CN101683323A - Colonic targeted micropill containing vancomycin and preparation method thereof - Google Patents
Colonic targeted micropill containing vancomycin and preparation method thereof Download PDFInfo
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- CN101683323A CN101683323A CN200810211739A CN200810211739A CN101683323A CN 101683323 A CN101683323 A CN 101683323A CN 200810211739 A CN200810211739 A CN 200810211739A CN 200810211739 A CN200810211739 A CN 200810211739A CN 101683323 A CN101683323 A CN 101683323A
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Abstract
The invention discloses a colonic targeted micropill using vancomycin as an active ingredient and a preparation method thereof. The targeted micropill preparation comprises a blank pill core, a medicine applying layer and a colonic enteric coating layer, wherein the blank pill core is a commercially available product; the medicine applying layer comprises vancomycin, an antisticking agent and methyl acrylate copolymer; and the colonic enteric coating layer comprises an antisticking agent, a plasticizing agent and methyl acrylate. A fluidized bed micropill coating method is used for preparing the colonic targeted micropill containing vancomycin. The colonic targeted micropill preparation is used for treating pseudomembranous colitis caused by difficult distinction of bacillus fusiformis because of taking broad-spectrum antibiotics for a long time, and the targeted positioning administration not only can increase the curative effect but also prevents the vancomycin from being exposed onthe non-acting part importantly, thereby effectively reducing the occurrence rate of vancomycin resistant enterococcus (VRE).
Description
Technical field
The present invention relates to a kind of is the colon-targeted pellets of active component with the vancomycin, is used for the treatment of owing to take for a long time and difficultly due to the broad ectrum antibiotic distinguish the pseudomembranous colitis that bacillus fusiformis causes.
Background technology
Difficulty distinguishes that bacillus fusiformis is a kind of gram-positive anaerobic bacterium that has, produces poison with the spore form, along with being extensive use of of broad ectrum antibiotic, distinguishes that by the difficulty that antibiotic causes the bacillus fusiformis colitis is increasing.Be used for the treatment of difficulty at present and distinguish that the medicine of bacillus fusiformis colitis mainly contains metronidazole and vancomycin, both cure rates are all more than 85%, the vancomycin curative effect slightly is better than metronidazole, but because metronidazole low price and clinical easy acquisition, so the first azoles is to become the clinical choice drug that difficulty is distinguished the bacillus fusiformis colitis that is used for the treatment of.Along with metronidazole being extensive use of clinically, its drug resistance is serious day by day, causes that its treatment is difficult distinguishes that the curative effect of bacillus fusiformis colitis progressively goes down.The difficulty of failing to respond to any medical treatment for metronidazole is distinguished the treatment of bacillus fusiformis colitis, and unique valid approach is to treat by oral vancomycin.
Vancomycin (Vancomycin) is a kind of glycopeptide class narrow-spectrum antibiotic that is produced by the east streptomycete bacterial strain.Mainly effective to gram positive bacteria, as staphylococcus aureus and staphylococcus epidermidis (comprising the methicillin-resistant bacterial strain) and streptococcus (comprising micrococcus scarlatinae, streptococcus pneumoniae, streptococcus agalactiae, Streptococcus viridans), corynebacterium, clostridium (difficulty is distinguished that clostridium is extremely sensitive), actinomycetes, Streptococcus, bargen's streptococcus, enterococcus, diphtheroid etc.Invalid to gram negative bacilli, mycobacterium or fungus.Vancomycin is brought into play quick-acting bactericidal actions by suppressing synthesizing of bacteria cell wall.The oral back of vancomycin gastrointestinal absorption is poor, and intramuscular injection can cause local pain, and therefore vancomycin is mainly made intravenous administration at present.Because the oral back of vancomycin absorbs hardly at gastrointestinal tract, therefore concentration height in feces, so difficulty is distinguished that the topical therapeutic of bacillus fusiformis colitis has significant curative effect, oral vancomycin is mainly used in the difficulty that metronidazole fails to respond to any medical treatment and distinguishes the bacillus fusiformis colitis.Still there is not oral vancomycin formulations supply in the market, so as need oral, can vancocin vial is oral after with dissolved in distilled water, but this administering mode makes vancomycin provide drug resistance environment extensively and for a long time at intestinal to enterococcus, thereby easily causes the appearance of the enterococcus (VRE) of vancomycin resistance.
Pellet preparations belongs to the multiple-unit dosage form, have the physiologic factor of being subjected to influence little, gastrointestinal tract distribute wide, the release variation is little, big etc. a bit with gastrointestinal tract mucous contact area, be specially adapted to the administration of gastrointestinal tract topical therapeutic.
