CN107019683A - A kind of crebanine transdermal patch and preparation method thereof - Google Patents
A kind of crebanine transdermal patch and preparation method thereof Download PDFInfo
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- CN107019683A CN107019683A CN201710170894.2A CN201710170894A CN107019683A CN 107019683 A CN107019683 A CN 107019683A CN 201710170894 A CN201710170894 A CN 201710170894A CN 107019683 A CN107019683 A CN 107019683A
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- crebanine
- transdermal patch
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4741—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having oxygen as a ring hetero atom, e.g. tubocuraran derivatives, noscapine, bicuculline
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7076—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising ingredients of undetermined constitution or reaction products thereof, e.g. rosin or other plant resins
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Abstract
The present invention relates to a kind of crebanine transdermal patch and preparation method thereof, stacked gradually and constituted by back sheet, pastille mucigel and protective layer, the pastille mucigel is made up of the component of following masses part：Crebanine or 0.03~0.135 part of Crebanine, 0.03~0.09 part of crosslinking agent, 0.3~0.9 part of pressure sensitive adhesive, 0.19~0.63 part of plasticizer, 0.1~0.3 part of NMF, 0.007~0.206 part of percutaneous penetrating agent.The present invention has preferable percutaneous absorbtion, than oral formulations action time persistently, good patient compliance more easy to use than ejection preparation, the characteristics of with safe and effective, easy to use, nonirritant and toxicity.Crebanine accumulation infiltration capacity in transdermal patch of the present invention is higher and the long period can maintain effective blood drug concentration, there is notable and lasting antiarrhythmic effect, and the arrhythmia cordis duration for overcoming intravenous or gastric infusion is shorter, the easy appearance phenomenon such as repeatedly.
Description
Technical field
The invention belongs to pharmaceutical technology field, and in particular to a kind of crebanine transdermal patch with antiarrhythmic effect
And preparation method thereof.
Background technology
Arrhythmia cordis system clinic common disease, the lighter's influence life and work quality, and the malignant arrhythmia such as room property heart
It is dynamic overrun, room is quivered, caused by atrial fibrillation etc. sudden cardiac death be angiocardiopathy main causes of death, the hair of China's cardiovascular disease
The raw existing rejuvenation of rate and ever-increasing trend.It can be divided into four currently used for the medicine of clinical prevention and treatment arrhythmia cordis
Class：I class：Sodium ion channel blocker, is divided into I A, I B, I C, tri- subclass.II class is beta receptor retarding agent, such as Mei Tuoluo
You.III class is potassium channel antagonistses, selectively extends multiple under the medicine of process of repolarization, their over reach potential durations and the internal membrane of heart
Soviet Union's ratio, such as Suo Tuoluoer；IV class is calcium antagonist, and such as Verapamil, most antiarrhythmic drugs have certain poison secondary
Effect.With multichannel retardance（Ikr, Iks, Ito, INa etc.）The compound antiarrhythmic drug of effect, can obviously reduce poison
Effect, becomes current study hotspot.
