CN106619490A - Levodopa transdermal patch and preparation method thereof - Google Patents
Levodopa transdermal patch and preparation method thereof Download PDFInfo
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- CN106619490A CN106619490A CN201710043790.5A CN201710043790A CN106619490A CN 106619490 A CN106619490 A CN 106619490A CN 201710043790 A CN201710043790 A CN 201710043790A CN 106619490 A CN106619490 A CN 106619490A
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- levodopa
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
- A61K31/198—Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- 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
Abstract
The invention relates to a levodopa transdermal patch, which is prepared from the following components in parts by weight: 0.1-10 parts of levodopa, 0-10 parts of auxiliary medicines, 5-40 parts of a non-ionic surface active agent, 1-30 parts of a co-surfactant, 1-20 parts of an oil phase, 0.1-1 part of an antioxidant, 15-60 parts of a water phase, 2-40 parts of disperse matrix and 0.1-1 part of a pH regulator. The novel transdermal patch takes the levodopa as an effective active ingredient, nano-emulsion as a carrier and a high-molecular polymer as matrix, and is used for treating Parkinson's disease and Parkinsonism.
Description
Technical field
The present invention relates to the preparing technical field of medical preparation, especially a kind of preparation skill of new transdermal patch product
Art.
Background technology
The neuropathological feature of Parkinson's (PD) is the denaturation of dopamine neuron and neurology in basal nuclei
Feature it is weak tremble, bradykinesia and equilibrium problem.It is estimated that the people more than 1,000,000 suffers from Parkinson's.From current
For medical level, Parkinsonian control and treatment remain a difficult problem.Anticholinergic drug such as levodopa is controlled for suiting the medicine to the illness
Treat the first medicine of PD.Levodopa (LD) fully controls the symptom of the disease in the getting up early stage of Parkinson.However, medicine
In use for some time validity will be gradually lowered thing, and key factor is in levodopa in the decarboxylation of brain peripheral tissues, O～methyl
Change, transamination and oxidation, significantly decrease bioavilability and subsequent therapeutic effect.
When LD is used alone, heavy dose is needed, because only that minimum dosage is steadily transported to central nervous system
In.In view of carbidopa can suppress the glutamic acid of periphery levodopa and be not passed through blood-brain barrier, generally in levodopa system
Give levodopa metabolic enzyme inhibitor in agent to improve the bioavilability of levodopa.At present, some medicines are had been developed that
Thing Transmission system.It is a kind of immediate release drug delivery system for LD, is made up of the LD for being combined with carbidopa
Tablet.Benserazide is another kind of DCI, and it is used in combination referred to as with LDThis two kinds of preparations, all
Periphery metabolism and the side effect such as nausea and vomiting of LD, but the Long-Time Service in control dyskinesia and with LD can be reduced
It is invalid on relevant motor fluctuations.
A kind of levodopa novel formulation containing carbidopa of viscogel formRecently by Sweden
NeoPharma AB, Uppsala list a company, and can significantly reduce the motor complication of disturbances in patients with Parkinson disease.The therapy intranasal
Duodenal probe or percutaneous electrode are directly administered to duodenum.Levodopa successive administration may be realized with this system, but
Still there is the restriction that stomach transports barrier.FromThe experience of accumulation and experimental infusion studies show, maintain surely
Fixed blood plasma LD concentration and low assessment level is avoided to seem effectively to reduce " switch " time, so as to increasing " switch " time but not pressing down
Dyskinesia processed, and compared with standard oral formulations, reduce the dyskinetic order of severity.However, these infusion therapies are to suffering from
It is extremely inconvenient for person.
Nanoemulsions are also called microemulsion, are according to matching somebody with somebody in right amount by water phase, oil phase, surfactant and cosurfactant
Than making, with the transparent or semitransparent system that low viscosity, isotropic thermodynamics and kineticses are stable.Its advantage is to increase
The solubility of insoluble drug, improves medicine stability and bioavilability, many insoluble drugs are made and have after nano-emulsion
Sustained release and targeting；Nano-emulsion good biocompatibility, it is biodegradable, therefore, it is used as fat-soluble medicine and to water sensitive
The carrier of medicine, it is possible to reduce the excitant and toxic and side effect of medicine, Thermodynamically stable, makes long not stratified, not breakdown of emulsion.
