CN103845296A - Aspirin lipid microsphere preparation and preparation method of aspirin lipid microsphere preparation - Google Patents
Aspirin lipid microsphere preparation and preparation method of aspirin lipid microsphere preparation Download PDFInfo
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- CN103845296A CN103845296A CN201410116135.4A CN201410116135A CN103845296A CN 103845296 A CN103845296 A CN 103845296A CN 201410116135 A CN201410116135 A CN 201410116135A CN 103845296 A CN103845296 A CN 103845296A
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- 238000002360 preparation method Methods 0.000 title claims abstract description 84
- 229960001138 acetylsalicylic acid Drugs 0.000 title claims abstract description 52
- 239000004005 microsphere Substances 0.000 title claims abstract description 45
- -1 Aspirin lipid Chemical class 0.000 title claims abstract description 9
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- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims abstract description 47
- 238000002347 injection Methods 0.000 claims abstract description 14
- 239000007924 injection Substances 0.000 claims abstract description 14
- 239000003995 emulsifying agent Substances 0.000 claims abstract description 10
- 239000007951 isotonicity adjuster Substances 0.000 claims abstract description 5
- 239000003381 stabilizer Substances 0.000 claims abstract description 5
- 239000007788 liquid Substances 0.000 claims abstract description 3
- 239000003921 oil Substances 0.000 claims description 34
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- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 25
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 20
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- 238000003756 stirring Methods 0.000 claims description 17
- 239000000843 powder Substances 0.000 claims description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 239000003549 soybean oil Substances 0.000 claims description 10
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 7
- 239000000787 lecithin Substances 0.000 claims description 7
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- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 2
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 claims description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 2
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- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 claims description 2
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- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 2
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- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 2
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Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention discloses an aspirin lipid microsphere preparation and a preparation method of the aspirin lipid microsphere preparation. The aspirin lipid microsphere preparation comprises the following components in parts by weight: 0.01-2.0 parts of aspirin, 1.0-200.0 parts of oil for injection, 0.1-20 parts of emulsifier, 0.1-20 parts of stabilizer and 4.0-10.0 parts of isotonic agent. The preparation disclosed by the invention not only has an ideal curative effect, but also overcomes the problem that the aspirin preparation is insoluble in water and the degradation product in the aqueous liquid is great in irritation, so that the degrading speed of the medicine is slowed down, the medicine stability is improved, and the irritation and toxic reaction are reduced. In addition, the encapsulation efficiency and the drug loading capacity of the product are further remarkably improved.
Description
Technical field
The present invention relates to a kind of aspirin fat micro sphere preparation and preparation method thereof, belong to pharmaceutical technology field.
Background technology
Aspirin is a kind of many target spots medicine, and the fibrosis, the control diseases of cardiovascular and cerebrovascular systems that particularly tool antitumor, inhibition atherosclerosis, inflammation-inhibiting are caused have obvious effect.But because the stimulation of its catabolite to gastric mucosa and the inhibitory action of platelet aggregation are limited to its application.
Lipoid microsphere, is that medicine is dissolved in to a kind of preparation of making in water through phospholipid emulsion dispersion in fatty oil, and mean diameter is at 200nm.Lipoid microsphere is the novel targeted preparation that medicine directly can be transported to human lesion position, as this class preparation of some anticarcinogens and anti-inflammatory medicaments, microcirculation disturbance medicine.If aspirin can be made to fat micro sphere preparation, be expected to overcome the series of problems that existing Genprin exists, improve dissolubility, stability, the leaching rate of medicine, thereby improve dissolution and the bioavailability of medicine, reduce toxic and side effects, reduce the incidence rate of untoward reaction, improve treatment speed and therapeutic effect.
But, the challenge of preparing lipoid microsphere is to select suitable composition and method for making.Because the character of lipoid microsphere is as directly closely related with the composition of lipoid microsphere in dissolubility, stability, zest, envelop rate and toxic and side effects etc., therefore the aspirin fat micro sphere preparation of, selecting which type of composition formation to have ideal treatment is problem urgently to be resolved hurrily.
