CN104666244B - Veterinary antiparasitic preparation containing brazil wax - Google Patents
Veterinary antiparasitic preparation containing brazil wax Download PDFInfo
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- CN104666244B CN104666244B CN201510118056.1A CN201510118056A CN104666244B CN 104666244 B CN104666244 B CN 104666244B CN 201510118056 A CN201510118056 A CN 201510118056A CN 104666244 B CN104666244 B CN 104666244B
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- brazil wax
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- oil
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- 239000004203 carnauba wax Substances 0.000 title claims abstract description 79
- 238000002360 preparation method Methods 0.000 title claims abstract description 73
- 230000002141 anti-parasite Effects 0.000 title claims abstract description 20
- 239000003096 antiparasitic agent Substances 0.000 title abstract description 3
- 239000003814 drug Substances 0.000 claims abstract description 58
- 238000002347 injection Methods 0.000 claims abstract description 58
- 239000007924 injection Substances 0.000 claims abstract description 58
- 239000000203 mixture Substances 0.000 claims abstract description 39
- 239000003921 oil Substances 0.000 claims abstract description 17
- 235000019198 oils Nutrition 0.000 claims abstract description 17
- 235000015112 vegetable and seed oil Nutrition 0.000 claims abstract description 17
- 239000008158 vegetable oil Substances 0.000 claims abstract description 17
- 239000005660 Abamectin Substances 0.000 claims abstract description 16
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 claims abstract description 10
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 claims abstract description 10
- 229940093471 ethyl oleate Drugs 0.000 claims abstract description 10
- 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 7
- 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 7
- 229960004454 oxfendazole Drugs 0.000 claims abstract description 7
- 229960002957 praziquantel Drugs 0.000 claims abstract description 7
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 5
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 26
- AZSNMRSAGSSBNP-UHFFFAOYSA-N 22,23-dihydroavermectin B1a Natural products C1CC(C)C(C(C)CC)OC21OC(CC=C(C)C(OC1OC(C)C(OC3OC(C)C(O)C(OC)C3)C(OC)C1)C(C)C=CC=C1C3(C(C(=O)O4)C=C(C)C(O)C3OC1)O)CC4C2 AZSNMRSAGSSBNP-UHFFFAOYSA-N 0.000 claims description 20
- SPBDXSGPUHCETR-JFUDTMANSA-N 8883yp2r6d Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O[C@@H]([C@@H](C)CC4)C(C)C)O3)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C.C1C[C@H](C)[C@@H]([C@@H](C)CC)O[C@@]21O[C@H](C\C=C(C)\[C@@H](O[C@@H]1O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C1)[C@@H](C)\C=C\C=C/1[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\1)O)C[C@H]4C2 SPBDXSGPUHCETR-JFUDTMANSA-N 0.000 claims description 20
- 229960002418 ivermectin Drugs 0.000 claims description 20
- 239000004480 active ingredient Substances 0.000 claims description 11
- 239000000463 material Substances 0.000 claims description 8
- 239000010495 camellia oil Substances 0.000 claims description 7
- 239000002245 particle Substances 0.000 claims description 7
- 239000000243 solution Substances 0.000 claims description 7
- 239000003549 soybean oil Substances 0.000 claims description 7
- 235000012424 soybean oil Nutrition 0.000 claims description 7
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical group CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 claims description 6
- 238000013019 agitation Methods 0.000 claims description 6
- 235000010354 butylated hydroxytoluene Nutrition 0.000 claims description 5
- 238000000227 grinding Methods 0.000 claims description 5
- -1 acetamido Avermectin Chemical compound 0.000 claims description 4
- 235000010388 propyl gallate Nutrition 0.000 claims description 3
- 239000000473 propyl gallate Chemical group 0.000 claims description 3
- 229940075579 propyl gallate Drugs 0.000 claims description 3
- SPSPIUSUWPLVKD-UHFFFAOYSA-N 2,3-dibutyl-6-methylphenol Chemical group CCCCC1=CC=C(C)C(O)=C1CCCC SPSPIUSUWPLVKD-UHFFFAOYSA-N 0.000 claims description 2
- QSHVAZMOLNGWSY-UHFFFAOYSA-N 3-butyl-4-methoxyphenol Chemical group CCCCC1=CC(O)=CC=C1OC QSHVAZMOLNGWSY-UHFFFAOYSA-N 0.000 claims description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 2
- 239000004359 castor oil Substances 0.000 claims description 2
- 235000019438 castor oil Nutrition 0.000 claims description 2
- 239000000084 colloidal system Substances 0.000 claims description 2
- 235000005687 corn oil Nutrition 0.000 claims description 2
- 239000002285 corn oil Substances 0.000 claims description 2
- 235000012343 cottonseed oil Nutrition 0.000 claims description 2
- 239000002385 cottonseed oil Substances 0.000 claims description 2
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 2
- YZBLFMPOMVTDJY-CBYMMZEQSA-N moxidectin Chemical compound O1[C@H](C(\C)=C\C(C)C)[C@@H](C)C(=N/OC)\C[C@@]11O[C@H](C\C=C(C)\C[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 YZBLFMPOMVTDJY-CBYMMZEQSA-N 0.000 claims 1
- 229960004816 moxidectin Drugs 0.000 claims 1
- 239000000263 2,3-dihydroxypropyl (Z)-octadec-9-enoate Substances 0.000 abstract description 38
- RZRNAYUHWVFMIP-GDCKJWNLSA-N 3-oleoyl-sn-glycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-GDCKJWNLSA-N 0.000 abstract description 38
- RZRNAYUHWVFMIP-UHFFFAOYSA-N monoelaidin Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-UHFFFAOYSA-N 0.000 abstract description 38
- 238000009472 formulation Methods 0.000 abstract description 23
- 230000000694 effects Effects 0.000 abstract description 9
- 241001494479 Pecora Species 0.000 description 45
