CN103330678A - Paeonol tiny sponge preparation and preparation method thereof - Google Patents
Paeonol tiny sponge preparation and preparation method thereof Download PDFInfo
- Publication number
- CN103330678A CN103330678A CN2013102215681A CN201310221568A CN103330678A CN 103330678 A CN103330678 A CN 103330678A CN 2013102215681 A CN2013102215681 A CN 2013102215681A CN 201310221568 A CN201310221568 A CN 201310221568A CN 103330678 A CN103330678 A CN 103330678A
- Authority
- CN
- China
- Prior art keywords
- paeonol
- preparation
- microsponge
- tiny
- phase
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention discloses a paeonol tiny sponge preparation and a preparation method thereof, and adopts an emulsion-like menstruum diffusion method. The preparation method comprises the following steps of: preparing an inner phase, and dissolving paeonol and a polymer into a pore-foaming agent; preparing an outer phase, and uniformly stirring distilled water and an emulsion; adding the inner phase into the outer phase to stir so as to form an emulsion-like; and stirring an organic solvent so as to volatilize, and filtering and separating the organic solvent. The paeonol tiny sponge preparation prepared by adopting the class emulsion menstruum diffusion method has the advantages that the yield and encapsulation efficiency of paeonol tiny sponge are improved, the paeonol tiny sponge preparation is used for covering the skin, the effects such as efficiency, safety and long efficiency are achieved, the obtained paeonol tiny sponge preparation can permeate the deep skin so as to play the pesticide effect role for a short time, the drug action time can continue at more than 12 hours, the bioavailability is effectively improved, and the paeonol tiny sponge preparation is further used in medicine and cosmetic fields.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, relate to a kind of novel medicament carrier, particularly a kind of paeonol microsponge preparation and preparation method thereof.
Background technology
Paeonol (paeonol) is the main active of Chinese medicine Cortex Moutan, have pharmacological actions such as antiinflammatory, antibiotic, antiallergic action, immunomodulating, analgesia, now be widely used in the common skin diseases treatment, can suppress the active and melanic generation of tryrosinase in the melanocyte, mottle, skin pruritus, psoriasis, herpes zoster, eczema etc. are had therapeutical effect preferably.Dosage form commonly used at present mainly contains paeonol unguentum agent, patch, tablet, injection etc.But the dissolubility of paeonol in water is very low, and the character instability is volatile, sees the easy oxidation Decomposition of light, has influenced its use and curative effect.And the skin permeability of paeonol is relatively poor, and bioavailability is low, has influenced its application at local skin.At present the paeonol percutaneous drug delivery dosage form of using mainly is ointment, and what be in conceptual phase has microemulsion, emulsion type gel and a phosphatide complexes etc., but shortcoming such as these dosage forms exist poor stability, and drug loading is little, and yield is low is not easy for industrialized great production.
(Microsponge Delivery System is a novel drug-supplying system that is used for sustained-release administration that developed in recent years MDS) to miniature sponge, is the cross linked polymer drug-supplying system that a lot of holes are contained on the surface, and a lot of spaces is contained in inside.The microsponge particle diameter can be prepared into different big or small microgranules with purposes according to the character of microgranule between 5～300 μ m.The microsponge medicine-releasing system is adsorbed in medicine in the internal void, discharging medicine lentamente in long period of time relatively as a kind of drug depot, have advantages such as the stability of drug of raising, reduction drug toxicity, raising drug bioavailability, be successfully applied to medicine and cosmetic field.Especially the application aspect skin and tract topical not only can realize medicine in the enrichment of target site, reduces the amount that drug osmotic enters the body circulation, improves local bioavailability, reduces drug toxicity.Preparation method commonly used is the free radical suspensioning polymerization method, be called again liquid-liquid suspension polymerization (as patent US Patent:4690825[P] .1987-09-01.; US Patent:5145675[P] .1992-09-08. reports).Its preparation process may be summarized to be: medicine at first is dissolved in the suitable solvent solutions, and redispersion is in the water that contains surfactant and/or suspensoid etc.; Add catalyst or intensification or radiation and start polymerization; The polymer particles separation, the washing that form are namely got microsponge.Suspensoid commonly used in this method is that styrene, cross-linking agent are divinylbenzene, and porogen is toluene.Another kind method is class Emulsion solvent diffusion method, and its preparation process can be divided into for three steps: phase in 60 ℃ of preparations at first, join among the foreign minister of room temperature, and stir and form Emulsion; Continue to stir 2h again and make the organic solvent volatilization; The last miniature sponge of isolated by filtration is used distilled water wash, drying, namely.
