CN101623280A - Compound sustained release preparation for easing pain and preparation method thereof - Google Patents
Compound sustained release preparation for easing pain and preparation method thereof Download PDFInfo
- Publication number
- CN101623280A CN101623280A CN200810116470A CN200810116470A CN101623280A CN 101623280 A CN101623280 A CN 101623280A CN 200810116470 A CN200810116470 A CN 200810116470A CN 200810116470 A CN200810116470 A CN 200810116470A CN 101623280 A CN101623280 A CN 101623280A
- Authority
- CN
- China
- Prior art keywords
- preparation
- oxycodone
- slow
- dexketoprofen
- arginine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to a compound sustained release preparation for easing pain and a preparation method thereof. The sustained release preparation consists of a sustained release part and a quick release part, wherein the sustained release part takes arginine dexketoprofen as an active component, and the quick release part takes oxycodone and diphenhydramine as active components. The sustained release preparation can be tablets, granules, sustained release pellets and sustained release capsules. Each preparation unit contains 1.25 to 20 milligrams preferably 2.5 to 10 milligrams of the active component of the oxycodone , 5 to 100 milligrams preferably 10 to 50 milligrams of the active component of the arginine dexketoprofen, and 5 to 80 milligrams preferably 10 to 40 milligrams of the active component of the diphenhydramine, wherein the preferred compound dosages of the three active components comprise 25 milligrams of the arginine dexketoprofen, 5 milligrams of the oxycodone and 25 milligrams of the diphenhydramine.
Description
Technical field
The present invention relates to a kind of analgesic compound slow release preparation and preparation method thereof, belong to medical technical field.
Background technology
Pain is a kind of offending sensation and emotional experience that is caused by tissue injury or disease, is called chronic pain if pain continued more than 3-6 month, and chronic pain often changes even dysfunction with psychology or spirit.According to statistics, about 30% adult suffers from pain, among per 3 outpatients, just has 2 to be patient with various antalgesics or symptom, and China has 100,000,000 above pain patients at least.Nonsteroidal antipyretic analgesic (NSAID) and opioid drug are the most frequently used medicines of treatment pain, it mainly is by suppressing to organize the medium ring oxidase active for the nonsteroidal antipyretic analgesic, disturb arachidonic acid metabolic, stop its synthesis of prostaglandins (PG), the performance antipyretic effect.The nonsteroidal antiinflammatory drug low dose can produce analgesic effect, and heavy dose then produces antiinflammatory action.Opioid drug has excitement and inhibitory action to the central nervous system, and cerebral cortex is mainly inhibitory action, and respiratory center is had powerful selective inhibitory, has pain relieving preferably and antitussive effect.Opioid drug treatment pain relieving definite effect, effect stability.
Summary of the invention
The present invention relates to a kind of analgesic compound slow release preparation and preparation method thereof, this slow releasing preparation is made up of slow-released part and immediate release section.Wherein slow-released part is an active component with the arginine dexketoprofen, and immediate release section is an active component with oxycodone, diphenhydramine.Slow releasing preparation of the present invention can be tablet, granule, slow-release pill, slow releasing capsule.The amount that each preparation unit contains the active component oxycodone is 1.25～20mg, is preferably 2.5～10mg, and the amount that contains active component arginine dexketoprofen is 5～100mg.Be preferably 10～50mg.The amount that contains the active component diphenhydramine is 5～80mg.Be preferably 10～40mg, the preferred compound dose of three is arginine dexketoprofen 25mg, oxycodone 5mg, diphenhydramine 25mg.
Arginine dexketoprofen slow-released part of the present invention, the stripping in the 1st hour of arginine dexketoprofen discharges the 25～40%, 4th hour and discharges release in the 40～75%, 8th hour more than 75% in the dissolution in vitro test.Described oxycodone immediate release section, in dissolution in vitro test after 40 minutes stripping greater than 65%.
