TW201436822A - Panax notoginseng broken wall preparation - Google Patents

Abstract

The present invention relates to a traditional Chinese herbal preparation. In particular, the present invention relates to a Panax notoginseng broken wall preparation, of which the preparation is produced by pulverizing powder of Panax notoginseng into ultrafine powder, further by ethanol - wet granulation, extrusion at a certain speed, and dried. The resulting preparation with broken wall of Panax notoginseng has higher bioavailability rate, stable preparation, and good disintegration.

Description

Sanqi broken wall preparation

The present invention relates to the field of traditional Chinese medicine, and more particularly to a Sanqi broken wall 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.

At present, the following technical problems exist in the broken wall preparation and its granulation process: (1) The current broken wall preparation is easy to be oxidized due to high utilization rate of traditional Chinese medicine ingredients, and the stability is not high, and the efficacy is low. It is easy to lose; (2) It is difficult to ensure the yield, disintegration and stability of the traditional Chinese medicine varieties obtained by soft material granulation; (3) Some Chinese medicine varieties are not suitable for using broken wall powder-soft Prepared by the granulation method, such as sputum, achyranthes, etc.; A large number of experimental explorations, screening the Chinese medicine varieties suitable for the broken wall powder-soft material granulation method, and exploring the conditions of each step.

Panax notoginseng is the dried roots and rhizomes of the Panax notoginseng (Burk.) FHChen. The active ingredient is a tetracyclic triterpenoid component: ginsenoside Rb ₁ , Rd, Re, Rg ₁ , Rg ₂ , Rh ₁ , notoginsenoside R ₁ , R ₂ , R ₃ , R ₅ , R ₆ , R ₇ , Heptaphylline, notoginsenoside A, B, C, D, etc.; also contains notoginseng, quercetin and polysaccharides, etc., using traditional boiling methods, easy to destroy its heat-sensitive ingredients, on the other hand, active ingredients decoction Incomplete, resulting in the loss of active ingredients. The preparation of Panax notoginseng into a fine powder of Panax notoginseng 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 further process and modify it to effectively overcome these unfavorable factors and maximize the therapeutic effect of the drug.

The technical problem to be solved by the present invention is to provide a Sanqi broken wall preparation in order to overcome the above-mentioned deficiencies of the prior art Sanqi broken wall powder.

The above technical problem to be solved by the present invention is achieved by the following technical solutions: The invention provides a Sanqi broken wall preparation, which adopts the following technical scheme: the smashing of the Sanqi is carried out to obtain an ultrafine powder, and the ethanol-water solution is fully added. Mixing, preparing soft material, further extruding to obtain wet granules, drying to obtain a broken saponin preparation, the ultra-fine powder has a wall breaking rate of 80 to 95%; 90% or more of the ultrafine powder The particle size is 35 μm or less.

Preferably, the ultrafine powder has a wall breaking rate of 80 to 95%.

The Sanqi broken wall preparation prepared by the invention can make the consumption of the active ingredient maximized by the consumer without decocting by washing with warm boiled water.

It is possible to pulverize Panax notoginseng to 100 mesh and further carry out ultrafine pulverization so that 90% or more of the ultrafine powder (for example, it may be 90%, 91%, 92%, 93%, 94% or 95%) The particle diameter is 35 μm or less. The ultrafine powder used in the solution of the present invention, 90% of the particles having a particle size of nearly 35 μm, preferably 28 to 35 μm (for example, 28, 29, 30, 31, 32, 33, 34 or 35 μm) . However, it will be apparent to those skilled in the art that these examples are not intended to be limiting of the present invention, and the present invention can be carried out as long as the particle diameter is 35 μm or less.

