CN1742708A - Transdermal administration pressure-sensitive gel composite substrate - Google Patents
Transdermal administration pressure-sensitive gel composite substrate Download PDFInfo
- Publication number
- CN1742708A CN1742708A CN 200510047335 CN200510047335A CN1742708A CN 1742708 A CN1742708 A CN 1742708A CN 200510047335 CN200510047335 CN 200510047335 CN 200510047335 A CN200510047335 A CN 200510047335A CN 1742708 A CN1742708 A CN 1742708A
- Authority
- CN
- China
- Prior art keywords
- composite substrate
- crystallization inhibitor
- transdermal administration
- medicine
- pressure
- 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.)
- Pending
Links
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The percutaneous medication pressure-sensitive adhesive matrix contains chemical accelerating agent nd pressure-sensitive adhesive component, and is characterized by that it also contains crystallization inhibitor, and utilizes the synergistic action of crystallization inhibitor and chemical accelerating agent to raise its medicine-loading capacity and retain the supersaturated dissolution of medicine, also can raise percutaneous permeability of medicine. The crystallization inhibitor is hydroxypropyl methyl cellulose or polyvinylpyrrolidone, and the chemical accelerating agent is formed from isopropyl myristate, oleic acid, laurocapram, oleum eucalypti and carbitol.
Description
Technical field
The invention belongs in the pharmaceutical pass through compounded technology blend obtain to macromolecular material can improve medicine percutaneous transmission rates the dressing technical field, promptly relate to and a kind ofly improve drug loading and keep the dissolved transdermal administration pressure-sensitive gel composite substrate of medicine over-saturation.
Background technology
Transdermal delivery system (TTS) can be avoided the first pass effect of liver to medicine, improves availability biology of medicine, is the effective route of administration of a kind of advanced person.Because the inhibition that keratodermatitis sees through medicine, many medicines are difficult to reach the skin penetration speed that produces therapeutic effect, have limited the medicament categories of percutaneous dosing.In order to overcome this obstacle of keratodermatitis, people have used and have comprised chemical promoter, ultrasound wave, iontophoresis, multiple physical chemistry means such as electric current pore change skin texture, improve the dissolubility of medicine in horny layer and mobile to increase skin seeing through medicine.But this approach is limited by skin itself and people's psychological bearing capability.
The matrix type percutaneous drug administration preparation of medicine dissolution in pressure sensitive adhesive, generally, because intermolecular stronger Van der Waals force, polar interaction or the hydrogen bond action that between pressure sensitive adhesive matrix and medicine, may exist, after preparation completes, high concentration medicine is in the supercritical dissolved state, but the dissolved substance that is in the thermodynamic instability state can slowly crystallize out.This crystallize process has reduced the availability of medicine.In addition, in pressure sensitive adhesive, add a large amount of Chinese medical concretes or some chemical promoter and can make pressure sensitive adhesive produce dilution phenomenon, the viscosity of pressure sensitive adhesive is descended even can lose.
Summary of the invention
Shortcoming at existing transdermal administration pressure-sensitive gel substrate, the present invention will seek a kind ofly can improve drug loading and keep the dissolved transdermal administration pressure-sensitive gel composite substrate of medicine over-saturation exactly, promptly prepares a kind of increase drug loading and medicine super saturated and soluble type skin administration medicinal pressure-sensitive gel composite substrate.Find after deliberation as long as in acrylate pressure-sensitive adhesive substrate, contain the performance stable for extended periods of time that crystallization inhibitor and chemical promoter raising drug loading and medicine over-saturation dissolving also can make substrate simultaneously.This substrate can make up with multiple medicine or Chinese medical concrete, by the thermodynamic activity of increase substrate Chinese medicine and the permeability of skin Chinese medicine, to reach the collaborative facilitation that the medicine percutaneous is seen through, not only can significantly improve the availability of medicine; The various Viscous Criterions of pressure sensitive adhesive matrix are remained unchanged, and can alleviate the anaphylaxis of skin medicine.
The present invention proposes a kind of transdermal administration pressure-sensitive gel composite substrate, it includes components such as chemical promoter and acrylate pressure-sensitive adhesive, it is characterized in that being added with in addition crystallization inhibitor, synergism by crystallization inhibition and chemical promoter, the over-saturation dissolving that both can improve drug loading and keep medicine can improve medicine percutaneous through performance again.
