CN101849927A - Hot-melt pressure-sensitive adhesive transdermal patch containing alpha-asarone and preparation method thereof - Google Patents
Hot-melt pressure-sensitive adhesive transdermal patch containing alpha-asarone and preparation method thereof Download PDFInfo
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- CN101849927A CN101849927A CN201010202354A CN201010202354A CN101849927A CN 101849927 A CN101849927 A CN 101849927A CN 201010202354 A CN201010202354 A CN 201010202354A CN 201010202354 A CN201010202354 A CN 201010202354A CN 101849927 A CN101849927 A CN 101849927A
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- Prior art keywords
- sensitive adhesive
- hot
- asaricin
- fusible pressure
- transdermal patch
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- 239000004820 Pressure-sensitive adhesive Substances 0.000 title claims abstract description 71
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- RKFAZBXYICVSKP-AATRIKPKSA-N alpha-asarone Chemical compound COC1=CC(OC)=C(\C=C\C)C=C1OC RKFAZBXYICVSKP-AATRIKPKSA-N 0.000 title abstract description 7
- 239000012943 hotmelt Substances 0.000 title abstract description 6
- 239000002994 raw material Substances 0.000 claims abstract description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- 230000001464 adherent effect Effects 0.000 claims description 12
- 238000001816 cooling Methods 0.000 claims description 11
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- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 8
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- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention discloses a hot-melt pressure-sensitive adhesive transdermal patch containing alpha-asarone, which comprises a back lining, a storage warehouse layer and an anti-sticking layer. The storage warehouse layer is prepared from the following raw materials in percentage by weight: 1-20 percent of alpha-asarone, 70-98 percent of hot-melt pressure-sensitive adhesive and 1-10 percent of transdermal accelerant. The transdermal patch adopts the hot-melt pressure-sensitive adhesive with both hot-melt and pressure-sensitive properties as a base material, has the advantages of no organic solvent and low pollution nuisance; in addition, the preparation of the transdermal patch has the advantages of high coating speed and high degree of automation.
Description
Technical field
The present invention relates to a kind of transdermal patch field, be specifically related to hot-fusible pressure-sensitive adhesive transdermal patch of a kind of α of containing-asaricin and preparation method thereof.
Background technology
α-asaricin has another name called alpha-ararin or asarone, and chemistry is called 2,4, and 5-trimethoxy-phenylpropyl alcohol-1-alkene is one of main effective ingredient in the acorus gramineus araceae plant, has following general structure:
From the sixties in 20th century, α-asaricin has been carried out extensive studies both at home and abroad, confirmed that it has very strong pharmacologically active, have cough-relieving, eliminate the phlegm, relieving asthma, calm, spasmolytic and anticonvulsant action, and human cancer cell is had active anticancer; Diplococcus pneumoniae, staphylococcus aureus and colibacillary growth also there is in various degree inhibitory action.α-asaricin is mainly used in the treatment of bronchial asthma, chronic gas inflammation, pneumonia and chronic obstructive pulmonary disease companion's pulmonary infection and other respiratory tract disease.
α-asaricin oral absorption is rapid, promptly reaches the highest blood drug level in 15 minutes, and is distributed in internal organs such as liver, kidney, bile and the heart, brain, lung, spleen rapidly.The combination rate of itself and plasma protein is 61%, wherein liver, kidney concentration approach plasma concentration, all the other successively decrease successively, part still absorbs through the intestinal liver by behind the bile excretion again, mainly discharges with urine at last, fraction is by liver metabolism, main metabolites is 2,4,5-trimethoxy acrylic acid (being cinnamic acid).
The half-life of α-asaricin is 3 hours~4 hours, and oral administration biaavailability is extremely low, only is 5%.Product on the domestic market has tablet, capsule and injection at present.Because α-asaricin is fat-soluble strong chemical compound, dissolubility is little in the water, and oral administration biaavailability is extremely low, is more suitable in making percutaneous drug administration preparation.
