CN101703492B - Tetrahydropalmatine transdermal patch and preparation method thereof - Google Patents
Tetrahydropalmatine transdermal patch and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a tetrahydropalmatine transdermal patch and a preparation method thereof. The patch comprises a back lining layer, a drug-storage layer and a protective layer, wherein the raw materials of the drug-storage layer comprise tetrahydropalmatine and pressure sensitive adhesive, or a moderate amount of transdermal accelerant and the like is added to finally prepare the tetrahydropalmatine patch. The tetrahydropalmatine patch has the advantages that the patch has convenient use, high bioavailability and lasting action and avoids liver 'first pass effect' and damages on gastrointestinal tract; and the patch reduces drug toxicity and side effects and increases drug bioavailability and therapeutic safety, thereby having outstanding anti-inflammatory and analgesic effects.
Description
Technical field
The present invention relates to a kind of percutaneous plaster and preparation method thereof, particularly a kind of tetrahydropalmatine transdermal patch and preparation method thereof.
Background technology
Pain is modal multiple common symptoms in the medical research clinical disease, and this difficult problem is a great challenge to research worker and doctor.The medicine of nowadays treating pain is based on Western medicine, mainly be divided into non_steroidal anti_inflammatory drug and narcosis analgesic two classes, in this two classes medicine, though anaesthetic analgesic effect is strong, but the side effect of self big (addiction), though and the non-steroidal anti-inflammatory analgesic does not have the so big side effect of narcotic analgesic medicine, and the untoward reaction of reverse side such as many gastrointestinal tract is also arranged.Medical domain is also constantly being sought the minimum anti-inflammation analgesia medicine of the good and side effect (as addiction) of analgesic effect.
The tetrahydropalmatine molecular formula
Tetrahydropalmatine is to extract and next a kind of alkaloid from the dry tuber of papaveraceae plant corydalis Corydalis yanhusuo W.T.Wang, is applied to clinical as analgesia and calm neuroleptic agent.Pain relieving mechanism explains it is " blood-activating and qi-promoting " from Chinese medicine, think that from present pharmacological research tetrahydropalmatine is relevant with the retardance central dopaminergic receptor, its analgesic activity than dolantin a little less than, but general antipyretic analgesic is strong, better to chronic rest pain effect, relatively poor to the effect of wound and postoperative pain.Except that analgesic activity, tangible sedative-hypnotic effect is arranged still.Advantage is that toxicity is low, and safety is big, no addiction.Be a non-narcotic analgesics, also do not belong to analgesic anti-inflammatory analgesic category.Since tetrahydropalmatine is founding of New.First nervous system medicine with the achieving success of modern science and technology research Chinese medicine.The present sulfate that is mainly tetrahydropalmatine that uses clinically.The tetrahydropalmatine molecular weight is 355.42, and fusing point is 143 ℃, is insoluble in water, petroleum ether, is soluble in ether, chloroform.Its preparation type is mainly oral formulations and injection, and the oral formulations bioavailability is lower, and the half-life is shorter, needs long-time oral administration, and has the medicine first pass effect; Injection administration inconvenience, pain during injection, prescription is relatively stricter, and improper use is easily caused danger.
Summary of the invention
The objective of the invention is to disclose a kind of tetrahydropalmatine transdermal patch; Another object of the present invention is to disclose the preparation method of this paster.
The objective of the invention is to be achieved through the following technical solutions:
Percutaneous plaster of the present invention comprises backing layer, drug storehouse layer and protective layer, it is characterized in that the raw material of drug storehouse layer consists of:
Tetrahydropalmatine: 0.1-2 weight portion
Percutaneous absorption enhancer: 0.1-2 weight portion
Pressure sensitive adhesive: 3-10 weight portion.