Summary of the invention
A kind of paeonol microsponge preparation that the purpose of this invention is to provide, its skin permeability is good, and drug effect continues for a long time, and bioavailability effectively improves.
Another object of the present invention provides above-mentioned paeonol microsponge formulation preparation method, and its yield and envelop rate improve.
The object of the present invention is achieved like this: a kind of preparation method of paeonol microsponge preparation, adopt class Emulsion solvent diffusion method, it is characterized in that may further comprise the steps: phase in (1) preparation, calculate by weight, 1～4 part paeonol, 0.5～1.5 part polymer be dissolved in 10～40 parts the porogen, standby; (2) preparation foreign minister calculates by weight, and the emulsifier for mixing of 100 parts distilled water and 1～8 part is even, standby; (3) the interior phase that step (1) is made joins among the foreign minister that step (2) makes again, stirs to form class Emulsion; (4) continue stirring and make the porogen volatilization; (5) the miniature sponge of isolated by filtration is used distilled water wash, drying, namely.
The present invention adopts class Emulsion solvent diffusion method to prepare paeonol microsponge preparation, yield and the envelop rate of paeonol microsponge have been improved, be used for that percutaneous drug delivery can also reach efficiently, effect such as safe, long-acting, the little silk floss of the paeonol of gained can infiltrate deep skin performance drug effect at short notice, and drug treating time can continue more than the 12h, bioavailability effectively improves, and can be further used for medicine and cosmetic field.
Description of drawings
Fig. 1 is the paeonol microsponge stereoscan photograph that the present invention prepares;
Fig. 2 is the transdermal test in vitro experimental result, and wherein a is paeonol microsponge ointment of the present invention, and b is the common ointment of paeonol, and c is the paeonol saturated aqueous solution;
Fig. 3 is skin hold-up experimental result;
Fig. 4 is that the microdialysis method detects the drug level result of variations in different time points subcutaneous rat and the blood.
The specific embodiment
The present invention is the preparation method of a kind of paeonol microsponge, adopts class Emulsion solvent diffusion method, and the foreign minister is water, and interior organic facies dissolved substance and the polymer of being made up of dichloromethane mutually may further comprise the steps:
(1) phase in the preparation is calculated by weight, 1～4 part paeonol, 0.5～1.5 part polymer is dissolved in 10～40 parts the porogen, and is standby.Polymer is for increasing the plasticity of medicine, and is preferred: ethyl cellulose or triethyl citrate.Porogen is selected from: one or both mixing in dichloromethane, chloroform, the ethanol.
(2) preparation foreign minister calculates by weight, and the emulsifier for mixing of 100 parts distilled water and 1～8 part is even, standby.Emulsifying agent preferably polyethylene alcohol, most preferably PVA1788.
(3) the interior phase that step (1) is made joins among the foreign minister that step (2) makes again, stirs to form class Emulsion.Preferably, mixing speed is 600～2500rpm.
(4) continue stirring and make the porogen volatilization.Preferably, mixing time is 2～4h, and mixing speed is 600～2500rpm.
(5) the miniature sponge of isolated by filtration is used distilled water wash, drying, namely.Preferably, filter and adopt post precipitation to filter, drying is normal temperature drying 16～48h.
Below by specifically be example the present invention is further elaborated, but the present invention is not limited to this specific examples.
Embodiment 1
Paeonol 2g, ethyl cellulose 1g is dissolved in the 20ml dichloromethane phase in the preparation, gets PVA17882g and is dissolved in the 100ml distilled water and prepares the foreign minister, under the mixing speed of 1000rpm, interior phase is slowly joined among the foreign minister, forms kind solvent.Continue to stir 4h, dichloromethane is volatilized fully.With the suspension that obtains, standing over night is filtered, normal temperature drying 24h, namely.