The said crystallization inhibitor of the present invention is hydroxypropyl emthylcellulose or polyvinylpyrrolidone, and the said chemical promoter of the present invention is isopropyl myristate, oleic acid, azone, carbitol (transcutol), Oleum Eucalypti and their combination.
The said crystallization inhibitor of the present invention, its addition percent by weight calculate, and hydroxypropyl emthylcellulose is 5～10, and polyvinylpyrrolidone is 10～30.
It is 5～20 that the addition of the said chemical promoter of the present invention is calculated the myristic acid isopropyl ester by weight percentage, and oleic acid is 5-15, and azone is 1-5, and Oleum Eucalypti is 1-5, and carbitol is 5-15.
Owing to used the crystallization inhibitor synergism of chemical promoter in addition, making medicine no matter dissolve in over-saturation also is in the non-over-saturation dissolving preparation, all can solve pressure sensitive adhesive " dilutionization " phenomenon that produces owing to chemical promoter and Chinese medical concrete, keep the form of pressure sensitive adhesive matrix and normal viscosity constant.And can alleviate the zest of pressure sensitive adhesive to skin.
The present invention is to influencing two factors 1 that the medicine percutaneous sees through relatively independent effect) thermodynamic activity (over-saturation dissolving) of substrate Chinese medicine; 2) skin permeability (comprising dissolubility, partition coefficient and the diffusion coefficient of medicine in horny layer) improves simultaneously, the collaborative technology that promotes that the medicine percutaneous sees through.
In the dissolved pressure sensitive adhesive matrix of medicine over-saturation, only add the crystallize that some chemical promoter can impel over-saturation dissolved substance in the substrate, make dissolved drug lowering of concentration in the substrate.Simultaneously, some Chinese medical concretes or chemical promoter can make the viscosity forfeiture of pressure sensitive adhesive again.The present invention has added crystallization inhibitor again when adding chemical promoter, suppressed the crystallize of substrate Chinese medicine, has kept the over-saturation dissolved state of substrate Chinese medicine.That is to say, utilize chemical promoter to improve the skin permeability of medicine, utilize crystallization inhibitor to keep the over-saturation dissolving drug loading of medicine in substrate, reach the medicine percutaneous through the collaborative facilitation that significantly increases.And can keep the normal viscosity of pressure sensitive adhesive matrix constant.
The present invention is owing to dissolve fully at preparation of Chinese medicine, thereby increased the effective availability of medicine; An amount of use of chemical promoter and crystallization inhibitor has reduced the stimulation of preparation to human body skin; This composite substrate and the percutaneous drug administration preparation that uses this substrate to make, preparation technology is fairly simple, and cost is cheaper; This composite substrate is fit to multiple medication preparation percutaneous drug administration preparation.
The present invention is in implementation process, be to use common pressure sensitive adhesive to be coated with the cream technology, the matrix solution that has prepared is coated on the plastic sheeting of being crossed by silicone treated with certain thickness with the full and uniform back of mixing of medicine, after the drying, cover with the surperficial press mold of not crossed, make the thick matrix type pressure sensitive adhesive percutaneous drug administration preparation of 0.1-1mm by silicone treated.The preparation punch forming of making, sealing is kept in room temperature or the refrigerator.
The specific embodiment
Transdermal administration pressure-sensitive gel composite substrate of the present invention is suitable for making the transdermal delivery system of matrix type and DIA (drug in adhesive) type, and it both had been suitable for making the Western medicine paster, is fit to make the Chinese medicine paster again.
Come content of the present invention is further described and replenishes below in conjunction with the embodiment that makes several transdermal administration pressure-sensitive gel preparations.Adopt these medicines to make embodiment, percutaneous dosing substrate extensive applicability of the present invention and the reliable technique effect that can obtain can be described, have nothing to do and whether possess novelty with these medicines itself.
