CN1660121A - Paste agent of penetrating through skin for treating arthritid and preparation method - Google Patents
Paste agent of penetrating through skin for treating arthritid and preparation method Download PDFInfo
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Abstract
A percutaneous plaster for treating arthritis is prepared from tuduranine, phosphotide, cholesterol, carbomer, buffering liquid, sodium polyacrylate and glycerine. Its preparing process is also disclosed.
Description
Technical field:
The present invention relates to a kind of medicinal preparation, a kind of pharmaceutical product that contains organic component particularly relates to a kind of sinomenine (C that contains
19H
23NO
4, transdermal patch Sinomenine) and preparation method thereof, this transdermal patch are applicable to treatment rheumatism and rheumatoid arthritis.
Background technology:
Sinomenine is to extract a kind of alkaloid monomer that obtains from menispermaceous plants Sinomenium acutum [Sinomenium acutum (Thunb) Rehd et Wils] or hair Sinomenium acutum [Sinomeniumacutum (Thunb) Rehd et Wils.var.cinereum Rehd.et Wils] ratan or other contain the plant of sinomenine, and treatment rheumatism and rheumatoid arthritis are had curative effect preferably.At present, be the medicine that main component is made treatment of arthritis with the sinomenine, mainly be the tablet of oral administration and the injection of drug administration by injection, as sinomenine slow releasing tablet and sinomenine injection etc.The administering mode of these two kinds of dosage forms, there be " first pass effect " through liver in tablet, and drug effect is subjected to the destruction of pipe intestinal digesting liquid, and action time is short; Injection needs frequent drug administration just can reach therapeutic effect, and patient compliance is poor.Modern medicine study shows, sinomenine is at the intravital oral administration biaavailability of rat only 15%.Secondly, oral administration or drug administration by injection, medicine absorbs through whole body, has found to have toxic and side effects in various degree.
Summary of the invention:
Technical problem to be solved by this invention provides a kind of new dosage form, improves the effect of sinomenine treatment rheumatism and rheumatoid arthritis.
The technical solution that the present invention addresses the above problem is:
A kind of transdermal patch of treatment of arthritis comprises backing layer, drug storage layer and adhered layer, it is characterized in that described drug storage layer contains following weight (part) component:
In order to prevent the especially oxidation of liposome of medicine, an optimum ratio weight (part) component of described drug storage layer is: sinomenine 1, phosphatidase 14～10, cholesterol 2～5, carbomer 5～10, buffer 200～1000, sodium polyacrylate 2～5, glycerol 10～100, antioxidant 0.1～0.5.
A best proportioning weight (part) component of described drug storage layer is:
Antioxidant described in above-mentioned optimum ratio and the optimum proportion scheme is vitamin E, the tert-butyl group to any one of the fragrant ether of hydroxyl piemarker, propyl gallate.
The preparation method of each component of above-mentioned arbitrary mix proportion scheme being made the saturating degree patch of treatment of arthritis of the present invention is:
The preparation of a, liposome: get sinomenine, phospholipid, cholesterol, add organic dissolution with solvents; Other gets buffer, is heated to 40～80 ℃ and keep constant temperature, and prepared organic solution is at the uniform velocity injected buffer under the continuous stirring, continues to stir and treats that organic solvent waved most back supersound process 10～60 minutes, makes milky sinomenine liposome turbid liquor.
The preparation of b, drug gel: get carbomer, sodium polyacrylate, glycerol, moistening grinds well, and adds in the prepared sinomenine liposome turbid liquor of step a, stirs and makes its swelling, transfers pH to 7-10, continues to stir, and makes the sinomenine lipidosome gel.
The preparation of c, transdermal patch: the sinomenine lipidosome gel that step b is prepared is coated on the backing layer equably, is coated with the pressure-sensitive adhesive paste layer around the gel, makes transdermal patch.
For fear of the volatilization at the storage and transport process Chinese medicine, protective layer is compound in addition with made transdermal patch at last, cuts out, and packs, and can dispatch from the factory.