- 210000004369 blood Anatomy 0.000 description 41
- 239000008280 blood Substances 0.000 description 41
- 238000012360 testing method Methods 0.000 description 16
- 210000002381 plasma Anatomy 0.000 description 14
- 239000003795 chemical substances by application Substances 0.000 description 13
- 241000509427 Sarcoptes scabiei Species 0.000 description 12
- 230000000052 comparative effect Effects 0.000 description 12
- 238000001514 detection method Methods 0.000 description 12
- 229940079593 drug Drugs 0.000 description 12
- 238000011282 treatment Methods 0.000 description 10
- 230000036765 blood level Effects 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 238000002156 mixing Methods 0.000 description 6
- 238000010008 shearing Methods 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- XINQFOMFQFGGCQ-UHFFFAOYSA-L (2-dodecoxy-2-oxoethyl)-[6-[(2-dodecoxy-2-oxoethyl)-dimethylazaniumyl]hexyl]-dimethylazanium;dichloride Chemical compound [Cl-].[Cl-].CCCCCCCCCCCCOC(=O)C[N+](C)(C)CCCCCC[N+](C)(C)CC(=O)OCCCCCCCCCCCC XINQFOMFQFGGCQ-UHFFFAOYSA-L 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 238000010241 blood sampling Methods 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- WPNHOHPRXXCPRA-TVXIRPTOSA-N eprinomectin Chemical compound O1[C@@H](C)[C@@H](NC(C)=O)[C@H](OC)C[C@@H]1O[C@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O3)C=C[C@H](C)[C@@H](C(C)C)O4)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C\C=C/[C@@H]2C)\C)O[C@H]1C WPNHOHPRXXCPRA-TVXIRPTOSA-N 0.000 description 4
- 229960002346 eprinomectin Drugs 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 210000004731 jugular vein Anatomy 0.000 description 4
- 239000003182 parenteral nutrition solution Substances 0.000 description 4
- 238000010254 subcutaneous injection Methods 0.000 description 4
- 239000007929 subcutaneous injection Substances 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 3
- 108010006025 bovine growth hormone Proteins 0.000 description 3
- 230000000857 drug effect Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 229920000669 heparin Polymers 0.000 description 3
- 239000004033 plastic Substances 0.000 description 3
- 238000004321 preservation Methods 0.000 description 3
- 239000000375 suspending agent Substances 0.000 description 3
- 239000000273 veterinary drug Substances 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 230000036592 analgesia Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 239000003292 glue Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 238000012856 packing Methods 0.000 description 2
- 230000036407 pain Effects 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- JGSARLDLIJGVTE-UHFFFAOYSA-N 3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 206010063409 Acarodermatitis Diseases 0.000 description 1
- 241000283725 Bos Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000036318 Callitris preissii Species 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 241000244206 Nematoda Species 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 208000030852 Parasitic disease Diseases 0.000 description 1
- 241000447727 Scabies Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 238000005498 polishing Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 208000005687 scabies Diseases 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007962 solid dispersion Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
A kind of veterinary antiparasitic injection containing brazil wax, preparation is mainly made up of anti-parasite medicine, brazil wax and oil medium；Anti-parasite medicine is Avermectins medicine, praziquantel, oxfendazole；Oily medium is vegetable oil, ethyl oleate or Ergol, but they more than one be applied in combination.Glyceryl monooleate, brazil wax and glyceryl monooleate combination application can be also added in the formulation, and the slow release effect of preparation is more preferable.The preparation composition of selection is (being calculated by 1000ml)：The 80g of Avermectins anti-parasite medicine 36, the 70g of brazil wax 10, the 120g of glyceryl monooleate 80, the 0.3g of antioxidant 0.1, the 20%g of phenmethylol 10, oil medium adds to final volume.
Description
Technical field
The invention belongs to veterinary drug preparation technology of preparing, and in particular to it is slow to use brazil wax or brazil wax and glyceryl monooleate
Material is released, the long-acting veterinary injection containing anti-parasite medicine is prepared.
Background technology
Brazil wax is also known as Brazil wax, and it is nontoxic, nonirritant, and it is safe pharmaceutic adjuvant to be recognized, in a medicament
Be often used as polishing agent, ointment bases, the suppository base of tablet or coating of pill, and solid dispersions decentralized medium and mouth
The slow-release material of formulation.About application of the brazil wax in injection, report it is few.Patent CN86105087C is disclosed
A kind of technical scheme for preparing the long-acting injection containing bovine growth hormone, bovine growth hormone is suspended in be made up of brazil wax and vegetable oil
Oil medium in, brazil wax Optimum Contents are 5-10%, are subcutaneously injected the finish, single-dose, bovine growth hormone it is effective
The sustained release time can reach 28 days or so.Also some patents are (such as：Patent CN1572302A, CN1698637A,
CN1236758A, CN1461640A, CN1444925A, CN1421199A, CN1572300A) available brazil wax is refer to as note
Slow-release material or suspending agent of agent etc. are penetrated, but for specific technology of preparing scheme (such as composition of formula) and its clinical effectiveness
All do not disclose or clearly discuss Deng core content.
