CN1615859A - Nimodipine adhesive sheet - Google Patents
Nimodipine adhesive sheet Download PDFInfo
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- CN1615859A CN1615859A CN 200410074344 CN200410074344A CN1615859A CN 1615859 A CN1615859 A CN 1615859A CN 200410074344 CN200410074344 CN 200410074344 CN 200410074344 A CN200410074344 A CN 200410074344A CN 1615859 A CN1615859 A CN 1615859A
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- film
- nimodipine
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- layer
- drug storage
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Abstract
The nimodipine plaster belongs to the field of medicine preparation form design, and consists of back lining film, medicine library layer, release controlling film, pressure-sensitive glue layer and protecting film. The medicine library layer is cross-linked polymer film containing nimodipine 10-20 wt% and transdermal osmosis promoter 2-10 wt%, and has thickness of 1.0-1.5 mm. The pressure-sensitive glue layer is cross-linked polymer film containing nimodipine 1-3 wt%, and has thickness of 0.05-0.3 mm. Animal experiment shows that after the nimodipine plaster is applied once on chest, steady medicine concentration in blood may be maintained for about one week. The present invention has obviously raised bioavailability of nimodipine and skin irritation and irritability within relevant stipulations.
Description
Technical field
The invention belongs to the dosage form design technical field of medicine.Be particularly related to the dosage form improvement of nimodipine.
Background technology
Cerebrovascular disease therapy medicine nimodipine (nimodipine) is the second filial generation 1,4-dihydropyridine calcium ion channel antagonist, by Bayer A.G's at first research and development listing in 1985, the trade name nimotop, December was examined by U.S. FDA on the 28th in 1988, expansion of cerebral vascular optionally, have neural and spiritual pharmacologically active concurrently, arteria coronaria is also had than the high selectivity dilating effect, be applicable to that the convalescent blood circulation of the posthemorrhagic cerebral vasospasm of subarachnoid space of a variety of causes and acute cerebrovascular disease improves, gently, also there is effect preferably the treatment aspect of moderate vascular dementia.The clinical diseases such as subarachnoid hemorrhage, migraine, apoplexy, sudden deafness, light moderate hypertension that are mainly used in, it now is the choice drug of prevention and treatment cerebrovascular disease and treatment senile dementia, its consumption only is 1/1000 of a vincamine, 1/60 of piracetam.
The administering mode that nimodipine is commonly used is intravenous drip and oral administration, and the former is mainly used in acute stage, changes into oral after 5～10 days; And oral administration, because short (elimination t of half-life
1/2Be about 1h), need frequent drug administration, be generally 3 times on the one, patient's compliance is relatively poor; And liver first-pass effect is serious, oral administration biaavailability very low (5%～13%), thereby cost height, and adverse reaction rate is higher, and clinical effect is subjected to very big restriction.
Summary of the invention
The objective of the invention is for overcoming the weak point that existing nimodipine adopts intravenous drip and oral way administration, a kind of transdermal patch of nimodipine is proposed, can avoid liver first-pass effect, reach rapidly and long time maintenance steady plasma-drug concentration, can significantly improve its bioavailability, reduce administration number of times, reduce its toxic and side effects, strengthen compliance of patients, and drug withdrawal at any time easy to use.
A kind of Nimodipine adhesive sheet that the present invention proposes is characterized in that, forms by stacking gradually all-in-one-piece backing film, drug storage warehouse layer, speed release-controlled film, pressure-sensitive adhesive layer and protecting film; The film that this drug storage warehouse layer is made by one of the crosslinked macromolecular material that contains nimodipine 10～20% and transdermal penetrating agent 2～10% such as polyvinyl alcohol (PVA), cellulose acetate, Triafol T etc., its thickness is 1.0～1.5mm.
This pressure-sensitive adhesive layer can be the film that one of the crosslinked macromolecular material that includes 1～3% nimodipine such as polyisobutylene, acrylic compounds, silicone rubber etc. are made, and its thickness is 0.05～0.3mm.
The film that this backing film is made for one of no infiltrative macromolecular material such as aluminium foil composite polyethylene, polyoxyethylene, nylon resin, cellulose acetate etc.
Tool that this speed release-controlled film can be made with the ethylene/vinyl acetate copolymer (EVA) of high density or low-density polyethylene film or improvement or the film of not having micropore.
This protecting film can adopt aluminium foil composite polyethylene film.
