CN1969971A - Transdermal absorption formulation of total alkaloid of common monkshood root and preparation process thereof - Google Patents
Transdermal absorption formulation of total alkaloid of common monkshood root and preparation process thereof Download PDFInfo
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- CN1969971A CN1969971A CNA2006101510859A CN200610151085A CN1969971A CN 1969971 A CN1969971 A CN 1969971A CN A2006101510859 A CNA2006101510859 A CN A2006101510859A CN 200610151085 A CN200610151085 A CN 200610151085A CN 1969971 A CN1969971 A CN 1969971A
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Abstract
The invention discloses a frame type percutaneous absorption externally-used preparation and process for preparing it, which comprises four portions of a storage layer, an adhesive layer, a back lining layer and a protection layer, wherein the storage layer comprises the following constituents (by weight ratio): Ligusticum wallichii alkaloid extract 7.5-12 parts, frame material 50-60 parts, methyl glycol 7-15 parts, azone 0.5-3 parts, and thickening agent 0-5 parts, other ingredients 5-35 parts. The preparation can be used for treating rheumatic and rheumatoid arthritis.
Description
(1) technical field
The present invention relates to a kind of external TDS preparation, particularly a kind of is the matrix-type transdermal absorbable preparation and the preparation technology thereof of principal agent with the total alkaloid of common monkshood root.
(2) background technology
Rheumatic and rheumatoid arthritis are at the category of Chinese medicine ownership " example joint ", " insensitive impediment ".In the name side of various treatment pain, the proved recipe, all be monarch drug on the medical science history records with the Aconitum carmichjaelii Debx..As " Medical Treasures of the Golden Chamber " it " apoplexy severe and migratory arthralgia " piece of writing say " suffering from arthritis can not save and bend and stretch pain, the Aconiti Decoction master it." Aconitum carmichjaelii Debx. is as the monarch drug of Aconiti Decoction, " its property is dredged rapidly sharp, opens the pass natural fibre line of meat, and the power of expulsion cold-damp is very prompt " (" the Changsha medicine is separated ") and be apt to into meridians, power can dredge chronic the moon and be trembled with fear with fixed attention.The modern pharmacology test shows that the Aconitum carmichjaelii Debx. total alkaloids has significant analgesia role, with the analgesic activity comparison there was no significant difference of pethidine.In addition, the big mice inflammation to due to various proinflammatory agents such as dimethylbenzene, histamine, 5-HT, Ovum Gallus domesticus album etc. all has significant inhibitory effect.Be commonly used to treat various rheumatism, rheumatoid arthritis and other various pain clinically.
Contain the existing administering mode of Aconitum carmichjaelii Debx. class Chinese medicine and mainly contain injection, tablet, pill, decoction, powder, black plaster etc., because oral formulations easily produces first pass effect and toxic to hepatocyte in gastrointestinal tract, injection easily produces pain and lump in the injection site, and access times are many, easily make patient produce psychological burden, traditional black plaster uses inconvenience, skin irritation is big, anaphylaxis is many, and that transdermal drug delivery system has an administration time is long, avoid first pass effect, reducing the untoward reaction and the advantage such as easy to use of medicine, is a kind of more satisfactory form of administration.Study at present seldom at home and abroad about the research of Aconitum carmichjaelii Debx. total alkaloids transdermal characteristic and galenic pharmacy, the slow control release type Aconitum carmichjaelii Debx. total alkaloids TDS system of compound skeleton that uses modern preparation technique preparation does not almost have yet.
(3) summary of the invention
The object of the present invention is to provide untoward reaction such as a kind of first pass effect that can avoid liver and gastrointestinal tract, blood drug level is constant, bioavailability is high, and can reduce administration number of times, prolong action time, reduce toxic and side effects, safe and reliable be matrix-type transdermal absorbable preparation of principal agent and preparation method thereof with the total alkaloid of common monkshood root.
The object of the present invention is achieved like this:
1, transdermal absorption formulation of total alkaloid of common monkshood root comprises storage layer, adhesive-layer, backing layer and protective layer four parts, and the weight ratio of drug-supplying system composition is: total alkaloid of common monkshood root extract 7.5-12 part, framework material 50-60 part, propylene glycol 7-15 part, azone 0.5-3 part, thickening agent 0-5 part and other 5-35 part.
2, the preparation method of transdermal absorption formulation of total alkaloid of common monkshood root is: medicine and penetration enhancer are dispersed in the framework material, are placed in the fixed mould then or on the clean glass plate, the shop film; dry; demoulding is put into to reinforce and is pasted, and adds that protective layer promptly.