Summary of the invention
The object of the invention is to, a kind of aspirin fat micro sphere preparation and preparation method thereof is provided.The present invention not only has desirable curative effect, and the present invention overcome the not large problem of catabolite zest in ease of solubility, aqueous solution of Genprin water, and the drug degradation speed that slowed down, has improved medicine stability, has reduced zest and toxic reaction.In addition, the present invention has also improved drug loading and the envelop rate of product significantly.
For solving the problems of the technologies described above, technical scheme provided by the invention is as follows: aspirin fat micro sphere preparation, comprises by weight;
In above-mentioned aspirin fat micro sphere preparation, comprise by weight;
In aforesaid aspirin fat micro sphere preparation, described oil for injection is one or more the combination in soybean oil, Semen Maydis oil, Oleum Arachidis hypogaeae semen, medium chain glycerol glyceride, safflower oil, Oleum Gossypii semen, olive oil, Oleum Sesami, fish oil, medium chain glycerol dibasic acid esters, medium chain triglyceride, ethyl oleate, acetylated monoglyceride, propylene glycol dibasic acid esters, glyceryl linoleate or Polyethylene Glycol glyceryl laurate ester.
In aforesaid aspirin fat micro sphere preparation, described oil for injection is soybean oil and medium chain triglyceride, and both weight ratios are l:3～3:l.
In aforesaid aspirin fat micro sphere preparation, described emulsifying agent is soybean phospholipid or Ovum Gallus domesticus Flavus lecithin; Described stabilizing agent is one or more the combination in oleic acid or its salt, cholic acid or its salt, deoxycholic acid or its salt; Described isotonic agent is one or more the combination in glycerol, mannitol, sorbitol, glucose, sucrose or trehalose.
In aforesaid aspirin fat micro sphere preparation, said preparation is injection, granule, powder, oral liquid, mixture, pill, various tablet, hard capsule, soft capsule or other dosage form.
In aforesaid aspirin fat micro sphere preparation, the method specifically comprises the following steps;
(1) get a part of emulsifying agent and be dissolved in solvent, add aspirin, stir it is dissolved, except desolventizing, obtain A product for subsequent use;
(2) preparation of oil phase: add respectively remaining emulsifying agent, stabilizing agent and A product in oil for injection, stir it is dissolved, obtain oil phase;
(3) preparation of water: isotonic agent is added to the water, stirs it is dissolved, obtain water;
(4) preparation of colostrum: the oil phase of step (2) is added in the water of step (3), disperse through high speed shear, obtain colostrum B product;
(5) a, by the homogenize of B product high pressure, obtain C product;
Or b, B product are sheared from speed after, then pushed film, obtain the uniform microemulsion D of particle diameter product;
(6) lyophilization: by C product or the lyophilization of D product, obtain lyophilized powder finished product;
(7) step (1) to (6) all operates under nitrogen protection.
In aforesaid aspirin fat micro sphere preparation, in step (1), the consumption of described emulsifying agent and the weight ratio of aspirin are l～15:l; Described solvent is one or more the combination in ethanol, ethyl acetate, chloroform, dichloromethane or acetone.
In aforesaid aspirin fat micro sphere preparation, in step (4), the time that described high speed shear is disperseed is 10～80 minutes, and the speed of shearing is 2000～l0000rpm, and temperature is 40～75 ℃.
In aforesaid aspirin fat micro sphere preparation, in the step a of step (5), described high pressure homogenize pressure is 500～2500bar, homogenize number of times 2～6 times, 12～35 ℃ of temperature; In the step b of step (5), described extruding film, the aperture of fenestra is 50nm～400nm, crossing film number of times is 1～6 time, 4～35 ℃ of temperature.