The inventor has carried out a series of comparative test, and with the drug effect of the transdermal patch of checking treatment of arthritis of the present invention, process of the test is as follows:
One, material and tool using:
1. medicine and reagent are invented the transdermal patch of described treatment of arthritis (application lot number name are called: sinomenine liposome transdermal patch, lot number is: 031021, and every subsides contain sinomenine 10mg, and paste every day one, become body weight for humans in 60kg, then daily dose is 0.17mg/kg); (do not contain liposome, lot number is the common transdermal patch of sinomenine: 031024); (do not contain sinomenine, lot number is the blank liposome transdermal patch: 031102); Sinomenine slow releasing tablet (the accurate word Z20010174 of traditional Chinese medicines, every day 2 times, each 1, every contained sinomenine 60mg, Coming-of-Age Day dosage be 2mg/kg); The sinomenine injection (the accurate word Z43020279 of traditional Chinese medicines, one day twice, each intramuscular injection 1ml, every milliliter contains sinomenine 25mg, Coming-of-Age Day dosage be 0.83mg/kg); Freund's complete adjuvant (production of U.S. sigma company).
2. instrument microdialysis system (U.S. BAS company); Summit P680 type high performance liquid chromatograph (German Dionex company); GJ-8402 hot plate dolorimeter (Shanghai experimental animal instrument plant), slide gauge, electronic analytical balance, 722 grating spectrophotometers (Shanghai Precision Scientific Apparatus Co., Ltd)
3. animal BALB/C nude mice, Wistar rat, NIH mice.
Two, test at the body transdermal penetration
Adopt the microdialysis method sinomenine liposome transdermal patch and the common transdermal patch of sinomenine to be carried out (not containing liposome) comparative test of local organization drug level.Process of the test is: nude mice abdominal cavity is injected pentobarbital solution (0.6ml/10g) anesthesia, microdialysis probe is implanted the subcutaneous tissue on top, nude mice joint, with Kreb ' s-Ringer is perfusate, about flow velocity perfusion 1h with 0.5 μ l/min, so that regional blood flow recovers normal, and treat that nude mice revives.Patch (dosage is for containing sinomenine 1.7mg/kg) closely is affixed on the skin surface of probe by the position, begins to collect the dialysis solution of probe outflow end simultaneously.Keep the nude mice waking state in the collection process, keep perfusate flow velocity 0.5 μ l/min, the sample interval is 30min, and each collecting amount is 15 μ l, and total acquisition time is 20h, and dialysis solution detects sinomenine content with high performance liquid chromatography.The results are shown in Table 1 and Figure of description.
Sinomenine assay result (n=3) in two kinds of patch joint parts of table 1 local organization
| Administration time (h) | Sinomenine content (μ g/ml) | Administration time (h) | Sinomenine content (μ g/ml) | ||
| The liposome patch | Common patch | The liposome patch | Common patch | ||
| ????0.5 ????1.0 ????1.5 ????2.0 ????2.5 ????3.0 ????3.5 ????4.0 ????4.5 ????5.0 ????5.5 ????6.0 ????6.5 ????7.0 ????7.5 ????8.0 ????8.5 ????9.0 ????9.5 ????10.0 | ??0.0190 ??0.0632 ??0.0400 ??1.3275 ??2.3599 ??2.7118 ??3.3714 ??3.6242 ??3.9803 ??3.7928 ??4.3701 ??3.9613 ??3.7654 ??4.3891 ??4.4670 ??4.1742 ??4.1931 ??4.4249 ??3.9192 ??3.9192 | ?0.0209 ?0.0697 ?0.0442 ?0.4185 ?0.1627 ?0.3487 ?0.4650 ?0.5347 ?0.3720 ?0.5579 ?0.9299 ?0.8695 ?0.9299 ?1.0927 ?0.6742 ?0.7439 ?0.8602 ?0.5347 ?0.4882 ?0.2557 | ????10.5 ????11.0 ????11.5 ????12.0 ????12.5 ????13.0 ????13.5 ????14.0 ????14.5 ????15.0 ????15.5 ????16.0 ????16.5 ????17.0 ????17.5 ????18.0 ????18.5 ????19.0 ????19.5 ????20.0 | ????4.2332 ????3.9613 ????4.4670 ????4.3617 ????4.2732 ????4.0772 ????3.8244 ????4.3111 ????4.1552 ????3.7654 ????3.7654 ????3.9613 ????3.7274 ????3.8834 ????3.4725 ????3.1016 ????3.2196 ????3.0237 ????2.6339 ????2.4779 | ?0.8602 ?0.6044 ?0.7904 ?0.5347 ?0.5579 ?0.5579 ?0.3255 ?0.5579 ?0.1162 ?0.4905 ?0.4487 ?0.4487 ?0.1069 ?0.3208 ?0.2302 ?0.2488 ?0.1348 ?0.5301 ?0.3441 ?0.3720 |