Because dissolubility of the levodopa in neutral pH is poor, there is presently no for intravenous, subcutaneous or intrathecal drug delivery
Pharmaceutical preparation listing.And can be effectively improved the solubility property and percutaneous abilities of LD by means of nano-emulsion technology.Relative to mouth
Formulation, the transdermal patch of levodopa has excellent performance, is expected to solve the deficiency of conventional dosage forms.The formulation will pass through
The blood plasma scope for reducing LD improves the LD dispensings of PD patient, and this will reduce " closing time phase ", and extend " closing time phase " and subtract
The time of " opening the phase " is reached less.
The content of the invention
For the problems referred to above that prior art is present, the applicant provides a kind of levodopa transdermal patch and its preparation
Method.The present invention is new with high molecular polymer as matrix with nanoemulsions as carrier with levodopa as effective active composition
Type transdermal patch, for treating Parkinson's and parkinson's syndrome.
Technical scheme is as follows：
It is an object of the invention to provide it is a kind of effectively, the lasting transdermal patch of conveying levodopa, for Parkinson's and
The treatment of parkinsonism.
It is a further object of the present invention to provide a kind of nanoscale emulsion technology of high percutaneous absorbability, for the conveying of medicine
Carrier.The nanoscale emulsion is by groups such as levodopa, nonionic surfactant, cosurfactant, oil and disperse matrix
Into.
A kind of levodopa transdermal patch, the transdermal patch is made up of the component of following parts by weight：
Levodopa：0.1 part～10 parts；
Ancillary drug：0 part～10 parts；
Nonionic surfactant：5 parts～40 parts；
Cosurfactant：1 part～30 parts；
Oil phase：1 part～20 parts；
Antioxidant：0.1 part～1 part；
Water phase：15 parts～60 parts；
Disperse matrix：2 parts～40 parts；
PH adjusting agent：0.1 part～1 part.
The water is preferably mutually deionized water.
The concrete preparation process of the levodopa transdermal patch is as follows：(1) by oil phase, nonionic surfactant, altogether
After surfactant mixing, it is well mixed by mechanical agitation；
(2) by levodopa, ancillary drug and deionized water mix, and pH adjusting agent is added dropwise until mixed solution is completely molten
Solution；
(3) under mechanical agitation, the solution that step (2) is obtained is added dropwise in the system that step (1) is obtained,
Solution becomes transparent gel-form solid from liquid；
(4) the gel solution pH in the system for being obtained step (3) with pH adjusting agent is adjusted between 4～7；
(5) weigh after disperse matrix is well mixed with the deionized water containing antioxidant, under mechanical stirring with step
(4) the system mixing for obtaining obtains final product transparent clear gel.
Twice plus the amount of deionized water is added up as the amount of total water phase, such as above 15 parts～60 parts.Wherein for the first time
Seldom, main purpose is dissolving medicine to the amount of the deionized water of addition.It is also total that twice the amount of addition pH adjusting agent is added up
The consumption of pH adjusting agent, each consumption is defined by the effect (such as solution colour, pH value) for reaching needs.
Preferably, the ancillary drug is carbidopa and/or benserazide.
Preferably, the nonionic surfactant be olein, rilanit special, in Tween 80, or sorbester p17
One kind or two kinds.
Preferably, the cosurfactant is isopropanol, PEG400, or tetraethylene-glycol.
Preferably, the oil phase is isopropyl palmitate, castor oil, olive oil, peanut oil, or rapeseed oil.
Preferably, the antioxidant is catechol, ascorbic acid, L～cysteine hydrochloride, or sodium pyrosulfite.
Preferably, the disperse matrix is that guar gum, polyvinyl alcohol, polyethylene glycol, polyvinylpyrrolidone, or shell are poly-
Sugar.
Preferably, the pH adjusting agent is hydrochloric acid, acetic acid, triethylamine, NaOH, or triethanolamine.
Particularly, the applicant provides a kind of levodopa transdermal patch, is made up of following component：
Medicine：Levodopa；
Ancillary drug：DCI carbidopa；
Nonionic surfactant：Olein, rilanit special；
Cosurfactant：Tetraethylene-glycol；
Oil phase：Isopropyl palmitate；
Antioxidant：Sodium pyrosulfite；
Water phase：Deionized water；
Disperse matrix：Guar gum；
PH adjusting agent：1% NaOH solution.
