CN105769766B - A kind of Topiroxostat nano-emulsion and preparation method thereof - Google Patents
A kind of Topiroxostat nano-emulsion and preparation method thereof Download PDFInfo
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- CN105769766B CN105769766B CN201610170435.XA CN201610170435A CN105769766B CN 105769766 B CN105769766 B CN 105769766B CN 201610170435 A CN201610170435 A CN 201610170435A CN 105769766 B CN105769766 B CN 105769766B
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- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
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- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
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Abstract
The present invention provides a kind of Topiroxostat nano-emulsions and preparation method thereof, it is characterised in that said preparation prescription parts by weight are：5 20 parts of Topiroxostat, 3 20 parts of oil phase, 10 30 parts of surfactant, 20 60 parts of deionized water；The present invention successfully prepares Topiroxostat nanoemulsion oral preparation, greatly improves the dissolubility of Topiroxostat, so as to improve its oral administration biaavailability under the premise of optimization water phase, oil phase, proportion of surfactant.
Description
Technical field
The invention belongs to field of medicine preparations, and in particular to a kind of Topiroxostat nano-emulsion and preparation method thereof.
Background technology
Gout is purine substance metabolic disorder, and serum Uric Acid Concentration, which persistently increases, leads to urate crystal deposition soft tissue institute
The one group of metabolic disease caused.Clinical signs are hyperuricemia, gouty acute arthritis, tophaceous deposition, characteristic
Chornic arthritis and arthritis deformans often involve kidney, cause arteriosclerotic kidney and kidney calculus urate, urarthritis are normal
First presentation for the syndrome.The biochemical marker of gout is hyperuricemia, with hypertension, hyperlipidemia, atherosclerosis,
Obesity, the generation of insulin resistance are closely related, it has also become threaten the serious metabolic disease of human health.In recent years, it is global
Gout incidence significantly increases, and especially in developed regions, the gout incidence in China affluence city is apparently higher than rural area, and gout is
It is increasingly becoming a kind of rich people's disease.However, the drug for the treatment of hyperuricemia is limited at present, and toxic side effect is big, and patient is usually not
It is resistant to.Therefore, as the research of hyperuricemia pathogenesis deepens continuously, the research of anti-gout drugs is also increasingly subject to close
Note.
Topiroxostat（Topiroxostat）It is researched and developed by Japanese fuji drug Co., Ltd., is obtained in June, 2013 in Japan
It must ratify listing.Topiroxostat has the XOR of oxidized form and reduced form significant inhibiting effect, thus it reduces the work of uric acid
With chronic hyperuricemia that is more powerful, lasting, therefore can be used for treatment gout.
A kind of 1,2,4- triazole class compounds and preparation method thereof are disclosed in CN1561340B.Disclosed in CN1826335A
A kind of 1,2,4- triazole compounds manufacturing methods and wherein mesosome.CN104230891A discloses a kind of system of Topiroxostat
Preparation Method.CN104042577A discloses a kind of Topiroxostat tablet of stabilization and preparation method thereof, but has no Topiroxostat nanometer
Milk oral preparation pertinent literature and patent information.
Nano-emulsion (nanoemulsion) is also known as micro emulsion (microemulsion), is by oil phase, water phase, surfactant
It is less than 100 nm, transparent or semitransparent thermodynamic stable system Deng a kind of grain size being mixed to form in appropriate proportions.As new
Type pharmaceutical carrier, it has the following advantages：Small toxicity, safe, preparation is simple, it is possible to increase is insoluble in the dissolving of water drug
Property can also improve the stability of facile hydrolysis drug.In view of many advantages of nano-emulsion, this research is on optimization water phase, oil phase, surface
Under the premise of activating agent matches, Topiroxostat nanoemulsion oral preparation is successfully prepared, greatly improves Topiroxostat
Dissolubility, so as to improve its oral administration biaavailability.