By above result as seen, sinomenine concentration liposome patch illustrates that apparently higher than the common patch that does not contain liposome sinomenine liposome patch is easier to be accumulated in the joint part local organization than common patch, can form the targeting to local lesion tissue.Sinomenine liposome patch sinomenine behind administration 2h begins to be detected, and 2～6h is in rising trend, and 6h～17h is a steady-state process, and drug level descends gradually behind the 17h, possesses the feature of controlled release preparation.Thus, the dosage of sinomenine liposome transdermal patch is defined as pasting every day 1.
Three, pharmacodynamics test:
1, antiinflammatory test
1.1 the transdermal patch of treatment of arthritis of the present invention (being sinomenine liposome transdermal patch, following identical) xylol causes the influence of mice ear
60 of Kunming mouses, male and female half and half are divided into 6 groups at random under equilibrium condition, 10 every group.The blank group gives the not transdermal patch of pastille (blank liposome), is affixed on the knee joint place; The large, medium and small dosage group of sinomenine dosage is respectively the sinomenine liposome transdermal patch (face and use preceding preparation) that contains sinomenine 3.4mg/kg, 1.7mg/kg, 0.85mg/kg, is affixed on the knee joint place; Sinomenine slow releasing tablet 20mg/kg[faces the medicinal liquid (in sinomenine) that is mixed with 1mg/ml with distilled water with preceding], gastric infusion; Sinomenine injection dosage is 8.3mg/kg, intramuscular injection.Each organized successive administration 7 days, and 0.5h only evenly smears dimethylbenzene 30 μ l/ with microsyringe to each group mouse right ear behind the last medicine, behind the 15min, cut the left and right sides auricle of mice, blunderbuss head blunderbuss with diameter 8mm is got the auricle of two ear same area, weighs respectively, calculates the ear swelling degree of each Mus.The result shows that the sinomenine liposome transdermal patch group of the large, medium and small dosage of sinomenine all has the effect of inhibition ear swelling degree in various degree.Result of the test see Table 2 (with the blank group relatively,
*P＜0.05,
*＜0.01,
* *P＜0.001, down together):
Table 2 mice caused by dimethylbenzene xylene ear swelling antiinflammatory result of the test (x ± s, n=10)
| Group | Ear swelling degree (mg) |
| Dosage group small dose group sinomenine slow releasing tablet group sinomenine injection group in the heavy dose of group of blank group | ????4.2±1.3 ????2.8±1.0** ????3.2±1.4** ????3.4±1.8 ????2.2±1.1*** ????2.1±0.9*** |
Cause the influence that the mouse peritoneal capillary permeability increases 1.2 invent the transdermal patch Dichlorodiphenyl Acetate of described treatment of arthritis
60 of Kunming mouses, male and female half and half are divided into 6 groups at random under equilibrium condition, 10 every group.Grouping and administration are all with 1.1.1h after the last administration, the azovan blue normal saline solution 0.1ml/10g of each caudal vein injection 2%, the acetum 0.2ml/ of lumbar injection 0.6% only simultaneously, behind the 20min, taking off neck puts to death, soft abdominal cavity, open the abdominal cavity, with the distilled water flushing abdominal cavity that amounts to 5ml 3 times, collect flushing liquor and supply the 5ml volume, the centrifugal 5min of 1000r/min gets supernatant and measures absorbance (OD) at 590nm wavelength place with 722 spectrophotometers, and the result shows that sinomenine is big, in, the effect that low dose of sinomenine liposome transdermal patch group all has inhibition blood capillary in various degree to ooze out.Result of the test sees Table 3.
