CN109481419A - A kind of Rosiglitazone nanometer formulation and its preparation method and application - Google Patents
A kind of Rosiglitazone nanometer formulation and its preparation method and application Download PDFInfo
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- A61K31/00—Medicinal preparations containing organic active ingredients
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
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- A—HUMAN NECESSITIES
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Abstract
The invention discloses a kind of Rosiglitazone nanometer formulations in the purposes for treating reangiostenosis, a kind of Rosiglitazone composition, including Rosiglitazone, polylactide-polyglycolic acid copolymer, lecithin and distearoylphosphatidylethanolamine-polyethylene glycol 2000, a kind of Rosiglitazone nanometer formulation, the nanoparticle that the nanometer formulation is formed by Rosiglitazone, polylactide-polyglycolic acid copolymer, lecithin and distearoylphosphatidylethanolamine-polyethylene glycol 2000, its structure is spherical structure, and particle size is between 250-300 nanometers.A kind of preparation method of Rosiglitazone nanometer formulation, this Rosiglitazone nanometer formulation can effectively treat the Restenosis occurred after endovascular stent implantation, and can reduce the toxicity of Rosiglitazone, improve biological safety.
Description
Technical field
The present invention relates to pharmaceutical fields, and in particular to a kind of Rosiglitazone nanometer formulation and its preparation method and application.
Background technique
Cardiovascular and cerebrovascular disease is currently one of the main reason for leading to death.Wherein, hemadostewnosis or occlusion are to lead to brain
The main reason for stroke.Currently, endovascular treatment and angioplasty are treatment one of hemadostewnosis or the effective means of occlusion,
Brain blood supply can be improved rapidly.But will appear reangiostenosis after intravascular stent implantation or form thrombus etc., it is traditional
Therapeutic scheme is the implantable intravascular bracket again at restenosis." Layer cake " the formula treatment of this support casing bracket undoubtedly will lead to
The drawbacks such as the generation of the reduction of blood vessel cavity area, again restenosis and the formation of advanced thrombus.Although using medicament elution at present
Bracket reduces the generation of Restenosis, but there are still expensive, can not entirely prevent Restenosis
Generation.Clinically need a kind of efficient, reasonable price and therapeutic scheme easy to use.By the nanometer system of anti-angiogenic restenosis
Agent is that the drug of suppressing cell reproduction is wrapped in nanometer formulation for treating the clinical research of reangiostenosis its method, will be received
After metric system agent to narrow positions, drug enters endangium by sustained release or controlled release and plays anti-restenosis effect, in vivo not
It leaves implantation material (such as rack beams) and has many advantages, such as, will be received later by more patients.
Rosiglitazone (Rosiglitazone) chemical name is 5- { 4- [2- (methyl -2- pridylamino) ethyoxyl] benzyl
Base } -2,4- thiazolidinedione, structure is as follows:
Rosiglitazone category Study of Thiazolidinedione derivatives as Insulin Sensitizer.Clinically commonly use the HCl preparation of Rosiglitazone, mouth
Clothes are mainly used for treating diabetes.
Rosiglitazone is the ligand of Peroxisome proliferator-activators γ (PPAR γ), in recent years studies have shown that
The drug also has other than increasing insulin sensitivity and inhibits the proliferation of vascular smooth muscle cells, migration and anti-inflammatory etc.
Effect, therefore Rosiglitazone is also used for the application prospect for the treatment of reangiostenosis.But the study found that traditional Rosiglitazone is oral
Preparation, has that degree of being absorbed and utilized is relatively low, and hemadostewnosis position blood concentration is lower, and the biological effect duration is long etc. many to be lacked
Point.Simultaneously as other target organs are produced side effect, such as liver function by the systemic effect that Rosiglitazone oral preparation generates
Damage, oedema, anaemia etc., therefore dysfunction of liver, have the patient of congestive heart failure that cannot use the drug.These factors
It all constrains Rosiglitazone and is used to treat the Restenosis occurred after endovascular stent implantation as drug.Clinic needs one
The new preparation of kind, so that the Restenosis occurred after the implantation of rosiglitazone in treating endovascular stent, while making Rosiglitazone
Site of action it is more acurrate, more limit to, can persistently maintain higher concentration in lesions position, generate lasting biological effect.From
And use scope is expanded, reduce the generation of side effect.