Compared with prior art, the present invention has following beneficial effect:
(1) the present invention has carried out lot of experiments to raw material and proportion relation, screening, compare and sum up, active component aspirin is made to lipoid microsphere, drug solubility and stability are greatly improved, the degradation speed of medicine has slowed down, extend medicine action time in vivo, the present invention has simultaneously reduced catabolite zest, there is targeting, persistence and high efficiency, the present invention can be simultaneously optionally in inflammation, blood vessel endothelium system, the diseased regions such as arteriosclerosis are built up, make several times that medicine exceeds conventional formulation in target area concentration to hundreds of times, therapeutic effect is ideal.
(2) the present invention adopts soybean oil, Semen Maydis wet goods as oil phase, adopt soybean phospholipid and Ovum Gallus domesticus Flavus lecithin as emulsifying agent, because mentioned component all has no side effect to human body, safe and reliable, and can be the metabolism of human body institute, feature safe and reliable, that have no side effect that this product therefore making with mentioned component also has.
(3) fat micro sphere preparation of the present invention has anticoagulant, thromboxane A2 generation, tremulous pulse medicated porridge sample Lipid Plaque to form and the Fibrotic effect of internal organs, and can expand periphery and arteria coronaria blood vessel, the formation of the vascular endothelial cell damage that the treatment to cardiovascular and cerebrovascular microcirculation disturbance, the alleviation of atheromatous plaque, many factors cause and inhibition Intravascular Thrombus, and internal organs fibrosis has played positive effect.
(4) in preparation method of the present invention, active component and phospholipid are first dissolved in suitable solvent, then except desolventizing, by this reaction, active component is embedded in phospholipid uniformly, form the structure of similar complex, thereby increased active component and phospholipid and the affinity with oil phase, and then improved the envelop rate of this product.
The specific embodiment
Below in conjunction with embodiment, the present invention is further illustrated.
Embodiment 1: aspirin fat micro sphere preparation, comprising:
Cumulative volume injects water to after 250～1000ml, adopts cryodesiccated method to be prepared into lyophilized injectable powder, uses before use after the water for injection dilution with 50～1000ml.
The preparation method of aspirin fat micro sphere preparation:
(1) get Ovum Gallus domesticus Flavus lecithin 50mg, add dissolve with ethanol, add aspirin, be stirred to dissolve, stir on one side, volatilize ethanol with nitrogen on one side, obtain A product for subsequent use;
(2) preparation of oil phase: will refine injection soybean oil and be heated to 70～80 ℃, and add respectively remaining Ovum Gallus domesticus Flavus lecithin, enuatrol and A product, and stir it is dissolved, and obtain oil phase;
(3) preparation of water: glycerol is added to the water, stirs it is dissolved, be heated to 70～80 ℃, obtain water;
(4) preparation of colostrum: oil phase is joined in water, 70～80 ℃ of temperature, high speed shear is disperseed, shear rate 8000rpm, 10 minutes time, form colostrum, fast cooling to 15～30 ℃, with sodium hydroxide adjusting pH value 4.0～6.0, obtain B product:
(5) then can adopt the high pressure homogenize of a step or b step to push film:
A step is: by B product, through high pressure homogenizer homogenize number of times 2～6 times, pressure is 500～2500bar, and 12～35 ℃ of temperature, obtain C product;
B step is: pushed film by after B product high speed shear, membrane aperture is 50nm～400nm, and crossing film number of times is 2～6 times; Obtain D product;
(6) lyophilization: C product or D product are injected after water, then adopt cryodesiccated method to be prepared into lyophilized injectable powder, get product, also can adopt common process to make other dosage form.Take lyophilized injectable powder as example, after the water for injection dilution with 50～1000ml, use before use.And injecting method is one day 1 time, each consumption 5-50ml, lower same.
(7) step (1) to (6) all operates under nitrogen protection.
