CN101032462A - Mexiletine Hydrochloride slow release reagent and preparing method thereof - Google Patents
Mexiletine Hydrochloride slow release reagent and preparing method thereof Download PDFInfo
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Abstract
The slow released mexiletine hydrochloride preparation consists of mexiletine hydrochloride as active component in 20-70 wt%, slow releasing material in 10-60 wt%, and medicinal supplementary material. It is prepared into slow released tablet or capsule through sieving the materials, mixing, pelletizing, and tabletting or encapsulating. It has both fast releasing and slow releasing feature, fast acting, high bioavailability, long acting period, taking safety and other advantages.
Description
Technical field:
The present invention relates to the chemicals formulation art, disclose the pharmaceutical composition that contains the active ingredient hydrochloric acid mexiletine, be specifically related to ARR Mexiletine Hydrochloride slow release reagent of a kind of oral medication and preparation method.
Background technology:
Arrhythmia (Cardiac arrhythmia) is the common clinical symptom of cardiovascular system, no matter heart has or not organic disease all arrhythmia can take place, arrhythmia is meant rhythm of the heart origin position, cardiac frequency and the rhythm and pace of moving things and exciting conduction etc., and each is unusual.Cardiac disorder, systemic blood and electrolytical disorder and autonomic nervous system function imbalance all may change myocardium electric physiological status, become to bring out ARR direct and remote cause.This factor can be brought out arrhythmia by single form, also can exist simultaneously to disturb myocardium normal electrical activity, causes ARR generation.Arrhythmia can take place in most of clinically myocardial infarction patients, especially usually the dying suddenly owing to sudden malignant arrhythmia causes ventricular fibrillation in early days of morbidity, so stops or prevents ARR generation rather important.Though development in recent years multiple therapy methods and means, comprise measures such as electric cardioversion, electric defibrillation, electric pace-making, catheter ablation art, Drug therapy especially is still main treatment means to tachy-arrhythmia.
Mexiletine hydrochloride, English name: Mexiletine Hydrochloride, chemical name: 1-(2, the 6-dimethyl phenoxy)-2-propylamin hydrochloride, molecular formula: C
11H
17NOHCl, molecular weight: 215.72, structural formula is as follows:
Mexiletine hydrochloride is white or off-white color crystalline powder; Odorless almost, bitter in the mouth.Fusing point: 203～205 ℃; PKa:9.2; Easily molten in water or ethanol, almost insoluble in ether.Mexiletine hydrochloride is an Ib class anti-arrhythmic, also has a convulsion drawn game anaesthetic effect.Its chemical constitution and electric physiological effect are all close with lignocaine, are membrane stabilizer, the Na of retardance cell membrane
+Passage and suppress Na
+Interior stream, current potential under reach prolongs effective refractory period relatively, reduces irritability.Therapeutic dose is very little to sinuatrial node, atrium and atrioventricular node conduction influence.The normal person of conducting system the self-disciplining of sinuatrial node, chamber conduction, QRS are involved the Q-T interval and all do not have obvious influence; so its electric physiological effect is also different because of dosage and myocardium state (as normal or ischemia, anoxia etc.); can prolong myocardium Conductive fiber refractory stage more significantly when blood drug level is high, this medicine is to almost unrestraint effect of cardiac muscle.Since nineteen sixty-eight, mexiletine hydrochloride was used for the treatment of arrhythmia, Chinese scholars had been done a large amount of research to its pharmacological action and clinical practice, had been widely used in ARR treatment at present clinically.
This medicine is rapid, complete in the gastrointestinal tract oral absorption, and bioavailability is about 80～90%.Mexiletine hydrochloride is that company of nineteen sixty-eight Boehringer Inghein pharmaceutical Co. Ltd has obtained the patent right of this product chemical compound by the medicine of German Boehringer Ingelheim pharmaceutical Co. Ltd exploitation listing.1976, mexiletine hydrochloride conventional tablet and capsule went on the market in Germany, used in country's listings such as Britain, France, Italy, Japan, the U.S. and China successively again thereafter.
