CN1739542A - Ivermectin Microsphere Sustained Release Solid Dosage - Google Patents
Ivermectin Microsphere Sustained Release Solid Dosage Download PDFInfo
- Publication number
- CN1739542A CN1739542A CN 200510029294 CN200510029294A CN1739542A CN 1739542 A CN1739542 A CN 1739542A CN 200510029294 CN200510029294 CN 200510029294 CN 200510029294 A CN200510029294 A CN 200510029294A CN 1739542 A CN1739542 A CN 1739542A
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- CN
- China
- Prior art keywords
- ivermectin
- microballoon
- alcohol
- soluble protein
- slowly releasing
- Prior art date
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- 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 title claims abstract description 51
- 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 title claims abstract description 51
- 229960002418 ivermectin Drugs 0.000 title claims abstract description 51
- 239000007787 solid Substances 0.000 title claims abstract description 12
- 239000004005 microsphere Substances 0.000 title claims description 28
- 238000013268 sustained release Methods 0.000 title 1
- 239000012730 sustained-release form Substances 0.000 title 1
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 45
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 45
- 238000002360 preparation method Methods 0.000 claims abstract description 12
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 6
- 239000004094 surface-active agent Substances 0.000 claims abstract description 5
- 239000011734 sodium Substances 0.000 claims description 8
- 229920002472 Starch Polymers 0.000 claims description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 6
- 239000008107 starch Substances 0.000 claims description 6
- 235000019698 starch Nutrition 0.000 claims description 6
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 5
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 4
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 4
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims description 4
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 claims description 4
- 239000000945 filler Substances 0.000 claims description 4
- 239000008103 glucose Substances 0.000 claims description 4
- 240000005979 Hordeum vulgare Species 0.000 claims description 3
- 235000007340 Hordeum vulgare Nutrition 0.000 claims description 3
- 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 claims description 3
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 3
- 240000008042 Zea mays Species 0.000 claims description 3
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 claims description 3
- 235000002017 Zea mays subsp mays Nutrition 0.000 claims description 3
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 3
- 239000001506 calcium phosphate Substances 0.000 claims description 3
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 3
- 235000013539 calcium stearate Nutrition 0.000 claims description 3
- 239000008116 calcium stearate Substances 0.000 claims description 3
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 3
- 235000005822 corn Nutrition 0.000 claims description 3
- 235000019700 dicalcium phosphate Nutrition 0.000 claims description 3
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 claims description 3
- 235000019359 magnesium stearate Nutrition 0.000 claims description 3
- 210000000582 semen Anatomy 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 claims description 3
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 3
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 3
- 235000019731 tricalcium phosphate Nutrition 0.000 claims description 3
- 229940078499 tricalcium phosphate Drugs 0.000 claims description 3
- 229910000391 tricalcium phosphate Inorganic materials 0.000 claims description 3
- 229930192734 Avilamycin Natural products 0.000 claims description 2
- 239000004190 Avilamycin Substances 0.000 claims description 2
- 241000283153 Cetacea Species 0.000 claims description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 2
- 229960005185 avilamycin Drugs 0.000 claims description 2
- 235000019379 avilamycin Nutrition 0.000 claims description 2
- 150000002432 hydroperoxides Chemical class 0.000 claims description 2
- 239000003120 macrolide antibiotic agent Substances 0.000 claims description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims description 2