We observe during anti-parasite medicine long-acting injection is developed：(1) containing vegetable oil and brazil wax
Oily injection, obvious long-acting is had more than oily injection prepared by alone vegetable oil；(2) drug concentration is to preparation
Slow releasing function have a significant effect, when preparation of traditional Chinese medicine concentration brings up to certain level, effective blood medicine in sheep body is dense
Spending the duration is obviously prolonged；(3) brazil wax and glyceryl monooleate combination application, slow release effect are more preferable.As can be seen here, with plant
Thing oil and brazil wax prepare the Avermectins containing higher concentration with vegetable oil, brazil wax and glyceryl monooleate (GMO)
The veterinary injection of anti-parasite medicine, has good commercial promise.
The content of the invention
The present invention will be described in detail with brazil wax or be prepared with brazil wax/glyceryl monooleate containing anti-parasite medicine
Long-acting injection.
1st, preparation is constituted：
Preparation includes anti-parasite medicine；Brazil wax；Vegetable oil or ethyl oleate or Ergol, they can it is a kind of with
On be used together.
Described anti-parasite medicine include one kind in Avermectins medicine, praziquantel, oxfendazole or it is a kind of with
On composition.Avermectins medicine includes AVM, ivermectin, doractin, Eprinomectin, Moses
Rhzomorph.They are mainly used in animal parasitosis preventing and treating in veterinary clinic, and (Zhu Mozhong is edited, veterinary drug handbook, and chemical industry is published
Society, July the 1st edition, the 167-174 pages in 2002).In the formulation, the concentration of Avermectins medicine is 1-15%, weight/body
Product ratio.Find under study for action, when AVM concentration reaches 3% or more than 3% in preparation, the slow releasing function of preparation substantially adds
By force (see embodiment 3).Therefore, from the consideration of durative action preparation angle is prepared, concentration of the Avermectins medicine in finish is more than 3%
More preferably.Consider the weight of animals size, wish the factors such as the duration of efficacy and dosage that reach, for pig or sheep
Preparation, drug concentration in 3-4% (weight/volume) preferably；For the preparation of the big animal such as ox, horse, drug concentration is 6%
(weight/volume) left and right is suitable；The semi-solid finish of the brazil wax containing high concentration is prepared, drug concentration is that 10-15% is suitable.Pyrrole
The suitable concentration of quinoline ketone or oxfendazole in the formulation is 8-20%, weight/volume.
Described brazil wax is also known as Brazil wax, and its concentration in the formulation is 0.7-10%.In finite concentration scope
Interior, the concentration of brazil wax is bigger, the drug release of preparation hold time it is also longer (see embodiment 2), but during brazil wax excessive concentration, meeting
Make preparation excessively sticky, the increase of adhesion rate needs larger thrust during injection, and needs longer time to complete injection process,
To using bringing inconvenience.In this preparation, the upper limit of brazil wax concentration is that should have preferable mobility by preparation or can be light
Pine by No. 16 needle for injection (semisolid preparation), while adherence and desired duration of efficacy referring also to decoction
Determined etc. key factor.Experiment shows that brazil wax preferable concentration range in this preparation is 0.7-6%, weight/volume
Than；When brazil wax concentration is less than 2% in preparation, the mobility and adherence of preparation are in acceptable state, with concentration
Further increase, viscosity increase is notable, when brazil wax concentration is more than 5%, be adapted to prepare semi-solid state, require the drug release phase
Longer finish, the suitable syringe of finish of this semi-solid state is (directly filling in injection by finish as packing container
In device), and drug concentration should improve as far as possible, can so overcome because adherence and caused by finish loss, it is possible to
Volume injected is reduced by improving drug concentration, to overcome the deficiencies such as administration difficulty.It is adapted to prepare brazil wax containing high concentration, contains
The characteristics of anti-parasite medicine of the semi-solid finish of high concentration medicine should possess active height, security is good, Avermectins medicine
Thing is the anti-parasitism of wide spectrum for being applied to clinical active highest (minimum effective dose is 0.01mg/kg b.w.) so far
Worm medicine.The semi-solid finish prepared with Avermectins medicine, with high dose subcutaneous administrations, duration of efficacy is notable
Extension, the semi-solid finish such as containing ivermectin 15% and brazil wax 6.5% is prevented and treated for Wintering Period sheep parasite disease, pressed
1.5mg/kg b.w. dosage, single subcutaneous injection, duration of efficacy is 103 days or longer (see embodiment 10)；For
Ox presses 1.5mg/kg b.w. dosage, lard of the single subcutaneous injection (implantation) containing ivermectin 15% and brazil wax 6.5%
Agent, effective blood drug concentration is held time up to 125 days (see embodiment 11).In addition, brazil wax may also function as in this finish
The effect of suspending agent.