Summary of the invention
According to an aspect of the present invention, the invention provides a kind of is the colon-targeted pellets preparation of active component with the vancomycin, this pellet preparations is by being released to active component vancomycin location effect target site colon, not only improved curative effect, the more important thing is and avoided the active component vancomycin to be exposed to positions such as non-site of action stomach, duodenum and small intestinal, thereby effectively reduce the incidence rate of vancomycin-resistant enterococcus (VRE), have not yet to see the relevant report of relevant vancomycin colon-targeted pellets.
The present invention contains the colon-targeted pellets of vancomycin, is made of the celphere that does not contain active component, the coating layer that contains the active component vancomycin and colon enteric coatings.
Wherein, described coating layer comprises vancomycin 0.5～25wt.%, antiplastering aid 2～20wt.% and methyl acrylate copolymer 55～97.5wt.%.
Wherein, described vancomycin comprises the derivant of the salt and the vancomycin of vancomycin.The salt of described vancomycin is a Lyphocin (Fujisawa); The derivant of described vancomycin is a norvancomycin hydrochloride.
Wherein, described colon enteric coatings comprises methyl acrylate copolymer 25～97.5wt.%, antiplastering aid 0.5～60wt.% and plasticizer 2～15wt.%.
Antiplastering aid in described coating layer or the colon enteric coat layer is preferably used Pulvis Talci; Plasticizer in the described colon enteric coat layer can be selected triethyl citrate, ethyl sebacate or 1,2-propylene glycol, optimization citric acid triethyl for use.
Wherein, described celphere is the cane sugar type medicinal micro.
Preferred following material of the present invention and proportioning preparation:
Coating layer (percentage by weight): vancomycin 5～15wt.%, antiplastering aid 5～10wt.%, methyl acrylate copolymer 75～90wt.%.
Colon enteric coat layer (percentage by weight): methyl acrylate copolymer 40～94wt.%, antiplastering aid 1～50wt.%, plasticizer 5～10wt.%.
Most preferably be:
Coating layer (percentage by weight): vancomycin 10wt.%%, antiplastering aid 8wt.%, methyl acrylate copolymer 82wt.%.
Colon enteric coat layer (percentage by weight): methyl acrylate copolymer 60wt.%, antiplastering aid 30wt.%, plasticizer 10wt.%.
For reaching end product quality preferably, to keep certain weight ratio between coating layer, colon enteric coat layer and the celphere.
The coating layer should be 1～30wt.% of celphere, is more preferably 5～20wt.% of celphere, most preferably is the 10wt.% of celphere.
The colon enteric coat layer should be 5～60wt.% of celphere, is more preferably 8～30wt.% of celphere, is more preferably the 15wt.% of celphere.
According to a further aspect in the invention, the present invention contains the preferred fluid bed coating method preparation of preparation method of vancomycin colon-targeted pellets, but is not limited only to this, and its fluidized-bed coating preparation thereof is as follows:
(1) at room temperature, take by weighing each material of coating layer such as vancomycin, antiplastering aid and methyl acrylate copolymer by described percentage by weight;
(2) vancomycin is joined in an amount of water dissolving fully, adding antiplastering aid again cuts the homogenize of homogenize machine with height and made the aqueous dispersion suspension in 10 minutes, this suspension is slowly joined in the aforementioned methyl acrylate copolymer that takes by weighing, stir with common blender middling speed simultaneously and mixed in 45 minutes, obtain mixed liquor, this mixed liquor is crossed 80 mesh sieves, be prepared into coating water dispersive suspension;
(3) take by weighing methyl acrylate copolymer, antiplastering aid and plasticizer by described percentage by weight;
(4) antiplastering aid and plasticizer are scattered in an amount of water made the aqueous dispersion suspension in 10 minutes with the homogenize of high shear homogenize machine, then this suspension is under agitation slowly joined in the aforementioned methyl acrylate copolymer that takes by weighing, stir with common blender middling speed simultaneously and mixed in 45 minutes, obtain mixed liquor, this mixed liquor is crossed 80 mesh sieves, make enteric coating water dispersive suspension;
(5) adopt the fluidized bed coating method, the aqueous dispersion suspension of step (2) preparation is sprayed on is prepared into the pastille micropill on the celphere;
(6) adopt and the identical condition of step (5), the colon enteric coatings water dispersive suspension that step (4) is prepared is sprayed on the prepared pastille micropill of step (5), is prepared into colon-targeted pellets.
