Application of andrographolide in the preparation of a pharmaceutical for treatment of inflammatory bowel disease, andrographolide enteric targeting micropellet, and method for preparation thereof

Abstract

The present invention relates to an andrographolide enteric targeting micropellet and method for preparation thereof; furthermore, the present invention also relates to uses of andrographolide and andrographolide enteric targeting micropellets in the preparation of a pharmaceutical for treatment of inflammatory bowel disease.

What is claimed is: 
     
         1 . A method of preparing an andrographolide enteric micropellet of composed of a blank pellet, a drug layer and an enteric coating layer, wherein said drug layer contains andrographolide, a polymer A that dissolves under a condition of pH≧7.0 and an excipient; where said ratio of the andrographolide and polymer A is 1:2˜1:0.2 by weight; and wherein the weight gain of the drug layer is 20 wt %˜100 wt %; said enteric coating layer containing a polymer B that dissolves under a condition of pH≧5.5 and an excipient; and wherein the weight gain of the enteric coating layer is 5 wt %˜30 wt %,
 comprising the following steps:
 (1) applying andrographolide to a blank micropellet by
 a). dispersing the polymer A into a pharmaceutical solvent to allow the polymer A to dissolve in the solvent fully by mechanical stirring to obtain a polymer A solution: adding an excipient into the polymer A solution and then adding andrographolide to the polymer A solution and then stirring well to provide a polymer A coating solution; 
 b). weighing the blank micropellet and charging the blank micropellet into a fluidized bed; adjusting the air flow in the fluidized bed to such a degree that the micropellet is well fluidized; starting a heating device and heating the well fluidized blank micropellet until temperature of the well fluidized blank micropellet material reaches a preset value; starting a peristaltic pump which atomizes the polymer A coating solution through a spray gun to uniformly disperse the polymer A coating solution on the surface of the blank micropellet to obtain a drug-loaded micropellet; 
 
 (2) preparing the enteric coating layer by
 a). dispersing the polymer B into a pharmaceutical solvent to allow the polymer B to dissolve in the solvent fully by mechanical stirring to obtain a polymer B solution; adding an excipient into the polymer B solution and then stirring well to provide a polymer B coating solution; 
 b). charging aforesaid andrographolide-loaded micropellet into a bottom-spray device of a fluidized bed, and uniformly spreading the polymer B coating solution to form the enteric coating layer; wherein the weight gain of the enteric coating layer is 5 wt %˜30 wt %. 
 
 
 
     
     
         2 . The preparation method according to claim  8  comprising following steps:
 (1) applying drug to the blank micropellet by
 a). dispersing the polymer A into the pharmaceutical solvent which is ethanol such that the content of polymer A is 5 wt %; fully dissolving the polymer A in the ethanol by mechanical stirring to form the polymer A solution and continuing to uniformly stir the polymer A solution; adding excipient which is plasticizer, anti-sticking agent and the surfactant sodium dodecyl sulfate into the polymer A solution, and then adding the andrographolide to the polymer A solution and then stirring well to provide the polymer A coating solution; 
 b). weighing the blank micropellet which is a sucrose micropellet having a diameter of 200˜600 μm and charging the sucrose micropellet into a fluidized bed; adjusting air flow to such a degree that the sucrose micropellet is well fluidized; starting the heating device and heating the well fluidized sucrose micropellet until the temperature reaches the preset value of 25˜35° C. starting the peristaltic pump which atomizes the polymer A coating solution through a spray gun to uniformly disperse the polymer A coating solution on the surface of the sucrose micropellet to obtain a drug-loaded sucrose micropellet; 
 
 (2) preparing the enteric coating layer by
 a). dispersing the polymer B into the pharmaceutical solvent ethanol to allow the polymer B to dissolve in the ethanol fully by high-speed shearing mechanical stirring to obtain a polymer B solution; adding the excipient of the plasticizer and anti-sticking agent into the polymer B solution and stirring well to provide the polymer B coating solution; 
 b). charging aforesaid drug-loaded sucrose micropellet into a bottom-spray device of the fluidized bed, and uniformly spreading the polymer B coating solution to form the enteric coating layer; wherein the weight gain of the enteric coating layer is 8 wt %˜20 wt %. 
 
 
     
     
         3 . The method of  claim 1  wherein the ratio of the andrographolide and polymer A is 1:2.5˜1:0.5 by weight. 
     
     
         4 . The method of  claim 1  wherein the excipient of the drug layer is selected from the group consisting of plasticizer, antisticking agent, pigment, hydrophilic polymer and surfactant and wherein the excipient of the enteric coating layer is selected from the group consisting of plasticizer and antisticking agent. 
     
     
         5 . The method of  claim 4  wherein the ingredients are present in proportion by weight parts: blank micropellet:andrographolide:polymer A:plasticizer:antisticking agent:surfactant=200: (10-100):(10-100):(1-15):(1-30):(0-3). 
     
     
         6 . The method of  claim 4  wherein the ingredients are present in proportion by weight parts: blank micropellet:andrographolide:polymer A:plasticizer:antisticking agent:surfactant=200:(15-66):(13-74):(2-13.5):(3-27):(0-1.32). 
     
     
         7 . The method of  claim 4  wherein the ingredients are present in proportion by weight parts: blank micropellet:andrographolide:polymer A:plasticizer:antisticking agent:surfactant=200: (20-50):(30-60):(5-10):(5-20):(0.5-1.2).