Summary of the invention
In view of the above-mentioned problems, the purpose of the present invention is to provide a kind of Rosiglitazone nanometer formulation and preparation method thereof and using
On the way.The nanometer formulation can effectively treat reangiostenosis.
To achieve the above object, present invention employs the following technical solutions:
A kind of Rosiglitazone nanometer formulation, the nanometer formulation include Rosiglitazone, polylactide-polyglycolic acid copolymer, ovum
The nanoparticle that phosphatide and distearoylphosphatidylethanolamine-polyethylene glycol 2000 are formed, nanometer formulation structure are micro-sphere structure,
Particle size is between 250~300 nanometers.
A kind of preparation method of Rosiglitazone nanometer formulation, preparation step are as follows:
(1) Rosiglitazone and polylactic acid-polyglycolic acid are dissolved with organic solvent；
(2) by lecithin and the organic solvent ultrasonic disperse of distearoylphosphatidylethanolamine-polyethylene glycol 2000, then
It adds water and continues ultrasonic disperse, and at 65 degrees Centigrade 30 minutes, be then cooled to room temperature；
(3) (1) acquired solution is added drop-wise in (2) solution, quickly stirs after dripping 3 minutes, then continues in room temperature
It is slowly stirred 1.5~2 hours, obtains Rosiglitazone nanometer formulation suspension；
(4) (3) described nanometer formulation suspension is centrifugated at 10000 turns, deionization is washed three times, and cured sieve is obtained
Lattice column ketone nanometer formulation.
This Rosiglitazone nanometer formulation is used to treat the Restenosis occurred after endovascular stent implantation.
Rosiglitazone nanometer formulation can reduce the toxic side effect of Rosiglitazone, improve Rosiglitazone mounting bracket blood vessel again
The concentration of narrow location, while Rosiglitazone has slow releasing function in restenotic lesions position.It is improved in reangiostenosis portion
The targeting of position, achievees the purpose that targeted therapy reangiostenosis.The present invention can be with slow release drug according to nanometer formulation
Feature uses the polylactide-polyglycolic acid copolymer of good biocompatibility for pharmaceutical carrier, utilizes lecithin and distearyl phosphorus
Acyl ethanol amine-polyethylene glycol 2000 is stabilizer, and Rosiglitazone is prepared into slow release nanometer formulation using nanoprecipitation method.This
The Rosiglitazone nanometer formulation of invention preparation shows preferable potential applicability in clinical practice.Wherein polylactide-polyglycolic acid copolymer
(PLGA) a kind of degradable functional polymer organic compound, has good biocompatibility, by U.S.'s food and medicine
Management board's approval can be used for a kind of intracorporal pharmaceutical carrier of people.
Compared with prior art, the present invention having the following beneficial effects:
1, the reangiostenosis after targeted therapy cerebrovascular stent implantation, the covering of Rosiglitazone nanometer formulation outer layer have
Lecithin and polyethylene glycol, therefore the nanometer formulation has a polymolecularity and internal macrocyclic characteristic, and hemadostewnosis position
Be frequently accompanied by inflammation, therefore vasopermeability increases, thus Rosiglitazone nanometer formulation can passive target be gathered in hemadostewnosis portion
Position, can be used for targeted therapy.
2, the toxic side effect of Rosiglitazone can be reduced.Rosiglitazone nanometer formulation energy higher concentration is gathered in lesion
Position, to reduce Rosiglitazone nanometer formulation in the aggregation of other internal organs, while Rosiglitazone nanometer formulation can also be sustained
Rosiglitazone maintains active drug concentration for a long time, avoids internal instantaneous blood concentration excessively high, so as to effectively reduce Roger
The toxic side effect of column ketone.
