CN103417484B - Wettable doramectin solid dispersion powder and preparation method and application thereof - Google Patents
Wettable doramectin solid dispersion powder and preparation method and application thereof Download PDFInfo
- Publication number
- CN103417484B CN103417484B CN201310366958.8A CN201310366958A CN103417484B CN 103417484 B CN103417484 B CN 103417484B CN 201310366958 A CN201310366958 A CN 201310366958A CN 103417484 B CN103417484 B CN 103417484B
- Authority
- CN
- China
- Prior art keywords
- doramectin
- parts
- wettable
- solid dispersion
- dispersion powder
- 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.)
- Active
Links
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides wettable doramectin solid dispersion powder. Raw materials and auxiliary materials for preparing pharmaceutical preparations of the wettable doramectin solid dispersion powder include 0.2 to 10 parts of doramectin, 2 to 20 parts of hydroxypropyl-beta-cyclodextrin, 8 to 2.5 parts of tween-800, 57.5 to 79 parts of anhydrous glucose, ,10 to 18 parts of anhydrous sodium citrate, and antioxidant which is 0.02 to 0.05% w/w of the doramectin and which is selected from one or a combination of two of hydroxy butyl toluene, butyl hydroxy anisole and propyl gallate. The invention further provides a preparation method and application. The wettable doramectin solid dispersion powder can be obtained by screening the auxiliary materials, dispersion of the doramectin can be guaranteed effectively, treatment effect of the doramectin preparations is improved significantly, and a new selection is provided for clinical pharmaceutical use.
Description
Technical field
The present invention relates to a kind of wettable doramectin solid dispersion powder and its production and use.
Background technology
Doractin (Doramectin) is the Macrolide antiparasitic of new generation developed the nineties in 20th century, for precursor with thiacyclohexane carboxylic acid (Cyclohexanecarboxylic acid), by a kind of Avermectins antibiotic of Avid kyowamycin (Streptomycete avermitilis) strain fermentation of gene recombinaton, molecular structure and ivermectin essential difference are C25 position is that cyclohexyl replaces.Its anthelmintic mechanism is identical with ivermectin, is all the realization that is used for by reinforcing gamma-amino butyric acid (GABA).
Research shows, doractin is used for cattle, and the expeling rate of cross-ox-eye worm (Thelazia skryabini, great Kou suck trematodiasis) is 100%; To the adult of 15 kinds of nematicides such as Ostertagia orloffi, lyrate ostertagi, Bai Shi haemonchus and the 4th the phase larva, and Dictyocaulus viviparus and cattle with the expeling rate of worm (sucking nematicide) adult more than 99%; Be 93% ~ 99% to Trichostrongylus longispicularis expeling rate; Be 96.5% to blunt thorn nematodirus expeling rate; Be 92.3% ~ 94.6% to Trichocephalus expeling rate.Doractin is the same with ivermectin and moxidectin, it is all the medicine that subcutaneous injection can maintain drug effect several weeks, the such as cattle of artificial challenge's cooperia oncophora larva, with after doractin 14 days and 21 days time worm reduction rate be respectively 99.2% and 90.7%, equally, the worm reduction rate of Ostertagia orloffi of worm 21 days and 28 days of attacking against each other is respectively 99.9% and 93.7%; 100% and 99.9% are respectively to viviparous Ah's filaria.Nature Crazing test, confirms according to faecal egg counting, the useful effect of application doractin to Ostertagia orloffi and cooperia oncophora can reach 19 ~ 22 days.Doractin is also very effective to cattle inside and outside various segmental appendage class parazoon.100% effective natural infection polypide has itch mite, acaricide, blood louse, bomb fly (1,2,3 ecdysis).Doractin is the same with other avilamycin to ox louse effective percentage is 82%, but more effective to cone fly, can 100% prevent calf from infecting in 14 days after medication.
Doractin to ascaris suum, Strongyloides ransomi, red Metastrongylus apri adult and the 4th the phase larva, and Pulmonis Sus domestica nematicide (rear strongylid), Ren sus domestica worm (stephanurus dentatus) adult all have splendid dispel effect.Doractin also has good repelling and killing efficacy to Sarcoptes suis, haematopinus suis adult and immaturity polypide.