Preferably, the levodopa transdermal patch by following percentage into being grouped into：
Levodopa 2%, carbidopa 2%, isopropyl palmitate 10%, rilanit special 20%, glycerin mono-fatty acid ester
10%, tetraethylene-glycol 15%, guar gum 20%, sodium pyrosulfite 0.2%, deionized water 20.5%, pH adjusting agent
0.3%.
Present invention also offers a kind of transdermal patch comprising nanoemulsions, by by levodopa, carbidopa, glycerine
Monoleate, rilanit special, tetraethylene-glycol carries out proportioning, reasonable mixture ratio, especially from guar gum as drug storage base
Matter.
The present invention is beneficial to be had technical effect that：
The Transdermal Therapeutic System that the present invention passes through offer LD, LD and DCI are allocated together, produce the medicine wanted
Dynamic attribute, i.e., interior over a long time more stable LD PCs, solution " switch " fluctuation of tradition Dopar at present,
" agent end " effect etc..
Due to the barrier action of skin, levodopa and carbidopa are difficult to be absorbed by organisms by skin barrier.This
Invention is wrapped in levodopa and carbidopa in nanoemulsions, can effectively increase levodopa and carbidopa transdermal
Absorbability, so as to expand the application of levodopa and carbidopa external preparation field.
What the present invention was provided prepares the preparation method of levodopa transdermal patch, which includes levodopa medicine, auxiliary
Medicine and surfactant and cosurfactant etc. are helped, medicament-carried nano emulsion is defined, the particle diameter of its nanoemulsions is less than
60nm, meanwhile, it can promote the Transdermal absorption of levodopa/carbidopa, and better than prior art.It is left-handed that the present invention is provided
DOPA transdermal patch, the preparation provides long-acting slow-releasing and controlled-releasing action, and relative to oral formulations, it is little that release time can extend to 24
When；The levodopa transdermal patch that the present invention is provided, keeps stable in the stability study of 3 months.
In addition, the method that the present invention provides the pharmaceutical preparation prepared and using the present invention.The method efficiently solves left-handed
The low water solubility of DOPA and low percutaneous absorbtion problem rate.
Description of the drawings
Fig. 1 is to carry medicine and not the DLS figures of medicament-carried nano emulsion；
Fig. 2 is levodopa transdermal test in vitro cumulant (Q) vs times (t) figures；
Particle diameter vs times (t) figure of Fig. 3 medicament-carried nano preparations.
Specific embodiment
With reference to the accompanying drawings and examples, the present invention is specifically described, but is not limited to the scope of the present invention.
Embodiment 1～5
(1) levodopa transdermal patch composition is shown in Table 1：
Table 1
(2) preparation method of levodopa transdermal patch
(A) by oil phase, nonionic surfactant after cosurfactant mixing, is well mixed by mechanical agitation；
(B) by levodopa, ancillary drug and deionized water mix, and pH adjusting agent is added dropwise until mixed solution is completely molten
Solution；
(C) under mechanical agitation, the solution that step (B) is obtained is added dropwise in the system that step (A) is obtained,
Solution becomes transparent gel-form solid from liquid；
(D) the gel solution pH in the system for being obtained step (C) with pH adjusting agent is adjusted between 4～7, wherein embodiment
1 to adjust to pH be 5.2, and it is 4.8 that embodiment 2 is adjusted to pH, and it is 6.7 that embodiment 3 is adjusted to pH, and embodiment 4 is adjusted to pH for 4.2,
Embodiment 5 is adjusted to pH for 6.2.
(E) after weighing disperse matrix and being well mixed containing antioxidant deionized water, under mechanical stirring with step (4)
The system mixing for obtaining obtains final product transparent clear gel.
Test case 1：Influence research of the different pharmaceutical content to nanoemulsions particle diameter
(1) test specimen：Preparation method according to step (A)～(D) in the formula shown in table 2 and embodiment is prepared not
Sample 1～5 containing disperse matrix emulsion.
The preparation of the sample 1～5 of table 2
(2) particle size determination：Using Malvern Zetasizer 3000HSA Analyzer testing result particle diameters, before measure, will
Sample deionized water dilutes 30 times.
(3) experimental result：It is shown in Table 3.