Detailed description of the invention
Fig. 1 is that Rosiglitazone of the invention prepares schematic diagram；
Fig. 2 is electron microscopic picture of the invention；
Fig. 3 is that Rosiglitazone free drug of the present invention and nanometer formulation compare the therapeutic effect that rat carotid artery damages
Figure.
Specific embodiment
Below by specific embodiment, the present invention is described in further detail:
As schematically shown in Figure 1, a kind of Rosiglitazone nanometer formulation, the nanometer formulation include Rosiglitazone, polylactic acid-polyethanol
The nanoparticle that acid copolymer, lecithin and distearoylphosphatidylethanolamine-polyethylene glycol 2000 are formed, nanometer formulation structure
For micro-sphere structure, particle size is between 250~300 nanometers.
A kind of preparation method of Rosiglitazone nanometer formulation, preparation step are as follows:
(1) Rosiglitazone and polylactic acid-polyglycolic acid are dissolved with organic solvent；
(2) by lecithin and the organic solvent ultrasonic disperse of distearoylphosphatidylethanolamine-polyethylene glycol 2000, then
It adds water and continues ultrasonic disperse, and at 65 degrees Centigrade 30 minutes, be then cooled to room temperature；
(3) (1) acquired solution is added drop-wise in (2) solution, quickly stirs after dripping 3 minutes, then continues in room temperature
It is slowly stirred 1.5~2 hours, obtains Rosiglitazone nanometer formulation suspension；
(4) (3) described nanometer formulation suspension is centrifugated, deionization is washed three times, is obtained cured Rosiglitazone and is received
Metric system agent.
It is calculated according to mass percent, Rosiglitazone is 5.3~6.25%, polylactide-polyglycolic acid copolymer 59.2
~64.9%, lecithin and distearoylphosphatidylethanolamine-polyethylene glycol 2000 are 29.2~35.5%.
Wherein the ratio of the Rosiglitazone in step (1) and polylactide-polyglycolic acid copolymer is 1:10~12.
Wherein the organic solvent in step (1) includes acetonitrile, dimethyl sulfoxide, N, N '-dimethyl formamide.
Wherein the lecithin in step (2) and 2000 ratio of distearoylphosphatidylethanolamine-polyethylene glycol be 1:1.5~
2, the ratio of polylactide-polyglycolic acid copolymer and lecithin is classified as 6.6~5:1.
Wherein the organic solvent in step (2) includes ethyl alcohol.
Wherein the ratio of water is 1: 10~20 in the organic solvent in step (2) and step (2).
This Rosiglitazone nanometer formulation is used to treat the Restenosis occurred after endovascular stent implantation.
The purpose for adding ethyl alcohol is to disperse lecithin, and cannot influence subsequent nanoparticle and be formed and drug loading, therefore second
Alcohol dosage cannot be too big, and the ratio of water is listed in 0.6:15 and is advisable.It will be apparent to those skilled in the art that being added dropwise containing Rosiglitazone and
The acetonitrile solution of polylactide-polyglycolic acid copolymer is dispersing to have lecithin and the poly- second two of Distearoyl Phosphatidylethanolamine-
After the aqueous solution of alcohol 2000, the purpose quickly stirred is to allow acetonitrile solution to be sufficiently mixed with aqueous solution, therefore mixing speed can make second
Nitrile solution is sufficiently mixed with aqueous solution to be advisable.The purpose being slowly stirred is under the premise of not influencing Nano medication self assembly, no
Nanoparticle coagulation is allowed to get off.The ratio of water is advisable in 1:15 in acetonitrile and step (2) in step (1), organic solvent and water ratio
Example is too low, and the Nano medication partial size of formation is too big, and ratio is too high, is hardly formed Nano medication, and Nano medication yield is low.
