Field
The invention relates to an antiparasitic drug, in particular to a compound preparation which is injected into an animal body and is used for preventing and treating adult and/or larva parasites.
Background
Schistosomiasis is a parasitic disease which is a serious hazard to both human and livestock, about 2 hundred million people are infected with schistosomiasis globally, most of the schistosomiasis is concentrated in Africa, 7.8 million people have the risk of schistosomiasis infection, and 20 million people die of the schistosomiasis every year. Schistosomiasis japonica is prevalent in China, wherein cattle is a main infectious source, the contribution rate to schistosomiasis japonica infection is as high as 90 percent, and thus, the schistosomiasis japonica can be effectively prevented by blocking the infectious source-cattle infection schistosomiasis japonica. The currently implemented policy of "cattle replacement" achieves good control effect, but there are improvements in terms of cost-benefit analysis and field implementation.
At present, the first-line medicine for preventing and treating schistosomiasis on site only is praziquantel, which has good treatment effect on adult worms, but cannot be applied to long-term prevention due to rapid metabolism. Niclosamide has strong effect of killing cercaria. The subject group applies a new slow release technology to prepare the niclosamide long-acting injection, the application target is livestock such as cattle and the like, the livestock directly acts on an infection source, only one-time administration is needed, the operation is simple and convenient, and the drug usage amount and manpower and material resources are saved; subcutaneous injection is adopted, light is not generated, and the medicine is stable and is not easy to decompose; the preparation process is simple, and only the substances in the prescription need to be mixed uniformly, thereby being beneficial to the implementation of on-site prevention and treatment work. The field test shows that the one-time administration can prevent the infection of the cattle with schistosomiasis for 4 to 6 months. However, the niclosamide long-acting injection can only prevent but has poor effect on schistosome imagoes. Therefore, the project combines the advantages of two anti-schistosomiasis drugs to prepare a compound sustained-release formulation for preventing and controlling schistosomiasis on site.
Echinococcosis (echinococcosis) is a zoonosis that seriously harms human health and the development of animal husbandry. Cystic echinococcosis is widely distributed in continents other than antarctica. It is estimated that the Global disease burden (GBD) of echinococcosis is 2X 10 7To 5X 107Disability regulates life years (DALY), while echinococcosis cystic disease-associated treatment costs and livestock losses are approximately $ 20 million per year. Therefore, the medicine for preventing and treating the hydatid has considerable international market demand. It is reported that the demand of anti-cestode and trematode medicines exceeds the market of 1/3, and the development of new praziquantel dosage forms for dogs and echinococcosis diagnostic reagents can achieve 8 billion yuan per year sales, 1.2 billion yuan profit, ensure the safety of 0.66 million people in the endemic area and over 5000 ten thousand domestic animals, and recover the economic loss of about 30 billion yuan.
Praziquantel has milestone significance for controlling echinococcosis, has ideal curative effect and has no drug resistance report in dogs and cats. The dog is used as the infection source of echinococcosis, reduces the infection of echinococcosis protocoid segment, and can effectively prevent and control the transmission of echinococcus taeniae in epidemic areas. Therefore, the current method of 'dog administration and monthly anthelmintic' is adopted, and the monthly feeding of praziquantel tablets to dogs is one of the important measures for controlling echinococcosis in the whole epidemic area. However, in the implementation process, due to the nomadic life habit of local people, the administration of the medicine to each dog cannot be carried out every month, the administration of the wild dog is more difficult to implement, and the control of the infection source to reduce the transmission level of the echinococcosis in the epidemic area is difficult to realize. The invention of a new sustained release technology is urgently needed to achieve the prevention and control effect of maintaining for months after 1 time of administration, so that the canine can only achieve the protection effect for months without monthly administration.