The different sample particle diameter sizes of table 3
| Title | Sample 1 (nm) | Sample 2 (nm) | Sample 3 (nm) | Sample 4 (nm) | Sample 5 (nm) |
| Average grain diameter (nm) | 60 | 62 | 73 | 60 | 112 |
Fig. 1 is the average grain diameter contrast of sample 1 and sample 5, it can be seen that the particle diameter of pastille nanoemulsions is less than not pastille
Nanoemulsions, this explanation levodopa and carbidopa have also assisted in the assembling of nanoemulsions, stably having to nano-micelle
Significant impact.
Test case 2：Permeation test in vitro
(1) test specimen：Levodopa transdermal patch prepared by embodiment 1, the patch includes matrix guar gum；
(2) reference substance：The nanoemulsions without disperse matrix are prepared by sample 1 in table 2；
(3) test method：The process of skin：The male rat of 200g or so is taken, after being anaesthetized with 5% yellow Jackets, will
Belly mouse hair rejects clean, and cervical dislocation puts to death rat, peels off skin, removes subcutaneous fat, dry with 0.5% normal saline flushing
Only store for future use after～70 DEG C.
Penetrating absorption：Logan types intelligence penetrating absorption instrument, sudden and violent leakage skin area is 1.77cm in diffusion cell2, reception tank appearance
Product is 12mL.Take the mouse skin handled well and be placed in diffusion cell mesocuticle upwards, PBS liquid 12mL are added in reception tank, put 32 ± 1
DEG C water bath with thermostatic control in, gel obtained in 0.2g embodiments 1 is uniformly applied into skin surface after balance half an hour, respectively at 1,3,
6th, 2.0mL solution is extracted from reception tank within 9,12,24 hours, and injects the new liquid of equivalent, under 284nm wavelength, using efficient liquid
Phase method carries out assay.
Calculate and permeate percentage amounts Q without the accumulation of time, with the time (h) as abscissa, accumulation infiltration capacity Q is ordinate work
Figure.
Accumulation infiltration capacity Q is calculated as follows：
Wherein, Mt：Unit area cumulative release amount；M∞：Drugloading rate in unit area application；V：Reception liquid volume；A：
Diffusion cell open area；Cn：The concentration of n-th sampling.Experimental result is shown in Table 4.
Levodopa unit area accumulation infiltration capacity M in the different preparations of table 4t(μg/cm2)
Fig. 2 is listed in transdermal test in vitro release test, and the cumulative in vitro of levodopa is oozed in transdermal patch and control sample
Saturating percentage composition, test shows that the transdermal patch rate of release containing matrix is faster than without substrate nano emulsion, wherein levodopa
In transdermal patch, the levodopa transdermal test in vitro burst size of 24 hours is be close to the 10% of total dose.
Fig. 3 is the result of study by particle size analyzer to the stability of the nanoemulsions in sample 1.As a result show in room temperature bar
Under part, in week age, the change of size very little of nanoemulsions shows that nanoemulsions have very high stability.
Claims (11)
1. a kind of levodopa transdermal patch, it is characterised in that the transdermal patch is made up of the component of following parts by weight：
Levodopa：0.1 part～10 parts；
Ancillary drug：0 part～10 parts；
Nonionic surfactant：5 parts～40 parts；
Cosurfactant：1 part～30 parts；
Oil phase：1 part～20 parts；
Antioxidant：0.1 part～1 part；
Water phase：15 parts～60 parts；
Disperse matrix：2 parts～40 parts；
PH adjusting agent：0.1 part～1 part.
2. levodopa transdermal patch according to claim 1, it is characterised in that the ancillary drug be carbidopa and/
Or benserazide.
3. levodopa transdermal patch according to claim 1, it is characterised in that the nonionic surfactant is oil
Acid glyceride, rilanit special, the one kind in Tween 80, or sorbester p17 or two kinds.
4. levodopa transdermal patch according to claim 1, it is characterised in that the cosurfactant is isopropanol,
PEG400, or tetraethylene-glycol.
5. levodopa transdermal patch according to claim 1, it is characterised in that the oil phase is isopropyl palmitate, castor
Sesame oil, olive oil, peanut oil, or rapeseed oil.
6. levodopa transdermal patch according to claim 1, it is characterised in that the antioxidant is catechol, anti-bad
Hematic acid, L～cysteine hydrochloride, or sodium pyrosulfite.