The present invention also has some technical characterictics like this:
1, described transdermal absorption formulation formation is followed successively by backing layer, adhesive-layer, storage layer, adhesive-layer, storage layer, adherent layer or backing layer, adhesive-layer, storage layer, adhesive-layer, adherent layer or backing layer, adhesive-layer, storage layer, adherent layer;
2, in the described transdermal absorption formulation of total alkaloid of common monkshood root, total alkaloid of common monkshood root is that employing X-5 type macroporous adsorbent resin technology is carried out purification and got on the basis of 95% ethanol extraction;
3, described framework material is polyvinylpyrrolidone (PVP) or polyvinyl alcohol (PVA) or polyacrylic resin and thickening agent thereof;
4, also contain penetration enhancer in the described storage layer, penetration enhancer is propylene glycol (PG), Azone, oleic acid or glyceryl monolaurate or wherein two combination;
5, described penetration enhancer is Azone: PG=1: 10;
6, described backing layer and adhesive-layer are to reinforce and paste;
7, described adhesive-layer surface also is provided with adherent layer, and adherent layer is a separate paper.
Penetration enhancer is at the Franz diffusion cell that adopts improvement among the present invention, with the normal saline is receiver media, with the isolated rat skin of back is the transdermal barrier, and the accumulation infiltration capacity Q and the relevant parameter of aconitum carmichaeli debx. Total alkaloids and mesaconitine filter out under calculating variable concentrations unit promoter and the effect of various combination promoter.
The present invention adopts the Franz diffusion cell of improvement, is receiver media with the normal saline, is the transdermal barrier with the isolated rat skin of back, and four kinds of pasters in conjunction with the embodiments carry out the transdermal test.
The kinetic parameter (n=3) of aconitum carmichaeli debx. Total alkaloids Transdermal absorption in four kinds of pasters
| patch | Huigui equation | R | P/μg/cm 2·h | Tlag/h |
| P-1 P-2 P-3 P-4 | Q＝0.008t+0.0206 Q＝0.0072t+0.0057 Q＝0.0092t+0.013 Q＝0.0048t+0.0055 | 0.9792 0.9415 0.9843 0.9904 | 8.0 7.2 9.2 4.8 | 2.5754 0.7917 1.4130 1.1458 |
Adhesive matrix type paster is carried out the release in vitro degree investigate, its release in vitro curve is seen Fig. 1.
The release profiles that can find out rhizome of Chinese monkshood total alkali patch in conjunction with Fig. 1 presents two-part, and namely 0-3 hour is the quick release stage, and 6-24h is for discharging at a slow speed the stage, and the release of 24 hours rhizome of Chinese monkshood total alkalis is about 77%. And its release in vitro meets regression equation, and the Higuchi equation is S (t)=13.32t1/2+ 18.428, r=0.9801. The release Mechanisms of prompting rhizome of Chinese monkshood total alkali paster is the result of the comprehensive effect of drug diffusion and bulk erosion, proves that also said preparation belongs to framework controlled release type TDS system simultaneously.
In addition, adhesive matrix type paster is carried out skin irritation, anaphylaxis and anti-inflammatory and antalgic test, the result is as follows:
1. analgesic test
(1) hot plate method
The result shows that adhesive matrix type paster senior middle school dosage (12.5%, 10% rhizome of Chinese monkshood total alkali extract/subsides) group all can improve the mouse pain threshold.
(2) acetic acid twisting method
The result shows that the high, medium and low dosage of adhesive matrix type paster (12.5%, 10% rhizome of Chinese monkshood total alkali extract/subsides) group all can prolong mouse eases pain incubation period, and can reduce the writhing number of times of mouse, and high dose group analgesia rate reaches 59%.
2. anti-inflammatory test
(1) the swollen test of caused by dimethylbenzene xylene
The result shows that adhesive matrix type paster paraxylene causes the mice ear inflammatory model inhibitory action, and the amount effect relationship. The high dose group inhibiting rate can reach 56%, and low dose group is 23%. Illustrate that the present invention has obvious antiinflammatory action.
(2) on the impact of small white mouse capillary permeability
The result shows that matrix type rhizome of Chinese monkshood total alkali paster senior middle school dosage group all can obviously reduce the mouse capillary permeability, reduces oozing out of inflammatory mediator.
3. irritation test
Tested rabbit the oedema phenomenon all do not occur in the administration part, occur erythema in administration after 72 hours, the stimulus intensity score value belongs to slight to stimulate, after 48 hours hardly as seen, illustrate that adhesive matrix type paster is lighter to the excitant of skin, and can in 48 hours of discontinuing medication, disappear. Test finds that also blank patch is extremely light to the excitant of skin, illustrates that the materials such as the selected backing of this patch, pressure sensitive adhesive and transdermal enhancer almost do not have excitant to skin.
4. skin allergy test
Erythema and oedema phenomenon all do not appear in tested cavy, illustrate adhesive matrix type paster to skin without allergic reaction.