Embodiment 2
Paeonol 2g, ethyl cellulose 1g is dissolved in the 20ml dichloromethane phase in the preparation, gets PVA17886g and is dissolved in the 100ml distilled water and prepares the foreign minister, under the mixing speed of 1000rpm, interior phase is slowly joined among the foreign minister, forms kind solvent.Continue to stir 4h, dichloromethane is volatilized fully.With the suspension that obtains, standing over night is filtered, normal temperature drying 24h, namely.
Embodiment 3
Paeonol 3g, ethyl cellulose 0.5g is dissolved in the 20ml dichloromethane phase in the preparation, gets PVA17882g and is dissolved in the 100ml distilled water and prepares the foreign minister, under the mixing speed of 1000rpm, interior phase is slowly joined among the foreign minister, forms kind solvent.Continue to stir 4h, dichloromethane is volatilized fully.With the suspension that obtains, standing over night is filtered, normal temperature drying 24h, namely.
Embodiment 4
Paeonol 3g, ethyl cellulose 0.5g is dissolved in the 20ml dichloromethane phase in the preparation, gets PVA17886g and is dissolved in the 100ml distilled water and prepares the foreign minister, under the mixing speed of 1000rpm, interior phase is slowly joined among the foreign minister, forms kind solvent.Continue to stir 4h, dichloromethane is volatilized fully.With the suspension that obtains, standing over night is filtered, normal temperature drying 24h, namely.
Paeonol 2g, ethyl cellulose 1g is dissolved in the 20ml dichloromethane phase in the preparation, gets PVA17882g and is dissolved in the 100ml distilled water and prepares the foreign minister, under the mixing speed of 2000rpm, interior phase is slowly joined among the foreign minister, forms kind solvent.Continue to stir 4h, dichloromethane is volatilized fully.With the suspension that obtains, standing over night is filtered, normal temperature drying 24h, namely.
Embodiment 6
Paeonol 2g, ethyl cellulose 1g is dissolved in the 20ml dichloromethane phase in the preparation, gets PVA17886g and is dissolved in the 100ml distilled water and prepares the foreign minister, under the mixing speed of 2000rpm, interior phase is slowly joined among the foreign minister, forms kind solvent.Continue to stir 4h, dichloromethane is volatilized fully.With the suspension that obtains, standing over night is filtered, normal temperature drying 24h, namely.
Embodiment 7
Paeonol 3g, ethyl cellulose 0.5g is dissolved in the 20ml dichloromethane phase in the preparation, gets PVA17882g and is dissolved in the 100ml distilled water and prepares the foreign minister, under the mixing speed of 2000rpm, interior phase is slowly joined among the foreign minister, forms kind solvent.Continue to stir 4h, dichloromethane is volatilized fully.With the suspension that obtains, standing over night is filtered, normal temperature drying 24h, namely.
Embodiment 8
Paeonol 3g, ethyl cellulose 0.5g is dissolved in the 20ml dichloromethane phase in the preparation, gets PVA17886g and is dissolved in the 100ml distilled water and prepares the foreign minister, under the mixing speed of 2000rpm, interior phase is slowly joined among the foreign minister, forms kind solvent.Continue to stir 4h, dichloromethane is volatilized fully.With the suspension that obtains, standing over night is filtered, normal temperature drying 24h, namely.
Embodiment 9
Paeonol 4g, ethyl cellulose 1g is dissolved in the 20ml dichloromethane phase in the preparation, gets PVA17880.64g and is dissolved in the 100ml distilled water and prepares the foreign minister, under the mixing speed of 1500rpm, interior phase is slowly joined among the foreign minister, forms kind solvent.Continue to stir 4h, dichloromethane is volatilized fully.With the suspension that obtains, standing over night is filtered, normal temperature drying 24h, namely.
Paeonol 4g, ethyl cellulose 1g is dissolved in the 20ml dichloromethane phase in the preparation, gets PVA17887.36g and is dissolved in the 100ml distilled water and prepares the foreign minister, under the mixing speed of 1500rpm, interior phase is slowly joined among the foreign minister, forms kind solvent.Continue to stir 4h, dichloromethane is volatilized fully.With the suspension that obtains, standing over night is filtered, normal temperature drying 24h, namely.