- 235000019341 magnesium sulphate Nutrition 0.000 claims description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 claims description 2
- 235000011152 sodium sulphate Nutrition 0.000 claims description 2
- 235000011132 calcium sulphate Nutrition 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 42
- 230000000694 effects Effects 0.000 abstract description 12
- 241001465754 Metazoa Species 0.000 abstract description 4
- 239000000463 material Substances 0.000 abstract description 2
- 244000045947 parasite Species 0.000 abstract description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract 3
- 230000000844 anti-bacterial effect Effects 0.000 abstract 1
- 239000011248 coating agent Substances 0.000 abstract 1
- 238000000576 coating method Methods 0.000 abstract 1
- 238000013270 controlled release Methods 0.000 abstract 1
- 239000003826 tablet Substances 0.000 description 26
- 229940079593 drug Drugs 0.000 description 23
- 230000002045 lasting effect Effects 0.000 description 7
- 239000007939 sustained release tablet Substances 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- 241000282472 Canis lupus familiaris Species 0.000 description 6
- 239000008280 blood Substances 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 238000000748 compression moulding Methods 0.000 description 5
- 238000000465 moulding Methods 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 241001494479 Pecora Species 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 239000005645 nematicide Substances 0.000 description 2
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 2
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- AZSNMRSAGSSBNP-XPNPUAGNSA-N 22,23-dihydroavermectin B1a Chemical compound 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 AZSNMRSAGSSBNP-XPNPUAGNSA-N 0.000 description 1
- 239000005660 Abamectin Substances 0.000 description 1
- 241000186046 Actinomyces Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 206010061217 Infestation Diseases 0.000 description 1
- 241000244206 Nematoda Species 0.000 description 1
- 208000030852 Parasitic disease Diseases 0.000 description 1
- 241001468227 Streptomyces avermitilis Species 0.000 description 1
- XIRGHRXBGGPPKY-OTPQUNEMSA-N [(2r,3s,4r,6s)-6-[(2'r,3's,3ar,4r,4'r,6s,7ar)-6-[(2s,3r,4r,5s,6r)-2-[(2r,3s,4s,5s,6s)-6-[(2r,3as,3'ar,6'r,7r,7's,7ar,7'ar)-7'-acetyl-7'-hydroxy-6'-methyl-7-(2-methylpropanoyloxy)spiro[4,6,7,7a-tetrahydro-3ah-[1,3]dioxolo[4,5-c]pyran-2,4'-6,7a-dihydro-3ah- Chemical compound O([C@H]1[C@H](O)C[C@@H](O[C@@H]1C)O[C@H]1[C@H](O)CC2(O[C@]3(C)C[C@@H](O[C@H](C)[C@H]3O2)O[C@H]2[C@@H](OC)[C@@H](C)O[C@H]([C@@H]2O)O[C@H]2[C@H](O)[C@H](OC)[C@H](OC3[C@@H]([C@@H]4O[C@]5(O[C@H]4CO3)[C@@H]3OCO[C@H]3[C@@](O)([C@@H](C)O5)C(C)=O)OC(=O)C(C)C)O[C@@H]2COC)O[C@@H]1C)C(=O)C1=C(C)C(Cl)=C(O)C(Cl)=C1OC XIRGHRXBGGPPKY-OTPQUNEMSA-N 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000002141 anti-parasite Effects 0.000 description 1
- RRZXIRBKKLTSOM-XPNPUAGNSA-N avermectin B1a Chemical compound C1=C[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 RRZXIRBKKLTSOM-XPNPUAGNSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 244000078703 ectoparasite Species 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000003194 forelimb Anatomy 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000002088 nanocapsule Substances 0.000 description 1
- 230000003071 parasitic effect Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The present invention belongs to the field of biotechnology. The slowly releasing solid ivermectin microballoon preparation consists of alcohol soluble botanical protein microballoon with ivermectin 3-90 wt%, stuffing 5-75 wt%, and disintegrating agent 4.5-20 wt%, except surfactant. The alcohol soluble botanical protein microballoon with ivermectin contains alcohol soluble botanical protein and ivermectin in the weight ratio of 10-60. The botanical protein microballoon is one kind of medicine carrier with wide material source, high biodegrading and biocompatibility performance, and certain bactericidal property. Coating the medicine ivermectin inside the protein microballoon results in the controlled release of the medicine and the treating effect may be maintained as long as 18-21 days so as to eliminate parasite inside or outside the animal body in once clinical treatment.