Percutaneous plaster of the present invention comprises backing layer, drug storehouse layer and protective layer, it is characterized in that the raw material composition of drug storehouse layer is preferably:
Tetrahydropalmatine: 0.5 weight portion
Percutaneous absorption enhancer: 1 weight portion
Pressure sensitive adhesive: 5 weight portions;
Percutaneous plaster of the present invention comprises backing layer, drug storehouse layer and protective layer, it is characterized in that the raw material composition of drug storehouse layer is preferably:
Tetrahydropalmatine: 1 weight portion
Percutaneous absorption enhancer: 0.5 weight portion
Pressure sensitive adhesive: 8 weight portions;
Percutaneous plaster of the present invention comprises backing layer, drug storehouse layer and protective layer, it is characterized in that the raw material composition of drug storehouse layer is preferably:
Tetrahydropalmatine: 1.5 weight portions
Percutaneous absorption enhancer: 1.5 weight portions
Pressure sensitive adhesive: 7 weight portions.
Also can add cosolvent and/or plasticizer in the drug storehouse layer raw material of the invention described above percutaneous plaster, wherein the amount of cosolvent or plasticizer be the amount of amount, Percutaneous absorption enhancer of tetrahydropalmatine and pressure sensitive adhesive amount total amount 1-5 doubly.
Also can add cosolvent and/or plasticizer in the drug storehouse layer raw material of the invention described above percutaneous plaster, wherein the amount of cosolvent or plasticizer all is preferably 3 times of total amount of the amount of the amount of amount, Percutaneous absorption enhancer of tetrahydropalmatine and pressure sensitive adhesive.
Percutaneous plaster preparation method of the present invention comprises the steps:
Get the raw material mixing and stirring of above-mentioned drug storehouse layer; Adopt curtain coating technology that said mixture is coated on the backing layer to solvent and volatilize, protective layer on the cooling bonnet, the tetrahydropalmatine paster; Or said mixture is coated on the backing layer, protective layer on the cooling bonnet, the tetrahydropalmatine paster.
Percutaneous absorption enhancer is meant Laurel nitrogen in the percutaneous plaster of the present invention
Ketone, Mentholum, Borneolum Syntheticum, eucalyptus oil, Fructus Zanthoxyli oil, Oleum Bulbus Allii and Rhizoma Chuanxiong extract, Semen Myristicae extract, propylene glycol, Laurel nitrogen
In ketone, methyl salicylate or the oleic acid one or more; Wherein pressure sensitive adhesive is meant Polyisobutylene PSA, acrylate pressure sensitive adhesive, polysiloxanes pressure sensitive adhesive or thermo-elasto-plasticity rubber.
In the percutaneous plaster of the present invention cosolvent refer to that the fatty acid Pyrusussuriensis is smooth, in the polyoxyethylene aliphatic alcohol ether, Polysorbate, fatty glyceride, polyoxyethylene fatty acid ester one or more; Plasticizer refers to one or more in Kaolin, zinc oxide, titanium dioxide, kieselguhr, glycerol, the propylene glycol etc.
The backing layer of percutaneous plaster of the present invention is made according to common process by polyurethane film, vinylacetate film, polychloroethylene film; The protective layer of paster is the polyethylene film that common process is made.
The invention provides a kind of easy to use, bioavailability is high, effect persistent tetrahydropalmatine transdermal patch and preparation method thereof.Tetrahydropalmatine ester dissolubility height helps the medicine percutaneous and absorbs, and easily makes paster; Experiment and clinical research show that tetrahydropalmatine transdermal patch has antiinflammatory, analgesic effect.Tetrahydropalmatine among the present invention is compared with tetrahydropalmatine sulfate, when guaranteeing drug effect, has reduced cost.The present invention adopts the paster agent, blood drug level is stable, lasting, avoided " first pass effect " and the gastrointestinal of liver to destroy, the toxicity and the side effect of medicine have been reduced, improved the safety of bioavailability of medicament and treatment, and medication is convenient, no pain, and is remarkable at antiinflammatory, ease pain effect.
Description of drawings
Fig. 1: the different transdermal enhancer Transdermal absorption of tetrahydropalmatine paster curve.
Following experimental example and embodiment are used to further specify but are not limited to the present invention.