GMO is a kind of monoglyceride class compound synthesized by glycerine and oleic acid, in a medicament generally as emulsifying agent or
Dispersant is used.Due to GMO have in vivo absorb moisture reach the characteristic undergone phase transition after 35% balanced contents (by laminar flow
Shape is converted into highly viscous Emission in Cubic), therefore, inquired into prepare the report of in-situ gelling long-acting injection very using GMO in recent years
It is many, and have commodity listing.We are had found during recipe determination, and appropriate GMO is added in preparation, can not only be overcome because planting
The deficiency (see embodiment 1) of medicament adhesion rate increase that brazil wax is caused is added in thing oil, more importantly, GMO is contained simultaneously
With the finish of brazil wax, its slow releasing function is remarkably reinforced, better than the only finish containing brazil wax, also superior to only contain vegetable oil and
GMO finish (see embodiment 4).Therefore, when preparing invention formulation, the sustained release effect of preparation can be improved by adding GMO
Really.GMO suitable concentration is 3-20% in preparation, and more preferable concentration is 8-12%, weight/volume.In addition, also being seen in experiment
Observe, the finish containing GMO and brazil wax is injected in water, the hydrophobicity agglomerate of formation does not dissipate closely, moisture is difficult to penetrate into, and this is carried
Show us, add the raising of slow releasing function after GMO, it appears that there is the characteristic of phase transformation without direct substantial connection with GMO.
Described vegetable oil is injection vegetable oil, preferably in soybean oil, corn oil, tea-seed oil, cottonseed oil, castor oil
It is a kind of.These vegetable oil are more used for the preparation of long-acting veterinary injection as medicinal solvent or oiliness decentralized medium
(such as patent CN102316876A, CN101703776A, CN104095812A, CN1215331A, CN1421199A, WO 00/
35445 etc.).Appropriate ethyl oleate or Ergol is added in the finish prepared with vegetable oil, it is possible to decrease finish it is viscous
Degree, and the solvability to Avermectins medicine can be improved, therefore suitable ratio is selected by vegetable oil and Ergol
Or ethyl oleate is applied in combination, the preferable finish of mobility can be prepared；Prepare the finish of the Avermectins medicine containing high concentration
When, adding appropriate Ergol can make preparation drug effect come soon, while preparation does not lose its long-term effect.
Due to there is oxidizable composition in preparation, therefore such as vegetable oil, ethyl oleate, (are not filling such as when necessary
In the case of nitrogen embedding), also need in finish to add antioxidant, the antioxidant of selection is tertiary butyl-4-hydroxy anisole
(BHA), the mixing of dibutyl hydroxy toluene (BHT) or one or more kinds of any ratios in propylgallate (PG)
Thing, the suitable concentration of antioxidant in the formulation is 0.1-0.5g/1000ml.In order to mitigate in the pain induced during injection, preparation
Appropriate local analgesia agent should be also added, the local analgesia agent of selection is phenmethylol, and its suitable concentration is 10-20g/1000ml systems
Agent.
2nd, preparation method：
This agent preparation process should be carried out aseptically, and the preparation method of selection is：
Active ingredient is dissolved with the 1.5-2 times of ethyl acetate measured, active ingredient/ethyl acetate solution is obtained；By brazil wax
Mixed with vegetable oil, be heated to 85-90 DEG C, after after brazil wax dissolving, mixed with active ingredient/ethyl acetate solution, in stirring
Under ethyl acetate is removed under reduced pressure, be cooled to room temperature, add remaining other compositions, homogenized with high-speed shearing machine, produce this oil
Agent.Or mix brazil wax with vegetable oil, 85-90 DEG C is heated to, after after brazil wax dissolving, under agitation, room temperature is down to,
Active ingredient and remaining other compositions are added, active ingredient particle diameter is ground to high-shear homogenizing machine or colloid mill less than 15 μ
M, produces this finish.Or mix active ingredient, brazil wax and other auxiliary material compositions, cross pipeline high shear grinding
Machine, through grinding repeatedly, diameter of aspirin particle is ground to less than 15 μm, this finish is produced.
3rd, the adherence of finish and easy assay method：
In general, when including the slow-release material with increase formulation viscosity in finish, have a certain amount of medicament and glue
On the chamber wall for containing medicament, in use, it is unnet with syringe extraction, so as to cause medicament to lose；Adhere in bottle wall
Medicament it is more, lose it is bigger.In the present invention, the part pharmaceutical quantities adhered in bottle wall are accounted for the weight of total pharmaceutical quantities/bottle
Measure percentage, referred to as adhesion rate (%)；The adhesion rate increase of finish, its commodity value declines, and finish level of adhesion is got over
Greatly, show that the viscosity of finish is bigger, the strength needed for extracting decoction and injection liquid with syringe can be bigger, cause administration time-consuming
Arduously, labor intensity and labor cost are added, and often induces the stress reaction and pain reaction of animal and is more strengthened
It is strong.It is presently believed that as the primary dcreening operation index of finish, the sliminess of preparation is reflected with adhesion rate, more intuitively, more practical,
And determine simple, it is easy to operate.The measure of adhesion rate is adopted in the present invention is carried out with the following method.
The finish prepared is filled to (the W that weighed1) 25ml cillin bottles in, per bottled amount be 25ml, it is filled
Finish, weigh (W2), W2-W1As 25ml dose weight (W3).Jumped a queue after weighing, Zha Gai, be stored at room temperature 1 month.During measure,
It is reciprocal to shake per bottle liquid medicine, it is allowed to be sufficiently mixed, after standing 10 minutes, removes aluminium lid and plug, pour out decoction, and keep bottle
It is inverted 3 minutes, weighs the dose weight (W poured out4), (W3-W4)/W3X 100 is the adhesion rate (%) of medicament.