Praziquantel has remarkable effect on mature or immature echinococcus granulosus, but the research finds that the praziquantel has limited or no effect on the encystation period of the echinococcus granulosus and has no killing effect on the eggs of the echinococcus granulosus. The oxfendazole is a novel high-efficiency, broad-spectrum and low-toxicity benzimidazole carbamate anthelmintic. The traditional Chinese medicine composition has a good treatment effect on experimental mouse oncosphere disease, particularly has a good effect on light and moderate infection of mouse oncosphere disease, can reduce the vesicle shrinkage and relieve the symptoms, and has a better effect on treating mouse oncosphere disease than albendazole.
Disclosure of Invention
According to the defects of the prior art, the invention mainly aims to provide a compound preparation which is a sustained-release preparation and can have good treatment effect on various schistosome-resistant adults and/or larvae.
Another object of the present invention is to provide a compound preparation, which can maintain long-term prevention, control and treatment effects through one-time administration of the compound preparation of a sustained-release formulation, can protect animals from being infected by pathogens in the season of infection or even for a longer time, and further can control the spread of parasitic diseases and block the spread chain of the parasitic diseases spread by the animals.
According to the above purpose, the present invention discloses a compound preparation, which comprises a first active ingredient and a second active ingredient, wherein the weight component of the antiparasitic compound preparation is 100, the weight component of the first active ingredient in the compound preparation is 5-95, and the weight component of the second active ingredient in the compound preparation is 5-95.
In a more preferred embodiment of the invention, the first active ingredient is praziquantel.
In a more preferred embodiment of the invention, the second active ingredient is niclosamide or oxfendazole.
In a more preferred embodiment of the present invention, the compound preparation further comprises a biodegradable polymer material, a dispersion medium and a solubilizer, wherein the biodegradable polymer material accounts for 14.7-45.5 wt% of the compound preparation, the dispersion medium accounts for 0-79.4 wt% of the compound preparation, and the solubilizer accounts for 0-45.5 wt% of the compound preparation.
In a more preferred embodiment of the present invention, the biodegradable polymer material is a poly (lactic-co-glycolic acid), polycaprolactone, or poloxamer 407.
In a more preferred embodiment of the invention, the dispersing medium may be N-methylpyrrolidone or polyethylene glycol 400.
In a more preferred embodiment of the invention, the solubilizer may be povidone (polyvinylpyrrolidone (PVP)), tween 80 or polyethylene glycol 6000.
In a more preferred embodiment of the invention, the compound preparation further comprises deionized water, and the deionized water accounts for 58.8-69.0 of the weight of the compound preparation.
The invention also discloses the use of the compound preparation in the preparation of medicaments for resisting parasites; wherein the parasite comprises adults and/or larvae of the parasite.
Therefore, the compound preparation of the invention can fully exert the advantages of two anti-schistosome drugs, only takes 1 time to maintain the prevention and control effect for months, can be used for preparing long-acting injection, is applied to livestock such as cattle and the like, has simple and convenient operation, and saves the drug use amount and manpower and material resources.
Description of the drawings:
fig. 1 is a graph showing the in vitro cumulative dissolution rates of oxfendazole and praziquantel in the compound preparation 14 of the present invention.
Detailed Description
To further clarify the objects, features and advantages of the present invention and in order to enable one skilled in the art to practice the invention, there is described in detail herein a preferred embodiment of the invention. The description of the embodiments related to the present invention will not be repeated, except for those skilled in the art.