The mexiletine hydrochloride oral formulations of listing is conventional tablet and capsule at present.
Because this product effective blood drug concentration is 0.5～2.0 μ g/ml, curative effect of medication and untoward reaction and blood drug level are closely related, blood drug level above 2.0 μ g/ml then adverse effect obviously increase.Because blood concentration fluctuation is bigger in common oral formulations (conventional tablet and the capsule) body, peak-to-valley ratio is big, peak concentration easily exceeds minimum poisoning concentration, and it is shorter to hold time in treatment valid density scope, cause the therapeutical effect persistent period short, the mexiletine hydrochloride curative effect is undesirable, rate of adverse reactions is high so cause; The oral ordinary preparation that has gone on the market needs to take every day 3～4 times usually, and medicining times is many, has brought many inconvenience to the patient, and the phenomenon that misses easily, causes patient's drug compliance poor.Research worker therefore of the present invention has been developed Mexiletine Hydrochloride slow release reagent through constantly exploring and research, compares with ordinary preparation, and tool improves curative effect, reduces poisonous side effect of medicine, and can improve patient's advantages such as drug compliance.
The Chinese patent of at present relevant mexiletine hydrochloride has: " tetrahydro isoquinoline derivative, its preparation method and pharmaceutical composition " (publication number: CN1769272, application number: 200410067674.X).The patent application of no Mexiletine Hydrochloride slow release reagent.
Summary of the invention
The purpose of this invention is to provide a kind of Mexiletine Hydrochloride slow release reagent, be made up of material and all the other pharmaceutic adjuvants of active ingredient hydrochloric acid mexiletine, a slow releasing function, each compositions in weight percentage is:
Mexiletine hydrochloride (active component) 20～70%
Play the material 10～60% of slow releasing function
All the other pharmaceutic adjuvants 10～40%
Preferred group becomes mexiletine hydrochloride 30～50%, and the material that plays slow releasing function is 20～50%, and all the other pharmaceutic adjuvant compositions are 20～30%.
The material of described slow releasing function is a slow-release material commonly used on the pharmaceutics, as the mixture of one or more components in the following slow-release material: hydroxypropyl emthylcellulose, carbomer, ethyl cellulose, Rikemal B 200 and acrylic resin etc.All the other pharmaceutic adjuvants are diluent, wetting agent, binding agent, lubricant and coating membrane material.Diluent can adopt lactose, Icing Sugar, calcium sulfate etc.; Wetting agent can adopt the ethanol-water solution of dehydrated alcohol, various concentration; Binding agent can adopt polyvinylpyrrolidone, hydroxypropyl methylcellulose, Polyethylene Glycol etc.; Lubricant can adopt magnesium stearate, Pulvis Talci, micropowder silica gel etc.; Membrane material can adopt ethyl cellulose, acrylic resin etc.
This slow releasing preparation comprises the various tablets of skeleton (as hydrophilic gel, bioerodable and insoluble skeleton) type, film controlling type, porous matrix type, also comprises after granule, piller are made with various slow-release materials by elder generation recharging the capsule of making.The mexiletine hydrochloride oral slow-releasing preparation according to preparation technology's difference, can be made into slow releasing tablet and slow releasing capsule.Take every day 2 times, make the Mexiletine Hydrochloride slow release reagent of blood drug level stable maintenance in the valid density scope.
Another object of the present invention provides the preparation method of Mexiletine Hydrochloride slow release reagent, realizes by following steps:
The preparation method of Mexiletine Hydrochloride slow release reagent provided by the invention: active component, the material that plays slow releasing function and all the other pharmaceutic adjuvants sieved adopt full powder behind the mixing directly compacting is in flakes; Add and make sheet with lubricant mixing repress after the wetting agent wet method is made granule; Adopt the film coating slow release method, prepare conventional tablet earlier, reuse plays the material coating of slow releasing function and makes slow releasing tablet; Tabletting after adopting solid dispersion method to granulate; Behind the material preparation granule or piller, film controlled release small pieces or piller with above-mentioned slow releasing function, recharge and make slow releasing capsule earlier.
