CN102188406A - Preparation method of taste-concealing micro-capsules of levofloxacin hydrochloride - Google Patents
Preparation method of taste-concealing micro-capsules of levofloxacin hydrochloride Download PDFInfo
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- CN102188406A CN102188406A CN2011101220378A CN201110122037A CN102188406A CN 102188406 A CN102188406 A CN 102188406A CN 2011101220378 A CN2011101220378 A CN 2011101220378A CN 201110122037 A CN201110122037 A CN 201110122037A CN 102188406 A CN102188406 A CN 102188406A
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- levofloxacin hydrochloride
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Abstract
The invention relates to a preparation method of taste-concealing micro-capsules of levofloxacin hydrochloride. The application of the levofloxacin hydrochloride to treating animal diseases is greatly limited by the bitterness of the levofloxacin hydrochloride. The preparation method of the taste-concealing micro-capsules of the levofloxacin hydrochloride comprises steps of dissolving 5% to 90% of the mixture of acrylic resin II or acrylic resin III or acrylic resin II and acylic resin III with 20% of sodium hydroxide solution to prepare 5% to 10% of wall material solution, adjusting the solution into an alkalescent solution, adding distilled water to dissolve levofloxacin hydrochloride to prepare 10% to 40% of core material solution, mixing the wall material solution and the core material solution, adding 0.5% to 5% of Span 80 to prepare 1-10 times of quality of atoleine, carrying out high-shear emulsification and dispersion to the mixture to prepare a stable WxO emulsion type emulsion, stirring the emulsion, dripping hydrochloric acid into the solution to adjust the solution to an acid solution, dissolving the wall material out to cover the surface of capsule core material, and filtering and drying the surface of the capsule core material, and adding a small amount of magnesium aluminum silicate to absorb the residual atoleine. The invention is applied to medicines.
Description
Technical field:
Invention relates to a kind of field of medicaments that is used for; Be specifically related to a kind of production method of levofloxacin hydrochloride taste masking microcapsule.
Background technology:
Levofloxacin hydrochloride (Levofloxacin Hydrochloride), have another name called the levofloxacin hydrochlorate, its chemical name is: (S)-(-)-and 9-fluoro-2,3-dihydro-3-methyl isophthalic acid 0-(4-methyl isophthalic acid-piperazinyl)-7-oxygen-7H pyridine benzene a pair of horses going side by side [1,2,3-de]-monohydrate of [1,4] benzene a pair of horses going side by side oxazines-6-carboxylic acid hydrochloric acid, molecular weight is 415.85.Modern pharmacological research proves, levofloxacin hydrochloride belongs to the quinolones extensive pedigree antibiotic, antibacterial action is strong, to most enterobacteriaceae lactobacteriaceaes, stronger antibacterial activity is arranged as gram-negative bacterias such as escherichia coli, Klebsiella, Proteus, Salmonella, Shigella and hemophilus influenza, legionella pneumophilia, Diplococcus gonorrhoeae.Gram positive bacterias such as staphylococcus aureus, streptococcus pneumoniae, micrococcus scarlatinae and mycoplasma pneumoniae, Chlamydia pneumoniae also there is antibacterial action.Can be used for treating diseases such as respiratory system infection, gastrointestinal infection and skin soft-tissue infection clinically.
But the levofloxacin hydrochloride bitter in the mouth adds the grazing rate or the amount of drinking water that can cause animal in feedstuff or the drinking-water to and reduces, and this has just limited the application of levofloxacin hydrochloride in the Animal diseases treatment greatly.
Summary of the invention:
The purpose of invention provides a kind of production method of levofloxacin hydrochloride taste masking microcapsule, to cover the bitterness of levofloxacin hydrochloride, improves the suitability and the palatability of taking.
Above-mentioned purpose realizes by following technical scheme:
A kind of production method of levofloxacin hydrochloride taste masking microcapsule, comprised for six steps: the first step, mixture with acrylic resin II or acrylic resin III or acrylic resin II and acrylic resin III, consumption is 5% ~ 90%, and with the dissolving of 20% sodium hydroxide solution, make 5% ~ 10% wall material solution, be adjusted to alkalescence;
In second step, levofloxacin hydrochloride is as core, and 10% ~ 40% core solution is made in the adding distil water dissolving;
The 3rd step, the first step and the wall material in second step and core solution are mixed, add volume and be 0.5% ~ 5% sorbester p17 after, add the liquid paraffin of 1 ~ 10 times of amount of volume again;
In the 4th step, with the mixed system of the 3rd step gained, high-shear emulsifying disperses, and makes stable water-in-oil emulsion type Emulsion;
In the 5th step, with the Emulsion stirring of the 4th step gained, the dripping hydrochloric acid regulation system is to acid lentamente simultaneously, and the surface of core-clad material is separated out and be coated on to the wall material;
In the 6th step, with the mixed system filtration of the 5th step gained, drying adds the residual liquid paraffin of a small amount of Magnesiumaluminumsilicate absorption and promptly gets levofloxacin hydrochloride taste masking microcapsule.