The invention discloses a compound preparation, in particular to a compound preparation with a sustained-release formulation, which can prevent adults and larvae of parasites simultaneously, can be administrated once due to the sustained-release function, can be sustained-released in vitro for 1 day or several months, has the potential of long-time treatment and can not be infected by pathogens. The compound preparation comprises a first active ingredient and a second active ingredient, wherein the weight component of the compound preparation is 100, the weight component of the first active ingredient accounts for 5-95 of the compound preparation, and the weight component of the second active ingredient accounts for 5-95 of the compound preparation. In one embodiment of the present invention, the first active ingredient is praziquantel and the second active ingredient is niclosamide or oxfendazole. In addition, the compound preparation also comprises a biodegradable high polymer material, a dispersion medium and a solubilizer, wherein the biodegradable high polymer material accounts for 14.7-45.5 of the weight component of the compound preparation, the dispersion medium accounts for 0-79.4 of the weight component of the compound preparation, and the solubilizer accounts for 0-45.5 of the weight component of the compound preparation, wherein the biodegradable high polymer material can be one or more of polylactic acid-glycolic acid copolymer, polycaprolactone, poloxamer 407, chitosan, polytrimethylene carbonate, polyglycolic acid, polylactic acid, polyhydroxybutyrate-hydroxyvalerate copolymer, polyhydroxybutyrate, polyorthoester and polyanhydride compounds and derivatives thereof, and the weight average molecular weight of the biodegradable high polymer material is preferably 10,000-150,000. The weight average molecular weight of the biodegradable high polymer material can be selected according to different slow release time, and when the slow release time of the medicine is longer, the biodegradable high polymer material with higher molecular weight is selected, such as the weight average molecular weight of 100,000-150,000; when the drug release time does not need to be long, biodegradable high molecular materials with low molecular weight, such as 16,000 weight average molecular weight, tend to be selected.
The dispersing medium may be N-methyl pyrrolidone or polyethylene glycol 400, and when polyethylene glycol is used as the dispersing agent, polyethylene glycol having a lower molecular weight, such as polyethylene glycol 200 or polyethylene glycol 400, is usually selected.
The solubilizer may be povidone (polyvinylpyrrolidone (PVP)), tween 80 or polyethylene glycol 6000. In addition, the compound preparation also comprises deionized water, wherein the deionized water accounts for 58.8-69.0 of the weight of the compound preparation.
The following is a detailed description of the present invention with respect to a preparation example of a compound preparation having a sustained-release dosage form.
Preparation example one (compound preparation 1):
dissolving 0.1g of praziquantel, 0.1g of niclosamide, 0.5g of polylactic acid-glycolic acid copolymer and 0.2g of tween 80 in 2mL of N-methylpyrrolidone to obtain a compound preparation 1.
Preparation example two (compound preparation 2):
dissolving 0.1g of praziquantel, 0.1g of niclosamide, 0.5g of polylactic acid-glycolic acid copolymer and 0.2g of polyethylene glycol 400 in 2mL of N-methylpyrrolidone to obtain a compound preparation 2.
Preparation example three (compound preparation 3):
and dissolving 0.5g of poloxamer 407 and 0.2g of tween 80 in 2mL of deionized water at low temperature (ice water bath) to form a mixed solution, adding 0.1g of praziquantel and 0.1g of niclosamide into the mixed solution, and uniformly mixing to obtain a compound preparation 3.
Preparation example four (compound preparation 4):
and dissolving 0.5g of poloxamer 407 and 0.2g of polyethylene glycol 400 in 2mL of deionized water at a low temperature (ice water bath) to form a mixed solution, adding 0.1g of praziquantel and 0.1g of niclosamide into the mixed solution, and uniformly mixing to obtain a compound preparation 4.
Preparation example five (compound preparation 5):
dissolving 1g of poloxamer 407 in 4mL of deionized water, stirring and dissolving at low temperature (ice water bath), adding 1.4mL of niclosamide hot solution with the weight percentage of 14.2% (the solvent is N-methylpyrrolidone), and continuously adding 0.2g of praziquantel and uniformly mixing to obtain a compound preparation 5.
Preparation example six (compound preparation 6):
0.1g of praziquantel, 0.1g of oxfendazole, 0.5g of polylactic acid-glycolic acid copolymer and 0.2g of polyethylene glycol 400 are dissolved in 2mL of N-methylpyrrolidone to obtain a compound preparation 6.
Preparative example seven (compound formulation 7):
dissolving 1g of poloxamer 407 in 4mL of deionized water, adding 1.2mL of 16.6 wt% oxfendazole solution (the solvent is N-methyl pyrrolidone, and the content of the povidone in the N-methyl pyrrolidone solvent is 0.1 g) while stirring, and continuously adding 0.2g of praziquantel and uniformly mixing to obtain a compound preparation 7.
