Formulation of a micro drop pill and the preparation method thereof

Abstract

The present invention relates to a preparation method for a traditional Chinese medicine drop pill and a traditional Chinese medicine micro drop pill prepared by using the method, and in particular, the present invention relates to a micro drop pill preparation method with high drug-loading capacity, simple preparation process and high production rate and a micro drop pill prepared by using the method. Specially, The drop pill preparation method used comprises the following steps: (1) material melting step: heat melting a medicine and a drop pill matrix to obtain a molten medicine liquid; (2) dropping step: delivering the molten medicine liquid to a dripper, and acquiring medicine drops of the molten medicine liquid by means of vibration dropping; and, (3) condensation step: cooling the medicine drops with a cooling gas to obtain micro drop pills.

1 . A preparation method for a micro drop pill comprising the following steps:
 (1) a material melting step comprising heat melting a medicine and a drop pill matrix to obtain a molten medicine liquid;   (2) a dropping step comprising delivering the molten medicine liquid under pressure to a dripper, and acquiring medicine drops of the molten medicine liquid by means of vibration dropping; and, (3) a condensation step comprising cooling the medicine drops with a cooling gas to obtain micro drop pills.   
     
     
         2 . The preparation method according to  claim 1 , wherein:
 (1) the material melting step comprises heat melting the medicine and the drop pill matrix at 40° C.˜120° C., homogenizing for 0.5˜4 hours to obtain a homogenized molten medicine liquid, and the ratio of the medicine to the drop pill matrix is 1:5˜5:1 by weight;   (2) the dropping step comprises delivering the molten medicine liquid under pressure to the dripper, and acquiring medicine drops at a vibration frequency for dropping of 2˜2000 Hz under a dropping pressure of 0.5˜4.0 Bar, a temperature of the dripper of 40° C.˜200° C. and a viscosity of the molten medicine liquid of 300˜1500 cp; and,   (3) the condensation step comprises cooling the medicine drops with a cooling gas for forming by solidifying, obtaining micro drop pills having a particle size of 0.2 mm˜4 mm, the temperature of the cooling gas is 0° C. or lower.   
     
     
         3 . The preparation method according to  claim 1 , wherein in Step (1), the drop pill matrix includes one or more selected from the group consisting of PEGs, sorbitol, xylitol, lactitol, maltose, starch, methylcellulose, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, arabic gum, alginic acid, dextrin, cyclodextrin, agar and lactose; preferably solid PEGs, such as PEG-1000, PEG-2000, PEG-3000, PEG-4000, PEG-5000, PEG-6000, PEG-7000 and PEG-8000; more preferably one or more selected from the group consisting of PEG-1000, PEG-2000, PEG-3000, PEG-4000, PEG-6000 and PEG-8000; most preferably PEG-6000, PEG-4000 or the combination of PEG-4000 and PEG-6000. 
     
     
         4 . (canceled) 
     
     
         7 . The preparation method according to  claim 1 , wherein in Step (2), the temperature of the dripper is at 60˜120° C., preferably at 60˜100° C.; the vibration frequency for dropping is preferably at 20˜300 Hz, more preferably 50˜300 Hz, more preferably 20˜200 Hz, more preferably 20˜150 Hz, most preferably 50˜150 Hz; the vibration mode includes magnetic/electronic vibration or pneumatic vibration, preferably electronic vibration; the viscosity of the molten medicine liquid is 500˜1000 cp, preferably 700˜1000 cp. 
     
     
         8 .- 10 . (canceled) 
     
     
         11 . The preparation method according to  claim 2 , wherein:
 (1) the material melting step comprises charging the medicine and the drop pill matrix into a homogenizer, mixing homogenously at 1000˜5000 rpm for 1˜200 min, then melting homogenously at 3000˜10000 rpm for 1˜100 min; during the melting process, the temperature is kept at 60˜100° C. to obtain the molten medicine liquid; the ratio of the medicine to the micro drop pill matrix is 1:5˜5:1 by weight;   (2) the dropping step comprises delivering the molten medicine liquid under pressure to the dripper, and acquiring medicine drops from the dripper by means of vibration dropping at a vibration frequency for dropping of 20˜300 Hz under a dropping pressure of 0.5˜4.0 Bar and the temperature of the dripper of 40° C.˜200° C., the dropping rate is matched with the melting rate in Step (1); and   (3) the condensation step comprises cooling the medicine drops with a cooling gas rapidly to solidify, and obtaining solid drop pills having a particle size of 0.2 mm˜4.0 mm wherein the temperature of the cooling gas is 0° C.˜−150° C.   
     
     
         12 . The preparation method according to  claim 11 , wherein in Step (1), the ratio of the medicine to the drop pill matrix is 1:3˜3:1 by weight, mixing homogeneously at 3000˜5000 rpm for 10˜60 min, then melting homogeneously at 4000˜9000 rpm for 5˜30 min, during the melting process, the temperature is kept at 70˜90° C. 
     
     
         13 . The preparation method according to  claim 11 , wherein in Step (1), the ratio of the medicine to the drop pill matrix is 1:(1˜3) by weight, mixing homogeneously at 3000˜4000 rpm for 10˜30 min, then melting homogeneously at 4000˜6000 rpm for 6˜30 min, during the melting process, the temperature is kept at 75˜85° C. 
     
     
         14 . The preparation method according to  claim 11 , wherein in Step (2), the temperature of the dripper is at 70˜100° C., the vibration frequency is at 90˜200 Hz, the dropping pressure is at 1.0˜3.0 Bar; preferably the vibration frequency is at 137 Hz, an acceleration speed is at 4G, the dropping pressure is at 1.8 Bar and the temperature of the dripper is at 75˜85° C. 
     
     
         15 . The preparation method according to  claim 11 , in Step (2), the dropping rate is 10˜40 Kg/h, preferably 12˜30 Kg/h, further preferably 15˜25 Kg/h. 
     
     
         16 . The preparation method according to  claim 1 , wherein the method additionally comprises a drying step as Step (4): drying the low-temperature drop pills from Step (3) on a fluidized-bed at 40˜150° C., preferably at 40˜60° C. for 1˜4 hours, preferably 1˜3 hours, most preferably 2 hours to obtain uncoated drop pills. 
     
     
         17 . The preparation method according to  claim 16 , wherein in Step (4), a gradient-rising temperature drying method is used as follows: fluidizing at −20˜30° C., drying at 15˜35° C. for 10˜120 min, drying at 35˜55° C. for 10˜60 min, drying at 55˜100° C. for 0˜60 min; preferably the gradient-rising temperature drying method is performed as follows: fluidizing at 0˜20° C., drying at 25° C. for 60 min, drying at 45° C. for 30 min, drying at 55° C. for 0˜30 min. 
     
     
         18 . The preparation method according to  claim 1 , wherein the method additionally comprises a coating step as Step (5): coating the uncoated drop pills obtained from Step (4) in a state of fluidization, wherein the concentration of the coating liquid is at 15˜25 wt %, preferably 18˜20 wt %; the coating material is selected from shellac, CAP, methyl acrylate, methyl methacrylate or Opadry; and the ratio of the coating material to the uncoated drop pill is 1:50˜1:25 by weight. 
     
     
         19 . The preparation method according to  claim 1 , wherein the method additionally comprises a pre-mixing step before Step (1): adding the medicine powder or extract with water, stirring for 10 min or longer at 30˜80° C. to obtain a pre-mixed medicine material. 
     
     
         20 . A formulation of micro drop pill, wherein in the micro drop pill, the ratio of the medicine to the drop pill matrix is 1:5˜5:1 by weight, a particle size of the micro drop pill is 0.2 mm˜4 mm, the micro drop pill is prepared by the method of  claim 1 , and the micro drop pill has no residual coolant. 
     
     
         21 . The formulation of micro drop pill according to  claim 20 , characterized in that the particle size is 0.2 mm˜2 mm. 
     
     
         22 . (canceled) 
     
     
         23 . The formulation of micro drop pill according to  claim 20 , wherein the formulation of micro drop pill is a Compound  Salvia Militiorrhiza  micro drop pill (CSMDP), the micro drop pill is prepared by the API of Compound  Salvia Militiorrhiza  and the drop pill matrix in a ratio of 1:5˜5:1 by weight, the particle size of the Compound  Salvia Militiorrhiza  micro drop pill is 0.2 mm˜4 mm, the API of Compound  Salvia Militiorrhiza  is prepared by the following crude drugs by weight parts:  Salvia Militiorrhiza  75.0˜90.0 parts,  Panax Notoginseng  10.0˜25.0 parts and borneol 0.1˜4.0 parts. 
     
     
         24 .- 25 . (canceled) 
     
     
         26 . The formulation of micro drop pill according to  claim 23 , characterized in that the particle size of the micro drop pill is 0.2 mm˜2 mm. 
     
     
         27 . The formulation of micro drop pill according to  claim 26 , characterized in that the particle size of the micro drop pill is 1 mm˜2 mm. 
     
     
         28 .- 29 . (canceled) 
     
     
         30 . The formulation of micro drop pill according to  claim 20 , wherein the formulation of micro drop pill is a Qishenyiqi micro drop pill (QMDP), characterized in that the micro drop pill is prepared by the API of Qishenyiqi and the drop pill matrix in a ratio of 1:5˜5:1 by weight, the particle size of the Qishenyiqi micro drop pill is 0.2 mm˜4 mm, the API is prepared by the following crude drugs by weight parts:  Astragalus membranaceus  100˜200 parts,  Salvia Militiorrhiza  50˜100 parts,  Panax Notoginseng  10 ˜ 20   parts and volatile oil from  Lignum Dalbergiae Odoriferae  0.5˜2 parts. 
     
     
         31 .- 32 . (canceled) 
     
     
         33 . The formulation of micro drop pill according to  claim 30 , wherein the particle size of the micro drop pill is 0.2 mm˜2 mm. 
     
     
         34 .- 36 . (canceled)