CN101199495A - Patch of abstention containing cola stationary medicament and preparing method thereof - Google Patents
Patch of abstention containing cola stationary medicament and preparing method thereof Download PDFInfo
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- CN101199495A CN101199495A CNA2006101302979A CN200610130297A CN101199495A CN 101199495 A CN101199495 A CN 101199495A CN A2006101302979 A CNA2006101302979 A CN A2006101302979A CN 200610130297 A CN200610130297 A CN 200610130297A CN 101199495 A CN101199495 A CN 101199495A
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Abstract
The invention discloses a detoxification plaster with clonidine and the related preparation method used for curing opioid and tobacco-dependentance. The detoxification plaster is structurally composed of a protective layer, an adhesive layer, a control release membrane layer, a medicine storehouse layer and a back lining layer. The ingredients of the preparation are that: the medicine storehouse layer contains 10 to 40 percent of clonidine and 0 to 20 percent of transdermal enhancer and the rest are soluble or non-soluble substrates; the adhesive layer contains 0 to 30 percent of clonidine and 2 to 20 percent of transdermal enhancer and the rest is pressure-sensitive adhesive; the back lining layer is a PET membrane or a non-woven fabric; the protective layer is a PET film processed with antisticking treatment; the control release membrane is an EVA polymer membrane. The area of each plaster is 1-5square centimeters; each plaster contains 1mg to 5mg of clonidine. The invention is not addictive but fast in effect, high in cure rate and safe and convenient. The external release of the invention reaches zero-degree rate process.
Description
Technical field
The present invention relates to pharmaceutical preparation for the treatment of opium, Nicotiana tabacum L. dependence and preparation method thereof.It specifically is a kind of drug rehabilitation patch that contains the clonidine medicine and preparation method thereof.
Background technology
Cola is decided to be the early stage synthetic imidazolidine derivatives sixties, belongs to α
2The adrenoceptor excitomotor, its tablet is widely used in clinical as antihypertensive.The eighties, the effects such as drug rehabilitation, analgesia and calmness of clonidine caused that people greatly pay close attention to.Discover that opiomaniac's nucleus ceruleus adrenergic neuron granting impulsion during giving up speeds up, the norepinephrine that each impulsion causes discharges and increases, and norepinephrine is excessive also to be increased.Laughable surely by activating the α of nucleus ceruleus synapse cephacoria
2Receptor, feedback suppress norepinephrine and discharge, thereby suppress highly active locus coeruleus adrenal gland serotonergic neuron, make protracted opioid abstinence syndrome be able to safe and effective treatment, and do not have the sense of euphoria.
But general oral medication exists the blood drug level shakiness, and that takes medicine is individual different, same dosage and effect difference, and some drugs has shortcomings such as easy addiction simultaneously.
Summary of the invention
The objective of the invention is to, overcome opioid drug detoxification therapy generation sense of euphoria in the prior art, easily addiction, can not in long-time, make medicine enter the intravital shortcoming of people with constant speed, and provide a kind of long-acting, through skin absorbs, be difficult for addiction, effect rapidly, cure the success rate height, portably use the drug rehabilitation patch that contains the clonidine medicine easily.
Another object of the present invention provides a kind of preparation method of this patch.
Purpose of the present invention is achieved through the following technical solutions:
The drug rehabilitation patch that contains the clonidine medicine of the present invention, by protective layer, adhesive-layer, controlled release rete, drug-reservoir layer and backing layer altogether five-layer structure forms, its effective ingredient is clonidine or itself and the salt of sour formation, example hydrochloric acid clonidine, sulphuric acid clonidine etc.Consisting of of said preparation: in the drug-reservoir layer: contain clonidine 10%～40%, penetration enhancer 0%～20%, other are water solublity or water-insoluble substrate.In the adhesive-layer: contain clonidine 0%～30%, penetration enhancer 2%～20%, other are pressure sensitive adhesive.
Its backing layer is PET film or non-woven fabrics, and protective layer is the PET film after the release treatment, and release-controlled film is the EVA polymeric membrane, and drug-reservoir layer and adhesive-layer are made of clonidine, pressure sensitive adhesive and penetration enhancer etc.