Slow releasing preparation of the present invention comprises the delivery system that the coated formula of arginine dexketoprofen slow release is formed by a sustained-release matrix or, and the delivery system that can make the rapid stripping of oxycodone.Sustained-release matrix comprises hydroxypropyl methylcellulose HPMC-4M, HPMC-15M, HPMC-100M, one or more in polyvinylpyrrolidone, ethyl cellulose, hydroxyethyl-cellulose, hexadecanol, octadecanol, Rikemal B 200, stearic acid, glyceryl monostearate, Brazil wax, sodium carboxymethyl cellulose, polyvinyl alcohol, sodium alginate, the chitin.Rapidly the delivery system of stripping system is prepared into immediate-release granules, piller etc. separately with oxycodone, or it is suspended in carries out coating in the coating system, generates immediate release layer.Wherein the main slow releasing agent in the coated formula comprises one or more in ethyl cellulose and aqueous dispersion thereof, stearic acid, cellulose acetate, the crylic acid resin (as RS100, RL100, RS 30D, RL30D, NE30D).
The specific embodiment
Be described further by the preparation method of following examples, but be not limited in this slow releasing preparation of the present invention.
Embodiment 1 double-layer sustained release tablets
Prescription:
Preparation method:
The arginine dexketoprofen is crossed 100 mesh sieves, and HPMC-15M, lactose are crossed 60 mesh sieves, and with 80% alcoholic solution system soft material, 16 mesh sieves are granulated behind the supplementary material mix homogeneously, 40 ℃ of dryings, and 16 mesh sieve granulate add the Pulvis Talci mix homogeneously, and are standby; With oxycodone, diphenhydramine and microcrystalline Cellulose, lactose mix homogeneously,, be prepared into the immediate-release granules of big or small basically identical with method in addition with purified water system soft material.Successively take by weighing above two kinds of granules in proportion, make double-layer sustained release tablets.
Embodiment 2 film-coat slow releasing tablet
Arginine dexketoprofen label prescription:
The coating prescription that contains oxycodone:
Preparation method:
The arginine dexketoprofen is crossed 100 mesh sieves, and microcrystalline Cellulose, lactose are crossed 60 mesh sieves, and water is made soft material in right amount behind the supplementary material mix homogeneously, and 20 mesh sieves are granulated, drying, and 18 mesh sieve granulate, tabletting, standby; Ethyl cellulose, acrylic resin RS100 are placed ethanol solution, and fully stirring makes it to dissolve fully, adds oxycodone, diphenhydramine, Pulvis Talci, tween 80 continuation stirring, obtains uniform suspension, and is standby; Open the coating pelletizing machine, regulate 30 ℃ of wind pressure 0.5bar, temperature, adjust rotary speed 150～200rpm, start peristaltic pump, spray into pastille suspendible coating solution, after coating finished, discharging got final product.
Embodiment 3 matrix sustained release tablets
Matrix tablet label prescription:
Rapid release coatings prescription:
Preparation method:
The arginine dexketoprofen is crossed 100 mesh sieves, and HPMC-4M, HPMC-15M cross 60 mesh sieves, and with 90% alcoholic solution system soft material, 16 mesh sieves are granulated, drying, 16 mesh sieve granulate, tabletting; Other gets oxycodone, diphenhydramine joins in Eudragit E 55 solution that prepare, and is standby; Regulate 30～50 ℃ of wind pressure 0.4～0.6bar, temperature, adjust rotary speed 150～200rpm, start peristaltic pump, spray into the suspendible coating solution of compositions such as containing Eudragit E 55, oxycodone, after coating finished, discharging got final product.
Embodiment 4 sustained-release micro-pill capsules
Prescription:
Preparation method:
The arginine dexketoprofen is crossed 100 mesh sieves, join stir in the fused octadecanol after, continue to add PVP as the porogen mix homogeneously, put condensation back porphyrize admittedly, with 70g microcrystalline Cellulose mix homogeneously, with the 0.5%HPMC aqueous solution as binding agent system soft material, 12～20 order apertures are extruded into the bar, the bottom rotary speed that are about 3～5cm and are adjusted to 600～1200rpm, round as a ball about 5 minutes, get final product, drying, standby; Other gets oxycodone, diphenhydramine and surplus microcrystalline Cellulose according to the equivalent principle mix homogeneously that sieves that progressively increases, and it is an amount of to add purified water, and the same method is prepared into micropill, and drying is standby.Proportionally, fill in the conventional capsule shell, promptly get above-mentioned slow releasing capsule behind two kinds of micropill mix homogeneously.