Embodiment one
3mg Rosiglitazone is weighed, 30mg polylactic acid-polyglycolic acid, which is placed in 1ml acetonitrile, dissolves to obtain solution 1.Weigh 6mg ovum
Phosphatide, 9mg distearoylphosphatidylethanolamine-polyethylene glycol 2000 are added in 0.6ml ethyl alcohol and carry out ultrasound by Ultrasound Instrument
Dissolution 3 minutes.Water 15ml is added to continue ultrasonic dissolution 3.5 minutes.It is subsequently placed in 65 DEG C of water-baths and is added 30 minutes, after taking-up
It is placed in room temperature and obtains solution 2.Solution 1 is instilled in solution 2 dropwise, after dripping, quickly stirring 3 minutes, are then stirred using magnetic force
It mixes device to be slowly stirred 1.5 hours, obtains Rosiglitazone nanometer formulation suspension after terminating stirring.Rosiglitazone nanometer is directly suspended
Liquid is centrifuged under 10000 turns with centrifuge, discards supernatant liquid.45ml deionized water is measured, rinses precipitating in three times
Object, finally cured Rosiglitazone nanometer formulation.
Embodiment two
3mg Rosiglitazone is weighed, 33mg polylactic acid-polyglycolic acid, which is placed in 1.2ml dimethyl sulfoxide, dissolves to obtain solution 1.Claim
5mg lecithin is taken, 10mg distearoylphosphatidylethanolamine-polyethylene glycol 2000 is added in 0.8ml ethanol water and passes through
Ultrasound Instrument carries out ultrasonic dissolution 3.5 minutes.Water 20ml is added to continue ultrasonic dissolution 3 minutes.It is subsequently placed in 65 DEG C of water-baths and adds
Enter 30 minutes, taking-up is placed on room temperature and obtains solution 2.Solution 1 is instilled in solution 2 dropwise, after dripping, is quickly stirred 3 minutes,
Then it is slowly stirred 2 hours using magnetic stirring apparatus, obtains Rosiglitazone nanometer formulation suspension after terminating stirring.By Rosiglitazone
Nanometer directly suspension is centrifuged under 10000 turns with centrifuge, discards supernatant liquid.30ml deionized water is measured, point
Rinse sediment three times, finally cured Rosiglitazone nanometer formulation.
Embodiment three
4mg Rosiglitazone is weighed, 45mg polylactic acid-polyglycolic acid is placed in 1ml N, dissolves in N '-dimethyl formamide
Solution 1.9mg lecithin is weighed, 18mg distearoylphosphatidylethanolamine-polyethylene glycol 2000 is added in 1ml ethanol water
And it is carried out ultrasonic dissolution 3 minutes by Ultrasound Instrument.Water 18ml is added to continue ultrasonic dissolution 3.5 minutes.It is subsequently placed in 65 DEG C of water
It is added 30 minutes in bath, taking-up is placed on room temperature and obtains solution 2.Solution 1 is instilled in solution 2 dropwise, after dripping, is quickly stirred
It 3 minutes, is then slowly stirred 1.8 hours using magnetic stirring apparatus, obtains Rosiglitazone nanometer formulation suspension after terminating stirring.It will
The direct suspension of Rosiglitazone nanometer is centrifuged under 10000 turns with centrifuge, discards supernatant liquid.Measure 45ml go from
Sub- water rinses sediment in three times, finally cured Rosiglitazone nanometer formulation.
Example IV
9mg Rosiglitazone is weighed, 100mg polylactic acid-polyglycolic acid, which is placed in 3ml acetonitrile, dissolves to obtain solution 1.Weigh 18mg
Lecithin, 27mg distearoylphosphatidylethanolamine-polyethylene glycol 2000 are added in 1.8ml ethanol water and pass through ultrasound
Instrument carries out ultrasonic dissolution 3.2 minutes.Water 45ml is added to continue ultrasonic dissolution 3 minutes.It is subsequently placed in 65 DEG C of water-baths and is added 30
Minute, taking-up is placed on room temperature and obtains solution 2.Solution 1 is instilled in solution 2 dropwise, after dripping, quick stirring 3 minutes, then
It is slowly stirred 1.6 hours using magnetic stirring apparatus, obtains Rosiglitazone nanometer formulation suspension after terminating stirring.Rosiglitazone is received
Rice directly suspension is centrifuged under 10000 turns with centrifuge, discards supernatant liquid.45ml deionized water is measured, divides three
Secondary flushing sediment, finally cured Rosiglitazone nanometer formulation.