The preparation method of above-mentioned drug storage warehouse layer may further comprise the steps:
1) takes by weighing nimodipine, transdermal penetrating agent and corresponding macromolecular material in proportion, be dissolved in ethyl acetate or the cyclohexane extraction, form the drug storage warehouse viscose;
2) this drug storage warehouse viscose is painted the uniform thin film of thickness with coating machine;
3) super saturated solid solution system transparent membrane will be formed after this thin film forced air drying.
The preparation method of above-mentioned pressure-sensitive adhesive layer may further comprise the steps:
1) takes by weighing nimodipine and corresponding macromolecular material in proportion, be dissolved in ethyl acetate or the cyclohexane extraction, form contact adhesive-layer viscose;
2) this viscose is painted the uniform thin film of thickness with coating machine;
3) after forced air drying, form super saturated solid solution system transparent membrane.
The present invention can be die-cut into circle, square or rectangular patch according to dosage with backing layer, drug storage warehouse, release-controlled film, pressure-sensitive adhesive layer and the protecting film that stacks gradually.
Nimodipine adhesive sheet of the present invention can be administered once behind front or ear, animal experiment shows can reach steady plasma-drug concentration rapidly, and about a sustainable week, significantly improved the bioavailability of nimodipine, and skin irritation and sensitivity test meet relevant regulations.
Description of drawings
Fig. 1 and Fig. 2 are Nimodipine adhesive sheet structure chart of the present invention.
The specific embodiment
It is as follows that the Nimodipine adhesive sheet that the present invention proposes reaches description of drawings in conjunction with the embodiments:
The composition structure of Nimodipine adhesive sheet of the present invention is formed by stacking gradually all-in-one-piece backing film 1, drug storage warehouse layer 2, speed release-controlled film 3, pressure-sensitive adhesive layer 4 and protecting film 5 as shown in Figure 1, 2.The composition of each rete and preparation method embodiment are described in detail as follows:
Backing film of the present invention 1 is no infiltrative macromolecular material composition, available aluminium foil composite polyethylene film, cellulose acetate membrane, nylon resin film, poly tetrafluoroethylene a kind of, and its thickness is about 0.05～0.3mm;
Drug storage warehouse layer of the present invention 2 is formed for containing nimodipine 10～20% and transdermal penetrating agent 2～10% crosslinked macromolecular materials, be to be lyase with ethyl acetate or cyclohexane give, the supersaturation high polymer solid solution Drug Storage system under the Nimodipine solid microgranule exists; Wherein, macromolecular material can be used a kind of of Butadiene block copolymer, ethylene/butadiene block copolymer, ethylene/vinyl acetate copolymer, gel, agar, normal temperature crosslinked silicone rubber, polyvinyl alcohol (PVA), cellulose acetate, Triafol T etc., and its thickness is 1.0～1.5mm; The step of its preparation method embodiment comprises: drug storage warehouse 10～20% is taken by weighing nimodipine and 2～10% transdermal penetrating agents in proportion, be dissolved in ethyl acetate or the cyclohexane extraction, add corresponding macromolecular material again, uniform mixing, form the drug storage warehouse viscose, paint the uniform 1.0～1.5mm thin film of thickness with coating machine, send into dry 1h in the air dry oven (hour), temperature is about 60 ℃, crystallize and devitrification phenomenon can not appear in whole process, otherwise illustrate that hypersaturated state has transferred saturation to, form super saturated solid solution system transparent membrane after this coating liquid drying.
Speed release-controlled film 3 of the present invention can be formed with the ethylene/vinyl acetate copolymer (EVA) of high density or low-density polyethylene film or improvement, has micropore (as shown in Figure 1) or does not have a micropore (as shown in Figure 2), and its thickness is about 0.05～0.3mm.
Pressure-sensitive adhesive layer 4 of the present invention is as adhesion layer and release layer, and its thickness is about 0.05～0.3mm; Available polyisobutylene, silicone rubber, polyacrylate a kind of includes 1～3% nimodipine and makes the rapid release part; The step of its preparation method embodiment comprises: pressure-sensitive adhesive layer is taken by weighing in proportion 1～3% nimodipine, be dissolved in ethyl acetate or the cyclohexane extraction, add corresponding macromolecular material again, uniform mixing, form contact adhesive-layer viscose, paint the uniform 0.05～0.3mm thin film of thickness, send in the air dry oven dry 1 hour with coating machine, temperature all forms super saturated solid solution system transparent membrane after the coating liquid drying about 60 ℃.