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 subjected to subsequent granulation and drying to form trichome granules 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 powder are parameters that need to be strictly controlled to make the moisture, solid content, viscosity, etc. of the soft material. It can be applied to the characteristics of the ultra-fine powder of Panax notoginseng, so that the ultra-fine powder can be effectively bonded; further, through the setting of specific extrusion parameters, the soft material is extruded into the Sanqi granule preparation with appropriate density and size. The density/fluffiness is made appropriate, whereby the oxidation of the air can be prevented even after being dried in the air at room temperature after being dried. 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 mass percentage of ethanol in the ethanol-water solution used is 30% to 90%; preferably, the mass percentage of ethanol is 40% to 80%. %, more preferably 50% to 75%. When the mass percentage of ethanol is 30% to 39%, the ratio of the ultrafine powder to the ethanol-water solution is 1:0.4 to 0.45 by weight, preferably 1:0.4; when the mass percentage of ethanol is 40% to 49%, The ratio of ultrafine powder to ethanol-water solution is 1:0.4~0.45, preferably 1:0.45; when the mass percentage of ethanol is 50%~59%, super The ratio of fine powder to ethanol-water solution is 1:0.4~0.6, preferably 1:0.4~0.5; when the mass percentage of ethanol is 60%~69%, the ratio of ultrafine powder to ethanol-water solution is by weight. The ratio is 1:0.4~0.7, preferably 1:0.5~0.7; when the mass percentage of ethanol is 70%~79%, the ratio of ultrafine powder to ethanol-water solution is 1:0.4~0.8 by weight, preferably It is 1:0.6~0.8; when the mass percentage of ethanol is 80%~90%, the ratio of ultrafine powder to ethanol-water solution is 1:0.4~1.0, preferably 1:0.6~0.9 by weight.

When the soft material is extruded into wet granules, it is preferably controlled under the following conditions: a pre-assembled 10 mesh to 30 mesh screen, a pressing force of 0.05 MPa to 1 MPa, and a rotational speed of 50 r/min to 100 r/min; preferably, The pressing force is 0.75Mpa~0.85Mpa, and the rotation speed is 65r/min~75r/min.

The wet particle size obtained by extrusion is 20 mesh to 40 mesh, the drying temperature during drying is 45 ° C to 85 ° C, and the drying time is 0.5 hour to 2.5 hours.

The obtained Sanqi broken wall preparation has a density of 0.35 g/ml to 0.75 g/ml.

Compared with the prior art, the present invention has the following beneficial effects: (1) The Sanqi preparation obtained by the method of the invention has greatly improved utilization rate of active ingredients, and the utilization rate is close to 100%; confirmed by bioequivalence test, adopted 1/4 part of the Sanqi broken wall preparation can be equivalent to 1 part of the traditional Sanqi effect; (2) The invention obtains a suitable wet granulation process by groping, so that the granulation process is not only the addition of ethanol-water Without any other additives, the soft material with moderate solid content and moderate viscosity can be obtained to smoothly carry out the extrusion granulation process, and the formed Chinese medicinal particles have strong stability and are not easy to collapse during storage and transportation; (3) The extrusion condition of the invention explores the appropriate rotation speed and the pressing force, thereby preparing the Sanqi granule preparation with moderate viscosity and moderate density, and at the same time obtaining the stability of the finished product, the volume is made during the taking process. It is easy to disintegrate and disperse, and is convenient for warm boiled water; (4) The Sanqi broken wall preparation of the invention dissolves uniformly in water, and overcomes the prior art, the ultrafine powder is prepared into a preparation, and the upper solution is diluted with water. The problem of the lower concentration of the solution, and the active ingredients are basically dissolved out as a solution, which does not exist in the dregs powder, and a good medicinal effect can be obtained by simply blunting.

In order to more clearly understand the technical content of the present invention, the following embodiments are specifically described, but the embodiments of the present invention are not limited thereto.

Example 1

Take the Sanqijing medicinal material and coarsely pulverize it to a coarse powder of about 100 mesh. After ultrafine pulverization into 90% of the ultrafine powder, the powder with a particle size of 35 μm or less is added to the ethanol-water solution (the mass percentage of ethanol is 30). %) Wet process soft material, the ratio of solution to ultrafine powder is 0.4:1 (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 are transferred into a hot air loop oven, set to a drying temperature of 85 ° C, dried for 2.5 hours to dryness, and the whole granules are sieved to obtain a Sanqi broken wall preparation.

Example 2

Take the Sanqijing medicinal material and coarsely pulverize it to about 100 mesh coarse powder, then superfinely pulverize into 90% of the ultrafine powder with a particle size of 35 μm or less, and add ethanol-water solution (B The mass percentage of alcohol is 50%). The wet process is made of soft material. The ratio of solution to ultrafine powder is 0.5:1 (by weight). After mixing, pre-loaded with 10 mesh sieve, the extrusion speed is 60r/min. Wet granules with a pressure of 0.8 MPa, wet granules were transferred into a vacuum microwave oven, set to a drying temperature of 45 ° C, dried for 0.75 hours to dryness, and the whole granules were sieved to obtain a Sanqi broken wall preparation.