Percutaneous drug administration preparation is meant that medicine is entered the systemic blood circulation and reached effective blood drug concentration by skin absorbs, realizes a class preparation of disease treatment or prevention.Percutaneous drug administration preparation is compared to other dosage forms and has unique advantage: (1) percutaneous dosing can avoid the first pass effect of the contingent liver of oral administration and medicine to degrade at gastrointestinal, make the absorption of medicine not influenced by gastrointestinal factors, reduce the individual variation of medication; (2) single administration can make medicine enter in the body with constant speed for a long time, reduces administration number of times; (3) can speed on demand be imported in the body by medicine, keep constant blood drug level, avoid the peak valley phenomenon of blood drug level, reduce toxic and side effects; (4) easy to use, interruption of the administration at any time, patient compliance is good.
As the pressure sensitive adhesive of percutaneous administration patch main material, major part is a solvent-borne type, thereby is accompanied by problems such as environmental pollution and energy consumption consumption is big.The emulsion-type pressure-sensitive that development in recent years is got up is owing to reasons such as rate of drying is slow, emulsifying agent migration also are very restricted.Hot-fusible pressure-sensitive adhesive (HMPSA) is the pressure sensitive adhesive based on thermoplastic polymer, and room temperature for solid, is coated with under the molten condition down, and the after-applied light pressure of hardening by cooling just can bond fast.Because it does not contain organic solvent, low public hazards, coating speed are fast, and the automaticity height is widely used in aspects such as packing, health care.
Summary of the invention
The invention provides a kind of steady quality, zest is little and drug loading the is high hot-fusible pressure-sensitive adhesive transdermal patch that contains α-asaricin.
A kind of hot-fusible pressure-sensitive adhesive transdermal patch that contains α-asaricin comprises backing layer, bin-storing layer and adherent layer, and described bin-storing layer is made by following raw materials by weight percent:
α-asaricin 1%~20%
Hot-fusible pressure-sensitive adhesive 70%~98%
Transdermal enhancer 1%~10%.
As preferably:
Described bin-storing layer is made by following raw materials by weight percent:
α-asaricin 8%~13%
Hot-fusible pressure-sensitive adhesive 83%~88%
Transdermal enhancer 3.5%~4.5%.
Described hot-fusible pressure-sensitive adhesive is meant with polymer such as thermoplastic elastomers to be the adhesive of major function material, have hot melt and pressure-sensitive double grading concurrently, can under molten condition, be coated with, have pressure-sensitive character after the hardening by cooling, it generally consists of thermoplastic elastomer, viscosifier, plasticizer, filler and antioxidant.The preferred fusing point of the present invention is 50 ℃~250 ℃ a hot-fusible pressure-sensitive adhesive, further the hot-fusible pressure-sensitive adhesive of preferably being made by the raw material that comprises following weight portion:
100 parts of thermoplastic elastomers
80~160 parts of viscosifier
40~80 parts of plasticizers
0~40 part of filler
0~10 part in antioxidant.
Described thermoplastic elastomer can be selected this area thermoplastic elastomer commonly used for use, as selecting in styrene-isoprene-phenylethene triblock copolymer (SIS), s-B-S triblock copolymer (SBS) or other medical thermoplastic elastomers one or more for use.The modulus of SIS is low, viscosity and melt viscosity are little, has good processing characteristics; Owing to have the characteristic of methyl chains on the SIS mid-block polyisoprene structure, make it have good cohesiveness and the good adhesive performance and the compatibility good with other additives.Therefore further preferred SIS.
Described viscosifier can be selected this area viscosifier commonly used for use, as selecting in terpene resin, Petropols, Foral or other the medicinal viscosifier etc. one or more for use.Characteristics such as Petropols have that acid number is low, cohesive good, water-fast and chemicals-resistant, therefore preferred Petropols.
Described plasticizer can be selected this area plasticizer commonly used for use, as selecting in liquid paraffin, dibutyl phthalate, white oil or other the medicinal plasticizers etc. one or more for use.Liquid paraffin is the plasticizer of function admirable, so preferred liquid paraffin.
Described filler can be selected this area filler commonly used for use, as selecting in titanium dioxide or other the medicinal filleies etc. one or more for use.The titanium dioxide stable in properties, reducing power is strong, and glossiness is big, so preferred titanium dioxide.