Doractin is considered to one of classic anti-parasite medicine in current avilamycin race, doublely kills agent, all have good repelling and killing efficacy to nematicide, arthropod for inside and outside.The avilamycin series products commercially available with other compares, wider general, the better effects if of its parasiticide, and the effective time that infects again of prevention parasite is longer, is one of antiparasite drugs for animals with potentiality to be exploited at present.But due to the poorly water-soluble of itself, existing doractin preparation is little, and usually adds irritant stronger organic solvent, therefore has certain zest during clinical practice, makes it apply and be very restricted.Therefore, in order to allow doractin better be applied in livestock-raising and raising pets, developing and being a kind ofly applicable to varying number fauna, steady quality, the easy to use and doractin novel formulation that side effect is less be very important.
Summary of the invention
Technical scheme of the present invention there is provided a kind of wettable doramectin solid dispersion powder.Another technical scheme of the present invention there is provided the preparation method of this wettable doramectin solid dispersion powder.
The invention provides a kind of wettable doramectin solid dispersion powder, it is the pharmaceutical preparation be prepared from by the supplementary material of following weight proportioning:
Doractin 0.2 ~ 10 part, HP-β-CD 2 ~ 20 parts, tween 80 0.8 ~ 2.5 part, anhydrous glucose 57.5 ~ 79 parts, 10 ~ 18 parts, anhydrous citric acid sodium, antioxidant; Described antioxidant consumption is 0.02 ~ 0.05%w/w of doractin;
Antioxidant is selected from the one or more kinds of combinations in hydroxy toluene butyl ester, Butylated hydroxyanisole, propyl gallate.
Further, it is the pharmaceutical preparation be prepared from by the supplementary material of following weight proportioning:
Doractin 0.6 ~ 4 part, HP-β-CD 4.8 ~ 16 parts, tween 80 1.2 ~ 2 parts, anhydrous glucose 66 ~ 77.4 parts, 12 ~ 16 parts, anhydrous citric acid sodium, antioxidant; Described antioxidant consumption is the 0.02%w/w of doractin.
Further, it is the pharmaceutical preparation be prepared from by the supplementary material of following weight proportioning:
Doractin 1.6 ~ 4 parts, HP-β-CD 9.6 ~ 16 parts, tween 80 1.6 ~ 2 parts, anhydrous glucose 66 ~ 73.2 parts, 12 ~ 14 parts, anhydrous citric acid sodium; Oxidation preventive content is the 0.02%w/w of doractin.
Preferably, it is the pharmaceutical preparation be prepared from by the supplementary material of following weight proportioning:
Doractin 1.6 parts, HP-β-CD 9.6 parts, tween 80 1.6 parts, anhydrous glucose 73.2 parts, 14 parts, anhydrous citric acid sodium, hydroxy toluene butyl ester content is the 0.02%w/w of doractin;
Or doractin 4 parts, HP-β-CD 16 parts, tween 80 2 parts, anhydrous glucose 66 parts, 12 parts, anhydrous citric acid sodium, hydroxy toluene butyl ester content is the 0.02%w/w of doractin.
Present invention also offers the preparation method of above-mentioned wettable doramectin solid dispersion powder, it is characterized in that: it comprises the steps:
A. supplementary material is taken by weight ratio;
B. get doractin, HP-β-CD, tween 80, add dehydrated alcohol and antioxidant, stirring and dissolving, then add anhydrous glucose and anhydrous citric acid sodium mix homogeneously, dry, pulverize, obtain wettable doramectin solid dispersion powder.
Present invention also offers the purposes of above-mentioned wettable doramectin solid dispersion powder in the veterinary drug of preparation anthelmintic.
The present invention screens the wettable doramectin solid dispersion powder obtained by adjuvant, effectively can not only ensure that the dispersibility of doractin, also significantly improve the therapeutic effect of doractin preparation, for clinical application provides new selection.
Detailed description of the invention
The preparation of embodiment 1 wettable doramectin solid dispersion powder of the present invention
Get doractin 0.02kg, HP-β-CD 0.2kg, tween 80 0.08kg, add dehydrated alcohol 200ml, Butylated hydroxyanisole 4mg, be stirred to dissolve, add anhydrous glucose 7.9kg, anhydrous citric acid sodium 1.8kg, mix homogeneously, 50 DEG C of oven dry of ventilating, pulverize, obtain the present invention 0.2% wettable doramectin solid dispersion powder.