The condition of described fluidized bed coating can be determined routinely according to the final needs of product, for example can be with the condition enactment of fluid bed: intake 0.7～1.4m
3/ min/kg, nebulizer pressure 1.5～2bar, 38～42 ℃ of inlet temperature, 25～30 ℃ of temperature of outgoing airs, 25～30 ℃ of temperature of charge, nozzle diameter 1mm, spray velocity 5～15ml/min/kg, 5 minutes drying times.
Best, the micropill for preparing is put under 40～50 ℃ of drying conditions and to be got final product in dry 1～3 hour.
Description of drawings
Fig. 1 is the release curve of the embodiment of the invention 1～7;
Fig. 2 is the release curve of the embodiment of the invention 7～14.
The specific embodiment
In order to understand the present invention better, the present invention is further described by the following embodiment, but the present invention is not limited to this.
In following examples of the present invention, methyl acrylate copolymer is all selected for use and is produced by DegussaRohm company
This product is that solid content is 30wt%, and is described in an embodiment with the aqueous dispersion suspension of the copolymer of methacrylic acid, acrylic acid methyl ester. and methyl methacrylate preparation
Amount all refer to the amount of its copolymer.
Used celphere is the cane sugar type micropill of commercially available particle diameter 0.5～0.7mm among the embodiment 1～14, ball core weight 500g.
Vancomycin colon-targeted pellets drug release determination method of the present invention is as follows: for investigating the release conditions of vancomycin colon-targeted pellets in gastrointestinal tract, respectively with the 0.1ml/L hydrochloric acid solution, ph value 6.8 and 7.4 phosphate buffers were as 0～2 hour, 2～4 hours, 4～8 hours dissolution medium, simulation stomach, duodenum, barnyard, ileum, caecum position and colon position, the release situation of investigation vancomycin colon-targeted pellets.The method of conversion dissolution medium is immediately medium to be inclined to after last medium experiment finishes, add the back a kind of medium of equality of temperature then with volume, continue test, each conversion was finished in 5 minutes, calculate the accumulative total dissolution according to the standard curve of medicine in each medium, thereby obtain the release profiles of vancomycin in each Gl tract environment.
Take by weighing 0.75g Lyphocin (Fujisawa) and 3g Pulvis Talci, earlier Lyphocin (Fujisawa) is dissolved in the 110g water, again Pulvis Talci is added in the solution and made suspension in 10 minutes with the homogenize of high shear homogenize machine; This suspension under agitation slowly is scattered in
In (in solid content) polymer suspension, cross 80 mesh sieves and be prepared into coating water dispersive suspension.Other takes by weighing Pulvis Talci 1.5g, triethyl citrate 6g, adds entry 220g mixing and makes the aqueous dispersion suspension, this suspension is slowly joined take by weighing
In, stir with common blender middling speed simultaneously and be mixed and made into the aqueous dispersion suspension in 45 minutes, and this suspension is crossed 80 mesh sieves, be prepared into the colon enteric coating liquid.Adopt the fluidized bed coating technology, successively pastille aqueous dispersion suspension and colon enteric coating liquid are sprayed on the celphere, 40～50 ℃ of dryings promptly got the Lyphocin (Fujisawa) colon-targeted pellets in 3 hours.The weight of the micropill coating layer of present embodiment preparation is 30% of celphere, and the weight of colon enteric coatings is 60% of celphere.Measure release and see Fig. 1.
Take by weighing 1.25 Lyphocin (Fujisawa)s and 1g Pulvis Talci, earlier Lyphocin (Fujisawa) is dissolved in the 10g water, again Pulvis Talci was made suspension in 10 minutes with the homogenize of high shear homogenize machine in adding solution; This suspension under agitation slowly is scattered in
In (in solid content) polymer suspension, cross 80 mesh sieves and be prepared into coating water dispersive suspension.Other takes by weighing Pulvis Talci 15, triethyl citrate 3.75g, adds entry 60g mixing and makes the aqueous dispersion suspension, this suspension is slowly joined take by weighing
In, stir with common blender middling speed simultaneously and be mixed and made into the aqueous dispersion suspension in 45 minutes, and this suspension is crossed 80 mesh sieves, be prepared into the colon enteric coating liquid.Adopt the fluidized bed coating technology, successively pastille aqueous dispersion suspension and colon enteric coating liquid are sprayed on the celphere, 40～50 ℃ of dryings promptly got the Lyphocin (Fujisawa) colon-targeted pellets in 1 hour.The weight of the micropill coating layer of present embodiment preparation is 1% of celphere, and the weight of colon enteric coatings is 5% of celphere.Measure release and see Fig. 1.