The production method of described levofloxacin hydrochloride taste masking microcapsule, the envelop rate of described levofloxacin hydrochloride is greater than 80%.
Beneficial effect:
1. technological operation of the present invention is simple, the envelop rate height, and equipment needed thereby is simple, inexpensive, be easy to get, and production cost is low, and the cycle is short, and the nontoxic and recyclable recycling of solvent for use realizes the zero-emission of producing.
2. gained powder of the present invention has good flowability, dispersibility and palatability, and is difficult for the moisture absorption, has greatly enlarged the range of application of levofloxacin hydrochloride; This product can directly make an addition in animal feed or the drinking-water, does not influence the grazing rate of animal.
3. of the present inventionly can effectively cover the bitterness of levofloxacin hydrochloride, and have good flowability, can mix interpolation, solve an above-mentioned difficult problem, have broad application prospects with any feedstuff.
4. acrylic resin of the present invention is by methacrylic acid and methyl methacrylate copolymerization by a certain percentage and get, be anionic polymer, when pH value greater than 7 time dissolvings, be mainly used in the preparation of enteric coating, slow-release material, microcapsule, the fine and close flexible of good film-forming property, film, the effect that has the moisture resistance effect and improve medicine stability.
5. microcapsule technology of the present invention is as a high and new technology, become various countries scholar's research focus, along with the continuous intensification of people to microcapsule understanding, the continuous appearance of new equipment, new preparation technology and new material, microcapsule technology will cut a conspicuous figure on the development history of human civilization.
6. the acrylic resin safety, nontoxic, the stable in properties that adopt of the present invention, good film-forming property, softgel shell densification; This product operation is simple, the envelop rate height, and equipment needed thereby is simple, inexpensive, be easy to get, and production cost is low, and the cycle is short; The powder of this product gained has good flowability, dispersibility and palatability, and is difficult for the moisture absorption, has greatly enlarged the range of application of levofloxacin hydrochloride.
7. powder of the present invention can directly make an addition in animal feed or the drinking-water, does not influence the grazing rate of animal.
8. solvent used in the present invention is water and liquid paraffin, and is nontoxic, environmentally safe, and can reuse, realize the zero-emission of production, saved production cost greatly, commercial production feasibility height.
The specific embodiment:
Embodiment 1:
1. the production method of a levofloxacin hydrochloride taste masking microcapsule, comprised for six steps: the first step, mixture with acrylic resin II or acrylic resin III or acrylic resin II and acrylic resin III, consumption is 5% ~ 90%, and with the dissolving of 20% sodium hydroxide solution, make 5% ~ 10% wall material solution, be adjusted to alkalescence;
In second step, levofloxacin hydrochloride is as core, and 10% ~ 40% core solution is made in the adding distil water dissolving;
The 3rd step, the first step and the wall material in second step and core solution are mixed, add volume and be 0.5% ~ 5% sorbester p17 after, add the liquid paraffin of 1 ~ 10 times of amount of volume again;
In the 4th step, with the mixed system of the 3rd step gained, high-shear emulsifying disperses, and makes stable water-in-oil emulsion type Emulsion;
In the 5th step, with the Emulsion stirring of the 4th step gained, the dripping hydrochloric acid regulation system is to acid lentamente simultaneously, and the surface of core-clad material is separated out and be coated on to the wall material;
In the 6th step, with the mixed system filtration of the 5th step gained, drying adds the residual liquid paraffin of a small amount of Magnesiumaluminumsilicate absorption and promptly gets levofloxacin hydrochloride taste masking microcapsule.
Embodiment 2:
The production method of embodiment 1 described levofloxacin hydrochloride taste masking microcapsule, the envelop rate of described levofloxacin hydrochloride is greater than 80%.