Preparation example eight (compound preparation 8):
dissolving 1g of poloxamer 407 in 4mL of deionized water, adding 1.2mL of 16.6 wt% oxfendazole solution (the solvent is N-methyl pyrrolidone, and the content of the povidone in the N-methyl pyrrolidone solvent is 0.05 g) while stirring, and continuously adding 0.2g of praziquantel and uniformly mixing to obtain a compound preparation 8.
Preparation example nine (compound preparation 9):
dissolving 1g of poloxamer 407 in 4mL of deionized water, adding 1.2mL of oxfendazole solution (solvent is N-methylpyrrolidone) with the weight percentage of 16.6 percent while stirring, continuously adding 0.2g of praziquantel, and uniformly mixing to obtain a compound preparation 9.
Preparation example ten (compound preparation 10):
heating, melting and uniformly mixing 0.1g of praziquantel and 1g of polycaprolactone, cooling in a refrigerator at-80 ℃ for 30 minutes, and drying in a drier for at least 24 hours to obtain a first intermediate. This first intermediate, a solid dispersion having large particles, was ground in a mortar, passed through a 60-mesh sieve, and the powder passed through the sieve after the sieving was collected to obtain a first powder. In addition, 0.1g of niclosamide and 1g of polyethylene glycol 6000 were uniformly heated and melted, placed in a refrigerator at-80 ℃ for cooling for 30 minutes, then placed in a dryer for drying for at least 24 hours to obtain a second intermediate, the second intermediate was ground through a mortar, and the powder sieved through a 60-mesh sieve was collected to obtain a second powder. Mixing the first powder and the second powder in a weight ratio of 1: 1 to obtain the compound preparation 10.
Preparation eleven (combined preparation 11):
0.1g of praziquantel and 1g of poloxamer 407 are heated, melted and mixed uniformly, placed in a refrigerator at-80 ℃ for cooling for 30 minutes, and then placed in a dryer for drying for at least 24 hours to obtain a first intermediate. This first intermediate, a solid dispersion having larger particles, was ground in a mortar, passed through a 60-mesh sieve, and the powder passed through the sieve after the sieving was collected to obtain a first powder. In addition, 0.1g of niclosamide and 1g of polyethylene glycol 6000 were uniformly heated and melted, placed in a refrigerator at-80 ℃ for cooling for 30 minutes, then placed in a dryer for drying for at least 24 hours to obtain a second intermediate, the second intermediate was ground through a mortar and sieved through a 60-mesh sieve, and the powder sieved through the sieve was collected to obtain a second powder. Mixing the first powder and the second powder in a weight ratio of 1: 1, and mixing uniformly to obtain the compound preparation 11.
Preparation example twelve (compound formulation 12):
heating, melting and uniformly mixing 0.1g of praziquantel and 1g of polycaprolactone, placing the mixture in a refrigerator with the temperature of-80 ℃ for cooling for 30 minutes, placing the mixture in a dryer for drying for at least 24 hours to obtain a first intermediate, grinding the first intermediate and a solid dispersion with larger particles through a mortar, sieving the ground first intermediate and the solid dispersion with the larger particles through a 60-mesh sieve, and collecting powder which passes through the sieve after sieving to obtain first powder. In addition, 0.1g of oxfendazole and 1g of polyethylene glycol 6000 are heated, melted, mixed uniformly, placed in a refrigerator at-80 ℃ for cooling for 30 minutes, then placed in a dryer for drying for at least 24 hours to obtain a second intermediate, the second intermediate is ground through a mortar, sieved through a 60-mesh sieve, and the powder sieved through the sieve is collected to obtain a second powder. Mixing the first powder and the second powder in a weight ratio of 1: 1 proportion to obtain the compound preparation 12.