Embodiment 2: aspirin fat micro sphere preparation, comprising:
Cumulative volume injects water to after 250～1000ml, adopts cryodesiccated method to be prepared into lyophilized injectable powder, uses before use after the water for injection dilution with 50～1000ml.
The preparation method of aspirin fat micro sphere preparation:
(1) get Ovum Gallus domesticus Flavus lecithin 50mg, add dissolve with ethanol, add aspirin 0.05g, be stirred to dissolve, decompression volatilizes ethanol, obtains A product;
(2) preparation of oil phase: will refine injection soybean oil and medium chain triglyceride and be heated to 70～80 ℃, and add respectively remaining Ovum Gallus domesticus Flavus lecithin, enuatrol and A product, and stir it is dissolved, and obtain oil phase;
(3) preparation of water: glycerol is added to the water, stirs it is dissolved, be heated to 70～80 ℃, obtain water;
(4) preparation of colostrum: the oil phase of step (2) is joined in the water of step (3), 70～80 ℃ of temperature, high speed shear is disperseed, shear rate 8000rpm, 10 minutes time, form colostrum, fast cooling to 15～30 ℃, with sodium hydroxide adjusting pH value 4.0～6.0, obtain B product;
(5) then can adopt the high pressure homogenize of a step or b step to push film:
A step is: by B product, through high pressure homogenizer homogenize number of times 2～6 times, pressure is 500～2500bar, and 12～35 ℃ of temperature, obtain C product;
B step is: pushed film by after B product high speed shear, membrane aperture is 50nm～400nm, and crossing film number of times is 2～6 times; Obtain D product;
(6) lyophilization: C product or D product are injected after water, then adopt cryodesiccated method to be prepared into lyophilized injectable powder, get product.After water for injection dilution with 50～1000ml, use before use.
(7) step (1) to (6) all operates under nitrogen protection.
Embodiment 3: aspirin fat micro sphere preparation, comprising:
Cumulative volume injects water to l000ml, adopts cryodesiccated method to be prepared into lyophilized injectable powder, uses before use after the water for injection dilution with 1000ml.
The preparation method of above-mentioned aspirin fat micro sphere preparation:
(1) get Ovum Gallus domesticus Flavus lecithin 50mg. and add acetic acid ethyl dissolution, add aspirin, be stirred to dissolve, stir on one side, volatilize ethanol with nitrogen on one side, obtain A product;
(2) preparation of oil phase: Semen Maydis oil is heated to 60～80 ℃, adds respectively remaining Ovum Gallus domesticus Flavus lecithin, enuatrol and A product, stir it is dissolved, obtain oil phase;
(3) preparation of water: sucrose is added to the water, stirs it is dissolved, be heated to 60～80 ℃, obtain water;
(4) preparation of colostrum: the oil phase of step (2) is added in the water of step (3), 60～80 ℃ of temperature, high speed shear is disperseed, shear rate 6000rpm, 40 minutes time, forms colostrum, fast cooling to 15～30 ℃, with sodium hydroxide adjusting pH value 4.0～6.0;
(5) then can adopt the high pressure homogenize of a step or b step to push film:
A step is: by B product, through high pressure homogenizer homogenize number of times 2～6 times, pressure is 800～2000bar, and 12～35 ℃ of temperature, obtain C product;
B step is: pushed film by after B product high speed shear, membrane aperture is 50nm～400nm, and crossing film number of times is 2～6 times; Obtain D product;
(6) aseptic filtration: the C product that step (5) is made or D product are through the degerming of 0.22Vm filtering with microporous membrane, aseptic embedding, lyophilization, gets product.
(7) step (1) to (6) all operates under nitrogen protection.
Embodiment 4: aspirin fat micro sphere preparation, comprising:
Cumulative volume injects water to l000ml, adopts cryodesiccated method to be prepared into lyophilized injectable powder, uses before use after the water for injection dilution with 1000ml.