1. wet method system granule method tabletting
Mexiletine hydrochloride, the material that plays slow releasing function and all the other pharmaceutic adjuvants are pulverized, and it is standby to cross 100 mesh sieves, takes by weighing recipe quantity, behind the abundant mixing of machinery, add an amount of wetting agent system soft material in the stirring, soft material is crossed 18 mesh sieve system granules, 55～65 ℃ of dryings are after 2 hours, and 18 mesh sieve granulate are with the dried particles behind the above-mentioned granulate, add lubricant, fully mix homogeneously is measured content, the calculating sheet is heavy, use the rotary tablet machine tabletting, promptly get the mexiletine hydrochloride slow releasing tablet, preparation flow figure is referring to Fig. 8.
2. direct compression of full-powder
After mexiletine hydrochloride, the material that plays slow releasing function and all the other pharmaceutic adjuvants were pulverized, it was standby to cross 100 mesh sieves, takes by weighing recipe quantity, after fully mixing, add the lubricant of recipe quantity, use the rotary tablet machine tabletting behind the mixing, promptly get the mexiletine hydrochloride slow releasing tablet, preparation flow figure is referring to Fig. 9.
3. coating behind the preparation label
After mexiletine hydrochloride, the material that plays slow releasing function and all the other pharmaceutic adjuvants were pulverized, it was standby to cross 100 mesh sieves, takes by weighing recipe quantity, and behind the mixing, system wet granular tabletting or direct compression prepare label.To label coating in coating pan, solidify back 50 ℃ of dryings 16 hours promptly with slow-release auxiliary material such as ethyl cellulose, acrylic resin and hydroxypropyl emthylcelluloses, preparation flow figure is referring to Figure 10.
4. preparation slow releasing capsule
After mexiletine hydrochloride, the material that plays slow releasing function and all the other pharmaceutic adjuvants were pulverized, it was standby to cross 100 mesh sieves, takes by weighing recipe quantity, fully behind the mixing, add an amount of wetting agent system soft material in the stirring, soft material is crossed 16 mesh sieve system granules, 50～60 ℃ of dryings are after 3 hours, 16 mesh sieve granulate, measure content, calculate, the direct filling capsule of the dried particles behind the above-mentioned granulate, promptly get the mexiletine hydrochloride capsule, preparation flow figure is referring to Figure 11.
Slow releasing preparation provided by the invention is a kind of oral ARR preparation that is used for the treatment of, in the harmonization of the stomach small intestinal, can slowly discharge absorption, and the rate of release of medicine is changed by gastrointestinal physiologic factor, pH value and peristaltic velocity etc. influences less, the blood plasma mexiletine level long period can be remained in the medicine concentration range, the curative effect prolongation of holding time, the fluctuation of blood drug level peak valley reduces, thereby has reduced poisonous side effect of medicine, improves therapeutic effect; Reduce medicining times, improve patient's drug compliance.
Advantage of the present invention is the Mexiletine Hydrochloride slow release reagent tool rapid release of development and the dual characteristics of slow release, takes 2 every day, and is rapid-action, keeps long action time, and prominent releasing can not taken place, and takes safety; It is steady to possess blood drug level, bioavailability height, characteristics such as toxic and side effects is little.Mexiletine Hydrochloride slow release reagent tool curative effect of medication height, untoward reaction is low; And reduce patient's medicining times, improve drug compliance, make patient take, easy to carry; Preparation technology is simple, and is easy to operate, favorable reproducibility, and steady quality does not need special installation, adopts existing preparation production line to finish, and production cost is low, is suitable for industrialized great production.
Description of drawings
Fig. 1 is the medicine stripping curve of the mexiletine hydrochloride ordinary tablet that goes on the market.
Fig. 2 is the drug release curve of embodiment 1 mexiletine hydrochloride slow releasing tablet.
Fig. 3 is the drug release curve of embodiment 2 mexiletine hydrochloride slow releasing tablet.
Fig. 4 is the drug release curve of embodiment 3 mexiletine hydrochloride sustained release coating sheets.