Preparation example thirteen (compound preparation 13):
heating, melting and uniformly mixing 0.1g of praziquantel and 1g of poloxamer 407, placing the mixture in a refrigerator with the temperature of-80 ℃ for cooling for 30 minutes, placing the mixture in a dryer for drying for at least 24 hours to obtain a first intermediate, grinding the first intermediate and a solid dispersion with larger particles through a mortar, sieving the first intermediate through a 60-mesh sieve, and collecting powder which passes through the sieve after sieving to obtain first powder. In addition, 0.1g of oxfendazole and 1g of polyethylene glycol 6000 were uniformly heated, melted, placed in a refrigerator at-80 ℃ for 30 minutes, and then placed in a dryer for drying for at least 24 hours to obtain a second intermediate, the second intermediate was ground in a mortar, passed through a 60-mesh sieve, and the powder passed through the sieve after the sieving was collected to obtain a second powder. Mixing the first powder and the second powder 1: 1 proportion to obtain the compound preparation 13.
Preparation example fourteen (compound preparation 14):
1.0g of praziquantel, 1.0g of oxfendazole and 0.5g of polylactic acid-glycolic acid copolymer (1.6 ten thousand molecular weight, PLGA 75: 25, of Jinan Dai big Dipper, Bio-engineering Co., Ltd.) were dispersed in 2mL of N-methylpyrrolidone to obtain a compound preparation 14.
The compound preparation 1-14 is shown in Table 1 after being matched and finished.
TABLE 1
The compound preparation is used for in vitro release degree research. Firstly, two buffers required for in vitro release degree research are required to be prepared, namely 0.5% Tween phosphate buffer (pH7.4) and 0.5% SDS phosphate buffer (pH7.4), and the preparation method comprises the following steps:
taking 1.36g of monopotassium phosphate, adding 79mL of 0.1mol/L sodium hydroxide solution, diluting with water to 200mL, adding 1g of Tween 80, and mixing uniformly to obtain 0.5% Tween phosphate buffer (pH 7.4).
1.56g of sodium dihydrogen phosphate dihydrate is taken, 79mL of 0.1mol/L sodium hydroxide solution is added, the solution is diluted to 200mL by water, 1g of SDS is added, and the mixture is mixed evenly, thus obtaining 0.5% SDS phosphate buffer solution (pH 7.4).
After the preparation of the buffer solution required for the in vitro release degree research is completed, the in vitro release degree research is carried out by the following steps of:
taking 0.2mL of the compound preparation 1 to 5, adding into 50mL of plugged EP tube, and adding 30mL of 0.5% Tween phosphate buffer solution (standing at 37 deg.C for 5min for compound preparation 3 to 5). Shaking at 150r/min in a constant temperature shaking instrument at 37 + -1 deg.C, sampling at fixed time, filtering the release medium with 0.22 μm microporous membrane, collecting the filtrate, and measuring OD values at 270nm and 340nm respectively; the concentration of the drug in the release medium was calculated according to the standard curve, and the cumulative release was calculated according to equation (1).
The formula (1) is as followsWherein Rn represents the cumulative release rate on day n, Rn-1Denotes the cumulative release on day n-1, CnIndicating the release medium concentration at day n.
Taking 0.2mL of the compound preparation 6 to 9 and 14, adding into 50mL of plugged EP tube, and adding 30mL of 0.5% SDS phosphate buffer (standing at 37 deg.C for 5 min, and adding). Oscillating at a constant temperature oscillator of 37 + -1 deg.C at a rotation speed of 150r/min, sampling at regular time, filtering the release medium with 0.22 μm microporous membrane, collecting filtrate, and measuring OD values at 270nm and 296nm respectively; the drug concentration in the release medium was calculated according to the standard curve, and the cumulative release was calculated according to equation (1). The in vitro cumulative dissolution rates of oxfendazole and praziquantel of compound preparation 14 are shown in fig. 1.
The compound preparation 10 and the compound preparation 11 take 0.1g of the preparation in each part, add into a 50mL plugged EP tube, and add 30 mL0.5% Tween phosphate buffer solution. Shaking at 150r/min in a constant temperature shaking instrument at 37 + -1 deg.C, sampling at fixed time, filtering the release medium with 0.22 μm microporous membrane, collecting the filtrate, and measuring OD values at 270nm and 340nm respectively; the concentration of the drug in the release medium was calculated according to the standard curve, and the cumulative release was calculated according to equation (1).