Protecting film 5 of the present invention adopts aluminium foil composite polyethylene film, and its thickness is about 0.05～0.3mm.
Above-mentioned backing layer, drug storage warehouse, release-controlled film, pressure-sensitive adhesive layer and protecting film stacked gradually be integral, being die-cut into area then is 4～8cm
2Circle, square or orthogonal paster.
Nimodipine adhesive sheet of the present invention can make the slow and constant speed ground release of nimodipine, with the oral formulations comparison of routine, when laboratory animal is rat, under same dose: during nimodipine 40mg, the t of oral nimodipine
1/2Be 1.45h, AUC is 2.45ng.ml
-1.h
-1, bioavailability only is 12.01%; The t of Nimodipine adhesive sheet
1/2Be 18.96h, AUC is 22.77ng.ml
-1.h
-1, bioavailability is 89.97%.Nimodipine adhesive sheet of the present invention compared with prior art, it is better to have a therapeutic effect, less adverse effect, the course of treatment is shorter, medical expense is lower, uses advantages such as easier, is a kind of ideal percutaneous absorption patch.
Embodiment 1: it forms structure as shown in Figure 1, and wherein: backing film 1 adopts aluminium foil composite polyethylene film, and its thickness is about 0.05mm; Drug storage warehouse layer 2 is for containing the crosslinked Butadiene block copolymer of nimodipine 10% and transdermal penetrating agent 2%, and its thickness is 1.5mm; Speed release-controlled film 3 adopts high density to have the polyethylene film of micropore, and its thickness is about 0.3mm; Pressure-sensitive adhesive layer 4 is as adhesion layer and release layer, and its thickness is about 0.05mm, adopts polyisobutylene, includes 3% nimodipine and loses no time and be interpreted into branch; Protecting film 5 adopts aluminium foil composite polyethylene film, and its thickness is about 0.05mm.Above-mentioned backing layer, drug storage warehouse, release-controlled film, pressure-sensitive adhesive layer and protecting film stacked gradually be integral, being die-cut into area then is 8cm
2Circular patch.
Embodiment 2: it forms structure as shown in Figure 1, and wherein: backing film 1 adopts cellulose acetate membrane, and its thickness is about 0.1mm; Drug storage warehouse layer 2 is for containing the crosslinked Butadiene block copolymer of nimodipine 12% and transdermal penetrating agent 4%, and its thickness is 1.4mm; Speed release-controlled film 3 adopts ethylene/vinyl acetate copolymer (EVA) thin film of the improvement with micropore, and its thickness is about 0.2mm; Pressure-sensitive adhesive layer 4 is as adhesion layer and release layer, and its thickness is about 0.1mm, adopts silicone rubber, includes 2% nimodipine and loses no time and be interpreted into branch; Protecting film 5 adopts aluminium foil composite polyethylene film, and its thickness is about 0.2mm.Above-mentioned backing layer, drug storage warehouse, release-controlled film, pressure-sensitive adhesive layer and protecting film stacked gradually be integral, being die-cut into area then is 6cm
2Square patch.
Embodiment 3: it forms structure as shown in Figure 2, and wherein: backing film 1 adopts the nylon resin film, and its thickness is about 0.2mm; Drug storage warehouse layer 2 is for containing nimodipine 16% and transdermal penetrating agent 7% normal temperature crosslinked silicone rubber, and its thickness is 1.2mm; Speed release-controlled film 3 adopts the low-density polyethylene film that does not have micropore, and its thickness is about 0.07mm; Pressure-sensitive adhesive layer 4 is as adhesion layer and release layer, and its thickness is about 0.1mm; Adopt polyacrylate, include 3% nimodipine and lose no time and be interpreted into branch; Protecting film 5 adopts aluminium foil composite polyethylene film, and its thickness is about 0.2mm.Above-mentioned backing layer, drug storage warehouse, release-controlled film, pressure-sensitive adhesive layer and protecting film stacked gradually be integral, being die-cut into area then is 5cm
2Square patch.