Embodiment 11
Paeonol 0.64g, ethyl cellulose 1g is dissolved in the 20ml dichloromethane phase in the preparation, gets PVA17884g and is dissolved in the 100ml distilled water and prepares the foreign minister, under the mixing speed of 1500rpm, interior phase is slowly joined among the foreign minister, forms kind solvent.Continue to stir 4h, dichloromethane is volatilized fully.With the suspension that obtains, standing over night is filtered, normal temperature drying 24h, namely.
Paeonol 3.68g, ethyl cellulose 0.5g is dissolved in the 20ml dichloromethane phase in the preparation, gets PVA17884g and is dissolved in the 100ml distilled water and prepares the foreign minister, under the mixing speed of 1500rpm, interior phase is slowly joined among the foreign minister, forms kind solvent.Continue to stir 4h, dichloromethane is volatilized fully.With the suspension that obtains, standing over night is filtered, normal temperature drying 24h, namely.
Embodiment 13
Paeonol 4g, ethyl cellulose 1g is dissolved in the 20ml dichloromethane phase in the preparation, gets PVA17884g and is dissolved in the 100ml distilled water and prepares the foreign minister, under the mixing speed of 660rpm, interior phase is slowly joined among the foreign minister, forms kind solvent.Continue to stir 4h, dichloromethane is volatilized fully.With the suspension that obtains, standing over night is filtered, normal temperature drying 24h, namely.
Embodiment 14
Paeonol 4g, ethyl cellulose 1g is dissolved in the 20ml dichloromethane phase in the preparation, gets PVA17884g and is dissolved in the 100ml distilled water and prepares the foreign minister, under the mixing speed of 2400rpm, interior phase is slowly joined among the foreign minister, forms kind solvent.Continue to stir 4h, dichloromethane is volatilized fully.With the suspension that obtains, standing over night is filtered, normal temperature drying 24h, namely.
Paeonol 4g, ethyl cellulose 1g is dissolved in the 20ml dichloromethane phase in the preparation, gets PVA17884g and is dissolved in the 100ml distilled water and prepares the foreign minister, under the mixing speed of 1500rpm, interior phase is slowly joined among the foreign minister, forms kind solvent.Continue to stir 4h, dichloromethane is volatilized fully.With the suspension that obtains, standing over night is filtered, normal temperature drying 24h, namely.
Embodiment 16
Paeonol 0.64g, ethyl cellulose 0.5g is dissolved in the 20ml dichloromethane phase in the preparation, gets PVA17880.64g and is dissolved in the 100ml distilled water and prepares the foreign minister, under the mixing speed of 2400rpm, interior phase is slowly joined among the foreign minister, forms kind solvent.Continue to stir 4h, dichloromethane is volatilized fully.With the suspension that obtains, standing over night is filtered, normal temperature drying 24h, namely.
Embodiment 17
Paeonol 4g, ethyl cellulose 1g is dissolved in the 20ml dichloromethane phase in the preparation, gets PVA17887.36g and is dissolved in the 100ml distilled water and prepares the foreign minister, under the mixing speed of 2400rpm, interior phase is slowly joined among the foreign minister, forms kind solvent.Continue to stir 4h, dichloromethane is volatilized fully.With the suspension that obtains, standing over night is filtered, normal temperature drying 24h, namely.
Embodiment 18
Paeonol 3.44g, ethyl cellulose 0.5g is dissolved in the 20ml dichloromethane phase in the preparation, gets PVA17882.84g and is dissolved in the 100ml distilled water and prepares the foreign minister, under the mixing speed of 1000rpm, interior phase is slowly joined among the foreign minister, forms kind solvent.Continue to stir 4h, dichloromethane is volatilized fully.With the suspension that obtains, standing over night is filtered, normal temperature drying 24h, namely.
Embodiment 19
Paeonol 3.44g, ethyl cellulose 0.5g is dissolved in the 20ml ethanol phase in the preparation, gets PVA17882.84g and is dissolved in the 100ml distilled water and prepares the foreign minister, under the mixing speed of 1000rpm, interior phase is slowly joined among the foreign minister, forms kind solvent.Continue to stir 4h, ethanol is volatilized fully.With the suspension that obtains, standing over night is filtered, normal temperature drying 24h, namely.
