CN105030671B - Methimazole micro emulsion, methimazole micro emulsion gel and its preparation method and application - Google Patents
Methimazole micro emulsion, methimazole micro emulsion gel and its preparation method and application Download PDFInfo
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- CN105030671B CN105030671B CN201510412626.8A CN201510412626A CN105030671B CN 105030671 B CN105030671 B CN 105030671B CN 201510412626 A CN201510412626 A CN 201510412626A CN 105030671 B CN105030671 B CN 105030671B
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- methimazole
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- 239000004530 micro-emulsion Substances 0.000 title claims abstract description 122
- PMRYVIKBURPHAH-UHFFFAOYSA-N methimazole Chemical compound CN1C=CNC1=S PMRYVIKBURPHAH-UHFFFAOYSA-N 0.000 title claims abstract description 92
- 229960002178 thiamazole Drugs 0.000 title claims abstract description 92
- 238000002360 preparation method Methods 0.000 title claims abstract description 27
- 239000003814 drug Substances 0.000 claims abstract description 55
- 229940079593 drug Drugs 0.000 claims abstract description 50
- 206010020850 Hyperthyroidism Diseases 0.000 claims abstract description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000003623 enhancer Substances 0.000 claims abstract description 12
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- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 claims description 16
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 12
- 239000000243 solution Substances 0.000 claims description 12
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Landscapes
- Medicinal Preparation (AREA)
Abstract
The present invention relates to a kind of methimazole micro emulsions, methimazole micro emulsion gel and its preparation method and application, methimazole micro emulsion contains following component: methimazole, oily phase, surfactant, cosurfactant, water and transdermal enhancer, weight ratio are 1:(1.40~4.25): (5.13~15.45): (5.13~15.45): (1.40~8.32): (0.26~1.26).Methimazole micro emulsion gel is that gel-type vehicle is added into methimazole micro emulsion to be made through swelling, after mixing evenly.Methimazole micro emulsion of the invention, methimazole micro emulsion gel can be applied directly to affected part, the drug such as patch or patch that can also be used for preparation treatment hyperthyroidism have many advantages, such as that dissolubility is good, penetrating power is strong, action time is lasting, can significantly improve curative effect of medication, reducing administration number of times, convenient drug administration.
Description
Technical field
The present invention relates to a kind of dosage forms that methimazole is new, micro- more particularly to a kind of methimazole for treating hyperthyroidism
Cream, micro emulsion gel preparation capable of permeating skin and its preparation method and application.
Background technique
Hyperthyroidism (hyperthyroidism, abbreviation hyperthyroidism) is that thyroid glands itself generate thyroid gland
Thyrotoxicosis caused by hormonosis, occurs that blood calcium increases, serium inorganic phosphorus reduces, the symptom that increases is discharged in urinary calcium and urine phosphorus, faces
Thyroid Gland Swell, failure of memory, emotional instability, and depressed, drowsiness, burnout, weakness of limbs, flesh are mainly shown as on bed
Atrophy, appetite stimulator, indigestion, constipation, Nausea and vomiting, diuresis, enuresis nocturna, thirsty, tachycardia, neuroticism and weight
The symptoms such as mitigation.The disease incidence of hyperthyroidism has become the division of endocrinology second for being only second to diabetes in trend is risen year by year at present
Big disease, data show that China about has more than 15,000,000 at present in international thyroid gland Knowledge Promotion week news briefing in 2013
Hyperthyroid patient.And hyperthyroidism can cause multiple complications, this disease is more with women, and 80% patient is young and middle-aged women, such as: first shape
Gland crisis, thyroid gland heart disease, thyroid gland merge period paralysis and oligoleukocythemia etc., seriously affect patient quality of life and
It is physically and mentally healthy.
The drug of currently used treatment hyperthyroidism has: 1. sulfonylurea receptors；2. iodine and iodide；3. radioiodine；4. β by
Body blocking agent class drug.Wherein Thiourea is most common anti-hyperthyroidism drug.Clinical Selection sequence is normal are as follows: methimazole (MML),
Propylthiouracil (PTU), Athyromazole (CMZ) and methylthiouracil.The dosage form of presently commercially available methimazole have tablet and
Two kinds of ointment.Thiamazole tablets can generate Nausea and vomiting, epigastric discomfort, arthritis and vasculitis etc. in use
The adverse reaction of system property, an a minority have caused hepatitis, pneumonia, ephritis, hepatic injury, grain during taking Thiamazole tablets
Leukopenia and involve the systemic side effects such as the vasculitis of kidney, therefore the dosage of Thiamazole tablets needs strict control.