Since Topiroxostat is the drug that is insoluble in water, the absorption of drug depends primarily on the dissolution rate of drug, existing
There are the defects of quality is unstable, dissolution rate is not high for Topiroxostat preparation.The advantages of this research is intended to utilize nano-emulsion is to drug
Topiroxostat carries out modified form, using nano-emulsion as pharmaceutical carrier, using Topiroxostat as model drug, develops dissolubility
Good, stable quality Topiroxostat nano-emulsion, therefore, develop novel form has important reference significance to its clinical application.
Invention content
The present invention is intended to provide a kind of high Topiroxostat nano-emulsion of oral administration biaavailability and preparation method thereof.
For achieving the above object, a kind of Topiroxostat nano-emulsion of the present invention and preparation method thereof, concrete scheme is：
A kind of Topiroxostat nano-emulsion of the present invention and preparation method thereof, it is characterised in that said preparation is by active constituent support
Him is taken charge of, oil phase, surfactant, deionized water composition.
A kind of Topiroxostat nano-emulsion of the present invention and preparation method thereof, it is characterised in that said preparation prescription parts by weight
For：5-20 parts of Topiroxostat, 3-20 parts of oil phase, 10-30 parts of surfactant, 20-60 parts of deionized water.
Oil phase of the present invention is soybean oil, olive oil, dimethicone, atoleine, ethyl oleate, peanut oil, meat
Isopropyl myristate, the combination of isopropyl palmitate one or more of which.
The surfactant of the present invention is Tween-20, Tween-80, Arlacel-80, Arlacel-60, lecithin, emulsification
Agent OP, Crodaret, the combination of castor oil polyoxyethylene ether one or more of which.
A kind of Topiroxostat nano-emulsion preparation method of the present invention is：
（1）Topiroxostat raw material is crossed into 60-100 mesh sieve, it is spare；
（2）Surfactant is added in deionized water, in 25-60 DEG C of dissolving；
（3）Again by dissolved with the oil phase of Topiroxostat, it is added gradually under the conditions of 25-60 DEG C, 50-600r/min（2）In,
5-30min is stirred, that is, prepares the O/W type Topiroxostat nano-emulsions of clear.
A kind of Topiroxostat nano-emulsion of the present invention and preparation method thereof, it is characterised in that the dosage form is oral system
Agent.
Dosage form of the present invention is oral liquid.
Beneficial effects of the present invention：The present invention is under the premise of optimization water phase, oil phase, proportion of surfactant, successfully
Topiroxostat nanoemulsion oral preparation is prepared, the dissolubility of Topiroxostat is greatly improved, reduces side effect, improve
Bioavilability.
Specific embodiment
Example below is only to further illustrate the present invention, range that the invention is not limited in any way.
Embodiment 1：
Prescription：
Topiroxostat 10g
Isopropyl palmitate 8g
Emulsifier op-10 18g
Tween 80 10g
Distilled water 54g
Preparation method：
（1）Topiroxostat raw material is crossed into 80 mesh sieve, it is spare；
（2）Emulsifier op-10, Tween 80 are added in deionized water, mixing is in 50 DEG C of dissolvings；
（3）Again by dissolved with the isopropyl palmitate of Topiroxostat, at 50 DEG C, it is added gradually under the conditions of 300r/min（2）
In, 20min is stirred, that is, prepares the O/W type Topiroxostat nano-emulsions of clear.
Embodiment 2：
Prescription：
Topiroxostat 10g
Isopropyl myristate 6g
Tween 80 20g
Sorbester p17 8g
Distilled water 56g
Preparation method：
（1）Topiroxostat raw material is crossed into 80 mesh sieve, it is spare；
（2）Tween 80 is added in deionized water, in 50 DEG C of dissolvings；
（3）Topiroxostat, sorbester p17 are added in isopropyl myristate, mixing, at 50 DEG C, under the conditions of 400r/min by
Gradually it is added to（2）In, 18min is stirred, that is, prepares the O/W type Topiroxostat nano-emulsions of clear.