Take by weighing 5g Lyphocin (Fujisawa) and 4g Pulvis Talci, earlier Lyphocin (Fujisawa) is dissolved in the 60g water, again Pulvis Talci was made suspension in 10 minutes with the homogenize of high shear homogenize machine in adding solution; This suspension under agitation slowly is scattered in
In (in solid content) polymer suspension, cross 80 mesh sieves and be prepared into coating water dispersive suspension; Other takes by weighing Pulvis Talci 22.5g, triethyl citrate 7.5g, adds entry 120g mixing and makes the aqueous dispersion suspension, this suspension is slowly joined take by weighing
In, stir with common blender middling speed simultaneously and be mixed and made into the aqueous dispersion suspension in 45 minutes, and this suspension is crossed 80 mesh sieves, be prepared into the colon enteric coating liquid.Adopt the fluidized bed coating technology, successively pastille aqueous dispersion suspension and colon enteric coating liquid are sprayed on the celphere, 40～50 ℃ of dryings promptly got the Lyphocin (Fujisawa) colon-targeted pellets in 2 hours.The weight of the micropill coating layer of present embodiment preparation is 10% of celphere, and the weight of colon enteric coatings is 15% of celphere.Measure release and see Fig. 1.
Take by weighing 1.25g Lyphocin (Fujisawa) and 1.25g Pulvis Talci, earlier Lyphocin (Fujisawa) is dissolved in the 30g water, again Pulvis Talci was made suspension in 10 minutes with the homogenize of high shear homogenize machine in adding solution; This suspension under agitation slowly is scattered in
In (in solid content) polymer suspension, cross 80 mesh sieves and be prepared into coating water dispersive suspension.Other takes by weighing Pulvis Talci 0.4g, triethyl citrate 2g, adds entry 35g mixing and makes the aqueous dispersion suspension, this suspension is slowly joined take by weighing
In, stir with common blender middling speed simultaneously and be mixed and made into the aqueous dispersion suspension in 45 minutes, and this suspension is crossed 80 mesh sieves, be prepared into the colon enteric coating liquid.Adopt the fluidized bed coating technology, successively pastille aqueous dispersion suspension and colon enteric coating liquid are sprayed on the celphere, 40～50 ℃ of dryings promptly got the Lyphocin (Fujisawa) colon-targeted pellets in 2 hours.The weight of the micropill coating layer of present embodiment preparation is 5% of celphere, and the weight of colon enteric coatings is 8% of celphere.Measure release and see Fig. 1.
Take by weighing 15g norvancomycin hydrochloride and 10g Pulvis Talci, earlier norvancomycin hydrochloride is dissolved in the 130g water, again Pulvis Talci was made suspension in 10 minutes with the homogenize of high shear homogenize machine in adding solution; This suspension under agitation slowly is scattered in
In (in solid content) polymer suspension, cross 80 mesh sieves and be prepared into coating water dispersive suspension.Other takes by weighing Pulvis Talci 75g, triethyl citrate 15g, adds entry 310g mixing and makes the aqueous dispersion suspension, this suspension is slowly joined take by weighing
In, stir with common blender middling speed simultaneously and be mixed and made into the aqueous dispersion suspension in 45 minutes, and this suspension is crossed 80 mesh sieves, be prepared into the colon enteric coating liquid.Adopt the fluidized bed coating technology, successively pastille aqueous dispersion suspension and colon enteric coating liquid are sprayed on the celphere, 40～50 ℃ of dryings promptly got the norvancomycin hydrochloride colon-targeted pellets in 3 hours.The weight of the micropill coating layer of present embodiment preparation is 20% of celphere, and the weight of colon enteric coatings is 30% of celphere.Measure release and see Fig. 1.
Take by weighing 5g norvancomycin hydrochloride and 4g Pulvis Talci, earlier norvancomycin hydrochloride is dissolved in the 60g water, again Pulvis Talci was made suspension in 10 minutes with the homogenize of high shear homogenize machine in adding solution; This suspension under agitation slowly is scattered in
In (in solid content) polymer suspension, cross 80 mesh sieves and be prepared into coating water dispersive suspension.Other takes by weighing Pulvis Talci 22.5g, ethyl sebacate 7.5g, adds entry 120g mixing and makes the aqueous dispersion suspension, this suspension is slowly joined take by weighing
In, stir with common blender middling speed simultaneously and be mixed and made into the aqueous dispersion suspension in 45 minutes, and this suspension is crossed 80 mesh sieves, be prepared into the colon enteric coating liquid.Adopt the fluidized bed coating technology, successively pastille aqueous dispersion suspension and colon enteric coating liquid are sprayed on the celphere, 40～50 ℃ of dryings promptly got the norvancomycin hydrochloride colon-targeted pellets in 2 hours.The weight of the micropill coating layer of present embodiment preparation is 10% of celphere, and the weight of colon enteric coatings is 15% of celphere.Measure release and see Fig. 1.