Taking 0.1g of the compound preparation 12 and 13, adding the preparation into a 50mL EP tube with a plug, and adding 30mL of 0.5% SDS phosphate buffer. Oscillating in a constant temperature oscillator at 37 + -1 deg.C at 150r/min, sampling at fixed time, filtering the release medium with 0.22 μm microporous membrane, collecting filtrate, and measuring OD values at 270nm and 296nm respectively; the drug concentration in the release medium was calculated according to the standard curve, and the cumulative release was calculated according to equation (1).
The results of the in vitro release study of niclosamide are shown in table 2, wherein in the compound preparation 10, the 4-hour cumulative release of niclosamide is 64.8%, and the 4-hour release of praziquantel is only 17.6%; in the compound preparation 11, the cumulative release rate of niclosamide in 4 hours is 75.3 percent, and the release rate of praziquantel in 4 hours is only 45.6 percent. The release speed of the niclosamide of the compound preparation 10 and the compound preparation 11 is faster than that of the praziquantel. In the compound preparation 5, the release rate of the niclosamide is not obviously different from that of praziquantel after the medicine is released for about three weeks. In the compound preparation 3 and the compound preparation 4, the medicament is released for about 2 months. The compound preparation 1 and the compound preparation 2 release the medicine for more than two months, wherein the niclosamide in the compound preparation 1 only releases 47.4 percent in 78 days, the praziquantel releases 100.0 percent in 78 days, and the release speed of the praziquantel is faster than that of the niclosamide.
The in vitro release dissolution rates of the compound preparations of praziquantel and niclosamide are collated and listed in Table 2.
TABLE 2
The results of the in vitro release degree study of oxfendazole are shown in table 3, and the compound preparation 7, the compound preparation 8, the compound preparation 9 and the compound preparation 13 are completely released in 1-6 days. The compound preparation 6 has the longest release time, wherein the release time of the oxfendazole is only 77.5 percent in 23 days, the release time of the praziquantel is 99.7 percent in 9 days, and the release speed of the praziquantel is faster than that of the oxfendazole. In the compound preparation 12, the oxfendazole is released by 97.2 percent in 1 day, the praziquantel is released by 61.8 percent in 11 days, and the oxfendazole is released more quickly than the praziquantel.
The in vitro release dissolution rates of the compound preparations praziquantel and oxfendazole are collated and listed in table 3.
TABLE 3
In conclusion, different compound preparations are prepared by the invention, and the sustained-release effect of 1 day to several months is achieved. Meanwhile, different prescription processes are adopted, so that the release speed of the compound traditional Chinese medicine can be adjusted, more medication schemes are provided for later field application, and the compound traditional Chinese medicine has a wide application prospect.
The application example is as follows: test of efficacy of alveolar echinococcosis
The compound preparation 14 of the invention is adopted to carry out the drug effect experiment on the echinococcus multilocularis for preventing the infection of mice, and the experimental process is as follows:
1. Experimental materials: a blank preparation (different from the blank preparation in that the first active ingredient and the second active ingredient of the compound preparation 14 are not contained and the dosage is equal to the compound preparation 14) and the compound preparation 14 of the invention.
2. Animals:
source and species strains: kunming mice;
providing a unit: experimental animal center of Shanghai national academy of sciences;
sex of the mice: and (4) female.
3. Grouping and animal number:
groups were randomized, with 10 mice per group.
4. The experimental method comprises the following steps:
(1) insect source
Echinococcus multilocularis primary joint and tissue: stock keeping animals (mice, rats or meriones unguiculatus, etc.) were provided by the echinococcus multilocularis stock keeping laboratory. The skin of the breeding rat was disinfected with iodine tincture and 75% ethanol, and after the abdominal cavity was dissected, the echinococcus multilocularis sac was removed aseptically. If there is cheese-like mass or aseptic cyst, it should be removed. Weighing the collected echinococcus multilocularis cysts, placing the echinococcus multilocularis cysts in a culture dish, shearing the cyst tissues into fine pieces as much as possible by using an ophthalmic elbow scissors, washing the cyst tissues by using HBSS (containing penicillin, streptomycin 50 ten thousand U/L and amphotericin B0.25 mg/L) for 10min each time for 5-8 times, and then diluting the cyst tissues to 80-100 mg/ml with HBSS containing antibiotics for later use.