Description
Technical field
The present invention relates to a kind of solid formulation that belongs to technical field of pharmaceuticals, specifically, is a kind of slowly releasing solid ivermectin microballoon preparation.
Background technology
Parasitic disease is animal one a big class disease, and the eighties, U.S. MERCK company successfully became the anti-parasite medicine for animal use thing with the ivermectin exploitation, and was had good effect by clinical proof.At present, this medicine has had multiple dosage form, comprises oral agents such as powder, tablet, oral liquid, cream preparation, nano-capsule and injection etc., and these dosage form lasting periods are short, needs multiple dosing often at the treatment ectoparasite disease, wastes time and energy and the use cost height.In addition, injection is effective, but has the big problem of toxicity, and it is big to drift about when cream preparation uses, and permeability is relatively poor and residual effect is shorter.
Find by prior art documents, R.P.Gogolewski etc. are at " a kind of sheep is used the ivermectin tablet: the effect of treatment gastrointestinal tract nematicide and with the comparison of ivermectin liquid dosage form bioavailability " (veterinary parasitology 1995,60:297-302) in the literary composition, mention a kind of ivermectin tablet, content of dispersion is the 10mg/ sheet, be used for the treatment of the sheep stomach intestinal nematodes, show this ivermectin tablet to the therapeutic effect of nematicide adult and larva up to more than 99%, blood reaches peak concentration (C
Max) be 6.4ng/mL, area under the drug-time curve (AUC) is 9.3ngdays/mL, the bioavailability of tablet is suitable with peroral dosage form.But medicine was released very soon, absorbs at the harmonization of the stomach intestinal after its weak point was oral administration, and the lasting period is short, often needs repetitively administered, thereby increased drug cost.
Summary of the invention
The objective of the invention is to overcome the deficiencies in the prior art, a kind of slowly releasing solid ivermectin microballoon preparation is provided, make it that medicine that wraps in protein microsphere inside is discharged in the disintegrate of specified time range by medicament, drug release is controlled, easy to use, reach the purpose of treatment.
The present invention is achieved by the following technical solutions, and component of the present invention and percentage by weight thereof are: contain Phytogenous alcohol-soluble protein microsphere 3%-90%, filler 5%-75%, the disintegrating agent 4.5%-20% of ivermectin, surplus is a surfactant; The described Phytogenous alcohol-soluble protein microsphere that contains ivermectin, the weight ratio that is meant Phytogenous alcohol-soluble protein and ivermectin is 10: 1-60: 1.
Described ivermectin (Ivermectin) is the tunning of a kind of actinomyces novel species Avid kyowamycin (Streptomyces avermitilis), avilamycin (Avermectin) macrolide 22, the two hydroperoxide derivatives of 23-.
Described Phytogenous alcohol-soluble protein is a kind of corn or Semen Tritici aestivi or Fructus Hordei Vulgaris or naked barley or avenaceous protein,alcohol-soluble of deriving from.
Described filler is calcium hydrogen phosphate (CaHPO
4), tricalcium phosphate (Ca
3(HPO
4)
2), magnesium sulfate (MgSO
4), calcium sulfate (CaSO
4), in starch and the glucose any one.
Described disintegrating agent is any one in carboxymethyl starch sodium (CMS-Na), low-substituted hydroxypropyl cellulose (L-HPC), cross-linked carboxymethyl cellulose sodium (CMC-Na) and the crospolyvinylpyrrolidone (PVPP).
Described surfactant is any one in magnesium stearate, aluminum monostearate, calcium stearate, sodium laurylsulfate, the hard pure sodium sulfate of whale and the aerosol OT.
Phytogenous alcohol-soluble protein and ivermectin (IVM) mix, adopt phase separation method to obtain the medicine carrying protein microsphere, add various adjuvants to this microsphere, then incubation under the thermophilic super-humid conditions, increasing the hardness of solid dosage forms, and the disintegration time of adjusting this dosage form is to meet the requirements.