Transdermal absorption formulation of total alkaloid of common monkshood root of the present invention is the percutaneous drug administration preparation take total alkaloid of common monkshood root as main component, by multi-level, multi-functional, polymorphic regulator control system, make between the drug ingedient mutually excite, work in coordination with, superposition, cause the physiology enlarge-effect. The bad reactions such as the first pass effect of liver and intestines and stomach have been avoided, and blood concentration is constant, bioavilability is high, reduces administration number of times, prolongs action time, reduce toxic and side effect, safe and reliable, can really reach the purpose of " control with interior control reach the same goal by different routes wonderful " outward, show that fully transdermal delivery system is in this neck advantage more, also for accelerating innovation of Chinese medicinal dosage form, for internationalization of tcm is made certain contribution.
(4) specific embodiment
Below in conjunction with specific embodiment total alkaloid of common monkshood root transdermal patch of the present invention and preparation method thereof is described in further detail:
Embodiment 1: multilamellar bank matrix type drug-supplying system
1, present embodiment comprises storage layer, adhesive-layer, backing layer and protective layer four parts, wherein the drug storehouse layer of storage layer comprises that drug storehouse layer 1 and drug storehouse layer 2 are two-layer, and the weight ratio of drug storehouse layer 1 is: 0.21 part of total alkaloid of common monkshood root extract, 2 parts of PVA+PVP (2: 1) solution, 0.3 part of propylene glycol, 0.03 part of azone, other 0.46 part; The weight ratio of drug storehouse layer 2 is: 0.15 part of total alkaloid of common monkshood root extract, 1.50 parts of pressure sensitive adhesives, 0.30 part of propylene glycol, 0.03 part of azone, other 1.12 parts; Adhesive-layer comprises 0.1 part of 1 part of pressure sensitive adhesive and thickening agent.Other composition is a water in the present embodiment.
3, technical process is:
After the medicine water heating for dissolving in the drug storehouse layer 1, with framework material solution, penetrating agent mix homogeneously, place on the clean smooth slick glass plate, make into a thin film, dry under the 60-80 ℃ of condition, demoulding.With pressure sensitive adhesive and thickening agent mixing, in separate paper upper berth film, drying.With the medicine in the drug storehouse layer 2, pressure sensitive adhesive, the penetrating agent mix homogeneously, the heating deaeration places the mould that is lined with separate paper, the shop film, remove mould, drying is 2 hours under 80 ℃ of conditions, the film in the drug storehouse layer 1 is pasted on the reinforcing of removing separate paper sticks, drug storehouse layer 1 and 2 is pasted together by adhesive-layer, cuts into 5*7cm
2Paster.
Through test, the used penetration enhancer of matrix type total alkaloid of common monkshood root paster is the Franz diffusion cell that adopts improvement in the present embodiment, with the normal saline is receiver media, with the isolated rat skin of back is the transdermal barrier, and the accumulation infiltration capacity Q and the relevant parameters such as steady state flow P and lag time of aconitum carmichaeli debx. Total alkaloids and mesaconitine screen under calculating variable concentrations unit penetration enhancer and the effect of various combination penetration enhancer.The penetration enhancer of transdermal absorption formulation of total alkaloid of common monkshood root the best is Azone: PG=1: 10.
Embodiment 2: polymer backbone type drug-supplying system
1, present embodiment comprises storage layer, adhesive-layer, backing layer and protective layer four parts, and wherein the drug storehouse layer of storage layer comprises: 0.30 part of total alkaloid of common monkshood root extract, 2 parts of PVA+PVP (2: 1) solution, 0.40 part of propylene glycol, 0.04 part of azone, other 1.26 parts; Adhesive-layer comprises 2 parts of pressure sensitive adhesives, 0.5 part of thickening agent.
Other composition is a water in the present embodiment.
2, technical process is:
With the medicine in the drug storehouse layer, framework material solution and penetrating agent mix homogeneously, place on the clean smooth slick glass plate, make into a thin film, dry under the 60-80 ℃ of condition, demoulding, be pasted on the reinforcing of removing separate paper and stick, with pressure sensitive adhesive and thickening agent mixing, at separate paper upper berth film, drying, with drug storehouse layer and adhesive-layer pressing promptly.
Other is with embodiment 1.
Embodiment 3: adhesive matrix type drug-supplying system
1, present embodiment comprises storage layer, adhesive-layer, backing layer and protective layer four parts, and wherein the drug storehouse layer of storage layer comprises: 0.30 part of total alkaloid of common monkshood root extract, 2 parts of pressure sensitive adhesives, 0.40 part of propylene glycol, 0.04 part of azone, other 1.26 parts.Other composition is a water in the present embodiment.