The pharmacodynamics test of experimental example 1 analgesic activity
One, the analgesic test of mice hot plate method (Hot plate test)
The hot plate method analgesic experiment is the experiment of the screening analgesic of classics, its principle is mice to be placed on be preheated on the 50-55 ℃ of metallic plate, constant temperature (change in ± 0.5 ℃), mice are subjected to the reaction that metapedes can occur licking after the thermostimulation, measure the hot plate reaction time (threshold of pain); Analgesic can improve the threshold of pain, prolongs the hot plate reaction time.
1 experiment material
1.1 trial drug
Tetrahydropalmatine transdermal patch; The negative control product are not for containing the paster (self-control) of medicine; Osmanthus ginseng analgesic combination, Kunming Yi Kang pharmaceutical factory product, specification 100ml/ bottle, lot number 20040517; The tetrahydropalmatine sulfate injection, Guangdong Boluo Pioneer Medicinal Group Co., Ltd., the accurate word H44021994 of traditional Chinese medicines, specification: 30mg/ml, lot number 20060106.
1.2 animal
The female Kunming mouse of healthy adult, (Lanzhou Institute of Biological Products's Experimental Animal Center provides body weight (20 ± 2) g, the quality certification number: the moving word 14-001 of doctor).
Instrument
GJ-8402 type hot plate dolorimeter, the white stone electronics medicine in Ninghai, Zhejiang instrument plant.
2 methods
Mice is placed on is preheated on the 50-55 ℃ of metallic plate, constant temperature (changing in ± 0.5 ℃), be threshold of pain index (be mice put into the hot plate dolorimeter lick the time that metapedes reacts to occurring) incubation period of licking the metapedes reaction with mice.Screening animal before the experiment, select 60 of the female mice of pain threshold within 5-30s, be divided into 6 groups at random, be respectively: osmanthus ginseng analgesic combination matched group (irritating stomach osmanthus ginseng analgesic combination 20ml/kg) (I), tetrahydropalmatine sulfate injection matched group (intramuscular injection 12mg/kg) (II), blank group (paster that does not contain medicine) (III), tetrahydropalmatine transdermal patch low dose group (2mg/ subsides) (IV), in the tetrahydropalmatine transdermal patch dosage group (4mg/ subsides) (V), tetrahydropalmatine transdermal patch high dose group (8mg/ subsides) (VI).I group mouse stomach is irritated stomach osmanthus ginseng analgesic combination 20ml/kg, II group intramuscular injection tetrahydropalmatine sulfate injection 12mg/kg, III～VI group mice is only pasted the corresponding thing that tried by 1cm2/, successive administration 3 days, every day 1 time is after the last administration, throw off and tried thing, use the warm water wiped clean, measure the pain threshold of each mice after the last administration respectively at 1h, 2h, 3h and 4h, surpass 60s person in 60s.Measure each mice pain threshold 2-3 time (5min at interval) before the experiment, averaging is its basic pain threshold.For preventing the foot scald, 60s deadline is set.
3 statistical analysis
(x ± s) expression adopts the SPSS11.5 statistical software to carry out date processing to all data with mean ± standard deviation.Carry out one factor analysis of variance, check with LSD when variance has homogeneous, heterogeneity of variance Dunnett ' s T3 check is carried out comparing between each group.P＜0.05 expression difference has significance.
4 results
Different Individual has different manifestations to the hot plate irritant reaction, and majority is licked foot, licks the sufficient pain indicator reaction that is so this test is adopted.Some reaction of animals easily jumps and does not lick foot, and the mice that also has is only walked about fast on hot plate and sufficient reaction do not occur licking.Licking foot reaction is a protective response, and jumping be escape reaction then, is index so only chosen wherein one in this test, other will take place well react Mus rejecting.Male mouse may be because of the rhacoma irriate, so this test female mice.Hot plate method is identical with tail-flick method to the sensitivity of analgesic, but the reaction property difference, the hot plate reaction has high-order maincenter to participate in, and the whipping reaction then is a kind of spinal reflex.