Plant source protein microsphere of the present invention is a kind of wide material sources, and biodegradable, biocompatibility is good, the pharmaceutical carrier of antibiotic property.By ivermectin being wrapped in protein microsphere inside, medicine discharges in the disintegrate of specified time range by medicament, and drug release is the characteristics that zero level discharges.The controllable release of medicine has long-lastingly, can keep more than curative effect 18-21 days, and a drug just can be got rid of responsive parasite, can be used for the clinical treatment of parasitic infestation disease inside and outside the animal fully, does not need repetitively administered.Through observing and detecting and find, three multiple dose group experimental animals all do not have adverse effect at duration of test and occur, and ivermectin microsphere sustained-release tablet toxic and side effects is little, safe, and therapeutic effect is good.Ivermectin microsphere sustained-release tablet is easy to use.Make the more commercially available conventional tablet of drug cost reduce 30%-40%.
The specific embodiment
Embodiment 1
Component of the present invention and percentage by weight thereof are: the Phytogenous alcohol-soluble protein microsphere 3%, the tricalcium phosphate (Ca that contain ivermectin
3(HPO
4)
2) 75%, carboxymethyl starch sodium (CMS-Na) 20%, surplus is an aluminum monostearate.The described Phytogenous alcohol-soluble protein microsphere that contains ivermectin, the weight ratio that is meant Phytogenous alcohol-soluble protein and ivermectin is 15: 1.Described Phytogenous alcohol-soluble protein is a kind of protein,alcohol-soluble that derives from corn.Tablet is reinforced molding at 37 ℃ ± 1 ℃ after the compression molding.Adopt LB-2B type disintegration time mensuration instrument to measure its disintegration, and investigate its fineness and hardness.The tablet disintegration time is less than 15min, and fineness and hardness are good.Drug controllable release, the medicine lasting period is long, can keep more than curative effect 18-21 days, does not need repetitively administered, and safe, therapeutic effect is good, and is easy to use, makes drug cost reduce greatly, and the more commercially available conventional tablet of drug cost reduces 30%-40%.
Embodiment 2
Component of the present invention and percentage by weight thereof are: contain Phytogenous alcohol-soluble protein microsphere 10%, starch 73.5%, the low-substituted hydroxypropyl cellulose (L-HPC) 15% of ivermectin, surplus is a sodium laurylsulfate.The described Phytogenous alcohol-soluble protein microsphere that contains ivermectin, the weight ratio that is meant Phytogenous alcohol-soluble protein and ivermectin is 10: 1.Described Phytogenous alcohol-soluble protein is a kind of protein,alcohol-soluble that derives from Semen Tritici aestivi.Tablet is reinforced molding at 37 ℃ ± 1 ℃ after the compression molding.Adopt LB-2B type disintegration time mensuration instrument to measure its disintegration, and investigate its fineness and hardness.The tablet disintegration time is less than 15min, and fineness and hardness are good.Drug controllable release, the medicine lasting period is long, can keep more than curative effect 18-21 days, does not need repetitively administered, and safe, therapeutic effect is good, and is easy to use, makes drug cost reduce greatly, and the more commercially available conventional tablet of drug cost reduces 30%-40%.
Embodiment 3
Component of the present invention and percentage by weight thereof are: the Phytogenous alcohol-soluble protein microsphere 30%, the calcium hydrogen phosphate (CaHPO that contain ivermectin
4) 50%, cross-linked carboxymethyl cellulose sodium (CMC-Na) 19%, surplus is a magnesium stearate.The described Phytogenous alcohol-soluble protein microsphere that contains ivermectin, the weight ratio that is meant Phytogenous alcohol-soluble protein and ivermectin is 15: 1.Described Phytogenous alcohol-soluble protein is a kind of protein,alcohol-soluble that derives from Fructus Hordei Vulgaris.Surplus is an adjuvant.Reinforce molding at 37 ℃ ± 1 ℃ after the compression molding.The disintegration test is the same, and investigates fineness and hardness.The tablet disintegration time is less than 15min, and fineness and hardness are good.Drug controllable release, the medicine lasting period is long, can keep more than curative effect 18-21 days, does not need repetitively administered, and safe, therapeutic effect is good, and is easy to use, makes drug cost reduce greatly, and the more commercially available conventional tablet of drug cost reduces 30%-40%.