Described pressure sensitive adhesive is polyacrylate, polyisobutylene class, silicone rubber kinds etc.; Penetration enhancer is thing or its two or more mixture such as azone class, propylene glycol, oleic acid.
This patch can be done the different shape of the combination of rectangularity, square, circle, ellipse, triangle or two or more figures; The preparation technology of patch is spreading formation process or extrusion forming process; Patch is affixed on the body skin surface and uses.
Good effect of the present invention
Percutaneous drug administration preparation is compared with conventional medication, and its unique advantage is arranged.1) single administration can make medicine enter in the human body with constant speed in long-time, is similar to long intravenous drip; 2) avoid the first pass effect of liver and the interference and the Degradation of gastrointestinal factors, reduced the individual variation of medication; 3) can keep constant effective blood drug level, the blood drug level peak valley phenomenon of having avoided other medication to produce; 4) easy to use, accepted by the patient easily.The seventies clonidine that abroad begins one's study is used for opium and gives up.The indication that clonidine is used for the opium drug rehabilitation proves that through vast amount of clinical it does not have the easy addiction of opioid drug detoxification therapy, produces some shortcomings of sense of euphoria, and effect is cured the success rate height rapidly.After particularly making percutaneous drug administration preparation, made things convenient for the patient, helped in the drug rehabilitation patient, promoting and using.
Clonidine percutaneous drug administration preparation of the present invention, its release in vitro process is a zero order process, transdermal test in vitro speed is near constant speed.Process stabilizing, favorable reproducibility, adhibit quality is good.
Fig. 1 is the cumulative in vitro release profiles;
Fig. 2 is a cumulative in vitro transdermal curve.
The specific embodiment
In an embodiment, used clonidine, as the raw material of excipient, penetration enhancer is commercially available pharmaceutical grade; Used ratio is weight percentage.Preparation method is an industry common process condition.
Embodiment 1:
Under the cleaning condition that meets the pharmacy requirement, according to the form below prescription, technology are prepared.
Embodiment 1 prescription is formed
Wherein backing layer is the PET film, and protective layer is the PET film after the release treatment, and release-controlled film is the EVA polymeric membrane, and drug-reservoir layer and adhesive-layer are made of clonidine, pressure sensitive adhesive and penetration enhancer etc.The gross area of patch is 2.5cm
2, every contains clonidine 2.5mg.Be shaped as the rectangle of 2.5cm * 1.0cm.
Preparation technology: mainly comprise: slurrying, coating, compound, cutting, exterior and interior packing etc.
(1) technological process is as follows: product
(2) the pastille glue preparing process of drug-reservoir layer and adhesive-layer
Dissolve polyacrylate with cyclohexane extraction before joining glue, make solid content reach 30%.Take by weighing the clonidine of azone and mistake 200 mesh sieves respectively by the prescription of drug-reservoir layer and adhesive-layer, progressively be added in the cyclohexane solution of polyacrylate, be fully mixed to evenly, promptly obtain the pressure-sensitive rubber cement of pastille of drug-reservoir layer and adhesive-layer separately.
(3) preparation technology of paster
The drug-reservoir layer that is mixed is uniformly coated on the PET backing film, and the wet glue thickness of coating is controlled according to 220um, and is after the drying, compound good standby with the EVA release-controlled film; The adhesive-layer pressure sensitive adhesive is uniformly coated on the PET protecting film with method, controlled release face and mucilage glue surface is compound in opposite directions after the drying with top coated drug storehouse layer, obtain the medicine plaster that contains of five-layer structure.
Be that Declot is decided control release paster after size is cut, cut in accordance with regulations.Carrying out release in vitro and transdermal measures.
Embodiment 2:
Under the cleaning condition that meets the pharmacy requirement, according to the form below prescription, technology are prepared.
Embodiment 2 prescriptions are formed
Preparation technology such as embodiment 1.
The using method of this patch:
Be affixed on arm, front or other skin part uses easily, every subsides can be pasted continuously with 5 days.Using dosage and therapeutic scheme: should adjust according to the side effect weight after patient age, body weight, health status, drug abuse history, the withdrawal symptom order of severity and the medication, can throw off or increase the quantity of patch at any time.Every transit dose that pastes every day is pressed 200ug and is calculated, and the highest transit dose was advisable with 14～17ug/kg/ day during drug rehabilitation.