Embodiment 20
Paeonol 3.44g, ethyl cellulose 0.5g is dissolved in the 20ml chloroform phase in the preparation, gets PVA17882.84g and is dissolved in the 100ml distilled water and prepares the foreign minister, under the mixing speed of 1000rpm, interior phase is slowly joined among the foreign minister, forms kind solvent.Continue to stir 4h, chloroform is volatilized fully.With the suspension that obtains, standing over night is filtered, normal temperature drying 24h, namely.
Embodiment 21
Paeonol 3.44g, triethyl citrate 0.5g is dissolved in the 20ml dichloromethane phase in the preparation, gets PVA17882.84g and is dissolved in the 100ml distilled water and prepares the foreign minister, under the mixing speed of 1000rpm, interior phase is slowly joined among the foreign minister, forms kind solvent.Continue to stir 4h, dichloromethane is volatilized fully.With the suspension that obtains, standing over night is filtered, normal temperature drying 24h, namely.
Experiment and interpretation of result
Get the paeonol microsponge that embodiment makes and carry out following test.
(1) measures the content of paeonol in the microsponge obtain with high-efficient liquid phase technique, according to the amount of the medicine of the content/interpolation of entrapment efficiency=polymer Chinese medicine, calculate its envelop rate.
(2) the paeonol microsponge that obtains with gravimetric detemination, the polymer quality according to the yield=actual polymer quality that obtains/theoretical gained calculates its yield.
(3) the paeonol microsponge of gained is measured its particle size distribution value with Ma Erwen laser light scattering particle size determination instrument, and measuring temperature is 25 ± 1 ℃, and the light scattering degree is 90 °.With the microsponge of its gained of H-3000N type sem observation, particle size range is between 5～300 μ m, and size is even, outward appearance clarification, as shown in Figure 1 be the paeonol microsponge of embodiment 18 gained.Experimental result such as following table 1.
Table 1.
By above-mentioned experiment (1)～(3), the method that confirms paeonol microsponge of the present invention is simple and reliable, the paeonol microsponge drug loading height of its formation, yield height, particle size distribution is even, can further be prepared into the preparation that is used for the treatment of diseases such as rheumatism according to clinical needs.
(4) mensuration of bioavailability
Get the paeonol microsponge that embodiment 18 makes and carry out following research.
The preparation of paeonol microsponge ointment: get stearic acid 7g, liquid paraffin 3.4g, Cera Flava 0.9g prepares oil phase, 65 ℃ of heating in water bath dissolvings; Get the 3.6g triethanolamine as water; Triethanolamine is slowly added in the oil phase of 65 ℃ of water-bath dissolvings; Magnetic agitation is until forming emulsifiable paste matrix.Paeonol microsponge 1.1g or paeonol with embodiment 18 gained joins in the ointment base at last, continues to stir to obtain paeonol microsponge ointment and the common ointment of paeonol respectively.
The nude mice transdermal experiment that exsomatizes: the nude mice cervical vertebra is put to death, and carefully peels off skin, rejects subcutaneous fat; The skin that takes off carries out the transdermal test immediately.With normal saline as acceptable solution and place the good Franz diffusion cell of preheating (the transdermal area is 3.14cm
2, receiving chamber's volume is 15ml, 37 ± 1 ℃ of whole experiment constant temperature, 300 ± 10rpm stirs).The nude mice skin of having handled well is fixed between the receiving chamber and supply chamber that has added stirrer.Add homemade paeonol unguentum or paeonol microsponge ointment 1g on Corium Mus, for preventing water evaporates, cover preservative film on the supply chamber, respectively at 0.5,1,1.5,2,3,4,5,6,7,8,9,10,11, the 12h 1ml that from acceptable solution, takes a sample, replenish the normal saline of equal volume simultaneously in accepting the pond.The sample that obtains is measured content with HPLC.
This experiment adopts paeonol saturated aqueous solution and paeonol unguentum to contrast, by the result as can be known, the unit are accumulative total transit dose of paeonol microsponge ointment is significantly higher than paeonol saturated aqueous solution and the common ointment of paeonol, paeonol saturated aqueous solution transit dose after 6h does not have significant change, the common ointment of paeonol infiltration rate after 7h also reduces gradually, and paeonol microsponge ointment demonstrates lasting, stable percutaneous rate in 12h, and the unit are accumulative total transit dose of medicine is up to 241.86 ± 14.08 μ gcm
-2Ml
-1, infiltration rate is 21.54 ± 1.25 μ gcm
-2Ml
-1H
-1, apparently higher than paeonol unguentum, bioavailability is improved, and the results are shown in Figure 2.