Embodiment 4: it forms structure as shown in Figure 2, and wherein: backing film 1 adopts poly tetrafluoroethylene, and its thickness is about 0.3mm; Drug storage warehouse layer 2 is for containing the crosslinked Butadiene block copolymer of nimodipine 20% and transdermal penetrating agent 10%, and its thickness is 1.0mm; Speed release-controlled film 3 adopts the low-density polyethylene film that does not have micropore, and its thickness is about 0.05mm; Pressure-sensitive adhesive layer 4 is as adhesion layer and release layer, and its thickness is about 0.1mm, adopts polyacrylate, includes 3% nimodipine and loses no time and be interpreted into branch; Protecting film 5 adopts aluminium foil composite polyethylene film, and its thickness is about 0.3mm.Above-mentioned backing layer, drug storage warehouse, release-controlled film, pressure-sensitive adhesive layer and protecting film stacked gradually be integral, being die-cut into area then is 4cm
2Rectangular patch.
Claims (4)
1, a kind of Nimodipine adhesive sheet is characterized in that, forms by stacking gradually all-in-one-piece backing film, drug storage warehouse layer, speed release-controlled film, pressure-sensitive adhesive layer and protecting film; The film that this drug storage warehouse layer is made by the crosslinked macromolecular material that contains nimodipine 10～20% and transdermal penetrating agent 2～10%, its thickness is 1.0～1.5mm; This pressure-sensitive adhesive layer is to include the film that the crosslinked macromolecular material of 1～3% nimodipine is made, and its thickness is 0.05～0.3mm.
2, Nimodipine adhesive sheet as claimed in claim 1 is characterized in that, the film that this backing film is made for no infiltrative macromolecular material; Tool that the ethylene/vinyl acetate copolymer (EVA) of this speed release-controlled film employing high density or low-density polyethylene film or improvement is made or the film of not having micropore; This protecting film adopts aluminium foil composite polyethylene film.
3, a kind of method for preparing the drug storage warehouse layer of Nimodipine adhesive sheet may further comprise the steps:
1) takes by weighing nimodipine, transdermal penetrating agent and corresponding macromolecular material in proportion, be dissolved in ethyl acetate or the cyclohexane extraction, form the drug storage warehouse viscose;
2) this drug storage warehouse viscose is painted the uniform thin film of thickness with coating machine;
3) super saturated solid solution system transparent membrane will be formed after this thin film forced air drying.
4, a kind of method for preparing the pressure-sensitive adhesive layer of Nimodipine adhesive sheet may further comprise the steps:
1) takes by weighing nimodipine and corresponding macromolecular material in proportion, be dissolved in ethyl acetate or the cyclohexane extraction, form contact adhesive-layer viscose;
2) this viscose is painted the uniform thin film of thickness with coating machine;
3) after forced air drying, form super saturated solid solution system transparent membrane.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410074344 CN1258363C (en) | 2004-09-10 | 2004-09-10 | Nimodipine adhesive sheet |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410074344 CN1258363C (en) | 2004-09-10 | 2004-09-10 | Nimodipine adhesive sheet |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1615859A true CN1615859A (en) | 2005-05-18 |
| CN1258363C CN1258363C (en) | 2006-06-07 |
Family
ID=34765349
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410074344 Expired - Fee Related CN1258363C (en) | 2004-09-10 | 2004-09-10 | Nimodipine adhesive sheet |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1258363C (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101933915A (en) * | 2010-09-03 | 2011-01-05 | 蚌埠丰原涂山制药有限公司 | Trans-dermal drug administration type Cilnidipine paster for treating hypertension and preparation method thereof |
| CN101703494B (en) * | 2009-11-27 | 2012-03-14 | 蚌埠丰原涂山制药有限公司 | Transdermal nitrendipine adhesive patch and preparation method thereof |
| CN103222977A (en) * | 2013-05-22 | 2013-07-31 | 南京工业大学 | Granisetron and dexamethasone compound percutaneous controlled release patch and preparation method thereof |
-
2004
- 2004-09-10 CN CN 200410074344 patent/CN1258363C/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101703494B (en) * | 2009-11-27 | 2012-03-14 | 蚌埠丰原涂山制药有限公司 | Transdermal nitrendipine adhesive patch and preparation method thereof |
| CN101933915A (en) * | 2010-09-03 | 2011-01-05 | 蚌埠丰原涂山制药有限公司 | Trans-dermal drug administration type Cilnidipine paster for treating hypertension and preparation method thereof |
| CN103222977A (en) * | 2013-05-22 | 2013-07-31 | 南京工业大学 | Granisetron and dexamethasone compound percutaneous controlled release patch and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1258363C (en) | 2006-06-07 |
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| PB01 | Publication | ||
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| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
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Granted publication date: 20060607 Termination date: 20160910 |