Take by weighing 5g Lyphocin (Fujisawa) and 4g Pulvis Talci, earlier Lyphocin (Fujisawa) is dissolved in the 60g water, again Pulvis Talci was made suspension in 10 minutes with the homogenize of high shear homogenize machine in adding solution; This suspension under agitation slowly is scattered in
In (in solid content) polymer suspension, cross 80 mesh sieves and be prepared into coating water dispersive suspension.Other takes by weighing Pulvis Talci 22.5g, 1, and 2-propylene glycol 7.5g adds entry 120g mixing and makes the aqueous dispersion suspension, this suspension is slowly joined take by weighing
In, stir with common blender middling speed simultaneously and be mixed and made into the aqueous dispersion suspension in 45 minutes, and this suspension is crossed 80 mesh sieves, be prepared into the colon enteric coating liquid.Adopt the fluidized bed coating technology, successively pastille aqueous dispersion suspension and colon enteric coating liquid are sprayed on the celphere, 40～50 ℃ of dryings promptly got the Lyphocin (Fujisawa) colon-targeted pellets in 2 hours.The weight of the micropill coating layer of present embodiment preparation is 10% of celphere, and the weight of colon enteric coatings is 15% of celphere.Measure release and see Fig. 1.
Take by weighing 5g Lyphocin (Fujisawa) and 4g Pulvis Talci, earlier Lyphocin (Fujisawa) is dissolved in the 60g water, again Pulvis Talci was made suspension in 10 minutes with the homogenize of high shear homogenize machine in adding solution; This suspension under agitation slowly is scattered in
In (in solid content) polymer suspension, cross 80 mesh sieves and be prepared into coating water dispersive suspension.Other takes by weighing Pulvis Talci 7.5g, triethyl citrate 2.5g, adds entry 40g mixing and makes the aqueous dispersion suspension, this suspension is slowly joined take by weighing
In, stir with common blender middling speed simultaneously and be mixed and made into the aqueous dispersion suspension in 45 minutes, and this suspension is crossed 80 mesh sieves, be prepared into the colon enteric coating liquid.Adopt the fluidized bed coating technology, successively pastille aqueous dispersion suspension and colon enteric coating liquid are sprayed on the celphere, 40～50 ℃ of dryings promptly got the Lyphocin (Fujisawa) colon-targeted pellets in 1 hour.
The weight of the micropill coating layer of present embodiment preparation is 10% of celphere, and the weight of colon enteric coatings is 5% of celphere.Measure release and see Fig. 2.
Embodiment 9
Take by weighing 5g Lyphocin (Fujisawa) and 4g Pulvis Talci, earlier Lyphocin (Fujisawa) is dissolved in the 60g water, again Pulvis Talci was made suspension in 10 minutes with the homogenize of high shear homogenize machine in adding solution; This suspension under agitation slowly is scattered in
In (in solid content) polymer suspension, cross 80 mesh sieves and be prepared into coating water dispersive suspension.Other takes by weighing Pulvis Talci 15g, triethyl citrate 5g, adds entry 80g mixing and makes the aqueous dispersion suspension, this suspension is slowly joined take by weighing
In, stir with common blender middling speed simultaneously and be mixed and made into the aqueous dispersion suspension in 45 minutes, and this suspension is crossed 80 mesh sieves, be prepared into the colon enteric coating liquid.Adopt the fluidized bed coating technology, successively pastille aqueous dispersion suspension and colon enteric coating liquid are sprayed on the celphere, 40～50 ℃ of dryings promptly got the Lyphocin (Fujisawa) colon-targeted pellets in 1 hour.
The weight of the micropill coating layer of present embodiment preparation is 10% of celphere, and the weight of colon enteric coatings is 10% of celphere.Measure release and see Fig. 2.
Embodiment 10
Take by weighing 5g Lyphocin (Fujisawa) and 4g Pulvis Talci, earlier Lyphocin (Fujisawa) is dissolved in the 60g water, again Pulvis Talci was made suspension in 10 minutes with the homogenize of high shear homogenize machine in adding solution; This suspension under agitation slowly is scattered in
In (in solid content) polymer suspension, cross 80 mesh sieves and be prepared into coating water dispersive suspension.Other takes by weighing Pulvis Talci 37.5g, triethyl citrate 12.5g, adds entry 200g mixing and makes the aqueous dispersion suspension, this suspension is slowly joined take by weighing
In, stir with common blender middling speed simultaneously and be mixed and made into the aqueous dispersion suspension in 45 minutes, and this suspension is crossed 80 mesh sieves, be prepared into the colon enteric coating liquid.Adopt the fluidized bed coating technology, successively pastille aqueous dispersion suspension and colon enteric coating liquid are sprayed on the celphere, 40～50 ℃ of dryings promptly got the Lyphocin (Fujisawa) colon-targeted pellets in 2 hours.