With the domesticated dog is experimental animal.12 adult domesticated dogs, 12-15 monthly age, male and female half and half, body weight (9.80 ± 0.48) kg.Be divided into 2 groups at random, 16h fasting before the test is only freely drunk water, and duration of test is normally raised.Every group six, divide two groups: 1 group oral to dog with the foregoing description 2 microspheres prepared slow releasing tablets; 2 groups of oral commercially available ivermectin sheets.Each group is all given the dog oral administration with 0.3mg/kgbw, adopt blank blood before the administration 1 time, after the administration respectively at 1,2,3,4,5,6,8,12,24,48,72,96,120,144,168h forelimb venous blood collection, measure blood drug level, provide pharmaceutical concentration-time curve, and calculate relevant pharmacokinetic parameter.The result shows, the elimination half-life (T of ivermectin microsphere sustained-release tablet in the present embodiment and conventional tablet
1/2 β) being respectively 58.15h and 42.73h, the elimination time of microsphere sustained-release tablet in blood prolongs 15.42h than conventional tablet; Drug plasma reaches peak concentration (C
Max) be respectively (9.89 ± 0.34) ng/mL and (9.64 ± 1.05) ng/mL; Peak time (T
Max) be respectively (11.33 ± 2.63) h and (7.26 ± 2.09) h; Two kinds of medicine area under the drug-time curve (AUC) are respectively 883.87ngh/mL and 666.30ngh/mL, show that the microsphere sustained-release tablet enters the intravital dose of dog and will be higher than conventional tablet, ivermectin microsphere sustained-release tablet and conventional tablet relatively its relative bioavailability (F) are 132.65%.Enter the intravital medication amount of dog and eliminate time ratio, ivermectin microsphere sustained-release tablet pharmacokinetics characteristic is better than conventional tablet.
Embodiment 4
Component of the present invention and percentage by weight thereof are: contain Phytogenous alcohol-soluble protein microsphere 60%, glucose 30%, cross-linked carboxymethyl cellulose sodium (CMC-Na) 9.0% of ivermectin, surplus is an aerosol OT.The described Phytogenous alcohol-soluble protein microsphere that contains ivermectin, the weight ratio that is meant Phytogenous alcohol-soluble protein and ivermectin is 60: 1.Described Phytogenous alcohol-soluble protein is a kind of protein,alcohol-soluble that derives from naked barley.Tablet is reinforced molding at 37 ℃ ± 1 ℃ after the compression molding.The disintegration test is the same, and investigates its fineness and hardness.The tablet disintegration time is less than 15min, and fineness and hardness are good.Drug controllable release, the medicine lasting period is long, can keep more than curative effect 18-21 days, does not need repetitively administered, and safe, therapeutic effect is good, and is easy to use, makes drug cost reduce greatly, and the more commercially available conventional tablet of drug cost reduces 30%-40%.
Embodiment 5
Component of the present invention and percentage by weight thereof are: contain Phytogenous alcohol-soluble protein microsphere 90%, glucose 5%, the crospolyvinylpyrrolidone (PVPP) 4.5% of ivermectin, surplus is a calcium stearate.The described Phytogenous alcohol-soluble protein microsphere that contains ivermectin, the weight ratio that is meant Phytogenous alcohol-soluble protein and ivermectin is 15: 1.Described Phytogenous alcohol-soluble protein is a kind of avenaceous protein,alcohol-soluble that derives from.Tablet is reinforced molding at 37 ℃ ± 1 ℃ after the compression molding.The disintegration test is the same, and investigates its fineness and hardness.The tablet disintegration time is less than 15min, and fineness and hardness are good.Drug controllable release, the medicine lasting period is long, can keep more than curative effect 18-21 days, does not need repetitively administered, and safe, therapeutic effect is good, and is easy to use, makes drug cost reduce greatly, and the more commercially available conventional tablet of drug cost reduces 30%-40%.