Described antioxidant can be selected this area antioxidant commonly used for use, as selecting N for use, one or more in N-dibutylamino dithio zinc formate, propyl gallate, 2,6 ditertiary butyl p cresol or other the medicinal antioxidant etc.N, the anti-aging of N-dibutylamino dithio zinc formate is effective, thus preferred N, N-dibutylamino dithio zinc formate.
The preparation method of described hot-fusible pressure-sensitive adhesive comprises step: will be used to prepare each raw material mixing of hot-fusible pressure-sensitive adhesive, and be heated to 160~180 ℃ under the nitrogen protection, and stir, cooling promptly gets hot-fusible pressure-sensitive adhesive.
Described transdermal enhancer is selected from one or more in isopropyl myristate, menthol, oleic acid, azone or the acceptable transdermal enhancer of other pharmaceuticss etc.
Described backing layer is used to cover and protect the bin-storing layer that contains medicine, selects for use this area good, impervious material of pliability commonly used to get final product, as contains aluminumpolyethylene composite membrane, non-woven fabrics or the acceptable back lining materials of other pharmaceuticss etc.
Described adherent layer can be selected this area antiseized protecting film commonly used for use, is used to cover and protect the bin-storing layer that contains medicine, tears off before the while is easy to use, as polyester film, siliconised paper or the acceptable adhesive of other pharmaceuticss etc. of silicidation.
The preparation method of described hot-fusible pressure-sensitive adhesive transdermal patch comprises the following steps:
(1) hot-fusible pressure-sensitive adhesive is heated to fusion under nitrogen protection, α-asaricin and transdermal enhancer are scattered in the fused hot-fusible pressure-sensitive adhesive, mix homogeneously is made the pressure sensitive adhesive of pastille;
(2) under heat-retaining condition the pressure sensitive adhesive of pastille is coated on adherent layer or the backing layer, the cooling back covers backing layer or adherent layer on the pressure sensitive adhesive of pastille, make the hot-fusible pressure-sensitive adhesive transdermal patch that contains α-asaricin.
Described heat-retaining condition is meant by attemperator or cool-bag and makes the pressure sensitive adhesive of pastille keep molten condition, so that the pressure sensitive adhesive of pastille is coated with.
The hot-fusible pressure-sensitive adhesive transdermal patch of the described α of containing-asaricin can be die-cut into suitable size as required.
The used pressure sensitive adhesive of the present invention is a hot-fusible pressure-sensitive adhesive, compared with prior art, have following advantage: do not contain organic solvent, low public hazards, zest is little, coating speed is fast and can be coated with thicker glue-line, the drug loading height can be with silk when die-cut yet, the automaticity height, product cost is low, is suitable for suitability for industrialized production.
Description of drawings
Fig. 1 is the structural representation that contains the hot-fusible pressure-sensitive adhesive transdermal patch of α-asaricin, and wherein, 1 is backing layer, and 2 is bin-storing layer, and 3 is adherent layer;
Fig. 2 is the transdermal test in vitro test accumulation transit dose-time graph that contains the hot-fusible pressure-sensitive adhesive transdermal patch of α-asaricin among the embodiment 5;
Fig. 3 is the transdermal test in vitro test accumulation transit dose-time graph that contains the hot-fusible pressure-sensitive adhesive transdermal patch of α-asaricin among the embodiment 6;
Curve when Fig. 4 is the medicine of rabbit behind α-asaricin oral administration;
Fig. 5 for the hot-fusible pressure-sensitive adhesive transdermal patch administration that contains α-asaricin among the embodiment 5 after curve during the medicine of rabbit.
The specific embodiment
Referring to Fig. 1, the transdermal patch that the present invention contains α-asaricin comprises backing layer 1, bin-storing layer 2 and adherent layer 3, and bin-storing layer 2 is coated on the adherent layer 3, and backing layer 1 covers the opposite side of bin-storing layer 2.
Embodiment 1
The preparation of hot-fusible pressure-sensitive adhesive:
(U.S. section rises, SIS-1161) 100g, hydrogenated petroleum resin (the preferential company of Huifeng, Lanzhou petrochemical industry, 1#) 140g, liquid paraffin 50g, N, N-dibutylamino dithio zinc formate 2g to get the styrene-isoprene-phenylethene triblock copolymer.After the above-mentioned material mixing, be heated to 160 ℃~180 ℃ under the nitrogen protection, stir 2h, cooling is promptly.