The weight of the micropill coating layer of present embodiment preparation is 10% of celphere, and the weight of colon enteric coatings is 25% of celphere.Measure release and see Fig. 2.
Embodiment 11
Take by weighing 5g Lyphocin (Fujisawa) and 4g Pulvis Talci, earlier Lyphocin (Fujisawa) is dissolved in the 60g water, again Pulvis Talci was made suspension in 10 minutes with the homogenize of high shear homogenize machine in adding solution; This suspension under agitation slowly is scattered in
In (in solid content) polymer suspension, cross 80 mesh sieves and be prepared into coating water dispersive suspension.Other takes by weighing Pulvis Talci 52.5g, triethyl citrate 17.5g, adds entry 280g mixing and makes the aqueous dispersion suspension, this suspension is slowly joined take by weighing
In, stir with common blender middling speed simultaneously and be mixed and made into the aqueous dispersion suspension in 45 minutes, and this suspension is crossed 80 mesh sieves, be prepared into the colon enteric coating liquid.Adopt the fluidized bed coating technology, successively pastille aqueous dispersion suspension and colon enteric coating liquid are sprayed on the celphere, 40～50 ℃ of dryings promptly got the Lyphocin (Fujisawa) colon-targeted pellets in 2 hours.
The weight of the micropill coating layer of present embodiment preparation is 10% of celphere, and the weight of colon enteric coatings is 35% of celphere.Measure release and see Fig. 2.
Embodiment 12
Take by weighing 5g Lyphocin (Fujisawa) and 4g Pulvis Talci, earlier Lyphocin (Fujisawa) is dissolved in the 60g water, again Pulvis Talci was made suspension in 10 minutes with the homogenize of high shear homogenize machine in adding solution; This suspension under agitation slowly is scattered in
In (in solid content) polymer suspension, cross 80 mesh sieves and be prepared into coating water dispersive suspension.Other takes by weighing Pulvis Talci 67.5g, triethyl citrate 22.5g, adds entry 360g mixing and makes the aqueous dispersion suspension, this suspension is slowly joined take by weighing
In, stir with common blender middling speed simultaneously and be mixed and made into the aqueous dispersion suspension in 45 minutes, and this suspension is crossed 80 mesh sieves, be prepared into the colon enteric coating liquid.Adopt the fluidized bed coating technology, successively pastille aqueous dispersion suspension and colon enteric coating liquid are sprayed on the celphere, 40～50 ℃ of dryings promptly got the Lyphocin (Fujisawa) colon-targeted pellets in 3 hours.
The weight of the micropill coating layer of present embodiment preparation is 10% of celphere, and the weight of colon enteric coatings is 45% of celphere.Measure release and see Fig. 2.
Embodiment 13
Take by weighing 5g norvancomycin hydrochloride and 4g Pulvis Talci, earlier norvancomycin hydrochloride is dissolved in the 60g water, again Pulvis Talci was made suspension in 10 minutes with the homogenize of high shear homogenize machine in adding solution; This suspension under agitation slowly is scattered in
In (in solid content) polymer suspension, cross 80 mesh sieves and be prepared into coating water dispersive suspension.Other takes by weighing Pulvis Talci 82.5g, triethyl citrate 27.5g, adds entry 440g mixing and makes the aqueous dispersion suspension, this suspension is slowly joined take by weighing
In, stir with common blender middling speed simultaneously and be mixed and made into the aqueous dispersion suspension in 45 minutes, and this suspension is crossed 80 mesh sieves, be prepared into the colon enteric coating liquid.Adopt the fluidized bed coating technology, successively pastille aqueous dispersion suspension and colon enteric coating liquid are sprayed on the celphere, 40～50 ℃ of dryings promptly got the norvancomycin hydrochloride colon-targeted pellets in 3 hours.
The weight of the micropill coating layer of present embodiment preparation is 10% of celphere, and the weight of colon enteric coatings is 55% of celphere.Measure release and see Fig. 2.