The adherence of invention formulation is determined with above method, as a result display is (see embodiment 1)：(1) brazil wax in finish
Concentration is bigger, and adhesion rate is bigger；(2) finish containing GMO, its adhesion rate is significantly lower than the finish without GMO.
Embodiment
Influence of the GMO presence to finish adhesion rate (%) in embodiment 1, brazil wax concentration and preparation
During finish 1 to finish 7 is the final volume that finish is added to using soybean oil as decentralized medium and with soybean oil, finish in table
AVM concentration (%), brazil wax concentration (%), GMO concentration (%), are weight/volume percent concentration；Finish is adhered
The measure of rate is carried out by the method described in the above content of the invention, and adhesion rate (%) is being averaged for 3 parallel samples in following table
Value, measure temperature is room temperature (21-24 DEG C).
It is as follows with the preparation process of oil agent 1 to finish 7：
Brazil wax is mixed with soybean oil, at 85-90 DEG C, dissolves brazil wax, transparent oil solution is obtained, is down to after room temperature,
AVM and GMO (finish 5, finish 7) are added, with high-shear homogenizer under the conditions of 12000-16000r/min, instead
Complex shears cuts grinding 1 hour, produces finish 1- finishes 7.
The formula composition for comparing finish 1 to finish 3 is visible, and brazil wax concentration is bigger in finish, and adhesion rate is higher；Compare oily
The formula of agent 4 and finish 5, finish 6 and finish 7 constitutes visible, finish 5 and finish 7 comprising GMO, and its adhesion rate, which is less than, to be free of
GMO finish 4, finish 6；When brazil wax concentration reaches 5%, adhesion rate is more than 8%, therefore, and brazil wax concentration is more than 5%
The unsuitable bottle of finish is adapted to special plastic injector as the container for containing finish as packing container.
The blood concentration inspection after finish 1, finish 2, finish 3 and Comparative formulation in embodiment 2, sheep injection embodiment 1
Survey.
(1) preparation of Comparative formulation：It is 96% (B to take purity1aContent) AVM 5.21g, it is mixed with 497ml soybean oils
Close, with high-shear homogenizer under the conditions of 12000-16000r/min, shear 1 hour, produced containing AVM 1% repeatedly
Comparative formulation.
(2) experimental animal, administration and blood specimen collection：Healthy sheep (Small-fat-tail sheep) 20 of the body weight at 38-45 kilograms is selected,
4 groups are randomly divided into, every group 5, numbering is group 1, group 2, group 3, group 4 respectively, and Comparative formulation 0.4mg/kg is subcutaneously injected in 1 neck of group
B.w., group 2, group 3, group 4 inject finish 1, finish 2, the finish 3 in embodiment 1 respectively, and neck is subcutaneously injected, and dosage is equal
For 0.4mg/kg b.w..Taken a blood sample on time from sheep jugular vein after administration, every time accurate blood sampling 4ml, by the same test group same time
The blood sample of collection is put into 20ml centrifuge tubes of the same branch containing liquaemin, is centrifuged 10min with 3000r/min after mixing, is taken
Layer liquid (blood plasma), is placed in -18 to -20 DEG C of preservations.
(3) AVM is detected in blood sample treatments and blood plasma：The detection method of AVM is pressed in blood sample treatments and blood plasma
Document [Pan Baoliang, Wang Yuwan, Wang Ming, avermectins long-effective parenteral solution (oil suspending agent) and medicine of the normal injection in sheep body
For dynamics comparative studies, Chinese veterinary drug magazine, 2003,37 (3)：18-21] in method carry out, testing result is shown in Table 1.
Table 1, the finish 1- finishes 3 in sheep injection embodiment 1 and the blood concentration (ng/ml) after Comparative formulation
In general, the blood concentration-time data of sustained release preparation are not suitable for entering line number with classical pharmacokinetic model
According to analysis.On the premise of not considering to carry out pharmacokinetic parameter system-computed, commented using blood levels in animal body
During the method screening formula estimated, blood sample only can be gathered at the representational time point for the drug effect maintenance period for requiring to reach, and
By the same group of blood sample with the time with after mixed in equal amounts carry out blood plasma separation, pretreatment and detect.So do, the detection limit of sample
Can pole substantially reduce, so as to greatly reduce workload, be beneficial to using blood concentration detect means carry out more extensively, more section
And the recipe determination closer to actual (being compared with external simulation test).Published result of the test and clinical practice are aobvious
Show, the commercially available 1% ivermectin injection or 1% AVM prepared using 1,2-PD and formal glycerine as cosolvent
Injection, with 0.2mg/kg b.w. dosage, single gives sheep to be subcutaneously injected, and duration of efficacy was up to 18 days or so, the
21 days or so blood levels about 0.2ng/ml；With 0.4mg/kg b.w. dosage, single is subcutaneously injected to sheep, drug effect
Hold time up to 26-28 days, the 26th day or so blood levels about 0.5ng/ml.