Crebanine（Crebanine, Cre）Belong to aporphine alkaloid, extract from Menispermaceae stephania plant Yunnan
Stephania epigaea（Stephania yunnanensis Lo.）In root tuber.Molecular formula is C20H21NO4, molecular weight is 339.38, belongs to different
Quinolines aporphine alkaloid.Sulfuric acid, hydrochloric acid, ethanol, methanol, chloroform are soluble in, is slightly soluble in petroleum ether and ether, it is insoluble
Yu Shui.Research shows that crebanine has relatively strong antiarrhythmic effect, and many animals arrhythmia model is significantly resisted
Effect, is a kind of lead compound of worth further investigation exploitation.The antiarrhythmic mouse intravenous effective dose of crebanine is
2.5~5mg/kg, LD50For 9.382mg/kg.Crebanine drug administration by injection induces barium chloride rat ventricular experiment, with NS groups
Compare, recovering the mouse number of sinus rhythm substantially increases（P ＜ 0.01=, the time needed for recovering sinus rhythm substantially shortens（P ＜
0.01=.Crebanine drug administration by injection is tested to Aconitine Induced rat ventricular, compared with NS groups, caused by improving aconitine
Rat Ventricular Tachycardia（P ＜ 0.05=, room property fibrillation（P ＜ 0.05=, heart arrest（P ＜ 0.05=consumptions.Crebanine is filled
Stomach induces barium chloride rat ventricular experiment, compared with NS groups, recovers the mouse number of sinus rhythm, can shorten recovery Dou Xingxin
The mouse number of time and maintenance sinus rhythm >=10min needed for rule, there is significant（P ＜ 0.01=.But study and send out simultaneously
Existing crebanine intravenous antiarrhythmic therapy index is small, and safe range is narrow, and dosage is improper may to cause poisoning or dead, and
Though the crebanine arrhythmia cordis through intravenous or gastric infusion is rapid-action, the duration is shorter, the easy appearance phenomenon such as repeatedly.By its
Action time can significantly be extended by being prepared into transdermal administration plaster, reduce its toxic side effect.
Transdermal delivery system (transdermal drug delivery system, TDDS) is to be pasted onto skin surface,
Drug percutaneous skin is absorbed into systemic blood circulation, treats or prevents a class preparation of epidemic disease.Percutaneous dosing has in treatment
Keep that blood concentration is stable, improve the foresight of medicine in vivo in effective range, it is to avoid drug oral through gastrointestinal circulation and
The first pass effect of liver and medicine to the excitants of intestines and stomach, can long duration of action, be easy to throw off in time and discontinue medication, improve patient
Compliance, improve the advantage such as security.
For transdermal drug delivery system, most drug is due to the physicochemical property of itself, and its percutaneous rate does not reach treatment will
Ask, and practical application constrains preparation capable of permeating skin area, thus it is exploitation transdermal drug delivery system to improve the percutaneous rate of medicine
Key, it is a kind of percutaneous rate method of conventional raising medicine to add percutaneous penetrating agent.Volatile oil is a kind of natural percutaneous
Accelerator, mechanism is good, and side effect is less, and it, which is developed, increasingly causes the concern of people, and has acted on preferably having and wave
Hair oil penetrating agent is applied in transdermal skin patches, is studied and is found that traditional medicine volatile oil is added in crebanine patch obvious promote percutaneously
Infiltration capacity effect.
The content of the invention
In view of the above-mentioned deficiencies in the prior art, it is an object of the present invention to provide a kind of anti-arrhythmic effects significantly, persistently and
Low crebanine transdermal patch of toxicity and preparation method thereof, safer medicine is provided for patients with arrhythmia.
Unless otherwise indicated, percentage of the present invention is mass percent, and number is mass parts.
The purpose of the present invention is achieved through the following technical solutions：A kind of crebanine transdermal patch, by back sheet, pastille viscose
Layer and protective layer stack gradually composition, and the pastille mucigel is made up of the component of following masses part：Crebanine or hydrochloric acid gram class
Peaceful 0.03~0.135 part, 0.03~0.09 part of crosslinking agent, 0.3~0.9 part of pressure sensitive adhesive, 0.19~0.63 part of plasticizer, NMF
0.1~0.3 part, 0.007~0.206 part of percutaneous penetrating agent.
The percutaneous penetrating agent is that the one or more in traditional medicine volatile oil are used in mixed way, or traditional medicine volatile oil and chemistry
Penetrating agent is used in mixed way, wherein, traditional medicine volatile oil refers to extract from armaticity Chinese medicine such as warm-pungent diaphoretic drug, aromatic damp-resolving drug, temperature
In volatile ingredient in medicine or drugs of causing resuscitation by administering aromatic drugs.
The preferred succinic acid of crosslinking agent.