Embodiment 3:
The production method of the described levofloxacin hydrochloride taste masking of above embodiment microcapsule, take by weighing acrylic resin II and acrylic resin III (1: 1) and mix wall material 1g, add 20%NaOH solution 10ml, treat that the wall material dissolves fully after, with dilute hydrochloric acid with solution furnishing alkalescence stand-by (wall material solution); Take by weighing the 1g levofloxacin hydrochloride, add 10ml water it is dissolved fully, with sodium hydroxide solution furnishing alkalescence stand-by (core solution); After wall material solution and the mixing of core solution, add sorbester p17 and the 30ml liquid paraffin of 0.5ml, with 10000rpm emulsifying 1min, be prepared into stable water-in-oil emulsion type Emulsion; Continue stirring with 1000rpm and drip dilute hydrochloric acid simultaneously when system is acidity, the wall material begins to separate out, and forms microcapsule, filters, and drying adds the residual liquid paraffin of a small amount of Magnesiumaluminumsilicate absorption and promptly gets levofloxacin hydrochloride taste masking microcapsule.This levofloxacin hydrochloride taste masking microcapsule taste masking is effective, and particle flow is good, satisfies the invention requirement.
Embodiment 4:
The production method of the described levofloxacin hydrochloride taste masking of above embodiment microcapsule, take by weighing acrylic resin II and acrylic resin III (1: 1) and mix wall material 2 g, add 20% NaOH solution, 15 ml, after treating that the wall material dissolves fully, with dilute hydrochloric acid with solution furnishing alkalescence stand-by (wall material solution); Take by weighing 1 g levofloxacin hydrochloride, add 5 ml water it is dissolved fully, with sodium hydroxide solution furnishing alkalescence stand-by (core solution); After wall material solution and the mixing of core solution, add sorbester p17 and the 35 ml liquid paraffin of 0.5 ml, with 14000 rpm emulsifyings, 0.5 min, be prepared into stable water-in-oil emulsion type Emulsion; Continue stirring with 1000 rpm and drip dilute hydrochloric acid simultaneously when system is acidity, the wall material begins to separate out, and forms microcapsule, filters, and drying adds the residual liquid paraffin of a small amount of Magnesiumaluminumsilicate absorption and promptly gets levofloxacin hydrochloride taste masking microcapsule.This levofloxacin hydrochloride taste masking microcapsule taste masking is effective, and particle flow is good, satisfies the invention requirement, and envelop rate is up to 89%.
Embodiment 5:
The production method of the described levofloxacin hydrochloride taste masking of above embodiment microcapsule, take by weighing acrylic resin II and acrylic resin III (1: 1) and mix wall material 1 g, add 20% NaOH solution, 10 ml, after treating that the wall material dissolves fully, with dilute hydrochloric acid with solution furnishing alkalescence stand-by (wall material solution); Take by weighing 1 g levofloxacin hydrochloride, add 10 ml water it is dissolved fully, with sodium hydroxide solution furnishing alkalescence stand-by (core solution); After wall material solution and the mixing of core solution, add sorbester p17 and the 50 ml liquid paraffin of 1 ml, with 10000 rpm emulsifyings, 1 min, be prepared into stable water-in-oil emulsion type Emulsion; Continue stirring with 1000 rpm and drip dilute hydrochloric acid simultaneously when system is acidity, the wall material begins to separate out, and forms microcapsule, filters, and drying adds the residual liquid paraffin of a small amount of Magnesiumaluminumsilicate absorption and promptly gets levofloxacin hydrochloride taste masking microcapsule.This levofloxacin hydrochloride taste masking microcapsule taste masking effect is fine, particle flow sexual satisfaction invention requirement, and envelop rate is up to 95%.
Embodiment 6:
The production method of the described levofloxacin hydrochloride taste masking of above embodiment microcapsule, take by weighing acrylic resin II and acrylic resin III (1: 2) and mix wall material 2 g, add 20% NaOH solution, 15 ml, after treating that the wall material dissolves fully, with dilute hydrochloric acid with solution furnishing alkalescence stand-by (wall material solution); Take by weighing 2 g levofloxacin hydrochlorides, add 10 ml water it is dissolved fully, with sodium hydroxide solution furnishing alkalescence stand-by (core solution); After wall material solution and the mixing of core solution, add sorbester p17 and the 100 ml liquid paraffin of 2 ml, with 12000 rpm emulsifyings, 3 min, be prepared into stable water-in-oil emulsion type Emulsion; Continue stirring with 1000 rpm and drip dilute hydrochloric acid simultaneously when system is acidity, the wall material begins to separate out, and forms microcapsule, filters, and drying adds the residual liquid paraffin of a small amount of Magnesiumaluminumsilicate absorption and promptly gets levofloxacin hydrochloride taste masking microcapsule.This levofloxacin hydrochloride taste masking microcapsule taste masking effect satisfies the invention requirement, and particle flow is good, and envelop rate is 87%.