Embodiment 14
Take by weighing 5g Lyphocin (Fujisawa) and 4g Pulvis Talci, earlier Lyphocin (Fujisawa) is dissolved in the 60g water, again Pulvis Talci was made suspension in 10 minutes with the homogenize of high shear homogenize machine in adding solution; This suspension under agitation slowly is scattered in
In (in solid content) polymer suspension, cross 80 mesh sieves and be prepared into coating water dispersive suspension.Other takes by weighing Pulvis Talci 90g, triethyl citrate 30g, adds entry 480g mixing and makes the aqueous dispersion suspension, this suspension is slowly joined take by weighing
In, stir with common blender middling speed simultaneously and be mixed and made into the aqueous dispersion suspension in 45 minutes, and this suspension is crossed 80 mesh sieves, be prepared into the colon enteric coating liquid.Adopt the fluidized bed coating technology, successively pastille aqueous dispersion suspension and colon enteric coating liquid are sprayed on the celphere, 40～50 ℃ of dryings promptly got the Lyphocin (Fujisawa) colon-targeted pellets in 2 hours.
The weight of the micropill coating layer of present embodiment preparation is 10% of celphere, and the weight of colon enteric coatings is 60% of celphere.Measure release and see Fig. 2.
Data analysis
According to aforementioned vancomycin colon-targeted pellets release test method as can be known, in the release curve chart, promptly simulated simulated gastric fluid for the 0.1mol/L hydrochloric acid solution in 0～2 hour, be mainly used in reflection for the release situation of test agent in the simulated gastric fluid environment, 2～4 hours is the phosphate buffer of pH value 6.8, be mainly used in reflection for test agent in duodenum release situation in the environment to the intestinal between the colon, for being 7.4 phosphate buffer, pH value was mainly used in reflection in 4～8 hours for the release situation of test agent at the colon position.
Fig. 1 shows: embodiment 1～7 sample was at 0～2 hour (being stomach) no drug release, there is small amount of drug to discharge (＜12%) 2～4 hours (being that duodenum is to intestinal between the colon), rapid at 4～5 hours (being colon portion) drug releases, basically can discharge fully by 6 hours, show for test agent to have the characteristic of significant segmented intestine targeted release.
Fig. 2 shows: the medicated layer of embodiment 8～14 is identical, and colon enteric coatings layer thickness increases successively from embodiment 8～14, is mainly used in to investigate the influence of colon enteric coatings to medicine-releasing performance.Write music line as can be seen from the cumulative release of Fig. 2, the colon enteric coatings all has the characteristic of significant segmented intestine targeted release in weightening finish 5～60wt% scope, along with the increase of colon enteric coatings layer thickness, rate of release slows down successively, but all can discharge fully in 7 hours.
Need to prove that the foregoing invention content and the specific embodiment are intended to prove the practical application of technical scheme provided by the present invention, should not be construed as qualification protection domain of the present invention.Those skilled in the art are in spirit of the present invention and principle, when doing various modifications, being equal to and replacing or improve.Protection scope of the present invention is as the criterion with appended claims.
Claims (13)
1, a kind of colon-targeted pellets that contains vancomycin is characterized in that, described colon-targeted pellets is made of the celphere that does not contain active component, the coating layer that contains the active component vancomycin and colon enteric coatings.
2, colon-targeted pellets according to claim 1 is characterized in that, described coating layer comprises vancomycin 0.5～25wt.%, antiplastering aid 2～20wt.% and methyl acrylate copolymer 55～97.5wt.%; Described colon enteric coatings comprises methyl acrylate copolymer 25～97.5wt.%, antiplastering aid 0.5～60wt.% and plasticizer 2～15wt.%.
3, colon-targeted pellets according to claim 2 is characterized in that, described coating layer comprises vancomycin 5～15wt.%, antiplastering aid 5～10wt.% and methyl acrylate copolymer 75～90wt.%; Described colon enteric coat layer comprises methyl acrylate copolymer 40～94wt.%, antiplastering aid 1～50wt.%, plasticizer 5～10wt.%.
4, colon-targeted pellets according to claim 3 is characterized in that, described coating layer comprises vancomycin 10wt.%, antiplastering aid 8wt.% and methyl acrylate copolymer 82wt.%; Described colon enteric coat layer comprises methyl acrylate copolymer 60wt.%, antiplastering aid 30wt.% and plasticizer 10wt.%.
According to the arbitrary described colon-targeted pellets of claim 2～4, it is characterized in that 5, described vancomycin comprises the derivant of the salt and the vancomycin of vancomycin.
6, colon-targeted pellets according to claim 5 is characterized in that, the salt of described vancomycin is a Lyphocin (Fujisawa); The derivant of described vancomycin is a norvancomycin hydrochloride.