Based on above-mentioned, in the formulation screening test scheme of present study, the requirement drafted is screened the effect that preparation reaches
It is really：It is administered with 0.4mg/kg b.w. dosage, the 3rd day to the 5th day blood concentration is if reach minimum effective blood upon administration
More than 10 times (being more than 10ng/ml) of concentration, and the 36th day or so upon administration, blood concentration remains to be maintained at 2ng/ml
(reported in literature, AVM or ivermectin are dense to minimum effective blood medicine of ox, the internal nematode of sheep and vermin for level
Spend for 0.5-1.0ng/ml), the preparation that is screened of such blood levels is can reach, just there is necessity of commercial development.Base
In this, this experiment have selected two representational time point collection blood samples, to understand the slow release effect for being screened finish.First
Individual blood sampling time point is the 3rd day and the 5th day upon administration, and time point of second collection blood sample is the 36th day and the upon administration
38 days.Data are detected from table 1, result of the test shows certain regularity, and gives notable difference
As a result：The 36th day to 38 days upon administration, the finish blood concentration without brazil wax was significantly lower than the finish containing brazil wax, with
The concentration increase of brazil wax in the formulation, the blood levels of the 36-38 days are improving.When brazil wax concentration reaches in preparation
(such as finish 3, brazil wax concentration is that 5%), can more effectively delay insoluble drug release, upon administration the 38th day, blood during certain level
Concentration is still in gratifying level of significance.
The detection of blood concentration after embodiment 3, the finish 2 in sheep injection embodiment 1, finish 4, finish 6.
(1) experimental animal, administration and blood specimen collection：Select healthy sheep (Small-fat-tail sheep) 15 of the body weight at 40 kilograms or so
Only, 3 groups are randomly divided into, every group 5, finish 2, finish 4, finish 6 in embodiment 1 is subcutaneously injected in neck respectively, to medicament
Amount is 0.4mg/kg b.w..Taken a blood sample on time from sheep jugular vein after administration, accurate blood sampling 4ml, same by same test group every time
The time blood sample of collection is put into 20ml centrifuge tubes of the same branch containing liquaemin, and 10min is centrifuged with 3000r/min after mixing,
Upper liquid (blood plasma) is taken, -18 to -20 DEG C of preservations are placed in.
(2) AVM is detected in blood sample treatments and blood plasma：The detection method of AVM is same in blood sample treatments and blood plasma
Embodiment 2, result of the test is shown in Table 2.
The blood concentration (ng/ml) after finish 2, finish 4 and finish 6 in table 2, sheep injection embodiment 1
As seen from Table 2, when preparation of traditional Chinese medicine concentration reaches more than 3%, slow releasing function is significantly improved, therefore, uses plant
During long-acting veterinary injection to prepare the anti-parasite medicine containing Avermectins of oil and brazil wax, the drug concentration in preparation reaches
During to more than 3%, there can be more preferable clinical effectiveness (long-acting).
The detection of blood concentration after embodiment 4, the finish 4 in sheep injection embodiment 1, finish 5 and Comparative formulation.
(1) preparation of Comparative formulation：It is 96% (B to take purity1aContent) AVM 9.375g mixed with GMO 30g,
Addition soybean oil is to 300ml, with high-shear homogenizer under the conditions of 12000-16000r/min, repeatedly shearing 1 hour, i.e.,
The Comparative formulation of AVM 3% must be contained.
(2) experimental animal, administration and blood specimen collection：Body weight is selected close to the healthy sheep (Small-fat-tail sheep) 24 of (about 40 kilograms)
Only, 4 groups, every group 6, the 1st group, the 2nd group, the 3rd group of finish 4, oil respectively in neck hypodermic injection embodiment 1 are randomly divided into
Agent 5 and Comparative formulation, dosage are 0.4mg/kg b.w., the 4th group of dose subcutaneous injection oil by 0.8mg/kg b.w.
Agent 5；Taken a blood sample on time from sheep jugular vein after administration, every time accurate blood sampling 4ml, the blood sample of the same time collection of same test group is put
Enter into 20ml centrifuge tube of the same branch containing liquaemin, 10min is centrifuged with 3000r/min after mixing, upper liquid (blood plasma) is taken, puts
In -18 to -20 DEG C of preservations.
(3) AVM is detected in blood sample treatments and blood plasma：The detection method of AVM is same in blood sample treatments and blood plasma
Embodiment 2, testing result is shown in Table 3.
The blood concentration (ng/ml) after finish 4, finish 5 and Comparative formulation in table 3, sheep injection embodiment 1
As seen from Table 3, in preparation containing GMO and brazil wax the slow releasing function of finish 5 (the 2nd group) is better than only containing Brazil
The finish 4 (the 1st group) of wax, is compared, both significant differences with the Comparative formulation (the 3rd group) only containing GMO.The result of the test table
It is bright, by the way that GMO is applied in combination with brazil wax, duration of efficacy can be extended.Compare the 2nd group of (dosage 0.4mg/kg
B.w. it is) visible with the 4th group of (dosage 0.8mg/kg b.w.) result of the test, increase dosage, can effectively improve the later stage
The blood levels of (after administration the 36-45 days).This teaches that finish of the present invention is when in use by increasing to medicament
Amount, can effectively extend the drug action time.
In summary embodiment 2, embodiment 3, the result of the test of embodiment 4 are visible, by aligning brazil wax concentration, medicine
Whether is the addition of concentration, dosage and GMO, and the long-acting injection with Expected Results can be made.
Embodiment 5, the preparation of several 3.6% ivermectin injections and the prevention effect to sheep itch mite
(1) preparation of preparation
Preparation a：It is 97% (B to take brazil wax 20g, GMO 100g, purity1aContent) ivermectin 37.11g, add oil
Acetoacetic ester is settled to 1 liter, is sufficiently mixed, and in 80-90 DEG C, brazil wax is completely dissolved, room temperature is down to, and uses high-shear homogeneous
Machine is sheared 1 hour under the conditions of 12000-16000r/min, produces preparation a repeatedly.