Embodiment 5 sustained release coating pellet capsules
Prescription:
Preparation method:
The arginine dexketoprofen is crossed 100 mesh sieves, microcrystalline Cellulose is crossed 60 mesh sieves, microcrystalline Cellulose mix homogeneously with arginine dexketoprofen and doubling dose, add the wet soft material of an amount of system of purified water, 14～20 order apertures are extruded into the bar, the bottom rotary speed that are about 3～5cm and are adjusted to 800～1000rpm, round as a ball about 3～5 minutes, get final product, drying, standby; Other gets oxycodone, diphenhydramine and the surplus microcrystalline Cellulose mix homogeneously that sieves, and it is an amount of to add purified water, and the same method is prepared into micropill, and drying is standby.Other gets the recipe quantity Aquacoat, adds suitable quantity of water and makes it to be uniformly dispersed, and is standby; Get and contain arginine dexketoprofen medicine carrying micropill, place the coating fluid bed, regulate 30～50 ℃ of wind pressure 0.4～0.6bar, temperature, adjust rotary speed 150～200rpm, start peristaltic pump, spray into the coating solution for preparing and carry out coating, make the arginine dexketoprofen reach satisfied release in vitro effect, the coating after drying that finishes; Get above exsiccant arginine dexketoprofen coated micropill and oxycodone, diphenhydramine medicine carrying micropill fills in the examples of suitable shell, promptly according to certain mixed.
Embodiment 6 slow-releasing granules capsules
Prescription:
Preparation method:
The arginine dexketoprofen is crossed 100 mesh sieves, and microcrystalline Cellulose is crossed 60 mesh sieves, mix homogeneously; In addition Brazil wax, glyceryl monostearate are added fusion, get the above-mentioned arginine dexketoprofen supplementary material that mixes and join wherein, continue to stir and allow its slow cooling, scrape concretion, cross 16 mesh sieves and granulate, standby; Other gets oxycodone, diphenhydramine, behind starch, dextrin mix homogeneously, adds an amount of purified water system soft material, and 18 mesh sieves are granulated, drying, 16 mesh sieve granulate; With above two kinds of granules mix homogeneously proportionally, add magnesium stearate, be filled in the suitable conventional capsule shell, promptly.
Embodiment 7, pharmacological evaluation
Further specify the compound slow release preparation of the present invention analgesia of (representing), sedative action by following pharmacological evaluation, but be not limited in this with A.
1. to the influence of mouse writhing reaction times
Get 30 of KM kind mices, male and female half and half, body weight 18-22g is divided into 3 groups at random, 10 every group.Each treatment group is irritated the suspension that stomach gives relative medicine by 10mLkg-1, and matched group gives isopyknic normal saline.Behind the administration 45min, each Mus lumbar injection 0.6% acetum 0.1mL/10g.The mouse writhing reaction times that occurs in the observation 15min is calculated the analgesia suppression ratio, compares between organizing.The result shows that with respect to matched group, each treatment group all has significant analgesia role, and the curative effect of A medicine is more remarkable.See Table 1
Table 1 medicine is to the inhibitory action of mice acetic acid writhing response (x ± S)
2. to the influence of the rat mechanical stimulus threshold of pain
Place special rat to survey on the pain device rat, the tenderness position is selected in most advanced and sophisticated 1/3 place of the higher tail of sensitivity, uses 120mmHg pressure, and shouting with generation is pain threshold, and administration before measurement pain 1 time does not make the person reject.Qualified rat is divided into 3 groups at random by body weight, 10 every group, each organize rat respectively after administration 60,90min surveys pain 1 time, medication is as testing 1, relatively t check between organizing.。The result shows that with respect to matched group, each treatment group all has significant analgesia role, and the curative effect of A medicine is more remarkable.See Table 2
The influence of the table 2 pair rat mechanical stimulus threshold of pain (x ± S)
3. to the influence of the length of one's sleep of pentobarbital sodium inducing mouse
Select 30 mices for use, male and female half and half, body weight 18-22g is divided into 3 groups at random, 10 every group.Press the 10mLkg-1 gastric infusion.Administration fasting in preceding 8 hours was prohibited water in preceding 1 hour, 1h after the administration, and ip in mice pentobarbital sodium 50mg/kg observes holding time of mice righting reflex loss.Table 2 result shows, with matched group relatively, all prolong the length of one's sleep, but sleep time expand of A medicine is longer.See Table 3
The influence of table 3. pair pentobarbital sodium inducing mouse length of one's sleep (x ± S)
Claims (8)
1, a kind of analgesic compound slow release preparation is characterized in that this slow releasing preparation is made up of slow-released part and immediate release section.Wherein slow-released part is an active component with the arginine dexketoprofen, and immediate release section is an active component with oxycodone, diphenhydramine.