Verification test:
One, partial size
The present invention uses particle size analyzer in laboratory and is characterized to Rosiglitazone nanometer formulation.As shown in Fig. 2, Roger
The partial size of column ketone nanometer formulation is between 250-300 nanometers, and polymerization dispersion index is lower than 0.2, and surface charge is in -3ev to -5ev
Between.From the analysis of above-mentioned particle size analyzer, it can be concluded that, which has the nano-scale for being suitble to vivo applications and polymerization dispersion
Index and surface charge.
Two, animal experiment in vivo
It is logical using SD rat as shown in Figure 3 in order to verify the validity of Rosiglitazone nanometer formulation prepared by the present invention
It crosses balloon expandable damage and establishes injury of carotid artery model, and have rated Rosiglitazone nanometer formulation, Rosiglitazone free drug
Therapeutic effect.
The carotid artery vascular image of normal SD rats (female).Lumen wall is smooth, and lumen diameter is larger, does not see different
The tissue of Chang Zengsheng.After the damage of SD rat carotid artery, if without any processing, lumen diameter becomes smaller, it is seen that intravascular
There is abnormal hyperplasia.After the damage of SD rat carotid artery, after giving the treatment of Rosiglitazone free drug, lumen diameter compares non-administration
Group is big, but lumen wall is rough, can see different degrees of hyperblastosis, still there is a situation where that part is narrow.When
SD rat carotid artery damage after, give Rosiglitazone nanometer formulation treatment after, lumen diameter and normally organize it is similar, than not giving medicine
Object group significantly increases, and than giving general formulation medicine group, lumen diameter is smooth, and apparent abnormal increasing has not been seen in lumen
It is raw.Results of animal shows that Rosiglitazone nanometer formulation can effectively treat hemadostewnosis, and effect is free better than Rosiglitazone
Drug.
Three, animal acute toxicity experiment
Mouse of the weight between 17~23g is chosen, is tested according to following experiment condition, calculates Rosiglitazone
LD50 and credibility interval.
The acute toxicity testing of one mouse mainline Rosiglitazone of table
The acute toxicity testing of two intragastric administration on mice Rosiglitazone of table
The acute toxicity testing of three mouse mainline Rosiglitazone nanometer formulation of table
The acute toxicity testing of four intragastric administration on mice Rosiglitazone nanometer formulation of table
The mouse between 17~23g is chosen, every 10 are divided into one group, are divided into control group, nanometer formulation group, conventional tablet
Group.Wherein the oral solvent without Rosiglitazone of control group, nanometer formulation group take orally the nanometer system of 7915.6 μm of ol/Kg dosage
Agent, conventional tablet group take orally the conventional tablet of 7915.6 μm of ol/Kg dosage, the result is as follows:
The measurement result of five Oral Administration in Rats different dosage forms Rosiglitazone plasma biochemical index of table
Table one and table three compare it can be concluded that the safety for the Rosiglitazone nanometer formulation being injected intravenously is greater than intravenous injection
Rosiglitazone, the LD50 of the Rosiglitazone nanometer formulation of intravenous injection is greater than common intravenous injection Rosiglitazone.Roger's column
Ketone nanometer formulation shows better safety when using intravenous injection mode, reduces the toxicity of Rosiglitazone.
Table two and table four compare it can be concluded that the safety of oral Rosiglitazone nanometer formulation is arranged greater than oral Roger
Ketone conventional tablet, the LD50 of oral Rosiglitazone nanometer formulation are greater than oral Rosiglitazone conventional tablet.Rosiglitazone nanometer
Preparation shows better safety when using oral way, reduces the toxicity of Rosiglitazone.