Table 3 acetic acid cause mouse peritoneal capillary permeability antiinflammatory result of the test (x ± s, n=10)
| Group | Absorbance (OD) |
| Dosage group small dose group sinomenine slow releasing tablet group sinomenine injection group in the heavy dose of group of blank group | ????0.296±0.040 ????0.189±0.044** ????0.234±0.035** ????0.212±0.058* ????0.157±0.080*** ????0.145±0.037*** |
1.3 invent of the influence of the transdermal patch of described treatment of arthritis to adjuvant arthritis rats
1.3.1 the transdermal patch of inventing described treatment of arthritis influences 60 of Wistar male rats to the adjuvant arthritis rats primary affection, under equilibrium condition, be divided into 6 groups at random, the blank group gives normal saline, sinomenine is big, in, small dose group dosage is respectively and contains sinomenine 2.38mg/kg, 1.19mg/kg, 0.595mg/kg sinomenine liposome transdermal patch (face and use preceding preparation, be affixed on rat knee joint place), sinomenine slow releasing tablet 14mg/kg (faces the medicinal liquid that is mixed with 1.4mg/ml with distilled water with preceding, gastric infusion), sinomenine injection group dosage is 5.81mg/kg.Measure the right back sufficient sole of the foot thickness of each Mus respectively as normal value with slide gauge, administration behind the Freund's complete adjuvant 1h of the subcutaneous injection of the right back sufficient sole of the foot of each administration group 0.1ml, successive administration 9 days, press the right back sufficient sole of the foot thickness of measure of time shown in the table 3 simultaneously, with the index of foot swelling rate as the arthritis effect, the result shows that the sinomenine liposome transdermal patch group of the large, medium and small dosage of sinomenine all can obviously suppress the adjuvant-induced arthritis primary affection, and effect is better than injection group and slow releasing tablet group.Result of the test sees Table 4.
Table 4 adjuvant arthritis rats primary affection (foot swelling rate) antiinflammatory result of the test (x ± s, n=10)
| Group | ????1d | ??????2d | ????3d | ????5d | ????7d | ????9d |
| Dosage group small dose group slow release group injection group in the heavy dose of group of blank group | ?0.404±0.041 ?0.342±0.033* ?0.350±0.045* ?0.364±0.076 ?0.375±0.048 ?0.352±0.055* | ??0.461±0.061 ??0.365±0.067* ??0.377±0.051 ??0.409±0.093 ??0.412±0.044* ??0.385±0.056** | ??0.520±0.061 ??0.402±0.053** ??0.418±0.087** ??0.454±0.103 ??0.453±0.054* ??0.432±0.063** | ?0.489±0.072 ?0.406±0.065** ?0.401±0.056** ?0.428±0.097 ?0.422±0.052* ?0.406±0.087* | ?0.437±0.062 ?0.361±0.058* ?0.354±0.051* ?0.373±0.085 ?0.382±0.054 ?0.360±0.086* | ?0.388±0.054 ?0.319±0.044* ?0.324±0.046* ?0.344±0.079 ?0.352±0.047 ?0.335±0.082 |
1.3.2 invent of the influence of the transdermal patch of described treatment of arthritis to adjuvant arthritis rats secondary affection (foot swelling rate)
The same 1.3.1 of dosage of grouping and each group.Measure the right back sufficient sole of the foot thickness of each Mus respectively as normal value with slide gauge, the Freund's complete adjuvant of the subcutaneous injection of the right back sufficient sole of the foot of each administration group 0.1ml, cause beginning in the 10th day administration of scorching back, last till end in the 28th day, divide the left back foot of each Mus (the non-inflammation foot that the causes) sole of the foot thickness of measuring out of the ordinary by the time shown in the table 4 with slide gauge, calculate the foot swelling rate.The result shows that the sinomenine liposome transdermal patch group of the large, medium and small dosage of sinomenine all can obviously suppress the secondary affection of adjuvant-induced arthritis, and effect is better than slow releasing tablet group, injection group.Result of the test sees Table 5.