Preparation b：It is 97% (B to take brazil wax 20g, purity1aContent) ivermectin 37.11g, add ethyl oleate constant volume
To 1 liter, it is sufficiently mixed, in 80-90 DEG C, brazil wax is completely dissolved, room temperature is down to, with high-shear homogenizer in 12000-
Under the conditions of 16000r/min, shear 1 hour repeatedly, produce preparation b.
Preparation c：It is 97% (B to take GMO 100g, purity1aContent) ivermectin 37.11g, add ethyl oleate constant volume
To 1 liter, it is sufficiently mixed, in 80-90 DEG C, ivermectin is completely dissolved, room temperature is down to, is existed with high-shear homogenizer
Under the conditions of 12000-16000r/min, shear 1 hour repeatedly, produce preparation c.
Preparation d：It is 97% (B to take purity1aContent) ivermectin 37.11g, 1 liter is settled to ethyl oleate, with a high speed
Shear homogenizer is sheared 1 hour under the conditions of 12000-16000r/min, produces preparation d repeatedly.
(2) evaluation of clinical curative effect
Experimental animal is 50 sheep for having made a definite diagnosis infection itch mite, and body weight is 30-45 kilograms, random point 5 groups, every group 10
Only.1st group is not gone and buy Chinese medicine；2nd group, the 3rd group, the 4th group, the 5th group of sheep distinguishes subcutaneous injection formulation a, preparation b, preparation c, system
Agent d.Dosage is 0.4mg/kg b.w., and group's stable breeding 55 days is mixed after administration.Result of the test is as follows：
1st group, 10 sheep can detect mite living during 0-55 days.
2nd group (ejection preparation a), upon administration the 8-11 days it is all infection itch mites sheep be all controlled effectively,
Net rate is driven up to 100%；In the 47th day after administration, there is 1 sheep to be detected mite living, this explanation preparation a duration of efficacy connects
It is bordering on 47 days.
3rd group (ejection preparation b), upon administration the 10-13 days it is all infection itch mites sheep be all controlled effectively,
Net rate is driven up to 100%；In the 44th day after administration, there are 2 sheep to be detected mite living, this explanation preparation b duration of efficacy connects
It is bordering on 44 days.
4th group (the 7-11 days all sheep for infecting itch mites are all controlled effectively ejection preparation c) upon administration, drive
Net rate is up to 100%；In the 35th day after administration, there are 2 sheep to be detected mite living, this explanation preparation c duration of efficacy is approached
In 35 days.
5th group (the 9-12 days all sheep for infecting itch mites are all controlled effectively ejection preparation d) upon administration, drive
Net rate is up to 100%；In the 36th day after administration, there are 3 sheep to be detected mite living, this explanation preparation d duration of efficacy close to
36 days.
Embodiment 6,6% Eprinomectin parenteral solution of preparation
The Eprinomectin 13.2g that purity is 90% is taken, is dissolved with 28ml ethyl acetate；By brazil wax 3g, GMO
10g, mixes with ethyl oleate 120ml and Ergol 60ml, in 80-90 DEG C of water-bath, dissolves brazil wax；Acetyl will be contained
The solution of amido AVM and the solution mixing containing brazil wax, are down to room temperature under agitation, with high speed shearing abrasive machine,
14000r/min, fully shearing 1 hour, obtain 6% Eprinomectin parenteral solution.
Embodiment 7,10% oxfendazole's injection of preparation
20g oxfendazoles, 2g brazil waxs, plus tea-seed oil are taken to 200ml, with high speed shearing abrasive machine, in 14000r/min,
Fully shearing, the particle diameter to oxfendazole is less than 5 μm, obtains 10% oxfendazole's parenteral solution.
Embodiment 8, the oily injection of 15% praziquantel of preparation
Preparation is constituted：Praziquantel 15% (folding hundred is counted), weight/volume；Brazil wax 6.5%, weight/volume；GMO
10%, weight/volume；BHT 0.03%, weight/volume；Injection tea-seed oil adds to final volume.
Preparation method：Praziquantel is mixed with tea-seed oil, is fully ground to praziquantel particle diameter and is less than 20 μm, brazil wax is added
And GMO, 80-90 DEG C is heated to, brazil wax is completely dissolved, 50-55 DEG C is cooled under agitation, high shear homogeneous is used
Finish is filled in 5ml plastic injectors that (sealing ring material is silicon by machine, further shear treatment, and under this temperature conditions
Glue), produce this preparation.
Embodiment 9, the oily injection of 15% ivermectin of preparation
Preparation is constituted：Ivermectin 15% (folding hundred is counted), weight/volume；Brazil wax 6.5%, weight/volume；GMO
10%, weight/volume；BHT 0.03%, weight/volume；Injection tea-seed oil adds to final volume.
Preparation method：Ivermectin is mixed with tea-seed oil, it is 15 μm or so to be fully ground to ivermectin particle diameter, is added
Brazil wax and GMO, are heated to 80-90 DEG C, are completely dissolved brazil wax, and 50-55 DEG C is cooled under agitation, use high shear
Homogenizer, further shear treatment, and under this temperature conditions, finish is filled in 5ml plastic injectors (sealing ring material
For silica gel), produce this preparation.