The pressure sensitive adhesive is polyisobutene class pressure sensitive adhesive, silicone pressure sensitive adhesive, polyacrylic resin class pressure sensitive adhesive or fiber
Plain class and its derivative.
The preferred diethyl phthalate of plasticizer or triethyl citrate.
The NMF preferably glycerine or propane diols.
The content of crebanine is 1.3~4mg/cm in the transdermal patch2。
The protective layer is using the low material of surface free energy, such as through paraffin or the treated poly- second of Organosilicon Release Agent
Alkene, poly- ethylbenzene alkene etc..
The present invention also aims to provide a kind of preparation method of crebanine transdermal patch, comprise the following steps：
（1）Pastille mucigel is got the raw materials ready by the component of following mass parts：Crebanine or 0.03~0.135 part of Crebanine, crosslinking
0.03~0.09 part of agent, 0.3~0.9 part of pressure sensitive adhesive, 0.19~0.63 part of plasticizer, 0.1~0.3 part of NMF, percutaneous rush are oozed
0.007~0.206 part of agent；
（2）By step（1）Crebanine or Crebanine together with crosslinking agent, add after ethanol in proper amount, ultrasound is allowed to dissolve
Entirely, add pressure sensitive adhesive, it is to be dissolved completely after add plasticizer, NMF and percutaneous penetrating agent, uniform and bubble-free to be mixed,
It is poured into the mould for completing back sheet, is sprawled using curtain coating technology, in 40 DEG C of curing oven 1h, drying at room temperature 12h, after taking-up
Protective layer is sticked, back sheet, pastille mucigel and protective layer is stacked gradually, then cut, sealing, produce crebanine transdermal patch
Agent.
The step（2）Concentration of alcohol be 70~85v/v%.
Relative to prior art, present invention tool advantages below：
1. crebanine molecular weight is small, with fat-soluble.Being made after transdermal patch in the presence of percutaneous penetrating agent has preferable warp
Skin absorbs, than oral formulations action time persistently, good patient compliance more easy to use than ejection preparation.Back sheet is to support
Pastille mucigel, with sealing and flexibility.
2. the blood concentration relatively stablized can be maintained after crebanine percutaneous absorbtion, it can pass through and change administration area control administration
Amount.The characteristics of with safe and effective, easy to use, nonirritant and toxicity.
3. being tested by transdermal penetration, rat Internal pharmacokinetics and pharmacodynamics are proved, gram class in transdermal patch of the present invention
Peaceful accumulation infiltration capacity is higher and the long period can maintain effective blood drug concentration.Barium chloride causes rat ventricular experiment to show this hair
Bright patch has good and sufficiently stable antiarrhythmic effect, than injection with persistent is administered orally, is difficult repeatedly, and
Toxic reaction is had no, the effect of Synergy and attenuation is reached.
4. show through Pharmacokinetic experiments, crebanine transdermal patch of the invention is AUC in the pharmacokinetic parameter of rat
(0-∞) = 204.5±170.496 mg/L·h;Tmax=10.333±0.745h;Cmax=1.968±0.147mg/L.Administration
48h blood concentrations remain within 1.328 ± 0.112 mg/L afterwards, and blood concentration change meets non-compartment model in rat；
Pharmacological evaluation proves there is notable and lasting antiarrhythmic effect, when the arrhythmia cordis for overcoming intravenous or gastric infusion continues
Between shorter, the easy appearance phenomenon such as repeatedly.
Brief description of the drawings
Fig. 1 is crebanine transdermal patch accumulative infiltration capacity curve map in-vitro percutaneous to nude mice 48h；
Fig. 2 is crebanine transdermal patch delivery blood concentration-time curve.
Embodiment
Below in conjunction with drawings and examples, the present invention is described in further detail, but embodiment and accompanying drawing are not
Restriction to technical solution of the present invention.