Fig. 5 is the drug release curve of embodiment 4 mexiletine hydrochloride slow releasing tablet.
Fig. 6 is the drug release curve of embodiment 5 mexiletine hydrochloride slow releasing capsule.
Fig. 7 is the drug release curve of embodiment 6 mexiletine hydrochloride slow releasing capsule.
Fig. 8 is wet method system granule method tabletting preparation flow figure of the present invention.
Fig. 9 is direct compression of full-powder preparation flow figure of the present invention.
Figure 10 prepares coating preparation flow figure behind the label for the present invention.
Figure 11 prepares slow releasing capsule preparation flow figure for the present invention.
The specific embodiment
Following specific embodiment is intended to that the invention will be further described, but means that never it limits the scope of the invention by any way.
Embodiment 1:
Mexiletine hydrochloride 100g
Hydroxypropyl emthylcellulose 122g
Lactose 124g
Micropowder silica gel 2g
Magnesium stearate 2g
Make 1000
Preparation method: mexiletine hydrochloride, hydroxypropyl emthylcellulose and all the other pharmaceutic adjuvant pulverize separately are crossed 100 mesh sieves, take by weighing by recipe quantity, cross the abundant mix homogeneously of 80 mesh sieve secondaries, measure content, the calculating sheet is heavy, and with the circular punch die tabletting of diameter 8.0mm, the sheet type is circular, every hydrochloric mexiletine 100mg, sheet heavily are 350mg.Through check, qualified back packing promptly gets the mexiletine hydrochloride slow releasing tablet.
Result of the test:
According to " 2005 editions commentaries on classics basket methods that test detects about slow releasing preparation vitro drug release degree of Chinese pharmacopoeia are carried out, get 6 of mexiletine hydrochloride slow releasing tablet, with the 900ml water recently distilled is medium, condition in the analogue body, temperature is controlled to be 37 ± 0.5 ℃, rotating speed 100 ± 1r/min, use RC806 medicine dissolution test instrument (Tianjin Tianda Tianfa Science and Technology Co. Ltd. product) to measure the drug release situation, the results are shown in Figure 2, show sustainable 12 hours of the release of mexiletine hydrochloride slow releasing tablet medicine, the tangible slow release characteristic of tool.Animal experiment is after 12 Canis familiaris L.s are taken medicine, and matched group taking medicine 30 minutes in, promptly reaches the highest blood drug level with mexiletine hydrochloride ordinary tablet (middle promise pharmaceutcal corporation, Ltd product), descends rapidly subsequently; And the mexiletine hydrochloride slow releasing tablet all can be kept in 30 minutes to 10 hours steadily and effective blood drug concentration taking medicine, blood concentration fluctuation is less, illustrates that thus the mexiletine hydrochloride slow releasing tablet has the good slow release characteristic, has reached 2 times the requirement of taking medicine every day.
Embodiment 2:
Mexiletine hydrochloride 150g
Hydroxypropyl emthylcellulose 140g
Polyvinylpyrrolidone (PVP K30) 10g
80% ethanol is an amount of
Lactose 48g
Magnesium stearate 2g
Make 1000
Preparation method: with mexiletine hydrochloride, hydroxypropyl emthylcellulose and all the other pharmaceutic adjuvant pulverize separately are crossed 100 mesh sieves, take by weighing by recipe quantity, adopt equivalent incremental method mix homogeneously, in the material of above-mentioned mix homogeneously, add 80% ethanol, the preparation soft material, soft material is crossed 18 mesh sieve system granules, 55～65 ℃ of dryings of wet granular are after 2 hours, and 18 mesh sieve granulate are with the dried particles behind the above-mentioned granulate, the magnesium stearate that adds recipe quantity, fully mix homogeneously is measured content, and it is heavy to calculate sheet, circular punch die tabletting with diameter 8.0mm, the sheet type is circular, and every hydrochloric mexiletine 150mg, sheet heavily are 350mg, through check, qualified back packing promptly gets the mexiletine hydrochloride slow releasing tablet.