The experiment of skin hold-up: the nude mice cervical vertebra is put to death, and carefully peels off skin, rejects subcutaneous fat; The skin that takes off carries out the transdermal test immediately.With normal saline as acceptable solution and place the good Franz diffusion cell of preheating (the transdermal area is 3.14cm2, and receiving chamber's volume is 15ml, 37 ± 1 ℃ of whole experiment constant temperature, 300 ± 10rpm stirs).The nude mice skin of having handled well is fixed between the receiving chamber and supply chamber that has added stirrer.Add homemade paeonol unguentum or paeonol microsponge ointment 1g on Corium Mus, for preventing water evaporates, cover preservative film on the supply chamber, respectively at 4h, 8h, 12h, 24h skin is taken off, clean 5 times with distilled water, each 10ml.Again Corium Mus is shredded and is placed in the tubule that contains 5ml methanol homogenate 5min, centrifugal 30min(10000rpm), get supernatant and measure content of medicines with the HPLC method.
This experiment adopts paeonol unguentum to contrast: paeonol microsponge ointment Chinese medicine the skin hold-up apparently higher than paeonol unguentum.Especially at 4h and 24h, the medicine hold-up is respectively 0.5675 ± 0.0394mg/cm2 and 1.3627 ± 0.0699mg/cm2, than the hold-up of paeonol unguentum Chinese medicine up to nearly 1 times, (see figure 3).By the result as can be known, paeonol microsponge ointment has improved the skin hold-up of medicine, and medicine more is present in the skin, and is significant for treatment local skin disease.
Rat is in the body experimentation: adopt microdialysis to study in the body experiment, rat through 10% chloral hydrate intraperitoneal injection of anesthesia (0.35ml/100g) (first the every 90min in injection back inject initial dose half to keep the narcotism of rat) after, it is fixing to lie on the back.Carefully remove abdominal part Mus hair with depilatory.Cut off the otch that is about 3mm at entrance and exit respectively with eye scissors, pass injection syringe needle of subcutaneous implantation from entrance, Y type microdialysis probe is inserted from the tip of syringe needle, draw from outlet with first of pumping needle then, carefully syringe needle is extracted out fully, the probe film places the position that will sample.With tissue glue probe entrance and exit position are fixed.Do perfusate with blank normal saline in the whole operation process, and in following whole experiment, keeping perfusion rate is 0.5 μ l/ml, meanwhile, the rat neck hair is wiped out, cut off the otch of a 0.5cm again at the right cervical region of rat, passivity is separated jugular vein, bundle closes distal end, cut at blood vessel with minor operation and to cut off an osculum, probe is implanted in the jugular vein to the right atrium direction, and with stitching thread probe and jugular vein ligation are fixed, get a cotton balls that dips in normal saline then and cover the operation on neck wound site.Same whole operation process, do perfusate with blank normal saline in the probe, and in following whole experiment, keeping perfusion rate is 0.5 μ l/ml, balance 1h, smear 1g paeonol unguentum or paeonol microsponge ointment (5%) at abdominal part again, begin to collect permeate, collect a pipe every 20min, collect 12h altogether, the dialysis solution that obtains is directly measured drug concentrations with the HPLC method, draws the drug level time plot.See Fig. 4, table 2.
The drug level that table 2. microdialysis method detects in different time points subcutaneous rat and the blood changes
By the result as can be known: paeonol microsponge ointment group is compared with the paeonol unguentum group, subcutaneous medicament accumulation transit dose in the paeonol microsponge ointment group and subcutaneous tissue liquid Chinese medicine concentration are all apparently higher than the paeonol unguentum group, and peak time is also significantly early than the paeonol unguentum group, illustrate that paeonol microsponge ointment can improve paeonol in the osmotic absorption of skin, improve the infiltration rate of paeonol.But the elimination time in the paeonol microsponge ointment group but obviously is later than the paeonol unguentum group, and is described the action time that the paeonol microsponge can prolong drug, reaches the purpose of slow release.And blood drug level and the area under curve of paeonol paeonol microsponge ointment group are starkly lower than the paeonol unguentum group.Therefore, paeonol microsponge ointment can improve bioavailability of medicament, prolong drug action time, reduces drug side effect.