Table 5 adjuvant arthritis rats secondary affection (foot swelling rate) antiinflammatory result of the test (x ± s, n=10)
| Group | ????10d | ????14d | ????18d | ????22d | ????26d | ????28 |
| Dosage group small dose group slow releasing tablet group injection group in the heavy dose of group of blank group | 0.349±0.051 0.293±0.048 *0.299±0.053 *0.311±0.075 0.297±0.083 0.305±0.061 | ?0.371±0.058 ?0.315±0.055 *?0.321±0.053 ?0.329±0.052 ?0.323±0.078 ?0.323±0.082 | 0.431±0.048 0.321±0.053 **0.326±0.045 ***0.336±0.046 ***0.333±0.073 **0.334±0.082 ** | ?0.337±0.052 ?0.280±0.057 *?0.276±0.048 *?0.283±0.077 ?0.295±0.082 ?0.286±0.052 * | 0.291±0.029 0.235±0.034 *0.247±0.047 *0.266±0.058 0.258±0.079 0.255±0.069 | ?0.205±0.032 ?0.141±0.026 **?0.145±0.020 **?0.165±0.043 *?0.195±0.015 ?0.154±0.026 ** |
2, analgesic test
Invent described treatment of arthritis transdermal patch Dichlorodiphenyl Acetate induced mice pain influence 60 of Kunming mouses, male and female half and half are divided into 6 groups at random under equilibrium condition, 10 every group.Grouping and administration are all with 1.1.Each organized successive administration 7 days, and the acetum of 1h lumbar injection 0.6% behind the last medicine, 0.2ml/ are only turned round the body number of times in the incubation period of interior each Mus generation writhing response of 15min and the 15min behind the record injection acetic acid.The result shows that the sinomenine liposome transdermal patch group of the large, medium and small dosage of sinomenine all has analgesic activity in various degree.Result of the test sees Table 6.
Table 6 analgesic test result (x ± s, n=10)
| Group | Incubation period (min) | Turn round body number of times (in the 15min) |
| Dosage group small dose group sinomenine slow releasing tablet group sinomenine injection group in the heavy dose of group of blank group | ????4.85±1.65 ????6.47±0.92 *????5.86±1.44 *????5.37±1.31 ????5.80±1.07 ????6.86±1.42 * | ????32.3±10.6 ????22.7±4.8 *????26.8±7.6 ????28.6±6.9 ????21.8±7.3 *????19.5±8.7 ** |
Above-mentioned results of pharmacodynamic test shows that the transdermal patch of inventing described treatment of arthritis has tangible local anti-inflammatory, analgesic activity and certain whole body antiinflammatory, analgesic activity.Wherein, the local anti-inflammatory effect to arthritis model is better than sinomenine slow releasing tablet and injection.The transdermal patch that treatment of arthritis of the present invention is described can make sinomenine be enriched in arthritis focus tissue, reduce its distribution relatively at other tissue of whole body, organ, promptly have targeting ground amelioration of inflammation, help arthritic treatment, and can alleviate medicine systemic toxic side effect.