Methimazole ointment is compared with tablet, because it is to significantly reduce systemic poison pair in use with transdermal means administration
Effect, but since said preparation is common ointment, and methimazole is water-soluble stronger drug, through when percutaneous drug delivery most
Main problem to be solved is how to make drug through fat-soluble keratoderma barrier, therefore percutaneously seeps to improve its
Permeability, ointment, which mainly passes through, is added a large amount of penetration enhancer to improve the transdermal ability of methimazole, however highly concentrated
The penetration enhancer of degree has certain irritation to skin, is especially easier to cause local adverse reaction when used for a long time, because
This methimazole tablet and ointment above all have certain limitation in application.
Transdermal drug delivery system (transdermal drug delivery systems, TDDS): refer to and stick mode through skin
Medication, drug are absorbed into systemic blood circulation by skin and are reached effective blood drug concentration, realize the one of disease treatment or prevention
Class preparation.Transdermal drug delivery system feature is as follows: (1) first pass effect and drug that transdermal drug delivery system can avoid liver are in gastrointestinal tract
Inactivation, drug absorption by gastrointestinal factors is not influenced reduction medication individual difference.(2) constant effective blood medicine is maintained
Concentration or physiological effect avoid blood concentration peak valley phenomenon caused by being administered orally, reduce toxicity.(3) administration time is reduced
Number improves therapeutic efficacy, extends action time, avoids multiple dose administration, most patient is made to be easy to receive.It is (4) easy to use,
Patient can autonomous medication, medication can also be terminated at any time.
Micro emulsion (microemulsion, ME) is water, oil, and surfactant and cosurfactant are mixed in appropriate ratio
It closes, the dispersion clear and bright with isotropism, Thermodynamically stable, appearance spontaneously formed.Micro emulsion has many in the tdds
Advantage, such as: the solubility of energy significantly increasing medicament maintains higher drug concentration, improves the drug concentration between micro emulsion and skin
Gradient increases percutaneous rate, increases the mobility of Stratum corneum lipids bilayer, improves the transdermal capability of drug, improves biological utilisation
Degree.
Micro emulsion gel (microemulsion-based gels, MBGs) is a kind of new agent having just emerged in recent ten years
Type, it is micro emulsion to be added to by high molecular materials such as natural polymers, cellulose derivative, block polymers to form
Gel-type vehicle in, form transparent, homogeneous, stable gel networks, micro emulsion drop contained in network structure.Micro emulsion gel
Not only inheriting micro emulsion can increase the solubility, the diffusion barrier for reducing skin, the transdermal penetration for increasing drug of insoluble drug
The advantages that amount, also improves the viscosity of micro emulsion, improves the adhesion and stretchability of micro emulsion and skin, due to the increasing of system viscosity
Greatly, diffusion hindered of the drug in MBGs, effective diffusion cofficient reduce, therefore drug can be made to maintain longer action time.With
Conventional microemulsion is compared, and micro emulsion gel is preferably to be used as carrier for transdermal delivery, can be applied directly to affected part, patch can also be made
It is affixed on affected part.
Methimazole (Methimazole, MML) molecular weight is 114.16, and fusing point is suitable for saturating between 143~146 DEG C
Skin administration, but contain sulfydryl in its structure, belong to hydrophilic medicament, solubility in water may be up to 200mg/mL, and hydrophilic
Property drug be difficult to again through skin, therefore limit its transdermal application.
Summary of the invention
The technical problem to be solved in the present invention is to provide one kind have dissolubility is good, penetrating power is strong, action time is lasting,
Reverse microemulsion, micro emulsion gel and its preparation side that curative effect of medication can be significantly improved, reduce the advantages that administration number of times, convenient drug administration
Method and preparation treatment hyperthyroidism drug application.
In order to achieve the above object, a kind of methimazole micro emulsion of the present invention, contain following component: methimazole, oily phase, surface are living
Property agent, cosurfactant, water and transdermal enhancer, weight ratio be 1:(1.40~4.25): (5.13~15.45): (5.13~
15.45): (1.40~8.32): (0.26~1.26)；Preferred weight ratio is 1:(1.40~4.21): (5.13~10.35):
(5.13~10.35): (2.76~8.32): (0.69~1.22)；More preferable weight ratio is 1:2.04:6.76:6.76:4:
1.09。
Methimazole micro emulsion of the invention, wherein it is preferred that the oil is mutually selected from soybean oil, olive oil, oleic acid, myristic acid
One of isopropyl ester (IPM), ethyl oleate and oleic acid LABRAFIL M 1944CS, more preferably isopropyl myristate (IPM).