Claims (6)
1. a slowly releasing solid ivermectin microballoon preparation is characterized in that, component and percentage by weight thereof are: contain Phytogenous alcohol-soluble protein microsphere 3%-90%, filler 5%-75%, the disintegrating agent 4.5%-20% of ivermectin, surplus is a surfactant; The described Phytogenous alcohol-soluble protein microsphere that contains ivermectin, the weight ratio that is meant Phytogenous alcohol-soluble protein and ivermectin is 10: 1-60: 1.
2. slowly releasing solid ivermectin microballoon preparation according to claim 1 is characterized in that, described ivermectin is the two hydroperoxide derivatives of avilamycin macrolide 22,23-.
3. slowly releasing solid ivermectin microballoon preparation according to claim 1 is characterized in that, described filler is any one in calcium hydrogen phosphate, tricalcium phosphate, magnesium sulfate, calcium sulfate, starch and the glucose.
4. slowly releasing solid ivermectin microballoon preparation according to claim 1 is characterized in that, described disintegrating agent is any one in carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, cross-linked carboxymethyl cellulose sodium and the crospolyvinylpyrrolidone.
5. slowly releasing solid ivermectin microballoon preparation according to claim 1, it is characterized in that described surfactant is any one in magnesium stearate, aluminum monostearate, calcium stearate, sodium laurylsulfate, the hard pure sodium sulfate of whale and the aerosol OT.
6. slowly releasing solid ivermectin microballoon preparation according to claim 1 is characterized in that, described Phytogenous alcohol-soluble protein is a kind of corn or Semen Tritici aestivi or Fructus Hordei Vulgaris or naked barley or avenaceous protein,alcohol-soluble of deriving from.
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| CNB2005100292941A CN100488514C (en) | 2005-09-01 | 2005-09-01 | Slowly released solid ivermectin microballoon preparation |
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| CNB2005100292941A CN100488514C (en) | 2005-09-01 | 2005-09-01 | Slowly released solid ivermectin microballoon preparation |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102302457A (en) * | 2011-09-14 | 2012-01-04 | 中国科学院近代物理研究所 | Preparation method of ivermectin sustained-release microspheres |
| CN103798232A (en) * | 2012-11-14 | 2014-05-21 | 中国农业科学院植物保护研究所 | Emamectin benzoate microsphere and preparation method thereof |
| CN107773554A (en) * | 2017-09-07 | 2018-03-09 | 华南农业大学 | A kind of ivermectin slow-releasing microcapsule and its preparation method and application |
| CN110292041A (en) * | 2019-06-18 | 2019-10-01 | 仲恺农业工程学院 | Nano pesticide preparation and preparation method thereof |
-
2005
- 2005-09-01 CN CNB2005100292941A patent/CN100488514C/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102302457A (en) * | 2011-09-14 | 2012-01-04 | 中国科学院近代物理研究所 | Preparation method of ivermectin sustained-release microspheres |
| CN103798232A (en) * | 2012-11-14 | 2014-05-21 | 中国农业科学院植物保护研究所 | Emamectin benzoate microsphere and preparation method thereof |
| CN107773554A (en) * | 2017-09-07 | 2018-03-09 | 华南农业大学 | A kind of ivermectin slow-releasing microcapsule and its preparation method and application |
| CN110292041A (en) * | 2019-06-18 | 2019-10-01 | 仲恺农业工程学院 | Nano pesticide preparation and preparation method thereof |
| CN110292041B (en) * | 2019-06-18 | 2021-06-04 | 仲恺农业工程学院 | A kind of nano pesticide preparation and preparation method thereof |
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