Because the transdermal patch of the described treatment of arthritis of invention is a kind of patch, especially adopts liposome as pharmaceutical carrier, therefore possess the characteristics of targeting, controlled release, at present the domestic Chinese medicine liposome transdermal patch launch that sustained release is not arranged as yet.The present invention the remarkable result of test of body transdermal penetration and results of pharmacodynamic test embodiment, also has following advantage except above-mentioned:
1, the advantage of dosage form:
1. avoid first pass effect: percutaneous dosing, without liver metabolism, no first pass effect has avoided the degraded of medicine to destroy, and reaches reduction dosage, improves the purpose of curative effect.
2. avoid GI irritation: percutaneous dosing, medicine need not pass through gastrointestinal tract, and can avoid stimulates gastrointestinal, reduces toxic and side effects.
3. controlled release preparation, efficacy stability: compare with other common external plaster agent such as rubber-emplastrum, cataplasma etc., medicine discharges with constant speed, effect is steady, lasting, duration of efficacy is long, has avoided frequent drug administration to cause peak, the paddy phenomenon of drug level, guarantees treatment safety, effective.
4. Zhi Liao compliance: using method is easy, and the length of holding time is avoided trouble and misery oral and that the frequent medication of injection type is produced, has improved the compliance of patient's medication.
2, the advantage of carrier:
Because with the carrier of liposome as medicine, compare with other common preparation capable of permeating skin, its advantage is as follows:
1. targeting: formed liposome of lipoid similar to sebum such as sphingomyelin and keratodermatitis lipid have the similarity of height, can increase the accumulation of medicine at local skin, play lasting drug release effect.In order to confirm this point, the inventor has prepared the common transdermal patch of sinomenine and has compared test, and the result shows, after the transdermal patch medication of the present invention, drug level in the skin is 4.39 times of common patch, and the drug level in the site of action muscle is 3.28 times of common patch.Illustrate make the sinomenine liposome after, see through cuticular dose and obviously increase in the hold-up of skin and muscle, can form targeting to local lesion tissue.This point is particularly favourable factor for arthritic topical therapeutic.
2. reduce toxic and side effects: Liposomal formulation has the speed limit barrier action that the medicine whole body absorbs, and can reduce the total amount that medicine enters blood circulation, reduces the whole body absorption, thereby avoids the toxic and side effects of medicine.The inventor shows that through in-vitro percutaneous permeability test result sinomenine only is 62.36% of a common patch through the amount that skin arrives whole body in the liposome patch.Illustrate make the sinomenine liposome after, sinomenine sees through the time lengthening that skin enters blood in the preparation, dose reduces.
3. solubilization: medicine is wrapped in the drug-supplying system preferably, and insoluble drug is had solubilization, can improve bioavailability of medicament.The inventor measures and has compared sinomenine at the dissolubility for preparing the liposome front and back, the dissolubility in buffer is 0.42mg/ml under the sinomenine room temperature as a result, make that the concentration of sinomenine is 2mg/ml behind the sinomenine liposome, drug loading has improved 4 times than ordinary preparation.
Description of drawings:
Figure of description is a sinomenine assay comparison diagram (n=3) as a result in two kinds of patch joint part local organizations.
The specific embodiment:
Embodiment 1:
Take by weighing raw material by following proportioning:
Sinomenine 10g, fabaceous lecithin 40g, cholesterol 20g, carbomer-940 50g
Sodium polyacrylate 20g, phosphate buffer 2kg, glycerol 100g, vitamin e1 g.
Preparation method is as follows:
The preparation of a, liposome: take by weighing sinomenine, fabaceous lecithin, cholesterol, vitamin E, dissolving adds diethyl ether; Other gets phosphate buffer, is heated to 40～80 ℃ and keep constant temperature, and prepared diethyl ether solution is at the uniform velocity injected buffer under the continuous stirring, continues to stir and treats that ether waved most back supersound process 10～60 minutes, makes milky sinomenine liposome turbid liquor.