The preparation of embodiment 2 wettable doramectin solid dispersion powder of the present invention
Get doractin 0.2kg, HP-β-CD 1.2kg, tween 80 0.2kg, add dehydrated alcohol 1000ml, hydroxy toluene butyl ester 40mg, be stirred to dissolve, add anhydrous glucose 15.6kg, anhydrous citric acid sodium 2.8kg, mix homogeneously, 50 DEG C of oven dry of ventilating, pulverize, obtain the present invention 1.0% wettable doramectin solid dispersion powder.
The preparation of embodiment 3 wettable doramectin solid dispersion powder of the present invention
Get doractin 1.0kg, HP-β-CD 4.0kg, tween 80 0.5kg, add dehydrated alcohol 2000ml, propyl gallate 200mg, be stirred to dissolve, add anhydrous glucose 16.5kg, anhydrous citric acid sodium 3kg, mix homogeneously, 50 DEG C of oven dry of ventilating, pulverize, obtain the present invention 5.0% wettable doramectin solid dispersion powder.
The recipe determination of embodiment 4 wettable doramectin solid dispersion powder of the present invention
Combinationally using of supplementary product kind, consumption and adjuvant is the key factor of preparation, and they can bring material impact to the quality of the pharmaceutical preparations and preparation (producing/preparation) process.For wettability solid dispersal powder for animals, then its dispersion and sedimentation velocity etc. of major effect.Be uniformly dispersed to prepare, solid dispersal powder that sedimentation velocity is slower, the present invention screens preparation prescription.
(1) preparation of different formulations product
Specify containing measuring doractin, HP-β-CD, tween 80 by under formula item each in table 1, add appropriate dehydrated alcohol, add antioxidant hydroxy toluene butyl ester (0.02% of doractin content) again, be stirred to dissolve, add anhydrous glucose and anhydrous citric acid sodium by ormal weight under corresponding formula item, be mixed into moistening soft material, 50 DEG C of oven dry of ventilating, pulverize, prepare wettable doramectin solid dispersion powder of the present invention.
The preferred version of table 1 wettable doramectin solid dispersion powder formula of the present invention
(2) quality evaluation of different formulations product
Dispersion is evaluated: get each 1g of wettable doramectin solid dispersion powder by the preparation of table 1 formula 1 ~ formula 6, drops in 1000ml water, observes or stir and observe its deployment conditions.Disperse slower and to be unevenly chosen as " poor "; Dispersion is comparatively slow, and have caking or granule in dispersive process, agitation as appropriate can be uniformly dispersed, and is chosen as " qualified "; Dispersion is fast, and gentle agitation can be uniformly dispersed, and is chosen as " good "; Dispersion is fast, need not stir and can be uniformly dispersed, be chosen as " excellent ".The results are shown in Table 2.
Sedimentation volume ratio measures: by " solution for oral administration in " People's Republic of China's veterinary drug allusion quotation (version in 2010) " annex, suspensoid for oral administration, Emulsion for oral administration " requirement of sedimentation volume ratio inspection technique, sedimentation volume ratio mensuration is carried out to the wettable doramectin solid dispersion powder prepared by formula 1 ~ formula 6, sample thief 0.25g puts in 50ml tool plug graduated cylinder, add water to 50ml, fill in close, firmly jolting 1min, write down suspended matter and start height H 0, leave standstill and within 3 hours, write down the final height H of suspended matter, be calculated as follows: sedimentation volume ratio=H/H0, sedimentation volume ratio should be not less than 0.90.The results are shown in Table 2.
Table 2 wettable doramectin solid dispersion powder quality evaluation result of the present invention
Listed 4 indexs of his-and-hers watches 1 are carried out comprehensive analysis and can be obtained: formula 2 ~ formula 6 is all qualified, be wherein optimum with formula 4, formula 5 again.
Beneficial effect of the present invention is illustrated below by way of test example.
The oral wettable doramectin solid dispersion powder of test example 1 is to the clinical tests of pig acariasis
Material: ivermectin powder (0.2%, commercially available prod); Wettable doramectin solid dispersion powder (0.2%, prepared by embodiment 1).
Case: (sick pig becomes thin pig acarid case 48 example of Chengdu suburbs and counties under the jurisdiction of a large city first pig farm natural occurrence, down in spirits, likes in wall friction, the vesicle, incrustation, depilation etc. that occur after visible galling skin; Collect the scurf of disease pig injury moistening, be directly coated on microscope slide, can be observed the demodicid mite that lives).