Table five it can be seen that the plasma biochemical index measurement result of the mouse of oral Rosiglitazone nanometer formulation closer to right
According to group, each plasma biochemical index is closer to normal value compared with the mouse of oral Rosiglitazone conventional tablet.Illustrate large dosage
Oral Rosiglitazone nanometer formulation toxicity caused by mouse is opposite small with the conventional tablet of Rosiglitazone.
It is possible thereby to learn that Rosiglitazone nanometer formulation disclosed by the invention has the effect for the treatment of reangiostenosis, and
The toxicity of Rosiglitazone can be effectively reduced, improve Rosiglitazone in the safety for the treatment of reangiostenosis.
Finally, it is stated that the above examples are only used to illustrate the technical scheme of the present invention and are not limiting, although referring to compared with
Good embodiment describes the invention in detail, those skilled in the art should understand that, it can be to skill of the invention
Art scheme is modified or replaced equivalently, and without departing from the objective and range of technical solution of the present invention, should all be covered at this
In the scope of the claims of invention.
Claims (9)
1. a kind of Rosiglitazone nanometer formulation, it is characterised in that: the nanometer formulation includes Rosiglitazone, polylactic acid-polyglycolic acid
The nanoparticle that copolymer, lecithin and distearoylphosphatidylethanolamine-polyethylene glycol 2000 are formed, nanometer formulation structure are
Micro-sphere structure, particle size is between 250~300 nanometers.
2. a kind of preparation method of Rosiglitazone nanometer formulation, it is characterised in that: its preparation step is as follows:
(1) Rosiglitazone and polylactic acid-polyglycolic acid are dissolved with organic solvent；
(2) by lecithin and the organic solvent ultrasonic disperse of distearoylphosphatidylethanolamine-polyethylene glycol 2000, then add again
Enter water and continue ultrasonic disperse, and at 65 degrees Centigrade 30 minutes, is then cooled to room temperature；
(3) (1) acquired solution is added drop-wise in (2) solution, quickly stirs 3 minutes, then continues in room temperature slow after dripping
Stirring 1.5~2 hours, obtains Rosiglitazone nanometer formulation suspension；
(4) (3) described nanometer formulation suspension is centrifugated, deionization is washed three times, and cured Rosiglitazone nanometer system is obtained
Agent.
3. a kind of Rosiglitazone nanometer formulation according to claim 1, it is characterised in that: it is calculated according to mass percent,
Rosiglitazone is 5.3~6.25%, polylactide-polyglycolic acid copolymer is 59.2~64.9%, lecithin and distearyl
Phosphatidyl-ethanolamine-polyethylene glycol 2000 is 29.2~35.5%.
4. a kind of preparation method of Rosiglitazone nanometer formulation according to claim 2, it is characterised in that: wherein step
(1) ratio of Rosiglitazone and polylactide-polyglycolic acid copolymer in is 1:10~12.
5. a kind of preparation method of Rosiglitazone nanometer formulation according to claim 4, it is characterised in that: wherein step
(1) organic solvent in includes acetonitrile, dimethyl sulfoxide, N, N '-dimethyl formamide.
6. a kind of preparation method of Rosiglitazone nanometer formulation according to claim 5, it is characterised in that: wherein step
(2) lecithin and 2000 ratio of distearoylphosphatidylethanolamine-polyethylene glycol in are 1:1.5~2, polylactic acid-polyethanol
The ratio of acid copolymer and lecithin is classified as 6.6~5:1.
7. a kind of preparation method of Rosiglitazone nanometer formulation according to claim 6, it is characterised in that: wherein step
(2) organic solvent in includes ethyl alcohol.
8. a kind of preparation method of Rosiglitazone nanometer formulation according to claim 7, it is characterised in that: wherein step
(2) ratio of water is 1: 10~20 in the organic solvent and step (2) in.
9. a kind of Rosiglitazone nanometer formulation according to claim 1 or 3, it is characterised in that: this Rosiglitazone nanometer
Preparation is used to treat the Restenosis occurred after endovascular stent implantation.
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