Embodiment 1
（1）Pastille mucigel is got the raw materials ready by the component of following mass parts：0.0624 part of crebanine, 0.03 part of succinic acid, polyacrylic acid
0.625 part of resinae pressure sensitive adhesive, 0.19 part of diethyl phthalate, 0.125 part of glycerine, 0.03 part of volatile clove oil；
（2）By step（1）Crebanine or Crebanine together with crosslinking agent, after adding appropriate concentration for 70v/v% ethanol,
Ultrasound is allowed to dissolving completely, adds pressure sensitive adhesive, completely rear addition plasticizer to be dissolved, NMF and percutaneous penetrating agent are waited to mix
Uniform and bubble-free is closed, is poured into the mould for completing back sheet, is sprawled using curtain coating technology, in 40 DEG C of curing oven 1h, room
Temperature dry 12h, the polyethylene protective layer crossed through Treating Cuttings with Paraffin Wax is sticked after taking-up, make back sheet, pastille mucigel and protective layer according to
Secondary stacking, then cut, sealing, the content for making crebanine in transdermal patch is 2mg/cm2, produce crebanine transdermal patch.
Embodiment 2
（1）Pastille mucigel is got the raw materials ready by the component of following mass parts：0.03 part of Crebanine, 0.05 part of succinic acid, poly- isobutyl
0.3 part of alkenes pressure sensitive adhesive, 0.55 part of diethyl phthalate, 0.1 part of propane diols, Fructus Tsaoko volatile oil and borneol（Chemical enhancement
Agent）0.206 part；
（2）By step（1）Crebanine or Crebanine together with crosslinking agent, after adding appropriate concentration for 80v/v% ethanol,
Ultrasound is allowed to dissolving completely, adds pressure sensitive adhesive, completely rear addition plasticizer to be dissolved, NMF and percutaneous penetrating agent are waited to mix
Uniform and bubble-free is closed, is poured into the mould for completing back sheet, is sprawled using curtain coating technology, in 40 DEG C of curing oven 1h, room
Temperature dries 12h, sticks protective layer after taking-up, and protective layer uses the poly- ethylbenzene alkene treated through Organosilicon Release Agent, make back sheet,
Pastille mucigel and protective layer are stacked gradually, then cut, sealing, and the content for making crebanine in transdermal patch is 1.3mg/cm2,
Produce crebanine transdermal patch.
Embodiment 3
（1）Pastille mucigel is got the raw materials ready by the component of following mass parts：0.135 part of crebanine, 0.09 part of succinic acid, silicone are pressure-sensitive
0.007 part of 0.9 part of glue, 0.63 part of diethyl phthalate, 0.3 part of glycerine, Herba Menthae Haplocalycis volatile oil and volatile clove oil；
（2）By step（1）Crebanine or Crebanine together with crosslinking agent, after adding appropriate concentration for 85v/v% ethanol,
Ultrasound is allowed to dissolving completely, adds pressure sensitive adhesive, completely rear addition plasticizer to be dissolved, NMF and percutaneous penetrating agent are waited to mix
Uniform and bubble-free is closed, is poured into the mould for completing back sheet, is sprawled using curtain coating technology, in 40 DEG C of curing oven 1h, room
Temperature dries 12h, sticks protective layer after taking-up, protective layer using the low material of surface free energy, make back sheet, pastille mucigel and
Protective layer is stacked gradually, then cut, sealing, and the content for making crebanine in transdermal patch is 4mg/cm2, produce crebanine transdermal
Patch.
Embodiment 4
Be the same as Example 2, only replaces with Chinese angelica volatile oil by Fructus Tsaoko volatile oil, and diethyl phthalate is replaced with into citric acid three
Ethyl ester.
Embodiment 5
Be the same as Example 3, only replaces with Chinese anise volatile oil by Herba Menthae Haplocalycis volatile oil, and silicone pressure sensitive adhesive is replaced with into cellulose family
Pressure sensitive adhesive.