This result of the test shows, tetrahydropalmatine transdermal patch high dose group (VI) can obviously improve the pain threshold of thermostimulation mice, and analgesia duration can reach 3h, and the analgesia duration of tetrahydropalmatine sulfate injection matched group (II) is 2h, with blank group comparing difference significance (P＜0.05 or P＜0.01) is arranged, the prompting tetrahydropalmatine transdermal patch can obviously suppress the pain reaction due to the thermostimulation, has certain analgesic activity, sees Table 1.
Table 1 tetrahydropalmatine transdermal patch is to the influence of mice hot plate method pain threshold (x ± s)
Annotate: compare with the blank group,
*P＜0.05,
*P＜0.01
Two, mice acetic acid twisting experiment
1 material
1.1 reagent, apparatus and medicine
Glacial acetic acid is available from the special chemicals company limited in Rui Jin, Tianjin, lot number: 2007-05-22, analytical pure; The portable balance of electronics (model: YB1201, Haikang, Shanghai Electronic Instruments Plant, precision 0.01g); Stopwatch (SW8-2008, Shenzhen epoch Powerise digital technology Co., Ltd); Syringe (specification: 1ml); Injection needle; Irritate the stomach syringe needle; Depilator; Pipettor; Psychrometer; Brown reagent bottle; The tetrahydropalmatine sulfate injection, Guangdong Boluo Pioneer Medicinal Group Co., Ltd., the accurate word H44021994 of traditional Chinese medicines, specification: 30mg/ml, lot number 20060106; Tetrahydropalmatine transdermal patch; The negative control product are not for containing the paster (self-control) of medicine.
1.2 laboratory animal
50 of healthy adult male mice in kunming, (Lanzhou Institute of Biological Products's Experimental Animal Center provides body weight (20 ± 2) g, the quality certification number: the moving word 14-001 of doctor).
2 methods
2.1 glacial acetic acid compound method
Face with preceding newly joining with distilled water be 0.6% glacial acetic acid solution.
2.2 grouping, administration and experimental technique
Mice is divided into 5 groups at random, every group 10, be respectively: positive controls (intramuscular injection tetrahydropalmatine sulfate injection 12mg/kg) (I), model control group (paster that does not contain medicine) (II), tetrahydropalmatine transdermal patch low dose group (2mg/ subsides) (III), in the tetrahydropalmatine transdermal patch dosage group (4mg/ subsides) (IV), tetrahydropalmatine transdermal patch high dose group (8mg/ subsides) (V).Slough the about 3cm of mouse web portion with depilator before the test
2Hair, I group mice intramuscular injection tetrahydropalmatine sulfate injection 12mg/kg, II～V group mice is pressed 1cm
2/ only paste the corresponding thing that tried, successive administration 3 days, every day 1 time, behind the last administration 6h, throw off and tried thing, use the warm water wiped clean, respectively only to the acetum 0.2ml/ of lumbar injection 0.6%, turn round body (abdominal part indent, stretching, extension hind leg, buttocks are raised) number of times behind the record injection acetic acid in the 15min, calculate medicine the suppression ratio of writhing response is passed judgment on medicine analgesic effect: suppression ratio %=(model control group is turned round body average-reagent group and turned round the body average)/model control group is turned round body average * 100%.Each is organized under mice the same terms and to feed, freely ingests, and drinking-water, room temperature is controlled at (20 ± 1) ℃, humidity about 60%.
2.3 statistical analysis
(x ± s) expression adopts the SPSS11.5 statistical software to carry out date processing to all data with mean ± standard deviation.Carry out one factor analysis of variance, check with LSD when variance has homogeneous, heterogeneity of variance Dunnett ' s T3 check is carried out comparing between each group.P＜0.05 expression difference has significance.