The fusing point of the hot-fusible pressure-sensitive adhesive that makes after testing, is 80 ℃.
The preparation of hot-fusible pressure-sensitive adhesive:
(U.S. section rises, SIS-1161) 100g, hydrogenated petroleum resin (the preferential company of Huifeng, Lanzhou petrochemical industry, 1#) 80g, dibutyl phthalate 40g, propyl gallate 2g to get the styrene-isoprene-phenylethene triblock copolymer.After the above-mentioned material mixing, be heated to 160 ℃~180 ℃ under the nitrogen protection, stir 2h, cooling is promptly.
The fusing point of the hot-fusible pressure-sensitive adhesive that makes after testing, is 126 ℃.
The preparation of hot-fusible pressure-sensitive adhesive:
(U.S. section rises, SIS-1161) 100g, hydrogenated petroleum resin (the preferential company of Huifeng, Lanzhou petrochemical industry, 1#) 160g, liquid paraffin 80g, 2,6 ditertiary butyl p cresol 2g to get the styrene-isoprene-phenylethene triblock copolymer.After the above-mentioned material mixing, be heated to 160 ℃~180 ℃ under the nitrogen protection, stir 2h, cooling is promptly.
The fusing point of the hot-fusible pressure-sensitive adhesive that makes after testing, is 72 ℃.
The preparation of hot-fusible pressure-sensitive adhesive:
(U.S. section rises, SIS-1161) 100g, hydrogenated petroleum resin (the preferential company of Huifeng, Lanzhou petrochemical industry, 1#) 160g, liquid paraffin 80g, propyl gallate 2g to get the styrene-isoprene-phenylethene triblock copolymer.After the above-mentioned material mixing, be heated to 160 ℃~180 ℃ under the nitrogen protection, stir 2h, cooling is promptly.
The fusing point of the hot-fusible pressure-sensitive adhesive that makes after testing, is 76 ℃.
The preparation of transdermal patch:
The prescription that contains the hot-fusible pressure-sensitive adhesive transdermal patch of α-asaricin: α-asaricin 15g, menthol 4g, oleic acid 1g, the hot-fusible pressure-sensitive adhesive 100g of embodiment 1.
Preparation method: hot-fusible pressure-sensitive adhesive is heated to fusion under nitrogen protection, adds α-asaricin, menthol and oleic acid, mix homogeneously is coated on the adherent layer (high temperature resistant release paper), and coating weight is 12mg/cm
2, the cooling back covers goes up backing layer (non-woven fabrics), and being die-cut into area is 60cm
2The hot-fusible pressure-sensitive adhesive transdermal patch that contains α-asaricin.
The preparation of transdermal patch:
The prescription that contains the hot-fusible pressure-sensitive adhesive transdermal patch of α-asaricin: α-asaricin 10g, isopropyl myristate 4g, the hot-fusible pressure-sensitive adhesive 100g of embodiment 1.
Preparation method: hot-fusible pressure-sensitive adhesive is heated to fusion under nitrogen protection, adds α-asaricin, menthol and oleic acid, mix homogeneously is coated on the adherent layer (high temperature resistant release paper), and coating weight is 12mg/cm
2, the cooling back covers goes up backing layer (non-woven fabrics), and being die-cut into area is 60cm
2The hot-fusible pressure-sensitive adhesive transdermal patch that contains α-asaricin.
Embodiment 7
The transdermal test in vitro test
1, skin treatments
The piglets isolated skin: the piglets of 9-10 age in days is put to death, peel off skin, be prepared into homogeneous thickness with dermatome ,-80 ℃ of cold preservations are standby.Thaw earlier before the use, normal saline is cleaned.