The preparation of b, drug gel: get carbomer, sodium polyacrylate, glycerol, moistening grinds well, and adds in the prepared sinomenine liposome turbid liquor of step a, stirs and makes its swelling, transfers pH to 7-10, continues to stir, and makes the sinomenine lipidosome gel.
The preparation of c, transdermal patch: the sinomenine lipidosome gel that step b is prepared is coated on the backing layer equably, is coated with the pressure-sensitive adhesive paste layer around the gel, makes transdermal patch.Protective layer is compound in addition with made transdermal patch at last, cuts out, and packs, and can dispatch from the factory.
Embodiment 2:
Take by weighing raw material by following proportioning:
Sinomenine 10g, sphingomyelin 60g, cholesterol 30g, carbomer-934 75g
Sodium polyacrylate 25g, acetate buffer 6kg, glycerol 500g, the tert-butyl group is to the fragrant ether 2.5g of hydroxyl piemarker.
Preparation method is as follows:
The preparation of a, liposome: take by weighing sinomenine, sphingomyelin, cholesterol, the tert-butyl group to the fragrant ether of hydroxyl piemarker, add dissolve with ethanol; Other gets acetate buffer, is heated to 40～80 ℃ and keep constant temperature, and prepared alcoholic solution is at the uniform velocity injected buffer under the continuous stirring, continues to stir and treats that ethanol waved most back supersound process 10～60 minutes, makes milky sinomenine liposome turbid liquor.
The preparation of b, drug gel: get carbomer, sodium polyacrylate, glycerol, moistening grinds well, and adds in the prepared sinomenine liposome turbid liquor of step a, stirs and makes its swelling, transfers pH to 7-10, continues to stir, and makes the sinomenine lipidosome gel.
The preparation of c, transdermal patch: the sinomenine lipidosome gel that step b is prepared is coated on the backing layer equably, is coated with the pressure-sensitive adhesive paste layer around the gel, makes transdermal patch.Protective layer is compound in addition with made transdermal patch at last, cuts out, and packs, and can dispatch from the factory.
Embodiment 3:
Take by weighing raw material by following proportioning:
Sinomenine 10g, dipalmitoyl-glycerol phosphatidase 11 00g, cholesterol 50g, carbomer-941 100g
Sodium polyacrylate 50g, citrate buffer 10kg, glycerol 1kg, propyl gallate 5g.
Preparation method is as follows:
The preparation of a, liposome: take by weighing sinomenine, dipalmitoyl-glycerol phospholipid, cholesterol, propyl gallate, add the chloroform dissolving; Other gets citrate buffer, be heated to 40～80 ℃ and keep constant temperature, prepared chloroformic solution is at the uniform velocity injected buffer under the continuous stirring, continue to stir and treat that chloroform waves most back supersound process 10～～60 minutes, make milky sinomenine liposome turbid liquor.
The preparation of b, drug gel: get carbomer, sodium polyacrylate, glycerol, moistening grinds well, and adds in the prepared sinomenine liposome turbid liquor of step a, stirs and makes its swelling, transfers pH to 7-10, continues to stir, and makes the sinomenine lipidosome gel.
The preparation of c, transdermal patch: the sinomenine lipidosome gel that step b is prepared is coated on the backing layer equably, is coated with the pressure-sensitive adhesive paste layer around the gel, makes transdermal patch.Protective layer is compound in addition with made transdermal patch at last, cuts out, and packs, and can dispatch from the factory.
Claims (4)
1, a kind of transdermal patch of treatment of arthritis comprises backing layer, drug storage layer and adhered layer, it is characterized in that described drug storage layer contains following weight (part) component:
Sinomenine 1, phosphatidase 14～10, cholesterol 2～5, carbomer 5～10, buffer 200～1000, sodium polyacrylate 2～5, glycerol 10～100.