Embodiment 7:
The production method of the described levofloxacin hydrochloride taste masking of above embodiment microcapsule, take by weighing acrylic resin II and acrylic resin III (2: 1) and mix wall material 1 g, add 20% NaOH solution, 15 ml, after treating that the wall material dissolves fully, with dilute hydrochloric acid with solution furnishing alkalescence stand-by (wall material solution); Take by weighing 2 g levofloxacin hydrochlorides, add 10 ml water it is dissolved fully, with sodium hydroxide solution furnishing alkalescence stand-by (core solution); After wall material solution and the mixing of core solution, add sorbester p17 and the 25 ml liquid paraffin of 1 ml, with 10000 rpm emulsifyings, 2 min, be prepared into stable water-in-oil emulsion type Emulsion; Continue stirring with 1000 rpm and drip dilute hydrochloric acid simultaneously when system is acidity, the wall material begins to separate out, and forms microcapsule, filters, and drying adds the residual liquid paraffin of a small amount of Magnesiumaluminumsilicate absorption and promptly gets levofloxacin hydrochloride taste masking microcapsule.This levofloxacin hydrochloride taste masking microcapsule taste masking is respond well, and particle flow is good, satisfies the invention requirement, and envelop rate is 82.6%.
Embodiment 8:
The production method of the described levofloxacin hydrochloride taste masking of above embodiment microcapsule takes by weighing acrylic resin III 1 g, adds 20% NaOH solution, 8 ml, treat that the wall material dissolves fully after, with dilute hydrochloric acid with solution furnishing alkalescence stand-by (wall material solution); Take by weighing 0.5 g levofloxacin hydrochloride, add 10 ml water it is dissolved fully, with sodium hydroxide solution furnishing alkalescence stand-by (core solution); After wall material solution and the mixing of core solution, add sorbester p17 and the 20 ml liquid paraffin of 0.6 ml, with 14000 rpm emulsifyings, 0.5 min, be prepared into stable water-in-oil emulsion type Emulsion; Continue stirring with 1000 rpm and drip dilute hydrochloric acid simultaneously when system is acidity, the wall material begins to separate out, and forms microcapsule, filters, and drying adds the residual liquid paraffin of a small amount of Magnesiumaluminumsilicate absorption and promptly gets levofloxacin hydrochloride taste masking microcapsule.This levofloxacin hydrochloride taste masking microcapsule taste masking is effective, and particle flow is good, satisfies the invention requirement, and envelop rate is 88%.
Embodiment 9:
The production method of the described levofloxacin hydrochloride taste masking of above embodiment microcapsule takes by weighing acrylic resin II 1 g, adds 20% NaOH solution, 20 ml, treat that the wall material dissolves fully after, with dilute hydrochloric acid with solution furnishing alkalescence stand-by (wall material solution); Take by weighing 1 g levofloxacin hydrochloride, add 20 ml water it is dissolved fully, with sodium hydroxide solution furnishing alkalescence stand-by (core solution); After wall material solution and the mixing of core solution, add sorbester p17 and the 100 ml liquid paraffin of 1 ml, with 12000 rpm emulsifyings, 4 min, be prepared into stable water-in-oil emulsion type Emulsion; Continue to stir simultaneously dripping hydrochloric acid when system is acidity with 1000 rpm, the wall material begins to separate out, and forms microcapsule, filters, and drying adds the residual liquid paraffin of a small amount of Magnesiumaluminumsilicate absorption and promptly gets levofloxacin hydrochloride taste masking microcapsule.This levofloxacin hydrochloride taste masking microcapsule taste masking is effective, and particle flow is good, satisfies the invention requirement, and envelop rate is 90%.
Embodiment 10:
The production method of the described levofloxacin hydrochloride taste masking of above embodiment microcapsule, experimental group is fed to tame chicken according to behind the levofloxacin hydrochloride taste masking microcapsule of embodiment 1 preparation and the feedstuff mix homogeneously; Matched group will be suitable with the experimental group drug loading levofloxacin hydrochloride directly with the feedstuff mix homogeneously after hello to matched group man chicken.By contrast grazing rate result, show the experimental group that adds levofloxacin hydrochloride taste masking microcapsule, grazing rate of tame chicken and daily grazing rate be (P＞0.05) quite, is much higher than the grazing rate (P＜0.05) of control experiment group; Illustrate that levofloxacin hydrochloride taste masking microcapsule has good taste masking performance.