Result of the test:
Detection method the results are shown in Figure 3 with embodiment 1, shows the tangible slow release characteristic of mexiletine hydrochloride slow releasing tablet tool, and the release of medicine can be kept 12 hours.
Embodiment 3:
(1) label: mexiletine hydrochloride 200g
10%PVP K30 ethanol liquid is an amount of
Lactose 60g
Magnesium stearate 2g
(2) coating solution: ethyl cellulose 25%
Polyethylene Glycol (PEG) 10%
Dibutyl sebacate (DBS) 30%
Purified water is an amount of
Make 1000
Preparation method: mexiletine hydrochloride and lactose pulverize separately are crossed 100 mesh sieves, take by weighing by recipe quantity, adopt equivalent incremental method mix homogeneously, in the material of above-mentioned mix homogeneously, add an amount of 10%PVP K30 ethanol liquid, the preparation soft material, soft material is crossed 18 mesh sieve system granules, and 55～65 ℃ of dryings of wet granular are after 2 hours, 18 mesh sieve granulate, with the dried particles behind the above-mentioned granulate, with the dried particles behind the above-mentioned granulate, add the magnesium stearate of recipe quantity, fully tabletting prepares label behind the mix homogeneously, label is put into coating pan, with the ethyl cellulose is the sustained release coating material, and Polyethylene Glycol (PEG) is a porogen, and dibutyl sebacate (DBS) carries out coating for plasticizer preparation coating solution, calculate weightening finish, after coating weightening finish 12%, room temperature were placed and solidified in 8 hours, 50 ℃ of dryings promptly got mexiletine hydrochloride sustained release coating sheet in 12 hours.
Result of the test:
Detection method the results are shown in Figure 4 with embodiment 1, shows the tangible slow release characteristic of mexiletine hydrochloride sustained release coating sheet tool, and the release of medicine can be kept 8-12 hour.
Embodiment 4:
Mexiletine hydrochloride 200g
Carbomer 160g
Polyvinylpyrrolidone (PVP K30) 10g
80% ethanol is an amount of
Lactose 26g
Magnesium stearate 4g
Make 1000
Preparation method: with mexiletine hydrochloride, carbomer and lactose pulverize separately are crossed 100 mesh sieves, take by weighing by recipe quantity, adopt equivalent incremental method mix homogeneously, add an amount of 80% alcohol in the material of above-mentioned mix homogeneously, the preparation soft material is crossed 18 mesh sieve system granules with soft material, 55～65 ℃ of dryings of wet granular are after 2 hours, 18 mesh sieve granulate with the dried particles behind the above-mentioned granulate, add the magnesium stearate of recipe quantity, abundant mix homogeneously, measure content, it is heavy to calculate sheet, with the circular punch die tabletting of diameter 10.0mm, the sheet type is circular, sheet heavily is 400mg, and through check, qualified back packing promptly gets the mexiletine hydrochloride slow releasing tablet.
Result of the test:
Detection method the results are shown in Figure 5 with embodiment 1, shows the tangible slow release characteristic of mexiletine hydrochloride slow releasing tablet tool, and the release of medicine can be kept 12 hours.
Embodiment 5:
Mexiletine hydrochloride 300g
Ethyl cellulose 80g
Acroleic acid resin 60g
Polyvinylpyrrolidone (PVP K30) 20g
80% ethanol is an amount of
Lactose 40g
Make 1000
Preparation method: mexiletine hydrochloride and lactose pulverize separately are crossed 100 mesh sieves, take by weighing by recipe quantity, get ethyl cellulose and acroleic acid resin, mixing, after adding an amount of dissolving of 80% ethanol, add mexiletine hydrochloride and lactose, the preparation soft material is crossed 16 mesh sieve system granules with soft material, 50～60 ℃ of dryings of wet granular are after 2 hours, 16 mesh sieve granulate with the dried particles behind the above-mentioned granulate, promptly get the mexiletine hydrochloride slow releasing capsule in the capsulae vacuus of packing into.
Result of the test:
Detection method the results are shown in Figure 6 with embodiment 1, shows the tangible slow release characteristic of mexiletine hydrochloride slow releasing capsule tool, and ethyl cellulose and acroleic acid resin have been the material of slow releasing function, and the release of medicine can be kept 10 hours.