Method: select the clinical onset growing and fattening pigs that body weight is substantially suitable, be divided into matched group, test group and negative control group at random under identical rearing conditions in same pig house; The commercially available ivermectin powder of matched group presses 0.1% concentration spice, feeding for sick pig, is used in conjunction 3; Wettable doramectin solid dispersion powder prepared by test group embodiment 1 converts drinking water by 0.05% concentration, drinks, be used in conjunction 3 days for sick pig; Negative control group is raised by daily feeding manner, not administration.
Efficacy determination method: medication is after 5 days, and spiritual appetite recovers normal, and microscopy, without the parasite lived or worm's ovum, is judged to recovery from illness; Medication is after 5 days, and spiritual appetite takes a turn for the better, the parasite that microscopy is lived as seen on a small quantity, is judged to effectively; Medication is after 5 days, and symptom is not improved, and it is invalid to be judged to.
Experimental result: in table 3.
The oral wettable doramectin solid dispersion powder of table 3 is to the clinical tests result of pig acariasis
As can be seen from the test results, oral wettable doramectin solid dispersion powder of the present invention is all better than commercially available ivermectin powder to the therapeutic effect of pig acariasis.The convenience that wettable doramectin solid dispersion powder of the present invention uses is better than commercially available ivermectin powder, greatly reduces the working strength of administration.Also find in test, owing to taking the mode administration added of drinking water, wettable doramectin solid dispersion powder of the present invention does not in use affect the feed intake of disease pig.
Test example 2 injects the clinical tests of wettable doramectin solid dispersion powder to pig acariasis
Material: Doramectin injection fluid (0.2%, commercially available prod); Wettable doramectin solid dispersion powder (5.0%, prepared by embodiment 3).
Case: (sick pig becomes thin pig acarid case 56 example of Chengdu suburbs and counties under the jurisdiction of a large city second pig farm natural occurrence, down in spirits, likes in wall friction, the vesicle, incrustation, depilation etc. that occur after visible galling skin; Collect the scurf of disease pig injury moistening, be directly coated on microscope slide, can be observed the demodicid mite that lives).
Method: select the clinical onset growing and fattening pigs that body weight is substantially suitable, be divided into matched group, test group and negative control group at random under identical rearing conditions in same pig house; The commercially available Doramectin injection fluid of matched group subcutaneous injection; Wettable doramectin solid dispersion powder prepared by test group embodiment 3 is watered intramuscular injection by 4% concentration; Negative control group is raised by daily feeding manner, not administration.
Efficacy determination method: with test 1.
Experimental result: in table 4.
The clinical tests result of wettable doramectin solid dispersion powder to pig acariasis injected by table 4
As can be seen from above result of the test, inject wettable doramectin solid dispersion powder of the present invention and commercially available Doramectin injection fluid is all better than to the therapeutic effect of pig acariasis.The convenience that wettable doramectin solid dispersion powder of the present invention uses is better than commercially available Doramectin injection fluid, greatly reduces the working strength of administration.Also find in test, it is less to inject the stimulation of wettable doramectin solid dispersion powder of the present invention to sick pig.
In sum, the present invention screens the wettable doramectin solid dispersion powder obtained by adjuvant, effectively can not only ensure that the dispersibility of doractin, also significantly improve the therapeutic effect of doractin preparation, for clinical application provides new selection.
Claims (3)
1. a wettable doramectin solid dispersion powder, is characterized in that: it is the pharmaceutical preparation be prepared from by the supplementary material of following weight proportioning:
Doractin 1.6 parts, HP-β-CD 9.6 parts, tween 80 1.6 parts, anhydrous glucose 73.2 parts, 14 parts, anhydrous citric acid sodium, hydroxy toluene butyl ester content is the 0.02%w/w of doractin;
Or doractin 4 parts, HP-β-CD 16 parts, tween 80 2 parts, anhydrous glucose 66 parts, 12 parts, anhydrous citric acid sodium, hydroxy toluene butyl ester content is the 0.02%w/w of doractin.
2. a preparation method for wettable doramectin solid dispersion powder described in claim 1, is characterized in that: it comprises the steps:
A. supplementary material is taken by weight ratio;
B. get doractin, HP-β-CD, tween 80, add dehydrated alcohol and hydroxy toluene butyl ester, stirring and dissolving, then add anhydrous glucose and anhydrous citric acid sodium mix homogeneously, dry, pulverize, obtain wettable doramectin solid dispersion powder.