Quitting drug abuse with 50～60kg people is example: subsides simultaneously in the 1st～4 day are pasted with 4, and beginning in the 5th day is used 3 instead and pasted new patch, throw off 1 subsides on the 7th day, throw off 1 subsides again on the 9th day, keep 1 and paste up to the 11st day.Only paste with 1 subsides after the 11st day if desired, finish up to treatment, the general treatment cycle is 10 days.The doctor can adjust according to patient.
Be used for smoking cessation, general paste to paste with 1 get final product, it is new to use 1 subsides instead in per five days.
Use and note: the patient who reaches medicaments insensitive on the low side should note observing to basic blood pressure, and the treatment initial stage should be measured blood pressure every day; Should lie in bed, and avoid aggravating activities in preceding 4 days of treatment.
The medicine release test
1. release in vitro degree assay method:
Release conditions: getting 6 of this product, carry out according to the Pharmacopoeia of the People's Republic of China 2005 editions (appendix XD, the three therapeutic methods of traditional Chinese medicine), is release medium with 500ml water, 32 ± 0.5 ℃ of temperature, rotating speed 100rpm.Spot sampling is measured, and 5ml takes a sample at every turn.
The assay condition: the HPLC method is measured.
Chromatographic column: octadecyl silane post, column length 25cm.Mobile phase is dehydrated alcohol-0.02mol/l hydrochloric acid solution-triethanolamine (80: 20: 0.15), and flow velocity 0.5ml/min detects wavelength 254nm.Carry out quantitatively with external standard method.
The external accumulative total release profiles of said preparation as shown in Figure 1.
2. transdermal test in vitro assay method:
Transdermal release condition determination: measure with improved Franz diffusion cell, see through skin with the conduct of nude mice intact skin, with water for accepting medium, 32 ± 0.5 ℃ of temperature, rotating speed 100rpm, patch are affixed on the colloid aspect of skin, the dermis of skin face with accept medium-tight and contact, spot sampling is measured, and 1ml takes a sample at every turn.
The assay condition is measured with external release.
Cumulative in vitro transdermal curve as shown in Figure 2.
Can find out that by Fig. 1, Fig. 2 the phase relation number average of its rectilinear regression illustrates that more than 0.99 release in vitro and transdermal test in vitro process all meet zero order process, sustained release is good.We have carried out the mensuration of transdermal test in vitro speed again respectively with rat, mouse skin, to with a collection of patch, the correlation coefficient of its percutaneous rate and rectilinear regression is all very approaching, it is less that the patch that this type be described is influenced by individual variation, its transdermal test in vitro speed is subjected to the control of preparation release good, has reached the purpose of design of preparation controlled release.
Claims (6)
1. drug rehabilitation patch that contains the clonidine medicine; it is made up of protective layer, adhesive-layer, controlled release rete, drug-reservoir layer and backing layer five-layer structure; it is characterized in that: its effective ingredient is the salt that clonidine or itself and acid form, example hydrochloric acid clonidine, sulphuric acid clonidine etc.Consisting of of said preparation: in the drug-reservoir layer: contain clonidine 10%～40%, penetration enhancer 0%～20%, other are water solublity or water-insoluble substrate.In the adhesive-layer: contain clonidine 0%～30%, penetration enhancer 2%～20%, other are pressure sensitive adhesive.
2. the drug rehabilitation patch that contains the clonidine medicine according to claim 1 is characterized in that: the consisting of of said preparation: in the drug-reservoir layer: contain clonidine 35%, and penetration enhancer 10%, other are water solublity or water-insoluble substrate.In the adhesive-layer: contain clonidine 10%, penetration enhancer 5%, other are pressure sensitive adhesive.
3. the drug rehabilitation patch that contains the clonidine medicine according to claim 1 is characterized in that: pressure-sensitive adhesive material is polyacrylate resinoid, polyisobutylene class, silicone rubber kinds.