3 results
This result of the test is found, be subjected to the reagent thing to show tangible analgesic effect, can suppress the mouse writhing reaction times significantly, wherein tetrahydropalmatine transdermal patch low dose group (2mg/ subsides) (III) and tetrahydropalmatine transdermal patch in dosage group (4mg/ subsides) inhibitory action (IV) suitable, tetrahydropalmatine transdermal patch high dose group (8mg/ subsides) inhibitory action (V) is more remarkable, and it is suitable with the inhibitory action of tetrahydropalmatine sulfate injection group, tetrahydropalmatine transdermal patch high dose group (8mg/ subsides) analgesia percentage rate (V) is 30.67%, the analgesia percentage rate of tetrahydropalmatine sulfate injection group is 34.68%, with the model control group comparing difference significance (P＜0.05 or P＜0.01) is arranged, see Table 2.
Table 2 acetic acid twisting method threshold of pain experimental result (x ± s)
Annotate: compare with matched group,
*P＜0.05,
*P＜0.01
The pharmacodynamics test of experimental example 2 tetrahydropalmatine paster antiinflammatory actions
(1) the tetrahydropalmatine paster is to the influence of mice granuloma induced by implantation of cotton pellets test
1 material
1.1 medicine
The tetrahydropalmatine paster; The negative control product are not for containing the paster (self-control) of medicine;
Contrast medicine: dexamethasone acetate (Zhangjiakou Yun Feng pharmaceutical factory, lot number: 070403).
1.2 animal
50 of healthy adult Male Kunming strain mice, (Lanzhou Institute of Biological Products's Experimental Animal Center provides body weight (20 ± 2) g, the quality certification number: the moving word 14-001 of doctor).
2 grouping and methods
Select the healthy adult Male Kunming strain mice for use, random packet, every group 10, be respectively: positive controls (irritate stomach dexamethasone acetate 1.8mg/kg) (I), model control group (paster that does not contain medicine) (II), tetrahydropalmatine paster low dose group (2mg/ subsides) (III), in the tetrahydropalmatine paster dosage group (4mg/ subsides) (IV), tetrahydropalmatine paster high dose group (8mg/ subsides) (V).
Each treated animal was tested preceding 1 day, in each Mus hypogastric region (comprising the both sides groin) depilation sterilization.During experiment, rat is under the pentobarbital sodium intraperitoneal injection of anesthesia, it is fixing to face upward the position, otch behind groin place, the both sides skin routine disinfection separates subcutaneous tissue of groin, respectively implants one piece of 5mg sterilization cotton balls (autoclaving in the both sides groin is subcutaneous, each adds each 1mg/0.1ml of ampicillin, 50 ℃ of stove-dryings) after, skin suture is raised with condition is conventional.The same day was organized dosage percutaneous dosing (except the positive controls in operation according to each, positive controls is irritated stomach dexamethasone acetate 1.8mg/kg), continuous 7 days, cervical vertebra dislocation in the 8th day is put to death, the complete both sides granuloma induced by implantation of cotton pellets of peeling off, claim dry weight after putting 60 ℃ of baking oven 12h, deduct the weight of former cotton balls own and be the granuloma net weight, respectively organize the difference of granuloma induced by implantation of cotton pellets net weight.
Granuloma suppression ratio (%)=(model control group granuloma net weight-be subjected to reagent group granuloma net weight)/model control group granuloma net weight * 100%.
3 statistical analysis
(x ± s) expression adopts the SPSS11.5 statistical software to carry out date processing to all data with mean ± standard deviation.Carry out one factor analysis of variance, check with LSD when variance has homogeneous, heterogeneity of variance Dunnett ' s T3 check is carried out comparing between each group.P＜0.05 (or P＜0.01) expression difference has significance.
4 results
This experimental result sees Table 3, the result shows: compare with model control group, positive controls and the equal significance of the basic, normal, high dosage group of tetrahydropalmatine paster mice granuloma induced by implantation of cotton pellets weight differential (P＜0.01 or P＜0.05), dexamethasone acetate and tetrahydropalmatine paster all can significantly reduce the granuloma dry weight, wherein, along with the increase of tetrahydropalmatine paster dosage, the granuloma suppression ratio strengthens successively, and the antiinflammatory action of prompting tetrahydropalmatine paster has dose dependent.This test shows that the tetrahydropalmatine paster has certain inhibitory action to the inflammation in late period of granulation tissue hyperplasia, promptly has antiinflammatory action.