2, transdermal test
Adopt the vertical type diffusion cell to carry out the transdermal test.The transdermal area is 2.83cm
2, the reception tank volume is 6.8mL, and bath temperature is 37 ℃, and mixing speed is 250r/min, and the concentration expressed in percentage by volume that receives liquid and be molecular weight and be 400 Polyethylene Glycol (PEG400) is 20% PEG400-normal saline solution.The transdermal patch of embodiment 5 or 6 preparations is pasted on skin surface, is fixed on the reception tank, fill it up with reception liquid, timing sampling 1.0mL, and the fresh reception liquid of additional equivalent equality of temperature.Sample uses high performance liquid chromatogram to measure concentration, and the high performance liquid chromatogram condition is as follows:
Instrument: Agilent 1100 high performance liquid chromatographs (Agilent company, the U.S.)
Chromatographic column: ZORBAX Eclipse XDB-C18 chromatographic column (4.6mm * 150mm, 5 μ m)
Mobile phase: methanol: water (70: 30, volume ratio)
Flow velocity: 1.0mlmin
-1
Column temperature: 40 ℃
Detect wavelength: UV-detector 257nm
Sampling volume: 20 μ L, external standard method is quantitative.
The results are shown in Figure 2, Fig. 3.
Pharmacokinetics test
6 of rabbit are divided into two groups at random.The oral administration group is mixed with 1% CMC-Na suspension, gastric infusion with α-asaricin reference substance 180mg.Get blood at 5min, 10min, 30min, 45min, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h from auricular vein respectively after the administration.The percutaneous dosing group respectively is 60cm with sticking two areas on the skin after the tame rabbit back unhairing processing
2The patch (containing α-asaricin 180mg altogether) of embodiment 5.1h, 2h, 4h, 6h, 8h, 10h, 12h, 16h, 20h, 24h get blood from auricular vein after administration.The blood sample anticoagulant heparin, centrifugal 5min (6000r/min), separated plasma.High-efficient liquid phase technique is measured behind the methanol extraction albumen, and the high performance liquid chromatogram condition is as follows:
Instrument: Agilent 1100 high performance liquid chromatographs (Agilent company, the U.S.)
Chromatographic column: ZORBAX Eclipse XDB-C18 chromatographic column (4.6mm * 250mm, 5 μ m)
Mobile phase: methanol: water (75: 25)
Flow velocity: 1.0mLmin-1
Column temperature: 25 ℃
Detect wavelength: fluorescence detector, excitation wavelength 265nm, emission wavelength 365nm
Sampling volume: 20 μ L, external standard method is quantitative.
See Fig. 3 and Fig. 4 respectively with the blood drug level-time graph after the skin administration behind the rabbit oral administration, use Thermo Kinetica 4.4.1 software to calculate the related drugs kinetic parameter, see Table 1 according to non-compartment model extravascular administration mode.
Table 1 pharmacokinetic parameter
Oral | Percutaneous dosing | |
??C max/μg·mL -1 | ??0.2929±0.1607 | ??0.4964±0.0763 |
??T max/h | ??0.56±0.19 | ??1.67±0.58 |
??AUC/μ·h·mL -1 | ??0.5259±0.2278 | ??7.860±2.151 |
??F | ??1494% |
Annotate: C
MaxPeak concentration, T
MaxPeak time, AUC area under the drug-time curve, F relative bioavailability
Compare with oral administration, carry out percutaneous dosing with patch of the present invention and postponed T
Max(P<0.1) has obviously improved AUC (P<0.05), and relative bioavailability F reaches 1494%.This explanation patch of the present invention is compared with oral administration, significantly improved bioavailability, and blood drug level is more steady.
Claims (10)
1. a hot-fusible pressure-sensitive adhesive transdermal patch that contains α-asaricin comprises backing layer, bin-storing layer and adherent layer, it is characterized in that described bin-storing layer is made by following raw materials by weight percent:
α-asaricin 1%~20%
Hot-fusible pressure-sensitive adhesive 70%~98%
Transdermal enhancer 1%~10%.
2. the hot-fusible pressure-sensitive adhesive transdermal patch that contains α-asaricin according to claim 1 is characterized in that described bin-storing layer is made by following raw materials by weight percent:
α-asaricin 8%~13%
Hot-fusible pressure-sensitive adhesive 83%~88%
Transdermal enhancer 3.5%~4.5%.
3. the hot-fusible pressure-sensitive adhesive transdermal patch that contains α-asaricin according to claim 1 is characterized in that, the fusing point of described hot-fusible pressure-sensitive adhesive is 50 ℃~250 ℃.