(2) Inoculation of
Adding a magnetic stirring seed into a beaker containing the echinococcus multilocularis cyst tissue suspension, placing the beaker on a magnetic stirrer, and adjusting the rotating speed to keep the original head and cyst tissues suspended. 0.3ml of echinococcus multilocularis cyst tissue (about 40-50 mg of cyst tissue) is sucked by a 1ml syringe, then the skin of the mouse is rubbed with 75% alcohol, and then the cyst tissue is injected into the abdominal cavity of the mouse.
(3) Drug screening and Experimental treatment
Treatment start time: 20 mice, randomly grouped, 10 per group. The negative control group inoculates 0.1mL of blank preparation per unit, and the administration group inoculates 0.1mL of compound preparation per unit. 1 hour after inoculation, 20 mice were re-inoculated with echinococcus multilocularis.
Mice were dissected 5 months after inoculation. Sacrifice by cervical dislocation, dissect the abdominal cavity, carefully dissect and remove the echinococcus multilocularis tissue, and weigh the bursa of each mouse.
Calculating the curative effect: the average bursa weight of the drug group and the control group is calculated, and the bursa weight inhibition rate is calculated according to the following formula.
The cyst weight inhibition rate (negative control cyst weight-administered cyst weight)/control cyst weight 100
The results of the experiments are shown in table 4 below.
TABLE 4 Effect of Economococcus multilocularis infected mice treated with albendazole soybean oil-span suspension (weight unit: g)
As can be seen from the results in Table 4, the compound preparation of the present invention has a significant effect of inhibiting bursal weight in mice infected with echinococcus multocida at an early stage, and the bursal weight inhibition rate is 67.4%. The compound preparation achieves better effect of inhibiting the development of the bursa weight, and the average' bursa weight: body weight "is 0.07943, and there are 6 cases of" pouch weight: body weight "values were lower than average. The compound preparation provided by the invention has good effect of preventing development of schistosomiasis due to the slow release effect, can delay the development trend of symptoms of animals infected with schistosomiasis, and strives for time for subsequent treatment.
The above are merely preferred embodiments of the present invention, which should not be construed as limiting the scope of the invention; while the foregoing is directed to embodiments of the present invention, other and further embodiments of the invention may be devised without departing from the basic scope thereof, and the scope thereof is determined by the claims that follow.
Claims (9)
1. The compound preparation is characterized by comprising a first active ingredient and a second active ingredient, wherein the weight component of the antiparasitic compound preparation is 100, the weight component of the first active ingredient in the compound preparation is 5-95, and the weight component of the second active ingredient in the compound preparation is 5-95.
2. The combination of claim 1, wherein the first active ingredient is praziquantel.
3. The combination of claim 1, wherein the second active ingredient is niclosamide or oxfendazole.
4. The compound preparation of claim 1, further comprising a biodegradable polymer material, a dispersion medium and a solubilizer, wherein the biodegradable polymer material accounts for 14.7-45.5 wt% of the compound preparation, the dispersion medium accounts for 0-79.4 wt% of the compound preparation, and the solubilizer accounts for 0-45.5 wt% of the compound preparation.
5. The compound preparation of claim 4, wherein the biodegradable polymer material is selected from poly (lactic-co-glycolic acid), polycaprolactone, and poloxamer 407.
6. The compound preparation of claim 4, wherein the dispersion medium is N-methylpyrrolidone or polyethylene glycol 400.
7. The compound preparation of claim 4, wherein the solubilizer is povidone (polyvinylpyrrolidone (PVP)), tween 80 or polyethylene glycol 6000.
8. The compound preparation of claim 1, further comprising deionized water, wherein the deionized water accounts for 58.8-69.0 weight percent of the compound preparation.