Table 3 is subjected to the reagent thing to the influence of mice granuloma induced by implantation of cotton pellets (x ± s)
Compare with model control group: * P＜0.05, * * P＜0.01
(2) the tetrahydropalmatine paster is to the pharmacological research of inductivity adjuvant arthritis rat
1 material
1.1 medicine and instrument
The tetrahydropalmatine paster; The negative control product are not for containing the paster (self-control) of medicine;
The contrast medicine: nimesulide (is provided lot number: 0041206) by Tianjin Medicine Research Academy Pharmaceutical Co., Ltd.Electron amount slide calliper rule (Shanghai measuring instruments and cutting tools plant).
1.2 laboratory animal
64 of SD rats, provide by Lanzhou Institute of Biological Products's Experimental Animal Center, room temperature 23-25 ℃, relative humidity 40-70%, per hour renew wind 15 times, drink water, freely drink for animal for the north material bottle of the canned polyethylene of purified water, change water every day once, feedstuff is provided by Lanzhou Institute of Biological Products's Experimental Animal Center.
2 methods
2.1AA rat animal model preparation and grouping
60 of body weight 150-180g SD rats, male and female half and half, be divided into four groups at random: blank group (A group), model control group (B group), positive controls (C group), tetrahydropalmatine paster low dose group (D group, the 2mg/ subsides), dosage group (E group in the tetrahydropalmatine paster, the 4mg/ subsides), tetrahydropalmatine paster high dose group (F group, 8mg/ pastes).After getting 1 (75mg) 80 ℃ of 1h deactivation of lyophilized bacillus calmette-guerin vaccine (BCG), sneak into sterilization paraffin oil, lanoline (1: 1), be emulsified into Freund ' s Freund's complete adjuvant (containing BCG 10mg/ml).B, C, D, E, F are organized the right back sufficient sole of the foot injection Freund ' s Freund's complete adjuvant 0.1ml of every Mus cause inflammation, produce the allergy inflammation after causing scorching 8 ~ 12d, promptly the Secondary cases autoimmune arthritis forms.The 13d beginning, A, B group gives not contain the paster of medicine, and the C group gives positive control drug nimesulide 80mg/kgd, and D group, E group, F group give the tetrahydropalmatine paster according to dosage respectively, continuously 15d.
2.2 the mensuration of experimental index
After grouping and the modeling success,, as the radix of estimating antiinflammatory action intensity, carry out administration then with this with the left and right sufficient sole of the foot thickness of every group of each Mus of electron amount kind of calliper.After the administration the 4th, 9, to measure the left and right metapedes sole of the foot of rat thickness difference respectively be the swelling degree to 15d.
3 statistical analysis
(x ± s) expression adopts the SPSS11.5 statistical software to carry out date processing to all data with mean ± standard deviation.Carry out one factor analysis of variance, check with LSD when variance has homogeneous, heterogeneity of variance Dunnett ' s T3 check is carried out comparing between each group.P＜0.05 (or P＜0.01) expression difference has significance.
4 results
In this experiment, cause beginning in the 13rd day medication of scorching back, continuous use 15 days, after administration the 4th, 9, to measure the left and right metapedes sole of the foot of rat thickness difference respectively be the swelling degree to 15d, the results are shown in Table 4, each administration group is along with the carrying out of treatment, injection side (right side) swelling degree of the paw and offside (left side) swelling degree of the paw all have alleviating clearly, prompting tetrahydropalmatine paster has the degree that suppresses rat paw edema, illustrates that the tetrahydropalmatine paster has therapeutical effect to the secondary affection of rat assist agent arthritis.
Respectively organize before and after table 4 administration left and right pedal swelling thickness of rat (mm) (x ± s, n=10)
Compare with model control group,
*P＜0.05,
*P＜0.01
The screening experiment of experimental example 3 various adjuvants
1, the selection of adhesive test:
Take by weighing tetrahydropalmatine, through method adding transdermal enhancer and the different adhesive of embodiment 1, mixing, coating, drying cuts, and measures and holds viscous force (the results are shown in Table 3).