Embodiment 6:
Mexiletine hydrochloride 200g
Rikemal B 200 200g
90% ethanol is an amount of
Pulvis Talci 5g
Make 1000
Preparation method: get the Rikemal B 200 of recipe quantity, after 80 ℃ of heating in water bath fusions, add mexiletine hydrochloride, constantly stir, abundant mixing is after the room temperature cooling, mechanical activation comminution is crossed 30 mesh sieves, adds an amount of 90% alcohol, the system soft material is crossed 18 mesh sieve system granules with soft material, after 40 ℃ of dryings of wet granular, 18 mesh sieve granulate with the dried particles behind the above-mentioned granulate, add the Pulvis Talci of recipe quantity, mixing promptly gets the mexiletine hydrochloride slow releasing capsule in the capsulae vacuus of packing into, the hydrochloric mexiletine 200mg of every capsules.
Result of the test:
Detection method the results are shown in Figure 7 with embodiment 1, show that the release of mexiletine hydrochloride slow releasing capsule agent medicine also can be kept 8～12 hours, has all reached 2 times the administration requirement of taking medicine every day.
The detection of embodiment 7 mexiletine hydrochloride slow releasing tablet slow release effects:
Mexiletine hydrochloride slow releasing tablet provided by the present invention carry out the test determination of release in vitro degree and the result as follows.
The drug release determination method:
According to slow releasing preparation vitro drug release degree test determination (" 2005 editions two appendix XIX D of Chinese pharmacopoeia), employing dissolution determination the 1st subtraction unit (" 2005 editions two appendix X C of Chinese pharmacopoeia), carry out with changeing the basket method, get 6 of mexiletine hydrochloride slow releasing tablet, with the 900ml water recently distilled is medium, inject each stripping rotor, condition in the analogue body, temperature is controlled to be 37 ± 0.5 ℃, rotating speed 100 ± 1r/min, use RC806 medicine dissolution test instrument (Tianjin Tianda Tianfa Science and Technology Co. Ltd. product) to measure the drug release situation, respectively at 0.5,1.0,2.0,3.0,4.0,6.0,8.0,10.0, got solution 5ml (replenishing medium 5ml simultaneously immediately) in 12 hours, with 0.8 μ m filtering with microporous membrane, discard filtrate just, subsequent filtrate is as need testing solution; Other the mexiletine hydrochloride reference substance that is dried to constant weight of learning from else's experience 105 ℃ is an amount of, accurate claim fixed, be dissolved in water and quantitatively dilution make the solution that contains 100 μ g among every 1ml, product solution in contrast.Respectively according to ultraviolet visible spectrophotometry (" 2005 editions two appendix IV A of Chinese pharmacopoeia), measure the absorbance of need testing solution and reference substance solution at 261nm wavelength place, calculate medicine accumulative total and discharge percent, calculate every burst size of this product and should be respectively more than 25～45%, 35～55%, 50～80% and 80% of labelled amount at 1,2,4,8 hour, the results are shown in accompanying drawing, all up to specification.Mexiletine hydrochloride ordinary tablet and slow releasing tablet release see Table 1 and table 2.The result shows that the mexiletine hydrochloride ordinary tablet all discharged in 1 hour, and discharges its drug release process Higuchi equation in the sustainable 8-12 of slow releasing tablet hour.
The dissolution (%) of table 1 mexiletine hydrochloride ordinary tablet
| Time (min) | 10 | 20 | 30 | 45 | 60 | 90 |
| Dissolution (%) | 36.5 | 65.5 | 89.3 | 96.7 | 99.02 | 99.56 |
The release (%) of table 2 mexiletine hydrochloride slow releasing tablet
From above-mentioned release result of the test as can be known, compare with ordinary tablet by the mexiletine hydrochloride slow releasing tablet that preparation method of the present invention provided, medicine was discharged in 8-12 hour continually and steadily, the not prominent phenomenon of releasing, the release profiles Higuchi equation, reach the purpose that rapid release adds slow release, releasable medicaments reaches more than 30% in 1 hour, this is to absorb rapidly in the body, quick acting has been established the pharmacodynamics basis, and slow releasing function can make medicine keep release more than 8 hours, keep the required blood drug level of treatment, thereby it is lasting to reach therapeutical effect, poisonous side effect of medicine and medicining times reduce, the purpose of taking convenience.