To the Ligustrazine hydrochloride Effect study of crebanine transdermal patch：
Preparation technology as described in embodiment 1, is made crebanine transdermal patch.
Positive controls：Be the same as Example 1, is only changed to azone by volatile clove oil.
Negative control group：Be the same as Example 1, only removes volatile clove oil, that is, is not added with percutaneous penetrating agent.
To remove the nude mice skin of subcutaneous layer of fat, using TK-12B type diffusion instruments, 37 ± 0.5 DEG C of bath temperature, stirring
Speed 250rmin-1, transdermal area 2.92cm2, reception medium is physiological saline.Standby nude mice skin is taken, is thawed.By skin
Skin cuticula is fixed on the receiving chamber equipped with rotor upwards, takes the crebanine patch prepared to be affixed on keratoderma side,
Back sheet upwards, is fixed with iron clamp, physiological saline will be filled in receiving chamber, cover sealed membrane.Respectively at 1,2,4,6,8,10,
12nd, 24,36, the separately sampled 8ml of 48h are in 10ml volumetric flasks and are settled to graduation mark, in time supplement equivalent equality of temperature fresh medium.
Sample determines crebanine content, such as Fig. 1 and table 1 through HPLC methods：
The crebanine patch 48h Ligustrazine hydrochloride exercising results of table 1
Note：* is compared with negative group：P<0.01
By Fig. 1 and table 1, compared with negative control group, embodiment 1 has conspicuousness（P<0.01）, anatonosis coefficient is 2.15,
Numerically it is better than positive controls, therefore, adding volatile clove oil as percutaneous penetrating agent has the preferably rush effect of oozing.
Influence research of the crebanine transdermal patch to the arrhythmia cordis of rat：
Model group：The crebanine transdermal patch of bare substrate patch, i.e. be the same as Example 1 without crebanine is given, only removal gram
The peaceful component of class；
Positive group：Verapamil gavage group, dosage is 30mg/kg；
Blank control group：Medical adhesive tape gives constraint processing after belly depilation；
Crebanine（It is low）；The gained crebanine transdermal patch of embodiment 1 is given, dosage is 79mg/kg；
Crebanine（In）；The gained crebanine transdermal patch of embodiment 1 is given, dosage is 158mg/kg；
Crebanine（It is high）；The gained crebanine transdermal patch of embodiment 1 is given, dosage is 316mg/kg.
Take SD rats, SPF grades, body weight 250-280g, male and female half and half.Every group 10, it is divided into 6 groups.Will in experiment the previous day
Rat abdomen hair removes clean (30cm2), it is stand-by that water is can't help in fasting.After positive group administration 30min, after other each groups administration 10h
10% chloraldurate 300mg/kg intraperitoneal injection of anesthesia, lies on the back and is fixed on mouse plate, connects BL-420E biological functional systems,
Sublingual vein after normal II lead electrocardiogram, 2min is recorded after stable 5min and injects 0.4%BaCl24mg/kg, the observed and recorded heart
Restrain not normal electrocardiogram and the electrocardiogram recovered.It the results are shown in Table 2：
Table 2
Note：Examine, compared with model group by t：*p<0.01,**p<0.005,*** p<0.001
From result above：Compared with model group, 20min can recover sinus rhythm after the low middle high dose group administration of crebanine
Mouse number be higher than model group（P ＜ 0.001）；Compared with model group, crebanine（It is low）It is less than 10min after group administration with regard to sinus can be recovered
Property the rhythm of the heart mouse number be higher than model group（P<0.005）, crebanine（In）Group and crebanine（It is high）It is less than 10min after group administration with regard to energy
Recover the mouse number of sinus rhythm apparently higher than model group（P ＜ 0.001）；Compared with model group, the low middle high dose group of crebanine is extensive
Time needed for multiple sinus rhythm substantially shortens（P<0.01）；Crebanine（It is low）Group, which is recovered to hold time after sinus rhythm, to be more than
20min mouse number is apparently higher than model group（P ＜ 0.001）.