The various adhesive of table 5 hold the viscous force correction data
Experimental result shows that acrylate pressure sensitive adhesive, Polyisobutylene PSA, these three kinds of raw materials of polysiloxanes pressure sensitive adhesive all can be used as the adhesive in the paster preparation process of the present invention, and with the increase of its consumption, and it is bigger to hold viscous force intensity.
2, the selection of transdermal enhancer test:
Take by weighing tetrahydropalmatine, method through embodiment 1 adds adhesive, adds the transdermal enhancer of various dose and kind again, adds acrylate pressure sensitive adhesive 80%, mixing, coating, drying cuts, measure drug transdermal absorbing state (the results are shown in accompanying drawing 1), experimental result shows that these three kinds of raw materials of azone, Mentholum and oleic acid all can be used as the transdermal enhancer in the paster preparation process of the present invention, and its skin transit dose all can reach requirement.
Following embodiment all can realize the effect of above-mentioned experimental example.
The specific embodiment
Embodiment 1: tetrahydropalmatine transdermal patch
Tetrahydropalmatine: 0.5kg
Laurel nitrogen
Ketone: 1kg
Acrylate pressure sensitive adhesive: 5kg;
Get tetrahydropalmatine 0.5kg, add acrylate pressure sensitive adhesive 5kg and Laurel nitrogen
Ketone 1kg, the dissolving mixing is prepared into solution; Adopt curtain coating technology, above-mentioned solution coat on backing layer, is volatilized to solvent, protective layer on the cooling bonnet must tetrahydropalmatine transdermal patch.
Embodiment 2: tetrahydropalmatine transdermal patch
Tetrahydropalmatine: 1kg
Mentholum: 0.5kg
Polyisobutylene PSA: 8kg;
Get tetrahydropalmatine 1kg, add Polyisobutylene PSA 8kg and Mentholum 0.5kg, the dissolving mixing is prepared into solution; Adopt curtain coating technology, above-mentioned solution coat on backing layer, is volatilized to solvent, protective layer on the cooling bonnet must tetrahydropalmatine transdermal patch.
Embodiment 3: tetrahydropalmatine transdermal patch
Tetrahydropalmatine: 1.5kg
Propylene glycol: 1.5kg
Polysiloxanes pressure sensitive adhesive: 7kg;
Get tetrahydropalmatine 1.5kg and add polysiloxanes pressure sensitive adhesive 7kg and propylene glycol 1.5kg, the dissolving mixing is prepared into solution; Adopt curtain coating technology, above-mentioned solution coat on backing layer, is volatilized to solvent, protective layer on the cooling bonnet must tetrahydropalmatine transdermal patch.
Embodiment 4: tetrahydropalmatine transdermal patch
Tetrahydropalmatine: 1.8kg
Eucalyptus oil: 0.2kg
Acrylate pressure sensitive adhesive: 4kg;
Get tetrahydropalmatine 1.8kg and add acrylate pressure sensitive adhesive 4kg and eucalyptus oil 0.2kg, the dissolving mixing is prepared into solution; Adopt curtain coating technology, above-mentioned solution coat on backing layer, is volatilized to solvent, protective layer on the cooling bonnet must tetrahydropalmatine transdermal patch.
Embodiment 5: tetrahydropalmatine transdermal patch
Tetrahydropalmatine: 0.4kg
Polysorbate: 0.2kg
Polysiloxanes pressure sensitive adhesive: 9kg
The fatty acid Pyrusussuriensis is smooth: 28.8kg;
Get tetrahydropalmatine 0.4kg, add polysiloxanes pressure sensitive adhesive 9kg, Polysorbate 0.2kg and the smooth 28.8kg of fatty acid Pyrusussuriensis, the dissolving mixing is prepared into solution; Adopt curtain coating technology, above-mentioned solution coat on backing layer, is volatilized to solvent, protective layer on the cooling bonnet must tetrahydropalmatine transdermal patch.