Methimazole micro emulsion of the invention, wherein it is preferred that the surfactant is selected from Labraso
(Labrasol), at least one of Crodaret, polysorbas20 (Tween 20) and Tween 80 (Tween 80),
More preferably Tween 80 (Tween 80).
Methimazole micro emulsion of the invention, wherein it is preferred that the cosurfactant is selected from dehydrated alcohol, propylene glycol, isopropyl
At least one of alcohol, glycerine, polyethylene glycol 400 (PEG 400), diethylene glycol monoethyl ether (TP), more preferably anhydrous second
Alcohol.
Methimazole micro emulsion of the invention, wherein it is preferred that the transdermal enhancer is selected from azone, menthol, NMP and the third two
One of alcohol, more preferably azone.
The preparation method of the above-mentioned methimazole micro emulsion of the present invention, comprising the following steps:
1) oily phase, the surfactant, cosurfactant of the weight proportion are weighed, is uniformly mixed under magnetic agitation；
2) transdermal enhancer is added in the solution that step 1) obtains, is uniformly mixed under magnetic agitation；
3) it in the mixed solution for obtaining water droplet addition step 2), is uniformly mixed under magnetic agitation molten up to blank micro emulsion
Liquid；
4) methimazole bulk pharmaceutical chemicals are added in the blank microemulsion solution that step 3) obtains, after ultrasound is completely dissolved, are obtained
To transparent methimazole micro emulsion, preferably ultrasonic temperature is 25~35 DEG C, and ultrasonic time is 3~7min.
The application of the above-mentioned methimazole micro emulsion of the present invention, can be applied directly to affected part, it can also be used to preparation treatment hyperthyroidism
Drug, the preferably described drug be patch or patch.
A kind of methimazole micro emulsion gel of the present invention, be added into above-mentioned methimazole micro emulsion gel-type vehicle through swelling,
Uniform semisolid preparation obtained is methimazole micro emulsion gel after mixing evenly.
It is preferred that the gel-type vehicle is selected from carbomer, methylcellulose, sodium carboxymethylcellulose and poloxamer, more preferably
Carbomer.
The weight ratio of methimazole micro emulsion gel of the invention, the preferably described gel-type vehicle and micro emulsion be 1:(16.23~
61.20), more preferably 1:(31.55~58.48), more preferably 1:54.13.
The application of the above-mentioned methimazole micro emulsion gel of the present invention, can be applied directly to affected part, it can also be used to preparation treatment
The drug of hyperthyroidism, the preferably described drug are patch or patch.
A kind of patche for treating hyperthyroidism of the present invention or medicine patch contain above-mentioned methimazole micro emulsion or above-mentioned
Patch or patch are affixed on skin position appropriate and play therapeutic effect by methimazole micro emulsion gel.
The present invention by methimazole, transdermal drug delivery system, micro emulsion and micro emulsion gel use in conjunction, be made toxic side effect it is small,
The anti-hyperthyroidism class drug that stability is good, curative effect is high.It there is no the open report of methimazole micro emulsion and micro emulsion gel preparation capable of permeating skin at present
Road, the present invention can significantly improve Drug loading capacity using micro emulsion and micro emulsion gel, significantly increase the transdermal ability of methimazole,
And effectively extend action time, increase unit area and accumulate infiltration capacity, and then improve curative effect, reduces administration number of times, convenient drug administration.
Methimazole is the strong drug of hydrophily, it is difficult to penetrate skin, in order to reach better curative effect, inventor be have passed through
Long-term research selects reverse microemulsion as carrier, and reverse microemulsion stability is good, and partial size is small, is easy to increase through skin follicle hole
Add the compatibility of difficult osmotic drug and skin, change lipid bilayer structure, increases skin hydrophily to promote hydrophily
The transdermal penetration of drug, and the weight proportion of each component has been determined.
Methimazole micro emulsion of the invention, methimazole micro emulsion gel and preparation method thereof are made into one with reference to the accompanying drawing
Walk explanation.
Detailed description of the invention
Fig. 1 is that ointment and embodiment accumulate percent penetration column diagram (n=3)；
Fig. 2 be different penetrating agents Ligustrazine hydrochloride curve (n=3,NMP；Azone；The third two
Alcohol；Menthol；Blank micro emulsion)；
Fig. 3 be micro emulsion containing not same amount azone accumulate infiltration capacity (5% azone；3% azone；
2% azone；1% azone；Blank)；
Fig. 4 is methimazole micro emulsion, micro emulsion gelWith commercially available ointmentIt is accumulative
Penetration curve.