The preparation method of above-mentioned aspirin fat micro sphere preparation:
(1) get soybean lecithin 50mg, add dichloromethane and alcohol mixed solvent (volume ratio l:1) to dissolve, add aspirin, be stirred to dissolve, decompression volatilizes dichloromethane and ethanol, obtains A product;
(2) preparation of oil phase: will refine injection soybean oil and medium chain triglyceride and be mixed and heated to 50～60 ℃, and add respectively soybean lecithin, enuatrol to dissolve, then add A product, and stir it is dissolved, and obtain oil phase;
(3) preparation of water: trehalose is added to the water to dissolving, is heated to 50～60 ℃, obtain water;
(4) preparation of colostrum: the oil phase of step (2) is added in the water of step (3), 50～60 ℃ of temperature, high speed shear is disperseed, shear rate 4000rpm, 50 minutes time, form colostrum, fast cooling to 15～30 ℃, with sodium hydroxide adjusting pH value 4.0～6.0, obtain B product;
(5) can adopt the high pressure homogenize of a step or b step to push film:
A step is: by B product, through high pressure homogenizer homogenize number of times 2～6 times, pressure is 800～1200bar, and 12～35 ℃ of temperature, obtain C product;
B step is: pushed film by after B product high speed shear, membrane aperture is 50nm～400nm, and crossing film number of times is 2～6 times; Obtain D product;
(6) aseptic filtration: the C product that step (5) is made and D product are through the degerming of 0.22Vm filtering with microporous membrane, aseptic embedding, lyophilization, gets product.
(7) step (1) to (6) all operates under nitrogen protection.
Comparative example 1:
Prescription:
Cumulative volume injects water to l000ml; Or inject water to after 500～1000ml, adopt cryodesiccated method to be prepared into lyophilized injectable powder, after the water for injection dilution with 50～1000ml, use before use.
Technical process:
(1) preparation of oil phase: will refine injection soybean oil and be heated to 70～80 ℃, enuatrol and aspirin stir and make its dissolving;
(2) preparation of water: glycerol is added to the water to dissolving, is heated to 70～80 ℃;
(3) preparation of colostrum: step (1) oil phase is added in step (2) water, 70～80 ℃ of temperature, high speed shear is disperseed, shear rate 8000rpm, 10 minutes time, forms colostrum, fast cooling to 15～30 ℃, with sodium hydroxide regulate pH value 4.0～9.0:
(4) high pressure homogenize or pushed film: through high pressure homogenizer homogenize number of times 2～6 times, pressure is 500～2500bar, 12～35 ℃ of temperature by step (3) colostrum; Or pushed film after high speed shear, and membrane aperture is 50nm～400nm, crossing film number of times is 2～6 times;
(5) or the microemulsion obtaining adopt again cryodesiccated method to be prepared into lyophilized injectable powder, before use with using after the water for injection dilution of 50～1000ml.
(6) step (1) to (4) all operates under nitrogen protection.
Comparative example 2:
Prescription:
Cumulative volume injects water to l000ml; Or inject water to after 500～1000ml, adopt cryodesiccated method to be prepared into lyophilized injectable powder, after the water for injection dilution with 50～1000ml, use before use.
Technical process:
(1) preparation of oil phase: will refine injection soybean oil and medium chain triglyceride and be heated to 70～80 ℃, add respectively lecithin,
Enuatrol and aspirin stir and make its dissolving;
(2) preparation of water: glycerol is added to the water to dissolving, is heated to 70～80 ℃;
(3) preparation of colostrum: step (1) oil phase is added in step (2) water, 70～80 ℃ of temperature, high speed shear is disperseed, shear rate 8000rpm, 10 minutes time, forms colostrum, fast cooling to 15～30 ℃, with sodium hydroxide adjusting pH value 4.0～9.0;
(4) high pressure homogenize or pushed film: through high pressure homogenizer homogenize number of times 2～6 times, pressure is 500～2500bar, 12～35 ℃ of temperature by step (3) colostrum; Or pushed film after high speed shear, and membrane aperture is 50nm～400nm, crossing film number of times is 2～6 times;
(5) or the microemulsion obtaining adopt again cryodesiccated method to be prepared into lyophilized injectable powder, before use with using after the water for injection dilution of 50～1000ml.