Embodiment 1: estradiol transdermal administration pressure-sensitive gel preparation
Allocate earlier percutaneous dosing composite substrate composition as following weight percent:
Composition percentage by weight (%)
Polyacrylic acid lipid pressure sensitive adhesive 60
Isopropyl myristate 20
Oleic acid 5
Polyvinylpyrrolidone 10
Hydroxypropyl emthylcellulose 5
And said components made composite substrate mother solution of the present invention, adding 4% the estradiol be equivalent to its weight again in mother solution evenly stirs, use the common cream technology that is coated with to be coated at last on the plastic sheeting of being crossed by silicone treated, promptly make the estradiol transdermal administration pressure-sensitive gel preparation of thick about 100 μ m after the drying.
Existing estradiol transdermal administration pressure-sensitive gel preparation, the concentration of estradiol is 1-2% in matrix content by weight percentage generally in the pressure sensitive adhesive, it mainly is the crystallization of worrying in pressure sensitive adhesive, to produce medicine, and for the preparation that contains chemical promoter in the substrate, the concentration of estradiol is generally all below 1%.Present embodiment is owing to added crystallization inhibitor so can adopt 4% high concentration, and chemical promoter is selected the most frequently used isopropyl myristate (IPM) for use.The human body skin allergic experiment shows that 20%IPM can not produce any harmful effect and sequela to skin.
Use the common cream technology that is coated with, the substrate mother solution that has prepared is coated on the plastic sheeting of being crossed by silicone treated, after the drying, be made into the pressure sensitive adhesive matrix type preparation of thick about 100 μ m.
The nude mouse skin of abdomen sees through test tube experiment (in vitro) result and shows, 24 hours transit doses of estradiol (Estradiol) percutaneous preparation of using the present technique preparation surpass the preparation ェ of the same type ス ト of Japanese Hisamitsu Pharmaceutical Co., Inc. ラ-Na
(ESTRANA) more than 1 times.Than some other identical or higher non-lysotype preparation of filling out the medicine carrying substrate concentration also be greatly improved (seeing Table 1).The stability of formulation experiment shows that under the room temperature condition, preserving the preparation in 2 years and the transit dose of novel formulation does not have significant difference (p＜0.05).
Table 1 (percentage by weight)
| Substrate/preparation | Estradiol | Cu Jin agent | Cu Jin agent Concentrated degree | 24 hours accumulation transit dose (μ g/cm 2) | Standard deviation (SD) | Crystallization suppresses the drug agent |
| Acrylic adhesive, decentralized preparation (contrast experiment) | 6％ | EAO9905 +IPM | 20％+10％ | 33.44 | 1.53 | Do not contain |
| The same (contrast experiment) | 4％ | IPM | 20％ | 15.01 | 0.45 | Do not contain |
| ェ ス ト ラ one Na (ESTRANA) (commercially available prod) | 0.72mg/ piece | 31.6 | 6.61 | Do not contain | ||
| Acrylic adhesive (embodiment) | 4％ | IPM | 20％ | 66.67 | 3.4 | Contain |
Embodiment 2: but hydrogenation Buddhist nun loose warp skin administration pressure-sensitive gel preparation
Earlier by following prescription modulation percutaneous dosing composite substrate:
Composition percentage by weight (%)
Polyacrylate pressure sensitive adhesive 50
Oleic acid 10
Isopropyl myristate 30
Hydroxypropyl emthylcellulose 10
And said components made composite substrate mother solution of the present invention, adding 4% the hydrogenation Bo Nisong be equivalent to other gross weight again in mother solution fully stirs, adopt the common cream technology that is coated with to be coated on the plastic sheeting of being crossed by silicone treated, but promptly make the hydrogenation Buddhist nun loose warp skin administration pressure-sensitive gel preparation of thick about 100 μ m after the drying.
Embodiment 3: melatonin transdermal administration pressure-sensitive gel preparation
Earlier by following prescription modulation percutaneous dosing composite substrate
Composition percentage by weight (%)
Polyacrylate pressure sensitive adhesive 65
Oleic acid 15
Polyvinylpyrrolidone 10
Hydroxypropyl emthylcellulose 10
And said components made composite substrate mother solution of the present invention, in mother solution, add 4% the melatonin (melatonin) be equivalent to mother solution weight again, be stirred to full and uniform after, adopt to be coated with the cream technology and to be coated on and to make melatonin transdermal administration pressure-sensitive gel preparation on the plastic sheeting of being crossed by silicone treated.