In barium chloride causes rat ventricular experiment, crebanine patch delivery is compared with crebanine drug administration by injection, administration
Required recovery time afterwards（P<0.01）Substantially shorten, the mouse number for recovering to hold time more than 20min after sinus rhythm has substantially
Improve（p<0.01）.
Crebanine transdermal patch is studied rat Internal pharmacokinetics：
Take rat 18, body weight（250~300）G, male and female half and half, fasting 24h can't help water.It is randomly divided into 3 groups.
Negative group：Be the same as Example 1, only removes volatile clove oil, that is, is not added with percutaneous penetrating agent.
Positive group：Be the same as Example 1, the volatile clove oil for being only 3wt% by content is changed to the azone that content is 1wt%.
Experimental group：Be the same as Example 1.
Slough within one day rat abdomen hair before administration respectively, cleaned with physiological saline, raise stand-by, depilation area 8cm ×
8cm.Each group 0.5h, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 30h, 36h, 48h, 60h, 72h metaplexus veins upon administration
Take a blood sample in liquaemin anticoagulant tube, take upper plasma, blood plasma to be analyzed after being handled through solvent extraction using HPLC methods sample introduction after centrifugation,
Pharmacokinetic Results DAS3.0 softwares.As a result Fig. 2, table 3 are seen：
The crebanine patch rat pharmacokinetic parameters of table 3
| Parameter | Unit | Negative group | Positive group | Experimental group |
| AUC(0-t) | kg/L*h | 54.399±19.697 | 73.232±23.221 | 75.76±9.559 |
| AUC(0-∞) | kg/L*h | 117.653±45.403 | 152.099±80.078 | 204.5±170.496 |
| MRT(0-t) | h | 33.351±1.750 | 33.214±1.683 | 31.741±1.553 |
| MRT(0-∞) | h | 122.100±74.640 | 120.76±114.646 | 187.428243.590 |
| t1/2 | h | 81.267±52.669 | 78.728±81.415 | 131.989±173.539 |
| Tmax | h | 14.000±10.066 | 9.333±0.943 | 10.333±0.745 |
| Cmax | mg/L | 1.299±0.647 | 1.801±0.710 | 1.968±0.147 |
As a result show, crebanine transdermal patch feminine gender group AUC (0- ∞)=117.65345.403kg/Lh, positive group AUC (0-
∞)=152.099 ± 80.078kg/Lh, experimental group AUC (0- ∞)=204.5 ± 170.496kg/Lh, illustrates in experimental group
The degree of absorption of crebanine is much larger than negative group.
Crebanine transdermal patch feminine gender group MRT (0- ∞)=122.100 ± 74.640h, positive group MRT (0- ∞)=
120.762 ± 114.646h, experimental group MRT (0- ∞)=187.428 ± 243.590h, illustrates experimental group stopping in rat body
The time is stayed to be more than negative group.
Crebanine transdermal patch feminine gender group t1/2=81.267 ± 52.669h, Tmax=14.000 ± 10.066h, Cmax=
1.299±0.647mg/L；Positive group t1/2=78.728 ± 81.415h, Tmax=9.333 ± 0.943h, Cmax=1.801±
0.710 mg/L；Experimental group t1/2=131.989 ± 173.539h, Tmax=10.333 ± 0.745h, Cmax=1.968±
0.147mg/L；Quickly entered after illustrating experimental group administration in rat body, eliminate slow, and blood concentration highest.
Claims (10)
1. a kind of crebanine transdermal patch, is stacked gradually and is constituted by back sheet, pastille mucigel and protective layer, it is characterised in that：
The pastille mucigel is made up of the component of following masses part：Crebanine or 0.03~0.135 part of Crebanine, crosslinking agent
0.03~0.09 part, 0.3~0.9 part of pressure sensitive adhesive, 0.19~0.63 part of plasticizer, 0.1~0.3 part of NMF, percutaneous penetrating agent
0.007~0.206 part.