Although the present invention has done detailed explanation in conjunction with the above embodiments, clearly still can make various changes and improvements to one skilled in the art according to the present invention, can not depart from spirit of the present invention and protection domain.
Claims (10)
1. a Mexiletine Hydrochloride slow release reagent is made up of the material and the pharmaceutic adjuvant of active ingredient hydrochloric acid mexiletine, a slow releasing function, it is characterized in that the percentage by weight of each component is:
Mexiletine hydrochloride 20～70%
Play the material 10～60% of slow releasing function
All the other pharmaceutic adjuvants 10～40%.
2. a kind of Mexiletine Hydrochloride slow release reagent according to claim 1 is characterized in that the percentage by weight of each component is:
Mexiletine hydrochloride 30～50%
Play the material 20～50% of slow releasing function
All the other pharmaceutic adjuvants 20～30%.
3. a kind of Mexiletine Hydrochloride slow release reagent according to claim 1 and 2 is characterized in that: the material that plays slow releasing function described in the component is the mixture of one or more components in the following adjuvant: hydroxypropyl emthylcellulose, carbomer, hydroxy methocel, hydroxyethyl-cellulose, hydroxypropyl cellulose, methylcellulose, ethyl cellulose, cellulose acetate, sodium carboxymethyl cellulose, sodium alginate, hexadecanol, stearic acid, stearyl alcohol, glyceryl monostearate, Brazil wax, chitosan, polyvinyl alcohol, Rikemal B 200 and acrylic resin etc.
4. a kind of Mexiletine Hydrochloride slow release reagent according to claim 1 and 2, it is characterized in that: all the other pharmaceutic adjuvants described in the component are diluent, wetting agent, binding agent, disintegrating agent, lubricant and coating membrane material, and wherein diluent is selected a kind of in starch, pregelatinized Starch, lactose, Icing Sugar, dextrin, microcrystalline Cellulose, the calcium sulfate for use; Wetting agent is selected a kind of in water, dehydrated alcohol, the ethanol-water solution for use; Binding agent is selected a kind of in polyvinylpyrrolidone, methylcellulose, hyprolose, hydroxypropyl methylcellulose, the Polyethylene Glycol for use; Disintegrating agent is selected a kind of in cross-linking sodium carboxymethyl cellulose, the microcrystalline Cellulose for use; Lubricant is selected a kind of in magnesium stearate, stearic acid, Pulvis Talci, the micropowder silica gel for use; Membrane material is selected a kind of in cellulose acetate, ethyl cellulose, the acrylic resin for use.
5. a kind of Mexiletine Hydrochloride slow release reagent according to claim 1 and 2 is characterized in that: prepared slow releasing preparation is an oral formulations, comprises slow releasing tablet and slow releasing capsule.
6. the preparation method of a kind of Mexiletine Hydrochloride slow release reagent according to claim 1 and 2; realize by following steps: mexiletine hydrochloride raw material and pharmaceutic adjuvant are sieved adopt full powder behind the mixing directly compacting is in flakes; add and make sheet with lubricant mixing repress after the wetting agent wet method is made granule; adopt the film coating slow release method; prepare conventional tablet earlier; the adjuvant coating of reuse tool slow releasing function is made slow releasing tablet; tabletting after adopting solid dispersion method to granulate; earlier prepare granule or piller with above-mentioned slow-release material; behind film controlled release small pieces or the piller, recharge and make slow releasing capsule.