2, the transdermal patch of a kind of treatment of arthritis according to claim 1 is characterized in that described drug storage layer made by following weight (part) component:
Sinomenine 1, phosphatidase 14～10, cholesterol 2～5, carbomer 5～10, buffer 200～1000, sodium polyacrylate 2～5, glycerol 10～100, antioxidant 0.1～0.5.
3, the transdermal patch of a kind of treatment of arthritis according to claim 2 is characterized in that described drug storage layer made by following weight (part) component:
Sinomenine 1, phosphatidase 16 .8, cholesterol 3.2, carbomer 7.5, buffer 500, sodium polyacrylate 2.5, glycerol 50, antioxidant 0.2.
4, a kind of method for preparing the transdermal patch of claim 1,2 or 3 described treatment of arthritis is:
The preparation of a, liposome: get sinomenine, phospholipid, cholesterol, add organic dissolution with solvents; Other gets buffer, is heated to 40～80 ℃ and keep constant temperature, and prepared organic solution is at the uniform velocity injected buffer under the continuous stirring, continues to stir and treats that organic solvent waved most back supersound process 10～60 minutes, makes milky sinomenine liposome turbid liquor.
The preparation of b, drug gel: get carbomer, sodium polyacrylate, glycerol, moistening grinds well, and adds in the prepared sinomenine liposome turbid liquor of step a, stirs and makes its swelling, transfers pH to 7-10, continues to stir, and makes the sinomenine lipidosome gel.
The preparation of c, transdermal patch: the sinomenine lipidosome gel that step b is prepared is coated on the backing layer equably, is coated with the pressure-sensitive adhesive paste layer around the gel, makes transdermal patch.
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| CN (1) | CN1274310C (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101066455B (en) * | 2007-03-06 | 2010-04-21 | 江门新时代胶粘科技有限公司 | Medicine carrying aquogel matrix for preparing plaster and its preparation process |
| CN103211758A (en) * | 2013-03-19 | 2013-07-24 | 广东医学院 | Liquid crystal nanoparticle transdermal agent and preparation method thereof |
| CN103648483A (en) * | 2011-06-24 | 2014-03-19 | 莫茨制药有限及两合公司 | Composition comprising an onion extract and liposomes |
| CN107648179A (en) * | 2017-09-21 | 2018-02-02 | 浙江中医药大学 | A kind of novel skin drug-delivery preparation for treating rheumatoid arthritis and preparation method thereof |
| CN111632054A (en) * | 2020-07-09 | 2020-09-08 | 安徽中医药大学 | A pharmaceutical preparation for treating rheumatoid arthritis by transdermal administration, and its preparation method |
-
2004
- 2004-12-27 CN CN 200410077596 patent/CN1274310C/en not_active Expired - Fee Related
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101066455B (en) * | 2007-03-06 | 2010-04-21 | 江门新时代胶粘科技有限公司 | Medicine carrying aquogel matrix for preparing plaster and its preparation process |
| CN103648483A (en) * | 2011-06-24 | 2014-03-19 | 莫茨制药有限及两合公司 | Composition comprising an onion extract and liposomes |
| US10967036B2 (en) | 2011-06-24 | 2021-04-06 | Hra Pharma | Composition comprising an onion extract and liposomes |
| CN103211758A (en) * | 2013-03-19 | 2013-07-24 | 广东医学院 | Liquid crystal nanoparticle transdermal agent and preparation method thereof |
| CN103211758B (en) * | 2013-03-19 | 2014-08-13 | 广东医学院 | Liquid crystal nanoparticle transdermal agent and preparation method thereof |
| CN107648179A (en) * | 2017-09-21 | 2018-02-02 | 浙江中医药大学 | A kind of novel skin drug-delivery preparation for treating rheumatoid arthritis and preparation method thereof |
| CN111632054A (en) * | 2020-07-09 | 2020-09-08 | 安徽中医药大学 | A pharmaceutical preparation for treating rheumatoid arthritis by transdermal administration, and its preparation method |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1274310C (en) | 2006-09-13 |
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