2. crebanine transdermal patch according to claim 1, it is characterised in that：The percutaneous penetrating agent is traditional medicine volatile oil
In one or more be used in mixed way, or traditional medicine volatile oil is used in mixed way with chemical enhancers, wherein, traditional medicine volatile oil refers to
Extract from the volatile ingredient in armaticity Chinese medicine.
3. crebanine transdermal patch according to claim 1, it is characterised in that：The crosslinking agent is succinic acid.
4. crebanine transdermal patch according to claim 1, it is characterised in that：The pressure sensitive adhesive is that polyisobutene class is pressure-sensitive
Glue, silicone pressure sensitive adhesive, polyacrylic resin class pressure sensitive adhesive or cellulose family and its derivative.
5. crebanine transdermal patch according to claim 1, it is characterised in that：The plasticizer is phthalic acid diethyl
Ester or triethyl citrate.
6. crebanine transdermal patch according to claim 1, it is characterised in that：The NMF is glycerine or propane diols.
7. crebanine transdermal patch according to claim 1, it is characterised in that：The content of crebanine in the transdermal patch
For 1.3~4mg/cm2。
8. crebanine transdermal patch according to claim 1, it is characterised in that：The protective layer is used through paraffin or organic
The treated polyethylene of silicon interleaving agent, poly- ethylbenzene alkene.
9. the preparation method of any crebanine transdermal patch in claim 1 to 8, it is characterised in that comprise the following steps：
（1）Pastille mucigel is got the raw materials ready by the component of following mass parts：Crebanine or 0.03~0.135 part of Crebanine, crosslinking
0.03~0.09 part of agent, 0.3~0.9 part of pressure sensitive adhesive, 0.19~0.63 part of plasticizer, 0.1~0.3 part of NMF, percutaneous rush are oozed
0.007~0.206 part of agent；
（2）By step（1）Crebanine or Crebanine together with crosslinking agent, add after ethanol in proper amount, ultrasound is allowed to dissolve
Entirely, add pressure sensitive adhesive, it is to be dissolved completely after add plasticizer, NMF and percutaneous penetrating agent, uniform and bubble-free to be mixed,
It is poured into the mould for completing back sheet, is sprawled using curtain coating technology, in 40 DEG C of curing oven 1h, drying at room temperature 12h, after taking-up
Protective layer is sticked, back sheet, pastille mucigel and protective layer is stacked gradually, then cut, sealing, produce crebanine transdermal patch
Agent.
10. preparation method according to claim 9, it is characterised in that：The step（2）Concentration of alcohol be 70~85v/
v%。
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| CN201710170894.2A CN107019683B (en) | 2017-03-21 | 2017-03-21 | A transdermal patch containing Spanish extract and its preparation method |
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| CN107019683B CN107019683B (en) | 2020-04-17 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022142083A1 (en) * | 2020-12-28 | 2022-07-07 | 广东红珊瑚药业有限公司 | Pressure-sensitive adhesive matrix and patch |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US20090318488A1 (en) * | 2008-06-20 | 2009-12-24 | Standard Chem. & Pharm. Co., Ltd. | Pharmaceutically acceprable salts of aporphine compounds of carboxyl group-containing agents and methods for preparing the same |
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| CN105343884A (en) * | 2015-10-20 | 2016-02-24 | 华南农业大学 | Preparation method and application of galvanic-response transdermal drug delivery system |
| CN106466317A (en) * | 2016-08-30 | 2017-03-01 | 云南中医学院 | Cepharanthine and its pharmaceutically acceptable salt and solvate are as the application preparing antiarrhythmic drug |
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| WO2022142083A1 (en) * | 2020-12-28 | 2022-07-07 | 广东红珊瑚药业有限公司 | Pressure-sensitive adhesive matrix and patch |
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| Publication number | Publication date |
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| CN107019683B (en) | 2020-04-17 |
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