2, technical process is:
With the medicine in the drug storehouse layer, pressure sensitive adhesive, the penetrating agent mix homogeneously, the heating deaeration places the mould that is lined with separate paper, and the shop film is removed mould, and drying is 2 hours under 80 ℃ of conditions, is pasted on the reinforcing of removing separate paper and sticks, promptly.
Other is with embodiment 1.
Embodiment 4: the matrix type drug-supplying system
1, present embodiment comprises storage layer, adhesive-layer, backing layer and protective layer four parts, and wherein the drug storehouse layer of storage layer comprises: 0.30 part of total alkaloid of common monkshood root extract, 1 part of pressure sensitive adhesive, 1 part of PVA+PVP (2: 1) solution, 0.40 part of propylene glycol, 0.04 part of azone, other 1.26 parts.Other composition is a water in the present embodiment.
2, technical process is:
With the medicine in the drug storehouse layer, pressure sensitive adhesive, framework material solution and penetrating agent mix homogeneously, heating deaeration, place the mould that is lined with separate paper, the shop film is removed mould, drying is 2 hours under 80 ℃ of ambient temperatures, is pasted on the reinforcing of removing separate paper and sticks, promptly.
Other is with embodiment 1.
Claims (10)
1. transdermal absorption formulation of total alkaloid of common monkshood root; it is characterized in that it comprises storage layer, adhesive-layer, backing layer and protective layer four parts, the weight ratio that storage layer becomes to be grouped into is: total alkaloid of common monkshood root extract 7.5-12 part, framework material 50-60 part, propylene glycol 7-15 part, azone 0.5-3 part, thickening agent 0-5 part and other 5-35 part.
2. transdermal absorption formulation of total alkaloid of common monkshood root according to claim 1 is characterized in that described transdermal absorption formulation formation is followed successively by backing layer, adhesive-layer, storage layer, adhesive-layer, storage layer, adherent layer or backing layer, adhesive-layer, storage layer, adhesive-layer, adherent layer or backing layer, adhesive-layer, storage layer, adherent layer.
3. transdermal absorption formulation of total alkaloid of common monkshood root according to claim 1 is characterized in that described total alkaloid of common monkshood root extract for passing through with behind 95% ethanol extraction, and the purification enrichment process of reuse X-5 purification with macroreticular resin makes.
4. transdermal absorption formulation of total alkaloid of common monkshood root according to claim 1, the framework material that it is characterized in that described storage layer are polyvinylpyrrolidone or polyvinyl alcohol or polyacrylic resin and thickening agent thereof.
5. transdermal absorption formulation of total alkaloid of common monkshood root according to claim 1 is characterized in that also comprising in the bank penetration enhancer, and penetration enhancer is selected from PG, Azone, oleic acid or glyceryl monolaurate or wherein two combination.
6. transdermal absorption formulation of total alkaloid of common monkshood root according to claim 5 is characterized in that described penetration enhancer is Azone: PG=1: 10.
7. transdermal absorption formulation of total alkaloid of common monkshood root according to claim 1 is characterized in that described adhesive-layer material is polyacrylate pressure-sensitive and thickening agent thereof.
8. transdermal absorption formulation of total alkaloid of common monkshood root according to claim 1 is characterized in that described backing layer and adhesive-layer are reinforcing and paste.
9. according to claim 1 or 7 described transdermal absorption formulation of total alkaloid of common monkshood root, it is characterized in that described adhesive-layer surface also is provided with adherent layer, adherent layer is a separate paper.
10. the preparation method of a transdermal absorption formulation of total alkaloid of common monkshood root is characterized in that: medicine and penetration enhancer are dispersed in the framework material, are placed in the fixed mould then or on the clean glass plate; the shop film, drying, demoulding; put into to reinforce and paste, add that protective layer promptly.
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| Application Number | Priority Date | Filing Date | Title |
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| CNA2006101510859A CN1969971A (en) | 2006-12-01 | 2006-12-01 | Transdermal absorption formulation of total alkaloid of common monkshood root and preparation process thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102973679A (en) * | 2012-12-21 | 2013-03-20 | 四川省中医药科学院 | Preparation method of total alkaloids extract in aconitum medical material or processed products of aconitum plants |
| CN104208042A (en) * | 2014-09-19 | 2014-12-17 | 四川兴科蓉药业有限责任公司 | Percutaneous absorption preparation |
-
2006
- 2006-12-01 CN CNA2006101510859A patent/CN1969971A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102973679A (en) * | 2012-12-21 | 2013-03-20 | 四川省中医药科学院 | Preparation method of total alkaloids extract in aconitum medical material or processed products of aconitum plants |
| CN104208042A (en) * | 2014-09-19 | 2014-12-17 | 四川兴科蓉药业有限责任公司 | Percutaneous absorption preparation |
| CN104208042B (en) * | 2014-09-19 | 2016-08-31 | 李淑兰 | A kind of transdermal absorption formulation |
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Open date: 20070530 |