Embodiment 4: clonidine transdermal administration pressure-sensitive gel preparation
Earlier by following prescription modulation percutaneous dosing composite substrate
Composition percentage by weight (%)
Polyacrylate pressure sensitive adhesive 55
Isopropyl myristate 20
Carbitol 5
Polyvinylpyrrolidone 10
And said components made composite substrate mother solution of the present invention, in mother solution, add 4% the clonidine be equivalent to mother solution weight again, be stirred to full and uniform after, adopt to be coated with the cream technology and to be coated on and to make clonidine transdermal administration pressure-sensitive gel preparation on the plastic sheeting of being crossed by silicone treated.
Embodiment 5: the szechuan lovage rhizome-angelica patch
Earlier by following prescription modulation percutaneous dosing composite substrate
Composition percentage by weight (%)
Polyacrylate pressure sensitive adhesive 65
Azone 2
Oleum Eucalypti 3
Polyvinylpyrrolidone 30
And said components made composite substrate mother solution of the present invention, in mother solution, add the szechuan lovage rhizome-angelica extractum made from the CO2 supercritical extraction technique again, its addition is 10% of a mother solution gross weight, through after stirring, use coating technique to be coated on and make the szechuan lovage rhizome-angelica patch on the plastic sheeting of being crossed by silicone treated.
Embodiment 6: the ligustrazine patch
Earlier by following prescription modulation percutaneous dosing composite substrate
Composition percentage by weight (%)
Polyacrylate pressure sensitive adhesive 48
Isopropyl myristate 20
Azone 2
Polyvinylpyrrolidone 30
Said components is made composite substrate mother solution of the present invention, in mother solution, add ligustrazine again, its addition is 20% of a mother solution gross weight, through after stirring, uses coating technique to be coated on and makes the ligustrazine patch on the plastic sheeting of being crossed by silicone treated.
Embodiment 7: grieved peaceful patch percentage by weight (%)
Earlier by following prescription modulation percutaneous dosing composite substrate
Polyacrylate pressure sensitive adhesive 40
Oleic acid 15
Isopropyl myristate 5
Polyvinylpyrrolidone 30
Hydroxypropyl emthylcellulose 10
Said components is made composite substrate mother solution of the present invention, in mother solution, add grieved peaceful extractum again, its addition is 40% of a mother solution gross weight, through after stirring, uses coating technique to be coated on and makes grieved peaceful patch on the plastic sheeting of being crossed by silicone treated.
The embodiment that can also enumerate more percutaneous dosing composite substrate of the present invention comes, and they can cooperate various suitable medicines well, and in order to make the system of percutaneous dosing, its processing technology no longer describes in detail, only its prescription is shown in table 2:
Table 2
| The embodiment sequence number | Percutaneous dosing composite substrate composition and content (wt%) | |||||
| Polypropene pressure sensitive adhesive | Polyvinylpyrrolidone | Hydroxypropyl emthylcellulose | Azone | Oleum Eucalypti | Carbitol | |
| 8 | 63 | 20 | 1 | 1 | 15 | |
| 9 | 70 | 10 | 8 | 2 | 2 | 8 |
| 10 | 65 | 15 | 10 | 3 | 2 | 5 |
| 11 | 62 | 10 | 10 | 5 | 3 | 10 |
| 12 | 63 | 5 | 10 | 2 | 5 | 5 |
Claims (8)
1, a kind of transdermal administration pressure-sensitive gel composite substrate, it includes chemical promoter and pressure sensitive adhesive component, it is characterized in that being added with in addition crystallization inhibitor, synergism by crystallization inhibitor and chemical promoter, both can improve drug loading and keep medicine over-saturation dissolving, can improve medicine percutaneous through performance again, crystallization inhibitor is hydroxypropyl emthylcellulose or polyvinylpyrrolidone, and chemical promoter synergistic with it is isopropyl myristate, oleic acid, azone, Oleum Eucalypti, carbitol and their combination.
2, by the described transdermal administration pressure-sensitive gel composite substrate of claim 1, it is characterized in that the hydroxypropyl emthylcellulose of said crystallization inhibitor, its addition percent by weight is calculated as 5～10.
3, by the described transdermal administration pressure-sensitive gel composite substrate of claim 1, when it is characterized in that said crystallization inhibitor is polyvinylpyrrolidone, its addition percent by weight is calculated as 10～30.