Specific embodiment
The following are implementation examples and test data, etc, but the contents of the present invention are not limited to the range of these embodiments.
1, the present invention has investigated oily phase, surfactant, cosurfactant at 37 DEG C to the solvability of MML, and
Using saturation solubility as index, saturation solubility measurement result is as shown in table 1:
Solubility of the MML in different solvents at 1.37 DEG C of table
As shown in Table 1: oil is preferably mutually IPM, and surfactant is preferably Tween 80, and cosurfactant is preferably nothing
Water-ethanol.
2, the present invention by transdermal permeation in vitro investigated a variety of transdermal enhancers (azone, propylene glycol, menthol,
NMP) to the influence of MML Ligustrazine hydrochloride, to accumulate infiltration capacity as index, as shown in Figure 1, the preferred azone of transdermal enhancer.
And combine transdermal enhancer to the size of skin irritation, influence of the different content azone to MML transdermal penetration has been investigated, has such as been schemed
Shown in 2, preferably azone content is 5% [i.e. azone: MML=1.09:1 (w/w)].
Embodiment 1:
Preparation process:
1) oily phase, the surfactant, cosurfactant of recipe quantity are weighed, is uniformly mixed under magnetic agitation；
2) water for weighing recipe quantity is added dropwise in above-mentioned mixed solution, under magnetic agitation after mixing, obtains sky
White microemulsion solution；
3) transdermal enhancer of recipe quantity is added in microemulsion solution, is uniformly mixed under magnetic agitation；
4) recipe quantity methimazole bulk pharmaceutical chemicals are added in blank micro emulsion, ultrasonic temperature is 25 DEG C, and 5min is completely dissolved
Afterwards, transparent drug containing microemulsion solution is obtained；
5) gel-type vehicle of recipe quantity is added in above-mentioned micro emulsion, is stirred evenly after it is sufficiently swollen up to uniform
Micro emulsion gel.
Embodiment 2:
Preparation method: with embodiment 1
Embodiment 3:
Preparation method: with embodiment 1
Embodiment 4:
Preparation method: with embodiment 1
Embodiment 5:
Preparation method: with embodiment 1
Embodiment 6:
Preparation method: with embodiment 1
One transdermal permeation in vitro of test example:
Prepare micro emulsion (MML:IPM:Tween80: dehydrated alcohol: water: azone=1:2.04:6.76:6.76:4:1.09, w/
W) it with micro emulsion gel (micro emulsion: carbomer=54.13:1, w/w) preparation capable of permeating skin, is done with commercially available methimazole ointment (good fine jade is sub-)
Cumulative in vitro infiltration capacity comparative experiments.
(1) laboratory apparatus: SH-3 heats magnetic stirring apparatus, TP-3A intelligence penetrating absorption instrument, KQ3200E medical ultrasonic
Washer, 1260 type high performance liquid chromatograph of Agilent.
(2) receive selecting for medium: MML is water soluble drug, and solubility may be up to 200.00mg/mL in water, measurement
Saturation solubility of the MML in physiological saline is 146.77mg/mL, it is sufficient to reach sink conditions, therefore can select physiology salt
Water makees reception medium.
(3) skin processing method: putting to death after SD rat (180~220g of weight) is anesthetized with ether, young with ophthalmically acceptable scissors
By skin peeling after the thin hair removed on skin of back.By on the inside of skin subcutaneous fat and adhesion object carefully picked with blade
It removes, after normal saline flushing, places it in magnetic agitation 2h in normal saline solution, after going through the integrality of skin,
Skin is placed in hermetic bag and is sealed, is placed in -80 DEG C of refrigerators and saves.Before experiment, takes out mouse skin and be placed in normal saline solution
Stirring is rinsed, and the visible breakage of any naked eyes must not be had by going through mouse skin.
(4) experimental method: being tested using TP-3A intelligence penetrating absorption instrument, and selected rat dorsum skin is fixed
Between reception tank and administration pond, cuticula is upward.Release area is 1.31cm2, receiving pool volume is 20mL.By methimazole
Reverse microemulsion 0.326g, micro emulsion gel 0.326g and commercially available ointment 0.326g are spread evenly across respectively on the skin of supply pool side.