7, according to claim 2,3,4 arbitrary described colon-targeted pellets, it is characterized in that described antiplastering aid is a Pulvis Talci; Described plasticizer is triethyl citrate, certain herbaceous plants with big flowers two diethyl phthalates or 1, the 2-propylene glycol; Described celphere is the cane sugar type medicinal micro.
8, colon-targeted pellets according to claim 1 is characterized in that, the weight of described coating layer is 1～30wt.% of celphere; The weight of described colon enteric coatings is 5～60wt.% of celphere.
9, colon-targeted pellets according to claim 8 is characterized in that, the weight of described coating layer is 5～20wt.% of celphere, and the weight of described colon enteric coatings is 8～30wt.% of celphere.
10, colon-targeted pellets according to claim 9 is characterized in that, the weight of described coating layer is the 10wt.% of celphere, and the weight of described colon enteric coatings is the 15wt.% of celphere.
11, the preparation method of the described colon-targeted pellets of a kind of claim 1～10, described method comprises the steps:
(1) at room temperature, take by weighing each material of coating layer by described percentage by weight, described coating layer comprises vancomycin, antiplastering aid and methyl acrylate copolymer;
(2) vancomycin is joined in an amount of water dissolving fully, add the antiplastering aid homogenize again and make the aqueous dispersion suspension, this suspension is slowly joined in the aforementioned methyl acrylate copolymer that takes by weighing again, mix simultaneously, obtain mixed liquor, this mixed liquor is crossed 80 mesh sieves, and being prepared into total solid content is the coating water dispersive suspension of 20～25wt%;
(3) take by weighing each material of colon enteric coat layer by described percentage by weight, described colon enteric coat layer comprises methyl acrylate copolymer, antiplastering aid and plasticizer;
(4) antiplastering aid and plasticizer are scattered in an amount of water homogenize and make the aqueous dispersion suspension, again this suspension is under agitation slowly joined in the aforementioned methyl acrylate copolymer that takes by weighing, mix simultaneously, obtain mixed liquor, this mixed liquor is crossed 80 mesh sieves, and making total solid content is the colon enteric coatings water dispersive suspension of 20～25wt%;
(5) adopt the fluidized bed coating method, the coating water dispersive suspension of step (2) preparation is sprayed on is prepared into the pastille micropill on the celphere;
(6) adopt and the identical condition of step (5), the colon enteric coatings water dispersive suspension that step (4) is prepared is sprayed on the prepared pastille micropill of step (5), is prepared into colon-targeted pellets.
12, preparation method according to claim 11 is characterized in that, the condition of described fluidized bed coating is: intake 0.7～1.4m
3/ min/kg, nebulizer pressure 1.5～2bar, 38～42 ℃ of inlet temperature, 25～30 ℃ of temperature of outgoing airs, 25～30 ℃ of temperature of charge, nozzle diameter 1mm, spray velocity 5～15ml/min/kg, 5 minutes drying times.
13, according to claim 11 or 12 described preparation methoies, it is characterized in that, also comprise the colon-targeted pellets for preparing was put under 40～50 ℃ of drying conditions dry 1～3 hour.
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| CN2008102117391A CN101683323B (en) | 2008-09-24 | 2008-09-24 | Colonic targeted micropill containing vancomycin and preparation method thereof |
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| CN101683323A true CN101683323A (en) | 2010-03-31 |
| CN101683323B CN101683323B (en) | 2011-12-28 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109589491A (en) * | 2019-01-29 | 2019-04-09 | 上海安翰医疗技术有限公司 | Automatic chemical feeding device |
| CN111374962A (en) * | 2018-12-28 | 2020-07-07 | 内蒙古京新药业有限公司 | Enteric coated preparation of periplaneta americana extract and preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10250543A1 (en) * | 2002-10-29 | 2004-05-19 | Röhm GmbH & Co. KG | Multilayer dosage form |
| CN1857716A (en) * | 2006-03-14 | 2006-11-08 | 浙江大学 | Vancomycin hydrochloride for injection and its preparing method |
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2008
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111374962A (en) * | 2018-12-28 | 2020-07-07 | 内蒙古京新药业有限公司 | Enteric coated preparation of periplaneta americana extract and preparation method thereof |
| CN111374962B (en) * | 2018-12-28 | 2022-08-23 | 内蒙古京新药业有限公司 | Enteric coated preparation of periplaneta americana extract and preparation method thereof |
| CN109589491A (en) * | 2019-01-29 | 2019-04-09 | 上海安翰医疗技术有限公司 | Automatic chemical feeding device |
| CN109589491B (en) * | 2019-01-29 | 2024-01-09 | 上海安翰医疗技术有限公司 | Automatic drug delivery device |
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| CN101683323B (en) | 2011-12-28 |
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