Embodiment 6: tetrahydropalmatine transdermal patch
Tetrahydropalmatine: 1kg
Semen Myristicae extract: 1kg
Thermo-elasto-plasticity rubber: 5kg
Polysorbate: 28kg
Kaolin: 14kg;
Get tetrahydropalmatine 1kg, add thermo-elasto-plasticity rubber 5kg, Semen Myristicae extract 1kg, Polysorbate 28kg and Kaolin 14kg, the dissolving mixing is prepared into solution; Adopt curtain coating technology above-mentioned solution coat on backing layer, volatilize to solvent, protective layer on the cooling bonnet must tetrahydropalmatine transdermal patch.
Embodiment 7: tetrahydropalmatine transdermal patch
Tetrahydropalmatine: 1.8kg
Laurel nitrogen
Ketone: 0.5kg
Acrylate pressure sensitive adhesive: 8kg
Kieselguhr: 20kg
Glycerol: 22kg;
Get tetrahydropalmatine 1.8kg, add acrylate pressure sensitive adhesive 8kg, Laurel nitrogen
Ketone 0.5kg, kieselguhr 20kg and glycerol 22kg, the dissolving mixing is prepared into solution; Adopt curtain coating technology above-mentioned solution coat on backing layer, volatilize to solvent, protective layer on the cooling bonnet must tetrahydropalmatine transdermal patch.
Claims (4)
1. tetrahydropalmatine transdermal patch is formed by three layers, comprises backing layer, drug storehouse layer and protective layer, it is characterized in that the raw material of drug storehouse layer consists of:
Tetrahydropalmatine: 0.5kg
Laurel nitrogen
Ketone: 1kg
Acrylate pressure sensitive adhesive: 5kg;
Get tetrahydropalmatine 0.5kg, add acrylate pressure sensitive adhesive 5kg and Laurel nitrogen
Ketone 1kg, the dissolving mixing is prepared into solution; Adopt curtain coating technology, above-mentioned solution coat on backing layer, is volatilized to solvent, protective layer on the cooling bonnet must tetrahydropalmatine transdermal patch.
2. tetrahydropalmatine transdermal patch is formed by three layers, comprises backing layer, drug storehouse layer and protective layer, it is characterized in that the raw material of drug storehouse layer consists of:
Tetrahydropalmatine: 1kg
Mentholum: 0.5kg
Polyisobutylene PSA: 8kg;
Get tetrahydropalmatine 1kg, add Polyisobutylene PSA 8kg and Mentholum 0.5kg, the dissolving mixing is prepared into solution; Adopt curtain coating technology, above-mentioned solution coat on backing layer, is volatilized to solvent, protective layer on the cooling bonnet must tetrahydropalmatine transdermal patch.
3. tetrahydropalmatine transdermal patch is formed by three layers, comprises backing layer, drug storehouse layer and protective layer, it is characterized in that the raw material of drug storehouse layer consists of:
Tetrahydropalmatine: 1.5kg
Propylene glycol: 1.5kg
Polysiloxanes pressure sensitive adhesive: 7kg;
Get tetrahydropalmatine 1.5kg and add polysiloxanes pressure sensitive adhesive 7kg and propylene glycol 1.5kg, the dissolving mixing is prepared into solution; Adopt curtain coating technology, above-mentioned solution coat on backing layer, is volatilized to solvent, protective layer on the cooling bonnet must tetrahydropalmatine transdermal patch.
4. has application in the medicine of anti-inflammatory and analgesic effect as claim 1,2 or 3 arbitrary described tetrahydropalmatine transdermal patch in preparation.
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| CN102178661B (en) * | 2011-04-21 | 2012-12-05 | 浙江省医学科学院 | Levo-tetrahydropalmatine transdermal drug delivery preparation |
| CN113768905A (en) * | 2021-10-10 | 2021-12-10 | 北京中医药大学 | Corydalis total alkaloid transdermal preparation and preparation method thereof |
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