Embodiment 10, the oily injection of embodiment 9 are used for the clinical trial of sheep preventing and treating verminosis
Experiment for the disease preventing and treating of Wintering Period sheep itch mite.The sheep 71 (a group) put in a suitable place to breed is selected, two groups are randomly divided into, the
1 group 20, the 2nd group 51.1% commercially available ivermectin injection of 1st group of hypodermic injection is (sweet with 1,2-PD, formaldehyde contracting
It is prepared by oil), dosage is 1.5mg/kg b.w., the oily injection 1.5mg/kg b.w. of the 2nd group of hypodermic injection embodiment 9,
Itch mite infection conditions are inspected periodically after administration, result of the test is as follows：
1st group has 4 sheep to infect itch mite before administration, upon administration the 12nd day check, 20 sheep check less than
Mite living is present；1 sheep of detection in the 36th day infects itch mite again upon administration, and 12 sheep of detection in the 41st day infect scabies again
Mite.
2nd group has 13 sheep to infect itch mite before administration, upon administration the 12nd day check, 51 sheep check less than
Mite living.The 103rd day upon administration detects mite living on 2 sheep bodies, and 11 sheep of detection in 117 days after administration are felt again
Contaminate itch mite.
The detection of embodiment 11, oily injection blood concentration in ox body of embodiment 9
(1) experimental animal, administration and blood specimen collection：The healthy ox 6 that body weight is 190-220 kilograms is selected, respectively in ox
The oily injection (with No. 16 syringe needles) of ear dorsal sc injection embodiment 9, dosage is 1.5mg/kg b.w., after administration
Taken a blood sample on time from bovine jugular vein, every time accurate blood sampling 3ml, the blood sample for 6 oxen that the same time is gathered injects same branch and contains liver
In the 20ml centrifuge tubes of plain sodium, 10min is centrifuged with 3000r/min after mixing, upper liquid (blood plasma) is taken, is placed in -18 to -20 DEG C of guarantors
Deposit.
(2) ivermectin is detected in blood sample treatments and blood plasma：The detection of ivermectin is with reference to real in blood sample treatments and blood plasma
The detection method for applying AVM in example 2 is carried out, and result of the test is shown in Table 4.
Plasma ivermectin concentrations (ng/ml) after the preparation of (1.5mg/kg b.w.) embodiment 9 are subcutaneously injected in 4 Ns of table
Claims (4)
1. a kind of injection containing brazil wax, it is characterised in that following each component is included in every 1000ml injections：
Described anti-parasite medicine is one kind or one kind in Avermectins anti-parasite medicine, praziquantel, oxfendazole
Composition above；
Described Avermectins anti-parasite medicine is AVM, ivermectin, doractin, acetamido Avermectin
Element, moxidectin；
Described oil medium is one or more kinds of combinations in injection vegetable oil, ethyl oleate, Ergol
Thing；Described vegetable oil is one kind in injection soybean oil, corn oil, tea-seed oil, cottonseed oil, castor oil；
Described antioxidant be tertiary butyl-4-hydroxy anisole, dibutyl hydroxy toluene or propylgallate in one kind or
More than one composition；
The preparation method of the injection includes：
It will be dissolved as the anti-parasite medicine of active component with the 1.5-2 times of ethyl acetate measured, obtain active ingredient/acetic acid
Ethyl ester solution；Brazil wax is mixed with the oil medium, 85-90 DEG C is heated to, after brazil wax dissolving after, with active ingredient/
Ethyl acetate solution is mixed, and ethyl acetate is removed under reduced pressure under agitation, is cooled to room temperature, remaining other compositions is added, with height
Fast cutter homogenizes, and produces this injection；
Or mix brazil wax with oil medium, 85-90 DEG C is heated to, after after brazil wax dissolving, under agitation, room is down to
Temperature, adds the anti-parasite medicine and remaining other compositions as active ingredient, with high-shear homogenizing machine or colloid mill
Active ingredient particle diameter is ground to less than 15 μm, this injection is produced；
Or will be mixed as the anti-parasite medicine of active ingredient, brazil wax and other auxiliary material compositions, cross pipeline
Formula high shear grinding machine, through grinding repeatedly, diameter of aspirin particle is ground to less than 15 μm, this injection is produced.
2. the injection as described in claim 1, it is characterised in that following each component is included in every 1000ml injections：
3. the injection as described in claim 1, it is characterised in that following each component is included in every 1000ml injections：
4. the injection as described in claim 1, it is characterised in that following each component is included in every 1000ml injections：
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1444925A (en) * | 2002-03-19 | 2003-10-01 | 王玉万 | Long acting injection containing ethyl cellulose for animal |
| CN1461640A (en) * | 2002-05-31 | 2003-12-17 | 王玉万 | Slow releasing injection contg. antiparasitic medicine |
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2015
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1444925A (en) * | 2002-03-19 | 2003-10-01 | 王玉万 | Long acting injection containing ethyl cellulose for animal |
| CN1461640A (en) * | 2002-05-31 | 2003-12-17 | 王玉万 | Slow releasing injection contg. antiparasitic medicine |
Non-Patent Citations (1)
| Title |
|---|
| "注射型原位凝胶植入剂的研究进展";董吉等;《药学进展》;20071231;第31卷(第3期);第109-113页 * |
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