4. the hot-fusible pressure-sensitive adhesive transdermal patch that contains α-asaricin according to claim 1 is characterized in that described hot-fusible pressure-sensitive adhesive is made by the raw material that comprises following weight portion:
100 parts of thermoplastic elastomers
80~160 parts of viscosifier
40~80 parts of plasticizers
0~40 part of filler
0~10 part in antioxidant.
5. the hot-fusible pressure-sensitive adhesive transdermal patch that contains α-asaricin according to claim 4, it is characterized in that described thermoplastic elastomer is selected from one or more in styrene-isoprene-phenylethene triblock copolymer, s-B-S triblock copolymer or other medical thermoplastic elastomers.
6. the hot-fusible pressure-sensitive adhesive transdermal patch that contains α-asaricin according to claim 4 is characterized in that, described viscosifier are selected from one or more in terpene resin, Petropols, Foral or other the medicinal viscosifier.
7. the hot-fusible pressure-sensitive adhesive transdermal patch that contains α-asaricin according to claim 4 is characterized in that, described plasticizer is selected from one or more in liquid paraffin, dibutyl phthalate, white oil or other the medicinal plasticizers.
8. the hot-fusible pressure-sensitive adhesive transdermal patch that contains α-asaricin according to claim 4 is characterized in that, described filler is selected from one or more in titanium dioxide or other the medicinal filleies;
Perhaps, described antioxidant is selected from N, one or more in N-dibutylamino dithio zinc formate, propyl gallate, 2,6 ditertiary butyl p cresol or other the medicinal antioxidant.
9. the hot-fusible pressure-sensitive adhesive transdermal patch that contains α-asaricin according to claim 1 is characterized in that, described transdermal enhancer is selected from one or more in isopropyl myristate, menthol, oleic acid, azone or other the medicinal transdermal enhancers.
10. according to each described preparation method that contains the hot-fusible pressure-sensitive adhesive transdermal patch of α-asaricin of claim 1~9, it is characterized in that, comprise the following steps:
(1) hot-fusible pressure-sensitive adhesive is heated to fusion under nitrogen protection, α-asaricin and transdermal enhancer are scattered in the fused hot-fusible pressure-sensitive adhesive, mix homogeneously is made the pressure sensitive adhesive of pastille;
(2) under heat-retaining condition the pressure sensitive adhesive of pastille is coated on adherent layer or the backing layer, the cooling back covers backing layer or adherent layer on the pressure sensitive adhesive of pastille, make the hot-fusible pressure-sensitive adhesive transdermal patch that contains α-asaricin.
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Cited By (3)
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CN102634307A (en) * | 2012-05-03 | 2012-08-15 | 河南羚锐制药股份有限公司 | Hot-melting pressure sensitive adhesive and preparation method thereof |
CN103877590A (en) * | 2014-04-17 | 2014-06-25 | 河南羚锐制药股份有限公司 | Novel pressure-sensitive adhesive matrix carrier for abdomen relaxing plaster and application of novel pressure-sensitive adhesive matrix carrier in preparation of abdomen relaxing plaster |
CN104706725A (en) * | 2013-12-10 | 2015-06-17 | 天津市山佳医药科技有限公司 | Compound red sage root transdermal absorption patch and preparation method thereof |
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CN1720908A (en) * | 2005-06-13 | 2006-01-18 | 广州中医药大学第一附属医院 | Beta-Asarone transdermal plaster |
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
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CN102634307A (en) * | 2012-05-03 | 2012-08-15 | 河南羚锐制药股份有限公司 | Hot-melting pressure sensitive adhesive and preparation method thereof |
CN104706725A (en) * | 2013-12-10 | 2015-06-17 | 天津市山佳医药科技有限公司 | Compound red sage root transdermal absorption patch and preparation method thereof |
CN103877590A (en) * | 2014-04-17 | 2014-06-25 | 河南羚锐制药股份有限公司 | Novel pressure-sensitive adhesive matrix carrier for abdomen relaxing plaster and application of novel pressure-sensitive adhesive matrix carrier in preparation of abdomen relaxing plaster |
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