2, the described slow releasing preparation of claim 1 is characterized in that, can be tablet, granule, slow-release pill, slow releasing capsule.
3, the slow releasing preparation of claim 1, the amount that described each preparation unit contains the active component oxycodone is 1.25～20mg, is preferably 2.5～10mg, the amount that contains active component arginine dexketoprofen is 5～100mg.Be preferably 10～50mg.The amount that contains the active component diphenhydramine is 5～80mg.Be preferably 10～40mg, the preferred compound dose of three is arginine dexketoprofen 25mg, oxycodone 5mg, diphenhydramine 25mg.
4, the slow releasing preparation of claim 1, it is characterized in that, described arginine dexketoprofen slow-released part, the stripping in the 1st hour of arginine dexketoprofen discharges 25～40% in the dissolution in vitro test, discharging the 40～75%, 8th hour on the 4th hour discharges more than 75%.Described oxycodone immediate release section, it is characterized in that oxycodone in dissolution in vitro test after 40 minutes stripping greater than 65%.
5, the described arbitrary slow releasing preparation of claim 1～4 is characterized in that, comprises the delivery system that the coated formula of arginine dexketoprofen slow release is formed by a sustained-release matrix or, and the delivery system that can make the rapid stripping of oxycodone.
6, the described slow releasing preparation of claim 5, it is characterized in that, sustained-release matrix comprises hydroxypropyl methylcellulose HPMC-4M, HPMC-15M, HPMC-100M, one or more in polyvinylpyrrolidone, ethyl cellulose, hydroxyethyl-cellulose, hexadecanol, octadecanol, Rikemal B 200, stearic acid, glyceryl monostearate, Brazil wax, sodium carboxymethyl cellulose, polyvinyl alcohol, sodium alginate, the chitin.
7, the described slow releasing preparation of claim 5 is characterized in that, rapidly the delivery system of stripping system is prepared into immediate-release granules, piller etc. separately with oxycodone, or it is suspended in carries out coating in the coating system, generates immediate release layer.
8, the described slow releasing preparation of claim 5, it is characterized in that the main slow releasing agent in the coated formula comprises one or more in ethyl cellulose and aqueous dispersion thereof, stearic acid, cellulose acetate, the crylic acid resin (as RS100, RL100, RS 30D, RL30D, NE30D).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810116470A CN101623280A (en) | 2008-07-10 | 2008-07-10 | Compound sustained release preparation for easing pain and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810116470A CN101623280A (en) | 2008-07-10 | 2008-07-10 | Compound sustained release preparation for easing pain and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101623280A true CN101623280A (en) | 2010-01-13 |
Family
ID=41519375
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200810116470A Pending CN101623280A (en) | 2008-07-10 | 2008-07-10 | Compound sustained release preparation for easing pain and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101623280A (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102058564A (en) * | 2010-12-29 | 2011-05-18 | 成都师创生物医药科技有限公司 | Zaltoprofen slow-release/controlled-release preparation and preparation method thereof |
| CN102743341A (en) * | 2012-07-28 | 2012-10-24 | 西安德天药业股份有限公司 | Dexketoprofen tromethamine sustained release particles and preparation method and sustained release medicinal preparation thereof |
| WO2013095315A1 (en) * | 2011-12-19 | 2013-06-27 | Mahmut Bilgic | Formulations comprising dexketoprofen (particle size 300-2500 micrometer) |
| WO2013100877A1 (en) * | 2011-12-27 | 2013-07-04 | Mahmut Bilgic | Dexketoprofen formulations |
| CN103655504A (en) * | 2012-09-26 | 2014-03-26 | 贵阳医学院 | Dexketoprofen trometamol quick-release/sustained-release double-layer tablet and preparation method thereof |
| WO2020022976A3 (en) * | 2017-12-29 | 2020-03-12 | NEUTEC AR-GE SANAYİ VE TĺCARET ANONİM ŞİRKETİ | A formulation comprising dexketoprofen |