Claims (2)
1. the production method of a levofloxacin hydrochloride taste masking microcapsule, it is characterized in that: the first step, mixture with acrylic resin II or acrylic resin III or acrylic resin II and acrylic resin III, consumption is 5% ~ 90%, and with the dissolving of 20% sodium hydroxide solution, make 5% ~ 10% wall material solution, be adjusted to alkalescence;
In second step, levofloxacin hydrochloride is as core, and 10% ~ 40% core solution is made in the adding distil water dissolving;
The 3rd step, the first step and the wall material in second step and core solution are mixed, add volume and be 0.5% ~ 5% sorbester p17 after, add the liquid paraffin of 1 ~ 10 times of amount of volume again;
In the 4th step, with the mixed system of the 3rd step gained, high-shear emulsifying disperses, and makes stable water-in-oil emulsion type Emulsion;
In the 5th step, with the Emulsion stirring of the 4th step gained, the dripping hydrochloric acid regulation system is to acid lentamente simultaneously, and the surface of core-clad material is separated out and be coated on to the wall material;
In the 6th step, with the mixed system filtration of the 5th step gained, drying adds the residual liquid paraffin of a small amount of Magnesiumaluminumsilicate absorption and promptly gets levofloxacin hydrochloride taste masking microcapsule.
2. the production method of levofloxacin hydrochloride taste masking microcapsule according to claim 1 is characterized in that: the envelop rate of described levofloxacin hydrochloride is greater than 80%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201110122037.8A CN102188406B (en) | 2011-05-12 | 2011-05-12 | Preparation method of taste-concealing micro-capsules of levofloxacin hydrochloride |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201110122037.8A CN102188406B (en) | 2011-05-12 | 2011-05-12 | Preparation method of taste-concealing micro-capsules of levofloxacin hydrochloride |
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| CN102188406A true CN102188406A (en) | 2011-09-21 |
| CN102188406B CN102188406B (en) | 2015-02-25 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105055374A (en) * | 2015-09-16 | 2015-11-18 | 山西沃德华兽生物技术有限公司 | Slow-release type sarafloxacin hydrochloride microcapsule and preparation method thereof |
| CN108567761A (en) * | 2018-07-25 | 2018-09-25 | 江苏黄河药业股份有限公司 | A kind of Levofloxacin Hydrochloride Capsules and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1878539A (en) * | 2003-12-15 | 2006-12-13 | 科学与工业研究委员会 | Taste masked pharmaceutical compositions comprising bitter drug and pH sensitive polymer |
-
2011
- 2011-05-12 CN CN201110122037.8A patent/CN102188406B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1878539A (en) * | 2003-12-15 | 2006-12-13 | 科学与工业研究委员会 | Taste masked pharmaceutical compositions comprising bitter drug and pH sensitive polymer |
Non-Patent Citations (1)
| Title |
|---|
| 杜洪建等: "蛋白药物肠溶微囊的制备及药物释放试验", 《中国医院药学杂志》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105055374A (en) * | 2015-09-16 | 2015-11-18 | 山西沃德华兽生物技术有限公司 | Slow-release type sarafloxacin hydrochloride microcapsule and preparation method thereof |
| CN105055374B (en) * | 2015-09-16 | 2017-11-03 | 山西沃德华兽生物技术有限公司 | A kind of spacetabs type hydrochloric acid sarafloxacin microcapsules and preparation method thereof |
| CN108567761A (en) * | 2018-07-25 | 2018-09-25 | 江苏黄河药业股份有限公司 | A kind of Levofloxacin Hydrochloride Capsules and preparation method thereof |
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| CN102188406B (en) | 2015-02-25 |
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Effective date of registration: 20170314 Address after: 150000 Heilongjiang City, Nangang Province, East District, the city of Victoria Street, unit 299, building 2, building 3 Patentee after: Wang Guanhong Address before: 150080 Harbin, Heilongjiang, Nangang District Road, No. 74 Patentee before: Heilongjiang University |
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Inventor after: Wang Guanhong Inventor before: Li Qiang Inventor before: Zhang Shiwei Inventor before: Zhao Xueling Inventor before: Su Yu Inventor before: Zhang Hua |
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Effective date of registration: 20170322 Address after: 210000 Jiangsu city of Nanjing province Nanjing economic and Technological Development Zone No. 3 Huimeilu Patentee after: NANJING ZHENGKE PHARMACEUTICAL CO., LTD. Address before: 150000 Heilongjiang City, Nangang Province, East District, the city of Victoria Street, unit 299, building 2, building 3 Patentee before: Wang Guanhong |