(6) step (1) to (4) all operates under nitrogen protection.
The performance test of drug loading of the present invention and packaging ratio:
1, the performance test of drug loading of the present invention:
The assay of medicine in water
Adopt two step centrifuging, get this product and be placed in low temperature supercentrifuge, design temperature is 25 ℃, adjusting rotary speed is to 5000rpm for the first time, be placed in respectively the centrifugal 3h of l0mL centrifuge tube high speed, take out, careful absorption lower floor's solution (thin emulsion) is appropriate, be placed in respectively low temperature supercentrifuge, adjusting rotary speed is 8000rpm for the second time, continue centrifugal 1h, to lower floor be clear aqueous solution, same aforesaid operations, draw respectively lower floor's clear aqueous solution, with 0.22Vm filtering with microporous membrane, get subsequent filtrate, according to method under assay item, measure the content of medicine in water.According to method under assay item, result is the medicine total content of this product.
Get three batch samples of each embodiment, detect according to said determination method, the results are shown in following table, can be found out by table, the average content of embodiment 1-4 tri-batch samples is all more than 2.5%.
The present invention has superior drug loading as can be seen here, has improved the curative effect of product.
2, drug effect contrast experiment of the present invention:
Get the sample of each embodiment, carry out the investigation on atherosclerotic blood vessel impact, result is visible, and Normal group endarterium is smooth complete, and monolayer endothelial cell connects closely, and under inner membrance, gap is less; Middle film smooth muscle cell is arranged in the form of a ring; Comparative example's 1 endotheliocyte part damage comes off, SES broadening; Comparative example's 2 intimal thickenings, protuberance, part comes off, and a large amount of foam cells of SES broadening infiltrate and lipidosis, middle film had significant proliferation, arrangement disorder, part is perpendicular to inner membrance growth, and visible vessels smooth muscle cell (VSMC) migrates into interior subcutaneous through interior elastic plate; 1 group, 2 groups, 3 groups inner membrances of embodiment are smooth complete, and monolayer endothelial cell is even to be had and come off, to the therapeutic effect of atherosclerotic blood vessel damage significantly better than comparative example.
3, the performance test of envelop rate of the present invention:
The mensuration of envelop rate
Because medicine is difficult to measure at the content of oil, oil-water interfaces, therefore the envelop rate of this product is as shown in the formula calculating and get final product.The content of envelop rate %=[(medicine total content-medicine in water)/medicine total content] × 100%.
As can be seen from the above table, envelop rate of the present invention can reach more than 93.7%, and the envelop rate of comparing comparative example 1 and comparative example's 2 product improves greatly, and effect is remarkable.
Claims (10)
1. aspirin fat micro sphere preparation, is characterized in that: comprise by weight;
2. aspirin fat micro sphere preparation according to claim 1, is characterized in that: comprise by weight;
3. aspirin fat micro sphere preparation according to claim 1 and 2, is characterized in that: described oil for injection is one or more the combination in soybean oil, Semen Maydis oil, Oleum Arachidis hypogaeae semen, medium chain glycerol glyceride, safflower oil, Oleum Gossypii semen, olive oil, Oleum Sesami, fish oil, medium chain glycerol dibasic acid esters, medium chain triglyceride, ethyl oleate, acetylated monoglyceride, propylene glycol dibasic acid esters, glyceryl linoleate or Polyethylene Glycol glyceryl laurate ester.
4. aspirin fat micro sphere preparation according to claim 1 and 2, is characterized in that: described oil for injection is soybean oil and medium chain triglyceride, and both weight ratios are l:3～3:l.