4. the drug rehabilitation patch that contains the clonidine medicine according to claim 1 is characterized in that penetration enhancer is thing or its two or more mixture such as azone class, propylene glycol, oleic acid.
5. the drug rehabilitation patch that contains the clonidine medicine according to claim 1 is characterized in that: wherein backing layer is PET film or non-woven fabrics; Protective layer is the PET film after the release treatment; Release-controlled film is the EVA polymeric membrane.
6. a preparation method that contains the drug rehabilitation patch of clonidine medicine is characterized in that, the following step of preparation technology's process of patch:
A. the pastille glue preparing process of drug storehouse layer and adhesive-layer:
1. with cyclohexane extraction the content of pressure sensitive adhesive is adjusted to 20～40%.Clonidine is crossed 200 purposes sieve.
2. the prescription by drug-reservoir layer and adhesive-layer takes by weighing penetration enhancer respectively, has crossed the clonidine of sieve, progressively is added in the pressure sensitive adhesive, and abundant mix homogeneously promptly obtains the pastille rubber cement of drug-reservoir layer and adhesive-layer separately.
B. the preparation technology of paster
The drug-reservoir layer rubber cement that 1. will be mixed is uniformly coated on the backing film, and oven dry is compounded on the drug-reservoir layer release-controlled film standby then.
2.. the adhesive layer rubber cement is uniformly coated on the protecting film, oven dry then, with step 1. in the release-controlled film not compound compound with mucilage glue surface, five-layer structure contain medicine plaster.
3.. cut, screening, quality inspection, packing.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006101302979A CN101199495A (en) | 2006-12-15 | 2006-12-15 | Patch of abstention containing cola stationary medicament and preparing method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006101302979A CN101199495A (en) | 2006-12-15 | 2006-12-15 | Patch of abstention containing cola stationary medicament and preparing method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101199495A true CN101199495A (en) | 2008-06-18 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2006101302979A Pending CN101199495A (en) | 2006-12-15 | 2006-12-15 | Patch of abstention containing cola stationary medicament and preparing method thereof |
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| CN (1) | CN101199495A (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103893155A (en) * | 2012-12-26 | 2014-07-02 | 江苏康倍得药业有限公司 | Drug transdermal patch |
| CN103933018A (en) * | 2013-01-18 | 2014-07-23 | 江苏康倍得药业有限公司 | Transdermal drug delivery system |
| CN105311002A (en) * | 2015-10-22 | 2016-02-10 | 安徽一灵药业有限公司 | Preparation method of clonidine controlled-release patch |
| CN106806893A (en) * | 2015-11-30 | 2017-06-09 | 北京泰德制药股份有限公司 | Skin external used patch containing calcium-sensing receptor activator |
| CN105362255B (en) * | 2015-12-09 | 2018-10-23 | 哈尔滨瀚钧药业有限公司 | A kind of Clonidine Patch and preparation method thereof |
| CN111035627A (en) * | 2020-01-09 | 2020-04-21 | 范小玲 | Clonidine transdermal patch and preparation method thereof |
-
2006
- 2006-12-15 CN CNA2006101302979A patent/CN101199495A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103893155A (en) * | 2012-12-26 | 2014-07-02 | 江苏康倍得药业有限公司 | Drug transdermal patch |
| CN103893155B (en) * | 2012-12-26 | 2018-11-06 | 江苏康倍得药业股份有限公司 | A kind of drug transdermal patch |
| CN103933018A (en) * | 2013-01-18 | 2014-07-23 | 江苏康倍得药业有限公司 | Transdermal drug delivery system |
| CN105311002A (en) * | 2015-10-22 | 2016-02-10 | 安徽一灵药业有限公司 | Preparation method of clonidine controlled-release patch |
| CN106806893A (en) * | 2015-11-30 | 2017-06-09 | 北京泰德制药股份有限公司 | Skin external used patch containing calcium-sensing receptor activator |
| CN105362255B (en) * | 2015-12-09 | 2018-10-23 | 哈尔滨瀚钧药业有限公司 | A kind of Clonidine Patch and preparation method thereof |
| CN111035627A (en) * | 2020-01-09 | 2020-04-21 | 范小玲 | Clonidine transdermal patch and preparation method thereof |
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| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20080618 |