-
2008
- 2008-07-10 CN CN200810116470A patent/CN101623280A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102058564A (en) * | 2010-12-29 | 2011-05-18 | 成都师创生物医药科技有限公司 | Zaltoprofen slow-release/controlled-release preparation and preparation method thereof |
| WO2013095315A1 (en) * | 2011-12-19 | 2013-06-27 | Mahmut Bilgic | Formulations comprising dexketoprofen (particle size 300-2500 micrometer) |
| WO2013100877A1 (en) * | 2011-12-27 | 2013-07-04 | Mahmut Bilgic | Dexketoprofen formulations |
| CN102743341A (en) * | 2012-07-28 | 2012-10-24 | 西安德天药业股份有限公司 | Dexketoprofen tromethamine sustained release particles and preparation method and sustained release medicinal preparation thereof |
| CN102743341B (en) * | 2012-07-28 | 2014-02-26 | 西安德天药业股份有限公司 | Dexketoprofen tromethamine sustained release particles and preparation method and sustained release medicinal preparation thereof |
| CN103655504A (en) * | 2012-09-26 | 2014-03-26 | 贵阳医学院 | Dexketoprofen trometamol quick-release/sustained-release double-layer tablet and preparation method thereof |
| CN103655504B (en) * | 2012-09-26 | 2016-06-29 | 贵阳医学院 | Dexketoprofen trometamol quick-release and slow-release double-layer tablet and preparation technology thereof |
| WO2020022976A3 (en) * | 2017-12-29 | 2020-03-12 | NEUTEC AR-GE SANAYİ VE TĺCARET ANONİM ŞİRKETİ | A formulation comprising dexketoprofen |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101476574B1 (en) | Controlled release hydrocodone formulations | |
| CN101987091B (en) | Venlafaxine hydrochloride sustained-release pellet capsules | |
| NO307028B3 (en) | Controlled release oxycodone formulations | |
| CN103181914B (en) | Memantine hydrochloride sustained-release capsule and preparation method thereof | |
| CN101623280A (en) | Compound sustained release preparation for easing pain and preparation method thereof | |
| KR101380507B1 (en) | Solid oral form with dual release profile, containing multiparticulates | |
| WO2021129735A1 (en) | Solid preparation, and preparation method therefor and use thereof | |
| CN103908456B (en) | Tenofovir, lamivudine and efavirenz three compound recipe pellet tablet and preparation method thereof | |
| CN107920987A (en) | Control delays to discharge Pregabalin | |
| CN104814923B (en) | A kind of tamsulosin hydrochloride sustained release preparation and preparation method thereof and its application | |
| Karvekar et al. | A brief review on sustained release matrix type drug delivery system | |
| CN105769773B (en) | Loxoprofen sodium sustained-release pellet | |
| CN101756981B (en) | Brufen loratadine pseudoephedrine release preparation and preparation method thereof | |
| CN101584683A (en) | Metolazone slow-release capsule and method for preparing same | |
| CN101214379A (en) | Novel composing prescription sustained-release preparation for treating high blood pressure and preparation method thereof | |
| CN109646417A (en) | A kind of Trimetazidine sustained release tablets and preparation method thereof | |
| CN101411702A (en) | Nefopam hydrochloride naproxen sodium compound sustained-release preparation and preparation method thereof | |
| CN101658507B (en) | Glyceryl guaiacolate and pseudoephedrine compound sustained release preparation | |
| CN108853044B (en) | Nifedipine sustained release tablet and preparation method thereof | |
| CN103655585A (en) | Gastrodin controlled release preparation and preparation method thereof | |
| CN101244068B (en) | Hemsleyadin sustained-release preparation | |
| CN102114003B (en) | Sustained-release pellet of hydroxysafflor yellow A as well as preparation method and applications thereof | |
| CN104013634A (en) | Capsule containing aspirin enteric part and dipyridamole quick-releasing part and preparation method thereof | |
| CN101756987A (en) | Compound sustained-release preparation of guaiacol olycerin ether, pseudoephedrine and dextromethorphan | |
| CN101829121B (en) | Hemsleyadin sustained-release preparation |
Legal Events
| 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: 20100113 |