Receive medium to be added in reception tank, be stirred in 32 ± 1 DEG C of water bath with thermostatic control constant speed, respectively at 1,2,3,4,6,8,10,12,16, for 24 hours
It takes and receives medium 1mL, while the blank reception medium of equivalent equality of temperature being added into acceptance pool.
(5) assay: the sample solution that each time point is taken out is filtered with 0.45 μm of filter membrane, discards primary filtrate, take
Subsequent filtrate receives the content of drug in medium with high effective liquid chromatography for measuring.Chromatographic condition: Diamonsil C18(200mm×
4.6mm, 5 μm) chromatographic column, mobile phase: acetonitrile-water (7:93), wavelength: 254nm, flow velocity: 1.0mL/min, sample volume: 10 μ L,
Column temperature: 25 DEG C.Concentration in each time is calculated with sample solution and the peak area ratio of reference substance solution, and brings formula into and calculates and tire out
Product infiltration capacity (Q), and draw accumulation penetration curve.
It is as follows to accumulate infiltration capacity formula: the drug concentration measured through HPLC is corrected with formula (1-1), substitutes into formula
Accumulation infiltration capacity (Q, the μ g/cm of (1-2) calculating drug2)。
In formulaThe cumulative concentration of time drug；
CiThe measurement concentration of-t time prodrug；
CnThe measurement concentration of-t time drug；
V-sample volume；
V0The volume of solution in-acceptance pool；
Qn- t chronomere's area accumulates infiltration capacity；
The effective diffusion area of A-skin.
Add up infiltration capacity as ordinate using unit area, the time is abscissa mapping, draws accumulation penetration curve.
2. methimazole micro emulsion, micro emulsion gel and commercially available ointment Drug loading capacity and assay result:
The Drug loading capacity of methimazole micro emulsion is 120mg/g, considerably beyond the content of dispersion of commercially available ointment, in order to it is commercially available soft
Cream is compareed, and the drugloading rate of micro emulsion and micro emulsion gel is fixed as 46.00mg.Content of dispersion measurement result is shown in Table 2.
The content of dispersion (unit: mg/g) of 2 methimazole micro emulsion of table, micro emulsion gel and commercially available ointment
3. accumulative infiltration capacity measurement result:
As shown in Figure 3 the result shows that, methimazole micro emulsion and micro emulsion gel preparation capable of permeating skin for 24 hours in sustained release drugs.
Infiltration capacity result: micro emulsion (10687.0 ± 1445.1 μ g/cm is accumulated in for 24 hours2) more commercially available ointment (3414.9 ± 1305.7 μ g/
cm2) 3.13 times high, micro emulsion gel (8674.6 ± 1259.6 μ g/cm2) 2.54 times higher than commercially available ointment.Steady-state permeation rate knot
Fruit: micro emulsion gel (346.0 ± 32.3 μ g/cm2/ h) it is higher than micro emulsion (271.3 ± 148.3 μ g/cm2/ h) and commercially available ointment (142.7
±60.5μg/cm2/ h), the steady-state permeation rate of micro emulsion gel is 2.42 times of commercially available ointment.It can be seen that methimazole is micro-
Cream and micro emulsion gel can effectively increase drug transit dose, improve curative effect of medication.
Test example two
The present invention has investigated the microemulsion formulation of Examples 1 to 6 to MML Ligustrazine hydrochloride by transdermal permeation in vitro
Influence, and compared using accumulating infiltration capacity as index and commercially available ointment, accumulation percent penetration (commercially available ointment is 100%) is such as
Shown in Fig. 1.
The accumulation infiltration capacity of micro emulsion gel is higher than ointment, and the accumulation infiltration capacity of micro emulsion is higher than micro emulsion gel, thus may be used
Know that the transdermal penetration ability of micro emulsion and micro emulsion gel according to the present invention is above commercially available ointment.
Micro emulsion gel prepared by the present invention can also with soft comfortable, ventilative water permeability is good and backing through silicic acid anhydride
Layer material (such as: spunlace non-woven cloth, cotton) and surface patch Protective coatings (such as polyester, poly- second through silicone oil release treatment
Alkene etc.) combine micro emulsion gel patch is made.Micro emulsion gel and gel adhesive can be used directly in affected part.
Embodiment described above only describe the preferred embodiments of the invention, not to model of the invention
It encloses and is defined, without departing from the spirit of the design of the present invention, those of ordinary skill in the art are to technical side of the invention
The various changes and improvements that case is made should all be fallen into the protection scope that claims of the present invention determines.