7. levodopa transdermal patch according to claim 1, it is characterised in that the disperse matrix is guar gum, poly- second
Enol, polyethylene glycol, polyvinylpyrrolidone, or shitosan.
8. levodopa transdermal patch according to claim 1, it is characterised in that the pH adjusting agent is hydrochloric acid, acetic acid,
Triethylamine, NaOH, or triethanolamine.
9. a kind of levodopa transdermal patch, it is characterised in that levodopa transdermal patch is made up of following component：
Medicine：Levodopa；
Ancillary drug：DCI carbidopa；
Nonionic surfactant：Olein, rilanit special；
Cosurfactant：Tetraethylene-glycol；
Oil phase：Isopropyl palmitate；
Antioxidant：Sodium pyrosulfite；
Water phase：Deionized water；
Disperse matrix：Guar gum；
PH adjusting agent：1% NaOH solution.
10. levodopa transdermal patch according to claim 10, it is characterised in that the levodopa transdermal patch by with
Lower percentage into being grouped into：
Levodopa 2%, carbidopa 2%, isopropyl palmitate 10%, rilanit special 20%, glycerin mono-fatty acid ester 10%,
Tetraethylene-glycol 15%, guar gum 20%, sodium pyrosulfite 0.2%, deionized water 20.5%, pH adjusting agent 0.3%.
The 11. levodopa transdermal patches according to any one of claim 1～10, it is characterised in that concrete preparation process is such as
Under：
(1) by oil phase, nonionic surfactant after cosurfactant mixing, is well mixed by mechanical agitation；
(2) by levodopa, ancillary drug and deionized water mix, and pH adjusting agent is added dropwise until mixed solution is completely dissolved；
(3) under mechanical agitation, the solution that step (2) is obtained is added dropwise in the system that step (1) is obtained, solution
Become transparent gel-form solid from liquid；
(4) the gel solution pH in the system for being obtained step (3) with pH adjusting agent is adjusted between 4～7；
(5) weigh after disperse matrix is well mixed with the deionized water containing antioxidant, under mechanical stirring with step (4)
To system mixing obtain final product transparent clear gel.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101933902A (en) * | 2009-07-03 | 2011-01-05 | 重庆医科大学 | Granisetron hydrochloride microemulsion-based gel and preparation method thereof |
| CN102335131A (en) * | 2011-10-10 | 2012-02-01 | 山西仁源堂药业有限公司 | Osthole micro emulsion, osthole micro emulsion sustained-release patch and preparation method thereof |
| CN103442693A (en) * | 2010-11-15 | 2013-12-11 | 纽罗德姆有限公司 | Continuous administration of L-dopa, dopa decarboxylase inhibitors, catechol-O-methyl transferase inhibitors and compositions for same |
| CN105030671A (en) * | 2015-07-14 | 2015-11-11 | 哈尔滨医科大学 | Methimazole microemulsion, methimazole microemulsion-based gel and preparation method and application of methimazole microemulsion |
-
2017
- 2017-01-19 CN CN201710043790.5A patent/CN106619490A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101933902A (en) * | 2009-07-03 | 2011-01-05 | 重庆医科大学 | Granisetron hydrochloride microemulsion-based gel and preparation method thereof |
| CN103442693A (en) * | 2010-11-15 | 2013-12-11 | 纽罗德姆有限公司 | Continuous administration of L-dopa, dopa decarboxylase inhibitors, catechol-O-methyl transferase inhibitors and compositions for same |
| CN102335131A (en) * | 2011-10-10 | 2012-02-01 | 山西仁源堂药业有限公司 | Osthole micro emulsion, osthole micro emulsion sustained-release patch and preparation method thereof |
| CN105030671A (en) * | 2015-07-14 | 2015-11-11 | 哈尔滨医科大学 | Methimazole microemulsion, methimazole microemulsion-based gel and preparation method and application of methimazole microemulsion |
Non-Patent Citations (3)
| Title |
|---|
| JUN-ICHI SUDO ET AL.: "Transdermal absorption of L-dopa from hydrogel in rats", 《EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES》 * |
| 詹水明 等: "左旋多巴固体脂质纳米粒的制备及包封率测定", 《中国医院药学杂志》 * |
| 颜耀东: "《缓释控制制剂的设计与开发》", 31 May 2006, 中国医药科技出版社 * |
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Application publication date: 20170510 |