3. the purposes of wettable doramectin solid dispersion powder described in claim 1 in the veterinary drug of preparation anthelmintic.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310366958.8A CN103417484B (en) | 2013-08-21 | 2013-08-21 | Wettable doramectin solid dispersion powder and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310366958.8A CN103417484B (en) | 2013-08-21 | 2013-08-21 | Wettable doramectin solid dispersion powder and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103417484A CN103417484A (en) | 2013-12-04 |
| CN103417484B true CN103417484B (en) | 2015-03-18 |
Family
ID=49643230
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310366958.8A Active CN103417484B (en) | 2013-08-21 | 2013-08-21 | Wettable doramectin solid dispersion powder and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103417484B (en) |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101292981A (en) * | 2007-04-29 | 2008-10-29 | 杨喜鸿 | Solid dispersion, composition of rimonabant, preparation and medicament application thereof |
| CN103083243A (en) * | 2011-11-03 | 2013-05-08 | 青岛康地恩药业股份有限公司 | Doramectin soluble powder and preparation method thereof |
-
2013
- 2013-08-21 CN CN201310366958.8A patent/CN103417484B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN103417484A (en) | 2013-12-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TWI352592B (en) | Anthelmintic combination | |
| CN101854926A (en) | Endoparasiticidal topical compositions | |
| CN112972379B (en) | Gamitmycin emulsion, preparation method and application thereof in prevention and treatment of porcine ileitis | |
| CN103417486B (en) | A kind of wettable ivermectin solid dispersion powder and its production and use | |
| CN101848710A (en) | Anthelmintic combination | |
| CN103405388B (en) | Wettable moxidectin solid dispersing powder as well as preparation method and application thereof | |
| CN105287607A (en) | Compound doxycycline-hydrochloride florfenicol sustained-release microsphere suspension injection for veterinary use | |
| CN103417484B (en) | Wettable doramectin solid dispersion powder and preparation method and application thereof | |
| AU2011268899B2 (en) | Injectable formulation of a macrocyclic lactone and levamisole | |
| WO2005074914A1 (en) | Anthelmintic composition | |
| RU2681214C1 (en) | Method of obtaining agent for the treatment of solid-hoofed animals with parasitosis | |
| CN1213756C (en) | Veterinary compositions for the treatment of parasitic diseases | |
| CN103417485B (en) | A kind of wettable eprinomectin solid dispersion powder and its production and use | |
| CN103006559A (en) | Doramectin injection and preparation method thereof | |
| AU2001235489A1 (en) | Veterinary compositions for the treatment of parasitic diseases | |
| CN1867341A (en) | Compositions for controlling parasites comprising a combination of abamectin and milbemycin | |
| CN101926764B (en) | Doramectin microemulsion transdermal agent and preparation method thereof | |
| CN1943554A (en) | Avermectins transdermal agent and preparing method | |
| CN106924204A (en) | Cattle and sheep anti parasitic disease sustained release tablets and preparation method thereof | |
| CN103393706B (en) | A kind of wettable ivermectin albendazole oxide powder | |
| BR102014031535A2 (en) | pharmaceutical formulation and process for obtaining an oral solution containing praziquantel and oral solution containing praziquantel thus obtained | |
| CN102415996B (en) | Valnemulin hydrochloride self-emulsified oral nano emulsion for veterinary use and preparation method thereof | |
| CN103393600B (en) | A kind of wettable milbemycin oxime solid divides loose powder and its production and use | |
| CN106474140A (en) | A kind of compound fluconazole injection and preparation method thereof | |
| CN104208021A (en) | Avermectin suspension and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C56 | Change in the name or address of the patentee | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 611130 Wenjiang, Chengdu, Chengdu cross strait science and Technology Industrial Development Zone, Jin Fu Road, Sichuan Patentee after: Chengdu Qiankun animal pharmaceutical Limited by Share Ltd Patentee after: Shanghai Simenon Biotech Co., Ltd. Address before: 611130 Wenjiang, Chengdu, Chengdu cross strait science and Technology Industrial Development Zone, Jin Fu Road, Sichuan Patentee before: Chengdu Qiankun Animal Pharmaceutical Co.,Ltd. Patentee before: Shanghai Simenon Biotech Co., Ltd. |