Claims (9)
1. the preparation method of a paeonol microsponge preparation adopts class Emulsion solvent diffusion method, it is characterized in that may further comprise the steps:
(1) phase in the preparation is calculated by weight, 1～4 part paeonol, 0.5～1.5 part polymer is dissolved in 10～40 parts the porogen, and is standby;
(2) preparation foreign minister calculates by weight, and the emulsifier for mixing of 100 parts distilled water and 1～8 part is even, standby;
(3) the interior phase that step (1) is made joins among the foreign minister that step (2) makes again, stirs to form class Emulsion;
(4) continue stirring and make the porogen volatilization;
(5) the miniature sponge of isolated by filtration is used distilled water wash, drying, namely.
2. the preparation method of paeonol microsponge preparation according to claim 1, it is characterized in that: the polymer of described step (1) is selected from ethyl cellulose or triethyl citrate.
3. the preparation method of paeonol microsponge preparation according to claim 1, it is characterized in that: the porogen of described step (1) is selected from one or both mixing in dichloromethane, chloroform, the ethanol.
4. the preparation method of paeonol microsponge preparation according to claim 1, it is characterized in that: the emulsifying agent of described step (2) is polyvinyl alcohol.
5. the preparation method of paeonol microsponge preparation according to claim 4, it is characterized in that: the emulsifying agent of described step (2) is PVA1788.
6. the preparation method of paeonol microsponge preparation according to claim 1, it is characterized in that: in the described step (3), mixing speed is 600～2500rpm.
7. the preparation method of paeonol microsponge preparation according to claim 1, it is characterized in that: in the described step (4), mixing time is 2～4h, and mixing speed is 600～2500rpm.
8. the preparation method of paeonol microsponge preparation according to claim 1 is characterized in that: in the described step (5), filter and adopt post precipitation to filter, drying is normal temperature drying 16～48h.
9. the paeonol microsponge preparation that the described method of arbitrary claim makes in the claim 1～8.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310221568.1A CN103330678B (en) | 2013-06-05 | 2013-06-05 | Paeonol tiny sponge preparation and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310221568.1A CN103330678B (en) | 2013-06-05 | 2013-06-05 | Paeonol tiny sponge preparation and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103330678A true CN103330678A (en) | 2013-10-02 |
| CN103330678B CN103330678B (en) | 2014-12-17 |
Family
ID=49238931
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310221568.1A Expired - Fee Related CN103330678B (en) | 2013-06-05 | 2013-06-05 | Paeonol tiny sponge preparation and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103330678B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107050012A (en) * | 2017-06-09 | 2017-08-18 | 南方医科大学 | A kind of licoflavone microsponge acted on whitening spot-removing and its preparation method and application |
| CN113456701A (en) * | 2021-06-11 | 2021-10-01 | 宋坪 | New application of cortex moutan extract |
| CN115670944A (en) * | 2022-11-04 | 2023-02-03 | 山东福瑞达生物股份有限公司 | Micro sponge with anti-aging effect and preparation method and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1279982A (en) * | 2000-06-22 | 2001-01-17 | 昆明市延安医院 | Draco nis sanguis micro sponge agent and its preparing technology |
| CN1817342A (en) * | 2005-10-01 | 2006-08-16 | 合肥立方制药有限公司 | Paeonal gel and its preparing method and quality control |
| WO2008017914A2 (en) * | 2006-08-08 | 2008-02-14 | Fernando Ahumada Ayala | Topical antiacne preparations containing retinoid (tazarotene or adapalene), antibiotic (clindamycin phosphate) and/or keratolytic (miscrosponged benzoyl peroxide) |
-
2013
- 2013-06-05 CN CN201310221568.1A patent/CN103330678B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1279982A (en) * | 2000-06-22 | 2001-01-17 | 昆明市延安医院 | Draco nis sanguis micro sponge agent and its preparing technology |