Claims (20)
1. a kind of methimazole micro emulsion, which is characterized in that contain following component: methimazole, surfactant, helps table at oily phase
Face activating agent, water and transdermal enhancer, weight ratio are 1:(1.40 ~ 4.25): (5.13 ~ 15.45): (5.13 ~
15.45): (1.40 ~ 8.32): (0.26 ~ 1.26)；
Wherein, the oil is mutually poly- selected from soybean oil, olive oil, oleic acid, isopropyl myristate (IPM), ethyl oleate and oleic acid
One of glycol glycerin ester；
The surfactant is selected from Labraso (Labrasol), Crodaret, spits
At least one of warm 20(Tween 20) and Tween 80 (Tween 80)；
The cosurfactant is selected from dehydrated alcohol, propylene glycol, isopropanol, glycerine, polyethylene glycol 400 (PEG 400), two
At least one of ethylene glycol monomethyl ether (TP)；
The transdermal enhancer is selected from one of azone, menthol, N-Methyl pyrrolidone (NMP) and propylene glycol.
2. methimazole micro emulsion according to claim 1, it is characterised in that: the weight ratio is 1:(1.40 ~ 4.21):
(5.13 ~ 10.35): (5.13 ~ 10.35): (2.76 ~ 8.32): (0.69 ~ 1.22).
3. methimazole micro emulsion according to claim 2, it is characterised in that: the weight ratio is 1:2.04:6.76:
6.76:4:1.09.
4. methimazole micro emulsion according to claim 1, it is characterised in that: the oil is mutually isopropyl myristate
(IPM).
5. methimazole micro emulsion according to claim 1, it is characterised in that: the surfactant is Tween 80 (Tween
80).
6. methimazole micro emulsion according to claim 1, it is characterised in that: the cosurfactant is dehydrated alcohol.
7. methimazole micro emulsion according to claim 1, it is characterised in that: the transdermal enhancer is azone.
8. the preparation method of the described in any item methimazole micro emulsions of claim 1-7, it is characterised in that: the following steps are included:
1) oily phase, the surfactant, cosurfactant of the weight proportion are weighed, is uniformly mixed under magnetic agitation；
2) transdermal enhancer is added in the solution that step 1) obtains, is uniformly mixed under magnetic agitation；
3) it in the mixed solution for obtaining water droplet addition step 2, is uniformly mixed under magnetic agitation up to blank microemulsion solution；
4) methimazole bulk pharmaceutical chemicals are added in the blank microemulsion solution that step 3) obtains, after ultrasound is completely dissolved, are obtained
Bright methimazole micro emulsion.
9. according to the method described in claim 8, ultrasonic time is 3 ~ 7 it is characterized by: ultrasonic temperature is 25 ~ 35 °C
min。
10. the application of the described in any item methimazole micro emulsions of claim 1-7, it is characterised in that: be used for preparation treatment
The drug of hyperthyroidism.
11. the application of methimazole micro emulsion according to claim 10, it is characterised in that: the drug is patch or patch
Agent.
12. a kind of methimazole micro emulsion gel, it is characterised in that: to the described in any item methimazole micro emulsions of claim 1-7
Middle addition gel-type vehicle is swollen, uniform semisolid preparation obtained is methimazole micro emulsion gel after mixing evenly.
13. methimazole micro emulsion gel according to claim 12, it is characterised in that: the gel-type vehicle is selected from card wave
Nurse, methylcellulose, sodium carboxymethylcellulose and poloxamer.
14. methimazole micro emulsion gel according to claim 13, it is characterised in that: the gel-type vehicle is carbomer.
15. methimazole micro emulsion gel according to claim 12, it is characterised in that: the weight of the gel-type vehicle and micro emulsion
Amount is than being 1:(16.23 ~ 61.20).
16. methimazole micro emulsion gel according to claim 15, it is characterised in that: the weight of the gel-type vehicle and micro emulsion
Amount is than being 1:(31.55 ~ 58.48).
17. methimazole micro emulsion gel according to claim 16, it is characterised in that: the weight of the gel-type vehicle and micro emulsion
Amount is than being 1:54.13.
18. the application of the described in any item methimazole micro emulsion gels of claim 12-17, it is characterised in that: be used for making
The drug of standby treatment hyperthyroidism.
19. application according to claim 18, it is characterised in that: the drug is patch or patch.
20. a kind of patche for treating hyperthyroidism or medicine patch, it is characterised in that: containing described in claim any one of 1-7
Methimazole micro emulsion or contain the described in any item methimazole micro emulsion gels of claim 12-17.
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