5. aspirin fat micro sphere preparation according to claim 1 and 2, is characterized in that: described emulsifying agent is soybean phospholipid or Ovum Gallus domesticus Flavus lecithin; Described stabilizing agent is one or more the combination in oleic acid or its salt, cholic acid or its salt, deoxycholic acid or its salt; Described isotonic agent is one or more the combination in glycerol, mannitol, sorbitol, glucose, sucrose or trehalose.
6. according to claim 1 or 2 any one aspirin fat micro sphere preparations, it is characterized in that: said preparation is injection, granule, powder, oral liquid, mixture, pill, various tablet, hard capsule, soft capsule or other dosage form.
7. the preparation method of the aspirin fat micro sphere preparation as described in claim 1 to 6 any one, is characterized in that: the method specifically comprises the following steps;
(1) get a part of emulsifying agent and be dissolved in solvent, add aspirin, stir it is dissolved, except desolventizing, obtain A product for subsequent use;
(2) preparation of oil phase: add respectively remaining emulsifying agent, stabilizing agent and A product in oil for injection, stir it is dissolved, obtain oil phase;
(3) preparation of water: isotonic agent is added to the water, stirs it is dissolved, obtain water;
(4) preparation of colostrum: the oil phase of step (2) is added in the water of step (3), disperse through high speed shear, obtain colostrum B product;
(5) a, by the homogenize of B product high pressure, obtain C product;
Or b, B product are sheared from speed after, then pushed film, obtain the uniform microemulsion D of particle diameter product;
(6) lyophilization: by C product or the lyophilization of D product, obtain lyophilized powder finished product;
(7) step (1) to (6) all operates under nitrogen protection.
8. the preparation method of aspirin fat micro sphere preparation according to claim 7, is characterized in that: in step (1), the consumption of described emulsifying agent and the weight ratio of aspirin are l～15:l; Described solvent is one or more the combination in ethanol, ethyl acetate, chloroform, dichloromethane or acetone.
9. the preparation method of aspirin fat micro sphere preparation according to claim 8, is characterized in that: in step (4), the time that described high speed shear is disperseed is 10～80 minutes, and the speed of shearing is 2000～l0000rpm, and temperature is 40～75 ℃.
10. the preparation method of aspirin fat micro sphere preparation according to claim 9, is characterized in that: in the step a of step (5), described high pressure homogenize pressure is 500～2500bar, homogenize number of times 2～6 times, 12～35 ℃ of temperature; In the step b of step (5), described extruding film, the aperture of fenestra is 50nm～400nm, crossing film number of times is 1～6 time, 4～35 ℃ of temperature.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104958266A (en) * | 2015-06-12 | 2015-10-07 | 海南灵康制药有限公司 | Nicergoline lipid microspheres agent |
| CN108606969A (en) * | 2018-06-20 | 2018-10-02 | 苏州大学附属第医院 | Aspirin is preparing the application in treating intervertebral disc degeneration drug |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1460469A (en) * | 2003-06-05 | 2003-12-10 | 浙江大学 | Preparation method of aspirin microsphere |
| CN101664390A (en) * | 2009-09-29 | 2010-03-10 | 北京中海康医药科技发展有限公司 | Preparation method of prostaglandin E1 |
-
2014
- 2014-03-26 CN CN201410116135.4A patent/CN103845296B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1460469A (en) * | 2003-06-05 | 2003-12-10 | 浙江大学 | Preparation method of aspirin microsphere |
| CN101664390A (en) * | 2009-09-29 | 2010-03-10 | 北京中海康医药科技发展有限公司 | Preparation method of prostaglandin E1 |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104958266A (en) * | 2015-06-12 | 2015-10-07 | 海南灵康制药有限公司 | Nicergoline lipid microspheres agent |
| CN108606969A (en) * | 2018-06-20 | 2018-10-02 | 苏州大学附属第医院 | Aspirin is preparing the application in treating intervertebral disc degeneration drug |
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