| CN1817342A (en) * | 2005-10-01 | 2006-08-16 | 合肥立方制药有限公司 | Paeonal gel and its preparing method and quality control |
| WO2008017914A2 (en) * | 2006-08-08 | 2008-02-14 | Fernando Ahumada Ayala | Topical antiacne preparations containing retinoid (tazarotene or adapalene), antibiotic (clindamycin phosphate) and/or keratolytic (miscrosponged benzoyl peroxide) |
Non-Patent Citations (2)
| Title |
|---|
| WU RUI-GUANG,ET AL: "Competitive molecular interaction among peaonol-loaded liposomes:Differential scanning calorimetry and synchrotron X-ray diffraction studies", 《INTERNATIONAL JOURNAL OF PHARMACEUTICS》 * |
| 李沙沙等: "微型海绵给药系统研究进展", 《中国实验方剂学杂志》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107050012A (en) * | 2017-06-09 | 2017-08-18 | 南方医科大学 | A kind of licoflavone microsponge acted on whitening spot-removing and its preparation method and application |
| CN113456701A (en) * | 2021-06-11 | 2021-10-01 | 宋坪 | New application of cortex moutan extract |
| CN115670944A (en) * | 2022-11-04 | 2023-02-03 | 山东福瑞达生物股份有限公司 | Micro sponge with anti-aging effect and preparation method and application thereof |
| CN115670944B (en) * | 2022-11-04 | 2023-11-10 | 山东福瑞达生物股份有限公司 | Microsponge with anti-aging effect and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103330678B (en) | 2014-12-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106420610B (en) | A kind of ionic liquid micro emulsion and its application | |
| CN102580111B (en) | Quercetin hydroxypropyl beta-cyclodextrin clathrate liposome, and preparation method thereof and application thereof | |
| CN102614107A (en) | Micro-emulsion thermosensitive gel for skin external use and preparation method thereof | |
| CN101366697A (en) | Novel nano-lipid carrier for injection embodying paclitaxel series substances and preparation method thereof | |
| CN104474551B (en) | Melatonin phosphatide complexes, its Percutaneously administrable preparation and preparation method thereof | |
| CN103570766B (en) | A kind of Novel platinum liposome preparation and preparation method thereof | |
| CN107303263B (en) | Tripterygium glycosides nanoemulsion gel and preparation method thereof | |
| CN101879138A (en) | Vinca alkaloid nano emulsion injection and preparation method thereof | |
| CN102579323B (en) | Paclitaxel ethosome gel and preparation method thereof | |
| CN102579340A (en) | Sinomenine vesicle and preparation and preparation method thereof | |
| CN109223712A (en) | Flurbiprofen axetil emulsion for injection and preparation method thereof | |
| CN103330678B (en) | Paeonol tiny sponge preparation and preparation method thereof | |
| CN115227644A (en) | Amphiphilic rapamycin gel and preparation method and application thereof | |
| CN103202803A (en) | Imiquimod vesicle gel and preparation method for same | |
| CN104958257B (en) | A kind of Cryptotanshinone skin keratin lipoid body preparation and preparation method thereof | |
| CN105055315A (en) | Cross-linked mitochondrial targeting doxorubicin liposome and preparation method thereof | |
| CN103340823B (en) | Formulation of paeonol proniosomes and preparing method thereof | |
| CN108743534B (en) | Tripterine or tripterine derivative vesicle and preparation method thereof | |
| CN114681403B (en) | Minoxidil delivery body with high drug loading and encapsulation efficiency, gel and preparation thereof | |
| CN113750033B (en) | Baicalin ethosome-loaded soluble hyaluronic acid microneedle array and preparation method and application thereof | |
| CN109528693B (en) | Rapamycin cataplasm and preparation method thereof | |
| CN107137345A (en) | A kind of liposome gel formulation and its preparation and use for suppressing scar proliferation | |
| CN114767738A (en) | Sanbai soup transfersome and preparation method thereof | |
| CN108079298B (en) | Percutaneous photodynamic drug 5-aminoketone hexyl valerate hydrochloride ethosome, and preparation method and application thereof | |
| CN111793030A (en) | Absorption enhancer and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20141217 Termination date: 20190605 |