9. Use of a combination according to any one of claims 1 to 8 in the manufacture of a medicament for combating parasites; wherein the parasite comprises an adult and/or a larva of a parasite.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110040115 | 2021-01-13 | ||
CN2021100401153 | 2021-01-13 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN114762690A true CN114762690A (en) | 2022-07-19 |
Family
ID=82365206
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202111655096.1A Pending CN114762690A (en) | 2021-01-13 | 2021-12-31 | Compound preparation |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN114762690A (en) |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2007221747A1 (en) * | 2006-09-29 | 2008-04-10 | Bayer New Zealand Limited | Medicament |
CN103877092A (en) * | 2012-12-21 | 2014-06-25 | 青岛康地恩药业股份有限公司 | Compound niclosamide chewing tablet used for dogs and cats |
CN107811967A (en) * | 2016-09-09 | 2018-03-20 | 中国疾病预防控制中心寄生虫病预防控制所 | Anti-parasite medicine in-situ solidification sustained-release injector and preparation method thereof |
-
2021
- 2021-12-31 CN CN202111655096.1A patent/CN114762690A/en active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2007221747A1 (en) * | 2006-09-29 | 2008-04-10 | Bayer New Zealand Limited | Medicament |
CN103877092A (en) * | 2012-12-21 | 2014-06-25 | 青岛康地恩药业股份有限公司 | Compound niclosamide chewing tablet used for dogs and cats |
CN107811967A (en) * | 2016-09-09 | 2018-03-20 | 中国疾病预防控制中心寄生虫病预防控制所 | Anti-parasite medicine in-situ solidification sustained-release injector and preparation method thereof |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2002527362A (en) | Oral formulation of lufenuron and nitenpyram for fleas | |
TW200800293A (en) | Benzimidazole non-aqueous compositions | |
WO2020225143A1 (en) | Injectable pharmaceutical compositions and uses thereof | |
JPH05246893A (en) | Long-acting antiparasitic injectable formulation containing hydrogenated castor oil | |
UA127456C2 (en) | Injectable isoxazoline pharmaceutical compositions and their use against parasite infestation | |
CN107773554A (en) | A kind of ivermectin slow-releasing microcapsule and its preparation method and application | |
AU660205B2 (en) | Systemic control of parasites | |
CN114762690A (en) | Compound preparation | |
RU1836084C (en) | A way of obtaining the preparation for therapy of parasite diseases in animals | |
AU2021277491B2 (en) | Injectable pharmaceutical compositions and uses thereof | |
ES2304371T3 (en) | STABLE COMPOSITIONS FOR PARENTERAL ADMINISTRATION. | |
KR101055689B1 (en) | Pharmaceutical composition of cow mastitis infusion comprising bee venom | |
CN110721152B (en) | Sustained-release composition for treating animal skin parasite and fungus infection | |
EP2744495B1 (en) | Anthelmintic formulations and treatments | |
US20080249153A1 (en) | Anthelmintic formulations | |
CN110772509A (en) | Imidacloprid and moxidectin diatomic alcohol plastid and preparation method and application thereof | |
RU2659174C1 (en) | Antiparasitic composition for protecting agricultural animals | |
CN1711077A (en) | Combination product for controlling insect pests | |
EA001623B1 (en) | Acyl urea compounds for the treatment of coccidiodomycosis in warm-blooded animals | |
ES2795449T3 (en) | Topical parasiticidal formulation for use against myiasis produced by fly attack in sheep | |
CN108295119A (en) | Special pest repellant of a kind of largemouth bass cultivation and preparation method thereof | |
CN112641723A (en) | Pharmaceutical composition for treating otoacarid and preparation method thereof | |
RU2140737C1 (en) | Agent for prophylaxis and treatment of animals with parasitic sicknesses | |
MX2014010957A (en) | Long acting compositions. | |
CN104721187B (en) | The pharmaceutical composition and its preparation and application containing Albendazole of the anti-microsporidian of silkworm |
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 |