7. the preparation method of a kind of Mexiletine Hydrochloride slow release reagent according to claim 6, it is characterized in that wet method system granule method tabletting realizes by following steps: supplementary material is pulverized, it is standby to cross 100 mesh sieves, take by weighing mexiletine hydrochloride and other adjuvant, behind the abundant mixing of machinery, add an amount of wetting agent system soft material in the stirring, soft material is crossed 18 mesh sieve system granules, 55～65 ℃ of dryings are after 2 hours, 18 mesh sieve granulate, with the dried particles behind the above-mentioned granulate, add the lubricant of recipe quantity, fully mix homogeneously, measure content, the calculating sheet is heavy, uses the rotary tablet machine tabletting, promptly gets the mexiletine hydrochloride slow releasing tablet.
8. the preparation method of a kind of Mexiletine Hydrochloride slow release reagent according to claim 6, it is characterized in that direct compression of full-powder realizes by following steps: after supplementary material is pulverized, it is standby to cross 100 mesh sieves, take by weighing mexiletine hydrochloride and other adjuvant of recipe quantity, after fully mixing, add the lubricant of recipe quantity, use the rotary tablet machine tabletting behind the mixing, promptly get the mexiletine hydrochloride slow releasing tablet.
9. the preparation method of a kind of Mexiletine Hydrochloride slow release reagent according to claim 6, coating is realized by following steps after it is characterized in that preparing label: after supplementary material is pulverized, it is standby to cross 100 mesh sieves, take by weighing mexiletine hydrochloride and other adjuvant of recipe quantity, behind the mixing, system wet granular tabletting or direct compression prepare label.To label coating in coating pan, solidify back 50 ℃ of dryings 16 hours promptly with slow-release auxiliary material such as ethyl cellulose, acrylic resin and hydroxypropyl emthylcelluloses.
10. the preparation method of a kind of Mexiletine Hydrochloride slow release reagent according to claim 6, it is characterized in that preparing slow releasing capsule realizes by following steps: supplementary material is pulverized, it is standby to cross 100 mesh sieves, take by weighing mexiletine hydrochloride, slow-release auxiliary material and other adjuvant, fully behind the mixing, add an amount of wetting agent system soft material in the stirring, soft material is crossed 16 mesh sieve system granules, 50～60 ℃ of dryings are after 3 hours, 16 mesh sieve granulate are measured content, calculate, with the direct filling capsule of the dried particles behind the above-mentioned granulate, promptly get the mexiletine hydrochloride capsule.
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| CN102326848A (en) * | 2010-07-13 | 2012-01-25 | 上海新菲尔生物制药工程技术有限公司 | Food preservative and preparation method thereof |
| CN105125515A (en) * | 2013-12-06 | 2015-12-09 | 温州智创科技有限公司 | Levo-oxiracetam tablet and preparation method thereof |
| WO2022258842A1 (en) | 2021-06-11 | 2022-12-15 | Lupin Atlantis Holdings Sa | Extended-release compositions of mexiletine for oral administration |
| WO2023080910A1 (en) * | 2020-11-18 | 2023-05-11 | Fb-Hrs, Llc | Compositions containing dofetilide and mexiletine and uses thereof |
-
2006
- 2006-12-20 CN CN 200610155351 patent/CN101032462A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102326848A (en) * | 2010-07-13 | 2012-01-25 | 上海新菲尔生物制药工程技术有限公司 | Food preservative and preparation method thereof |
| CN101897677A (en) * | 2010-07-14 | 2010-12-01 | 西安交通大学 | Imperatorin sustained release tablets and preparation method thereof |
| CN105125515A (en) * | 2013-12-06 | 2015-12-09 | 温州智创科技有限公司 | Levo-oxiracetam tablet and preparation method thereof |
| CN105125515B (en) * | 2013-12-06 | 2018-07-13 | 重庆润泽医药有限公司 | A kind of levo-oxiracetam tablet and preparation method thereof |
| WO2023080910A1 (en) * | 2020-11-18 | 2023-05-11 | Fb-Hrs, Llc | Compositions containing dofetilide and mexiletine and uses thereof |
| WO2022258842A1 (en) | 2021-06-11 | 2022-12-15 | Lupin Atlantis Holdings Sa | Extended-release compositions of mexiletine for oral administration |
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