4, by the described transdermal administration pressure-sensitive gel composite substrate of claim 1, it is characterized in that said chemical promoter of working in coordination with crystallization inhibitor is an isopropyl myristate, its addition percent by weight is calculated as 5～20.
5, by the described transdermal administration pressure-sensitive gel composite substrate of claim 1, it is characterized in that said chemical promoter of working in coordination with crystallization inhibitor is an oleic acid, its addition percent by weight is calculated as 5～15.
6, by the described transdermal administration pressure-sensitive gel composite substrate of claim 1, it is characterized in that said chemical promoter of working in coordination with crystallization inhibitor is an azone, its addition percent by weight is calculated as 1～5.
7, by the described transdermal administration pressure-sensitive gel composite substrate of claim 1, it is characterized in that said chemical promoter of working in coordination with crystallization inhibitor is an Oleum Eucalypti, its addition percent by weight is calculated as 1～5.
8, by the described transdermal administration pressure-sensitive gel composite substrate of claim 1, it is characterized in that said chemical promoter of working in coordination with crystallization inhibitor is a carbitol, its addition percent by weight is calculated as 5～15.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510047335 CN1742708A (en) | 2005-09-30 | 2005-09-30 | Transdermal administration pressure-sensitive gel composite substrate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510047335 CN1742708A (en) | 2005-09-30 | 2005-09-30 | Transdermal administration pressure-sensitive gel composite substrate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1742708A true CN1742708A (en) | 2006-03-08 |
Family
ID=36138336
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200510047335 Pending CN1742708A (en) | 2005-09-30 | 2005-09-30 | Transdermal administration pressure-sensitive gel composite substrate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1742708A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102552220A (en) * | 2012-01-06 | 2012-07-11 | 天津大学 | Method of preparing polymer electrospinning fiber and application in transdermal drug delivery patch |
-
2005
- 2005-09-30 CN CN 200510047335 patent/CN1742708A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102552220A (en) * | 2012-01-06 | 2012-07-11 | 天津大学 | Method of preparing polymer electrospinning fiber and application in transdermal drug delivery patch |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1232389A (en) | Patch | |
| CN1298326C (en) | Transdermal patch for external use comprising fentanyl | |
| CN1231592A (en) | Fatty acid esters of glycolic and its salts as permeation enhancers | |
| TW200418487A (en) | Pharmaceutical composition for topical delivery of meloxicam comprising an amine or amine as penetration enhancer. | |
| CN1209108C (en) | Transdermal composition of antivomiting agent and preparation containing the same | |
| CN102413821A (en) | Transdermal preparation | |
| KR20120089336A (en) | Pharmaceutical composition for external use | |
| CN100341577C (en) | Transdermal absorption preparation | |
| CN1697656A (en) | Phentanyl-containing adhesive patch for application to oral-cavity mucosa | |
| CN103432104A (en) | Transdermal patch containing pramipexole | |
| CN105287361A (en) | External preparation containing non-steroid anti-inflammatory drug microemulsion and used for skin | |
| JP2024500424A (en) | Insoluble transdermal microneedle patch and its preparation method and application | |
| CN100534421C (en) | Hydrophillia Babu agent for treating depression | |
| TW200902090A (en) | Transdermal administration device for bisoprolol | |
| CN105147642A (en) | Transdermal patch containing formoterol or fumarate thereof | |
| CN1400897A (en) | Transdermal delivery LASOFOXIFENE | |
| CN1742708A (en) | Transdermal administration pressure-sensitive gel composite substrate | |
| CN1899290A (en) | Epristeride slow release preparation | |
| CN1824319A (en) | Hormone kind anticancer medicine slow release agent | |
| CN1663999A (en) | Chitosan water-retaining gel adhesive substrate materials and method for preparing same | |
| CN1414856A (en) | Antiprurity agents for external use | |
| CN1613463A (en) | External applied Chinese medicinal paste for treating arthralgia | |
| CN1861059A (en) | Hydrophilic gel type percutaneous plaster contg. capsaicin, and its prepn. method | |
| CN1164272C (en) | Compsn. containing ligustrazine, penetrating skin paste agent of igustrazine and its preparation method | |
| CN106890166A (en) | Preparation for external application to skin containing Galcium receptor-active compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |