TW201436820A - Method for preparing Herba Dendrobii wall-breaking dosage form - Google Patents

Abstract

The present invention relates to a Chinese medicine dosage form and relates specifically to a method for preparing a Herba Dendrobii wall-breaking dosage form. The present invention pulverizes Herba Dendrobii into wall-broken powder, which is subjected to an alcohol-water wetting process granulation through quality control of alcohol solution and the wall-broken powder and is also subjected to extrusion forming under a predetermined rotational speed and then dried. The granulation rate of the present inventive process is high and the Herba Dendrobii wall-breaking dosage form so manufactured has an increased bioavailability and the doesage form has improved stability and good disintegrability. The method comprises the following steps: (1) performing ultrafine wall-breaking pulverization to Herba Dendrobii to obtain ultrafine wall-broken powder; (2) mixing alcohol-water solution and the ultrafine wall-broken powder at a weight ratio of 1-1.6:1 to form a soft material; and (3) extruding to form wet granules, which is then dried to form the dosage form.

Description

Preparation method of stone smash breaking preparation

The invention relates to the field of traditional Chinese medicine, and more particularly to a preparation method of a stone wall breaking preparation.

Superfine pulverization technology is a new technology that has developed rapidly in recent years. Most of the active ingredients in Chinese herbal medicines are distributed in the cells. When the conventional decoction pieces are boiled, only some of the active ingredients can be released, and the effective ingredient utilization rate is 10-30%; and the broken wall crushing technology, such as the Chinese medicine decoction pieces, is crushed to 300 mesh. Left and right, the cell wall breaking rate will reach 86.7%, which improves the dissolution of the active ingredients in the medicinal materials, greatly enhances its efficacy, and the utilization rate of the active ingredients is above 90%, thereby reducing the amount of medicinal materials used and protecting the medicinal materials, and also improving the medicines. The quality of the product increases the efficacy. However, the current main ultrafine powder technology still stays at the stage of pulverizing Chinese herbal medicines to ultrafine preparations. Due to the increased cell wall breaking rate of the ultrafine preparation, the surface area of the broken wall preparation is increased, the shape is irregular, the fluidity, the dispersibility is poor, the moisture absorption is easy, and the stability is poor, and the granulation is performed to improve the stability of the product. The preparation prepared by the invention solves the above problems well and maximizes the utilization and use of the medicine.

Dendrobium is a dry stem of the orchid family, the genus Dendrobium, Dendrobium or Dendrobium and its similar species. Dendrobium nobile contains mainly alkaloids: Dendrobium, Dendrobium sulphate, Dendrobium phenol, 6-hydroxy saponin, Dendrobium bromide, 6-hydroxy saponin, etc.; and also contains scutellarin, β-sitosterol and the like. Dendrobium Dendrobium mainly contains phenanthrene components: Drumstick Philippine, Mao Lanfei, etc.; bibenzyl components: lanolin, drumstick bibenzyl. The tassels are mainly composed of phenanthrene components: taupe, Maolanfei, etc.; they also contain rhein, emodin, and the like. Using traditional boiling methods, it is easy to destroy its heat-sensitive ingredients. On the other hand, the active ingredients are not fully cooked, resulting in the loss of active ingredients. The preparation of Dendrobium candidum into an ultrafine powder of Dendrobium is beneficial to increase the utilization rate of the active ingredient, but at the same time, due to the increase of the specific surface area of the powder, it has the disadvantages of easy moisture absorption, oxidation, deterioration and the like. Therefore, on the basis of preparation of ultrafine powder, it is necessary to carry out further processing and transformation to effectively overcome these unfavorable factors and maximize the therapeutic effect of the drug.

The invention provides a stone smash breaking preparation with high yield, good disintegration and stability, and provides a preparation method of the stone smash breaking preparation, the steps are as follows, S1. The sarcophagus is subjected to ultra-fine wall pulverization to obtain ultra-fine breakage. Wall powder, S2. Ethanol-water solution and ultra-fine broken wall powder are mixed by weight ratio of 1~1.6:1 to obtain soft material, S3. Squeeze to obtain wet granules and dry.

The ethanol-water solution and the ultra-fine wall-breaking powder in the step S2 are preferably mixed at a weight ratio of 1.3 to 1.5:1.

The ethanol-water solution in the step S2 has a mass fraction of ethanol of 50% to 95%, preferably 60% to 90%.

More preferably, the ethanol-water solution in step S2 has a mass fraction of ethanol of 65% to 75%, and the ethanol-water solution and the ultra-fine wall-breaking powder are mixed at a weight ratio of 1.3 to 1.5:1. The soft material under this condition has suitable viscosity, easy sieving, high yield of the finished product, and excellent shape.

The breaking rate of the ultrafine broken powder in the step S1 is 80 to 95%.

More than 90% of the particles of the ultrafine wall breaking powder in the step S1 have a particle diameter of 45 μm or less.

The pressing condition in the step S3 is: pressing force 0.05Mpa~1Mpa, rotating speed 50r/min~100r/min, preferably, pressing force 0.15Mpa~0.25Mpa, rotating speed 80r/min~90r/min .

The soft material obtained in the step S2 is passed through a screen of 10 to 30 mesh.

Finally, a stone smashing wall preparation obtained by the above method is provided, which has a bulk density of 0.15 to 0.35 g/mL.

In order to better understand the present invention, the following description of the present invention is further illustrated in conjunction with the reaction scheme, which is not intended to limit the scope of the invention.

The object of the invention is to overcome the following technical problems: 1. The current broken wall preparation has high utilization rate of the traditional Chinese medicine component, but the broken wall powder is easily oxidized, the stability is not high, and the efficacy is easily lost; Some Chinese medicine varieties are obtained by soft material granulation, it is difficult to ensure the yield, disintegration and stability at the same time; 3. Some Chinese medicine varieties can not be made by breaking the wall powder-soft material granulation method, such as枸杞, Achyranthes and the like; and the invention through a large number of experimental exploration, the appropriate Chinese medicine varieties of broken wall-soft granulation method are screened out, and the conditions of each step are explored.

The invention provides a traditional Chinese medicine preparation which is simple in granulation process and does not require a binder, and is granulated while being broken, and good disintegration and stability are obtained by adjusting parameters.

The invention provides a stone smashing wall breaking preparation, which adopts the following technical scheme: the wall smash is crushed and smashed to obtain the broken wall powder, and the ethanol-water solution is added to be fully mixed to obtain a soft material, which is further extruded to obtain wet granules, and dried to obtain sarcophagus. In the broken wall preparation, the ultrafine powder has a wall breaking rate of 80 to 95%. The stone smashing wall preparation prepared by the invention can make the consumption of the active ingredient maximized by the consumer without decocting by washing with warm water.

The sarcophagus can be first pulverized to 100 mesh, and further subjected to ultrafine pulverization so that 90% or more of the ultrafine powder (for example, 90%, 91%, 92%, 93%, 94% or 95%) may be granulated. The diameter is less than or equal to 45 μm. The ultrafine powder used in the scheme, 90% of the particles have a particle size of 15-45 μm (for example, 15, 17, 19, 21, 23, 25, 27, 30, 32, 34, 36 or 38 μm), but It will be apparent to those skilled in the art that these examples are not to be construed as limiting the invention, as long as the particle size is less than or equal to 45 μm.

The present invention employs an ethanol-water solution for wet granulation, which has the outstanding advantage that the ultrafine powder of the present invention can be passed into the granules of the sarcophagus preparation by subsequent granulation and drying without any other additives. However, in the process, what concentration of ethanol-water solution should be used, and the ratio between the solution and the ultrafine preparation are parameters that need to be strictly controlled, so that the humidity, solid content, viscosity, etc. of the soft material can be It is suitable for the characteristics of the stone smashing wall preparation, so that the preparation can be effectively bonded; further, through the setting of specific extrusion parameters, the soft material is extruded into a suitable density and size of the sarcophagus granule preparation, so that the density/fluffiness is appropriate. Therefore, after drying into a finished product, even if it is placed in air at room temperature, the oxidation of air can be prevented. Moreover, when the finished product obtained is washed with warm water, the ultrafine preparation can be dispersed relatively quickly, so that the active ingredient dissolves and diffuses rapidly and fully, and the utilization ratio of the active ingredient is improved.

The invention has repeatedly selected the following schemes: in the wet granulation, the ethanol component in the ethanol-water solution has a quality fraction of 50% to 95%; preferably, the ethanol quality fraction is 60% to 90%. More preferably, it is 64% to 84%. The ratio of the ultrafine powder to the ethanol-water solution is 1:1.0 to 1.6, and the weight is 1:1.0 to 1.6, preferably 1:1.1 to 1.5.

When the soft material is extruded into wet granules, it is preferably controlled under the following conditions: a pre-packed 10 mesh to 30 mesh screen, a pressing force of 0.05 MPa to 1 MPa, a rotational speed of 50 r/min to 100 r/min; preferably, extrusion The force is 0.15Mpa~0.25Mpa, and the speed is 80r/min~90r/min.

The wet particle size obtained by extrusion is 14 mesh to 40 mesh, the drying temperature during drying is 45 ° C to 85 ° C, and the drying time is 0.5 h to 2.5 h.

The obtained dendrobium breaking preparation has a density of 0.15 g/ml to 0.33 g/ml.

Compared with the prior art, the present invention has the following beneficial effects:

1. The sarcophagus preparation obtained by the method of the invention has greatly improved utilization rate of active ingredients, and the utilization rate is close to 100%; it is confirmed by bioequivalence test that 1/4 part of the sarcophagus broken wall preparation can be equivalent to 1 part. The efficacy of traditional sarcophagus;

2. The invention obtains a suitable wet granulation process by groping, so that in addition to the addition of ethanol-water, the granulation process can obtain a soft material with a solid content and a moderate viscosity without any other additives, so as to smoothly squeeze. Pressed into a granulation process, the formed traditional Chinese medicine particles have strong stability and are not easy to collapse during storage and transportation.

3. The extrusion conditions of the present invention explore the appropriate rotation speed and pressing force, thereby preparing a viscous, moderately dense sarcophagus granule preparation, which is easy to disintegrate during the taking process while obtaining stable stability of the finished product. Dispersed, easy to warm water and wash.

4. It is generally believed that when the ultrafine powder is subjected to wet granulation, the control of the soft material is mainly the ethanol concentration of the aqueous ethanol solution, but the present inventors have found that although the ethanol concentration of the aqueous ethanol solution has an effect on the soft material formation, the ultrafine powder and the ethanol The quality ratio of the aqueous solution is also one of the necessary conditions. The present invention achieves a good shape of the soft material by controlling the quality ratio of the ethanol-water solution and the ultra-fine broken wall powder, and provides a good foundation for the final broken wall preparation.

The invention will be further described in detail below with reference to the drawings and specific embodiments. Unless otherwise stated, the reagents, devices, and methods employed in the present invention are conventionally commercially available reagents, equipment, and methods of routine use.

Example 1: Take the medicinal material of Dendrobium serrata, and after coarsely pulverizing to a coarse powder of about 100 mesh, it is ultrafinely pulverized into 90% of the powder having a particle size of 45 μm or less in the ultrafine powder, and an ethanol-water solution is added (the ethanol quality fraction is 50%) Wet process soft material, the ratio of solution to ultrafine powder is 1.0:1 (by weight), after mixing, pre-loaded with 10 mesh sieve, select extrusion speed 50r/min, extrusion force 1MPa to make wet The granules and wet granules are transferred into a hot air loop oven, set to a drying temperature of 85 ° C, dried for 2.5 h to dryness, and the whole granules are sieved to obtain a stone smashing wall preparation.

Remarks: The full score is 10.

Example 2: Taking the medicinal material of Dendrobium sinensis, after coarsely pulverizing to a coarse powder of about 100 mesh, ultrafine pulverization into 90% of the powder having a particle size of 45 μm or less in the ultrafine powder, and adding an ethanol-water solution (the ethanol quality fraction is 60%) Wet process soft material, the ratio of solution to ultrafine powder is 1.1:1 (by weight). After mixing, pre-loaded with 10 mesh sieve, the extrusion speed is 50r/min, and the extrusion force is 0.8MPa. The wet granules and the wet granules were transferred into a vacuum microwave drying oven, and the drying temperature was set at 45 ° C, dried for 0.75 h to dryness, and the whole granules were sieved to obtain a stone smashing wall preparation.

Remarks: The full score is 10.

Example 3: Take the medicinal material of Dendrobium sinensis. After coarsely pulverizing to a coarse powder of about 100 mesh, it is ultra-finely pulverized into 90% of the powder with a particle size of 45 μm or less in the ultrafine powder, and added with an ethanol-water solution (ethanol quality fraction of 90%). The legal soft material, the solution and the ultrafine powder are added in a ratio of 1.5:1 (by weight). After mixing, the pre-packed 30 mesh sieve is used, and the extrusion speed is 80 r/min, and the pressing force is 0.3 MPa to make wet particles. The granules are placed in a hot air loop oven, and the drying temperature is set at 85 ° C, dried for 2.5 h to dryness, and the whole granules are sieved to obtain a stone smashing wall preparation.

Remarks: The full score is 10.

Example 4: Taking the medicinal material of Dendrobium sinensis, after coarsely pulverizing to a coarse powder of about 100 mesh, ultrafine pulverization into 90% of the powder having a particle size of 45 μm or less in the ultrafine powder, and adding an ethanol-water solution (the ethanol quality fraction is 65%) Wet process soft material, the ratio of solution to ultrafine powder is 1.4:1 (by weight), after mixing, pre-assembled 30 mesh sieve, using extrusion speed 60r/min, extrusion force 0.5MPa The wet granules and the wet granules were transferred into a vacuum microwave drying oven, and the drying temperature was set at 50 ° C, dried for 0.5 h to dryness, and the whole granules were sieved to obtain a stone smashing wall preparation.

Remarks: The full score is 10.

Example 5: Taking the medicinal material of Dendrobium sinensis, after coarsely pulverizing to a coarse powder of about 100 mesh, it is pulverized by ultrafine pulverization into 90% of a powder having a particle diameter of 45 μm or less in an ultrafine powder, and an ethanol-water solution (B quality fraction) is added. 95%) wet process soft material, the ratio of solution to ultrafine powder is 1.6:1 (by weight), after mixing, after Pre-assembled 20 mesh sieve, select the extrusion speed 100r/min, squeeze the strength 0.05MPa wet particles, wet particles transfer hot air loop wind box, set the drying temperature 70 ° C, dry 2.0h to dry, whole sieve After that, the stone wall breaking preparation was obtained.

Remarks: The full score is 10.

Example 6: Taking the medicinal material of Dendrobium sinensis, after coarsely pulverizing to a coarse powder of about 100 mesh, it is pulverized by ultrafine pulverization into 90% of the powder having a particle diameter of 45 μm or less in the ultrafine powder, and the mass fraction of the ethanol-water solution added is 75% solution is made of wet method, the ratio of solution to ultrafine powder is 1.3:1 (by weight). After mixing, pre-loaded with 20 mesh sieve, the extrusion speed is 50r/min, and the extrusion force is 0.2MPa. The wet granules are boiled and dried, and the dry air temperature is set to 85 ° C, dried for 0.5 h to dryness, and the whole granules are sieved to obtain the stone smashing wall preparation.

Remarks: The full score is 10.

Example 7: Taking the crude medicinal material of Dendrobium sinensis, after coarsely pulverizing to a coarse powder of about 100 mesh, ultrafine pulverization into 90% of the powder having a particle diameter of 45 μm or less in the ultrafine powder, and adding an ethanol-water solution (the ethanol quality fraction is 60%) Wet process soft material, the ratio of solution to ultrafine powder is 1.3:1 (by weight), after mixing, pre-loaded with 10 mesh sieve, the extrusion speed is 50r/min, and the extrusion strength is 1MPa. The granules and wet granules were transferred into a vacuum microwave drying oven, and the drying temperature was set at 45 ° C, dried for 0.75 h to dryness, and the whole granules were sieved to obtain a stone smashing wall preparation.

Remarks: The full score is 10.

Example 8: Taking the medicinal material of Dendrobium sinensis, after coarsely pulverizing to a coarse powder of about 100 mesh, it is pulverized by ultrafine pulverization into 90% of the powder having a particle diameter of 45 μm or less in the ultrafine powder, and the mass fraction of the ethanol-water solution added is 75% solution wet process soft material, the ratio of solution to ultrafine powder is 1.4:1 (by weight), after mixing, pre-installed 20 mesh sieve, using extrusion speed 80r/min, extrusion force 0.1MPa The wet granules are boiled and dried, and the dry air temperature is set to 85 ° C, dried for 0.5 h to dryness, and the whole granules are sieved to obtain the stone smashing wall preparation.

Remarks: The full score is 10.

Example 9: Taking the medicinal material of Dendrobium sinensis, after coarsely pulverizing to a coarse powder of about 100 mesh, it is pulverized by ultrafine pulverization into 90% of the powder having a particle diameter of 45 μm or less in the ultrafine powder, and the mass fraction of the ethanol-water solution added is 75% of the solution is made by wet method, the ratio of solution to ultrafine powder is 1.7:1 (by weight). After mixing, pre-loaded with 20 mesh sieve, the extrusion speed is 70r/min, and the extrusion force is 0.7MPa. The wet granules are boiled and dried, and the dry air temperature is set to 85 ° C, dried for 0.5 h to dryness, and the whole granules are sieved to obtain the stone smashing wall preparation.

Remarks: The full score is 10.

Example 10: Take the medicinal material of Dendrobium serrata, and after coarsely pulverizing to a coarse powder of about 100 mesh, it is pulverized by ultrafine pulverization into 90% of the powder having a particle diameter of 45 μm or less in the ultrafine powder, and the mass fraction of the ethanol-water solution added is 75% solution is made of wet method, the ratio of solution to ultrafine powder is 1.4:1 (by weight). After mixing, pre-loaded with 20 mesh sieve, the extrusion speed is 103r/min, and the extrusion force is 1.2MPa. The wet granules are boiled and dried, and the dry air temperature is set to 85 ° C, dried for 0.5 h to dryness, and the whole granules are sieved to obtain the stone smashing wall preparation.

Remarks: The full score is 10.

Example 11: Taking the medicinal material of Dendrobium sinensis, after coarsely pulverizing to a coarse powder of about 100 mesh, it is pulverized by ultrafine pulverization into 90% of the powder having a particle diameter of 45 μm or less in the ultrafine powder, and the mass fraction of the ethanol-water solution added is 75% solution is made of wet method, the ratio of solution to ultrafine powder is 1.4:1 (by weight). After mixing, pre-loaded with 20 mesh sieve, the extrusion speed is 40r/min, and the extrusion force is 0.04MPa. The wet granules are boiled and dried, and the dry air temperature is set to 85 ° C, dried for 0.5 h to dryness, and the whole granules are sieved to obtain the stone smashing wall preparation.

Remarks: The full score is 10.

The finished products of Examples 1~6 and 8 were tested according to the finished product quality standards, and the results were all in accordance with the requirements of the relevant Chinese Pharmacopoeia related dosage forms. The results are shown in Table 1.

Further, the Examples 1 to 6 and 8 of the lower sarcophagus breaking preparation, the sarcophagus ultrafine powder and the sarcophagus conventional decoction pieces were used as indicators for evaluation of traits, moisture and extracts, all of which were sealed in a sealed plastic bag and placed at a temperature of 40 ° C. The stability of each formulation was evaluated after standing for 3 months at ± 2 ° C and a relative humidity of 75% ± 5%. The results are as follows:

In the following step, the advancement of the present invention is illustrated by the comparative experiment of the efficacy, and the Dendrobium preparation prepared in Example 6 is compared with the conventional decoction piece. The traditional decoction group (conventional decoction group) was obtained by traditional decoction method. The preparation group was prepared by immersing the preparation for 90 days with about 60° warm water, and taking the supernatant to administer the stomach.

Eighty SPF Kunming mice, 18g~22g, male and female, were randomly divided into control group, model group, tazobactam group, calendidin conventional decoction group (0.64g/kg), broken wall preparation and other dose groups. (0.64g/kg), 1/2 dose group (0.32g/kg), 1/4 dose group (0.16g/kg), broken wall preparation 1/8 dose group (0.08g/kg) ).

Compared with the model group: *P<0.05, **P<0.01; compared with the group of Dendrobium nodules, △△P<0.01.

Compared with the model group: *P<0.05, **P<0.01; compared with the group of Dendrobium nodules, △△P<0.01.

Compared with the model group: *P<0.05, **P<0.01.

The results of Tables 2, 3 and 4 show that the efficacy of the stone wall breaking powder is better than that of the Shiqi traditional cake, which is equivalent to 1/4 volume.

Claims (10)

The invention discloses a preparation method of a stone smashing wall breaking preparation, which comprises the following steps, S1. The sarcophagus is subjected to ultra-fine wall breaking and pulverized to obtain ultra-fine broken wall powder, and S2. ethanol-water solution and ultra-fine broken wall powder are ratio by weight. 1~1.6:1 mixing, made of soft material, S3. Squeeze to obtain wet granules, dry and get. The method for preparing a sarcophagus broken wall preparation according to claim 1, wherein the ethanol-water solution and the ultra-fine broken wall powder in the step S2 are mixed at a weight ratio of 1.3 to 1.5:1. The method for preparing a sarcophagus wall breaking preparation according to claim 1, wherein the ethanol-water solution in the step S2 has a mass fraction of ethanol of 50% to 95%. The method for preparing a sarcophagus wall breaking preparation according to claim 3, wherein the ethanol-water solution in the step S2 has a mass fraction of ethanol of 60% to 90%. The method for preparing a sarcophagus wall breaking preparation according to any one of claims 1 to 4, wherein the ethanol-water solution in the step S2 has a mass fraction of ethanol of 65% to 75%, and the ethanol-water solution and the solution The ultra-fine broken wall powder is mixed in a weight ratio of 1.3 to 1.5:1. The method for preparing a sarcophagus wall breaking preparation according to claim 1, wherein the ultrafine breaking powder in the step S1 has a wall breaking rate of 80 to 95%. The method for producing a sarcophagus wall breaking preparation according to claim 1, wherein the particle size of the ultrafine breaking powder in the step S1 is 90% or more and the particle diameter is 45 μm or less. The preparation method of the stone smashing wall breaking preparation according to claim 1, wherein the pressing condition in the step S3 is: a pressing force of 0.05 MPa to 1 MPa, and a rotation speed of 50 r/min to 100 rpm. The preparation method of the stone smashing wall breaking preparation according to claim 8, characterized in that the pressing condition in the step S3 is: a pressing force of 0.15 MPa to 0.25 MPa, and a rotation speed of 80 r/min to 90 rpm. According to the preparation method of claim 1, the stone smash breaking preparation is obtained, wherein the bulk density is 0.15 to 0.35 g/mL.