Embodiment 3：
Prescription：
Topiroxostat 10g
Isopropyl palmitate 10g
Emulsifier op-10 18g
Tween 80 8g
Distilled water 54g
Preparation method：
（1）Topiroxostat raw material is crossed into 80 mesh sieve, it is spare；
（2）Emulsifier op-10, Tween 80 are added in deionized water, mixing is in 50 DEG C of dissolvings；
（3）Again by dissolved with the isopropyl palmitate of Topiroxostat, at 50 DEG C, it is added gradually under the conditions of 300r/min（2）
In, 20min is stirred, that is, prepares the O/W type Topiroxostat nano-emulsions of clear.
Embodiment 4：
Prescription：
Topiroxostat 10g
Isopropyl myristate 16g
Emulsifier op-10 24g
Distilled water 50g
Preparation method：
（1）Topiroxostat raw material is crossed into 80 mesh sieve, it is spare；
（2）Emulsifier op-10 is added in deionized water, in 50 DEG C of dissolvings；
（3）Again by dissolved with the isopropyl myristate of Topiroxostat, at 50 DEG C, it is added gradually under the conditions of 500r/min
（2）In, 15min is stirred, that is, prepares the O/W type Topiroxostat nano-emulsions of clear.
Embodiment 5：
(1) 1-4 of the embodiment of the present invention is compared in every experimental data：
| Appearance | Grain size（nm） | Zeta potential（-mV） | Content（%） | |
| Embodiment 1 | Clarification, transparent, uniform, good fluidity | 22.36 | 30.1 | 99.32 |
| Embodiment 2 | Clarification, transparent, uniform, good fluidity | 25.61 | 28.6 | 94.12 |
| Embodiment 3 | Clarification, transparent, uniform, good fluidity | 35.89 | 22.5 | 90.11 |
| Embodiment 4 | Clarification, transparent, uniform, good fluidity | 30.74 | 27.3 | 96.21 |
It is seen by result of the test：Nano-emulsion prepared by embodiment 1-4 prescriptions is basically identical in appearance, grain size, current potential index, but
Nanometer milk content highest prepared by 1 prescription of embodiment.
(2) embodiment of the present invention 1 stores the stability experiment data of 0,1,2,3,6 month at different temperatures：
It is seen by result, the Topiroxostat nano-emulsion prepared by 1 formulation and technology of embodiment is store under the conditions of 4 DEG C, 25 DEG C, 40 DEG C
It deposits and stablizes.
Claims (2)
1. a kind of Topiroxostat nano-emulsion, it is characterised in that said preparation prescription is calculated by weight as：5-20 parts of Topiroxostat, oil
3-20 parts of phase, 10-30 parts of surfactant, 20-60 parts of deionized water, wherein the oil phase is isopropyl myristate, palm
Isopropyl propionate one of which；The surfactant is Tween-80, one or more combinations in Arlacel-80, polyoxyethylene nonylphenol ether.
A kind of 2. Topiroxostat nano-emulsion according to claim 1, which is characterized in that the Topiroxostat nano-emulsion preparation method
For：
（1）Topiroxostat raw material is crossed into 60-100 mesh sieve, it is spare；
（2）Surfactant is added in deionized water, in 25-60 DEG C of dissolving；
（3）Again by dissolved with the oil phase of Topiroxostat, it is added gradually under the conditions of 25-60 DEG C, 50-600r/min（2）In, stirring
5-30min prepares the O/W type Topiroxostat nano-emulsions of clear.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102166246A (en) * | 2011-04-06 | 2011-08-31 | 西北农林科技大学 | Oil-in-water type atractylis oil nano emulsion oral liquid |
| CN105579037A (en) * | 2013-05-31 | 2016-05-11 | 武田制药美国有限公司 | Methods of treatment and compositions with xanthine oxidase inhibitors |
| CN103638020A (en) * | 2013-12-20 | 2014-03-19 | 中美华世通生物医药科技（武汉）有限公司 | Novel pharmaceutical composition for treating gout |
| CN104189890A (en) * | 2014-09-17 | 2014-12-10 | 朱忠良 | Medicinal composition for treating gout and application thereof |
| CN104523690A (en) * | 2015-02-08 | 2015-04-22 | 长沙佰顺生物科技有限公司 | Topiroxostat oral preparation and preparation method thereof |
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