Example 3

Take the Sanqijing medicinal material and coarsely pulverize it to a coarse powder of about 100 mesh, then ultrafinely pulverize into 90% of the ultrafine powder with a particle size of 35 μm or less, and add an ethanol-water solution (the mass percentage of ethanol is 90). %) Wet method soft material, the ratio of solution to ultrafine powder is 0.8:1 (by weight), after mixing, pre-assembled 30 mesh sieve, using extrusion speed 80r/min, extrusion force 0.3MPa Wet granules, wet granules are transferred into a hot air loop oven, set to a drying temperature of 85 ° C, dried for 2.5 hours to dry, and the whole granules are sieved to obtain a Sanqi broken wall preparation.

Example 4

Take the Sanqijing medicinal material and coarsely pulverize it to about 100 mesh coarse powder, then superfinely pulverize into 90% of the ultrafine powder with a particle size of 35 μm or less, and add ethanol-water solution (B The mass percentage of alcohol is 80%). The wet process is made of soft material. The ratio of solution to ultrafine powder is 0.8:1 (by weight). After mixing, pre-loaded with 30 mesh sieve, and the extrusion speed is 60r/min. Wet granules with a pressure of 0.5 MPa, wet granules were transferred into a vacuum microwave oven, set to a drying temperature of 50 ° C, dried for 0.5 hours to dryness, and the whole granules were sieved to obtain a Sanqi broken wall preparation.

Example 5

Take the Sanqijing medicinal material and coarsely pulverize it to about 100 mesh coarse powder, then pulverize it into ultrafine powder to 90% of the powder with particle size less than or equal to 35μm, and add ethanol-water solution (ethanol mass percentage is 75%) Wet process soft material, the ratio of solution to ultrafine powder is 0.5:1 (by weight), after mixing, pre-installed 20 mesh sieve, select extrusion speed 100r/min, extrusion force 0.05MPa Wet granules, wet granules are transferred into the hot air circulation bellows, set the drying temperature to 85 ° C, dry for 2.0 hours to dry, and the whole granules are sieved to obtain the Sanqi broken wall preparation.

Example 6

Take the Sanqijing medicinal material and coarsely pulverize it to a coarse powder of about 100 mesh, and then pulverize it into ultrafine powder to 90% of the powder with a particle size of 35 μm or less, and add ethanol-water soluble solution. The mass percentage of the liquid is 40% of the solution wet-process soft material, the ratio of the solution to the ultra-fine powder is 0.45:1 (by weight), and after mixing, the pre-packed 20 mesh sieve is used, and the extrusion speed is 50r/min. The wet granules with a pressing force of 0.2 MPa are used for boiling drying, and the dry air inlet temperature is set to 85 ° C, dried for 1.0 hour to dryness, and the whole granules are sieved to obtain the Sanqi broken wall preparation.

Example 7

Take the Sanqijing medicinal material and coarsely pulverize it to about 100 mesh coarse powder, then pulverize it into ultrafine powder to 90% of the powder with particle size less than or equal to 35μm, and add ethanol-water solution (ethanol mass percentage is 65%) Wet process soft material, the ratio of solution to ultrafine powder is 0.6:1 (by weight). After mixing, pre-loaded with 20 mesh sieve, the extrusion speed is 70r/min, and the extrusion force is 0.75MPa. Wet granules, wet granules are transferred into the hot air circulation bellows, set the drying temperature to 85 ° C, dry for 2.0 hours to dry, and the whole granules are sieved to obtain the Sanqi broken wall preparation.

Example 8

Take the Sanqijing medicinal material and coarsely pulverize it to a coarse powder of about 100 mesh, and then pulverize it into ultrafine powder to 90% of the powder with a particle size of 35 μm or less, and add ethanol-water soluble solution. The liquid (40% by mass) solution is made into a wet material, and the ratio of the solution to the ultrafine powder is 0.6:1 (by weight). After mixing, the pre-packed 14 mesh sieve is used, and the extrusion speed is 50r/min. The wet granules with a pressing force of 0.8 MPa are used for boiling drying, and the dry air inlet temperature is set to 85 ° C, dried for 1.0 hour to dryness, and the whole granules are sieved to obtain a Sanqi broken wall preparation.

Example 9

Take the Sanqijing medicinal material and coarsely pulverize it to a coarse powder of about 100 mesh, then ultrafinely pulverize into 90% of the ultrafine powder with a particle size of 35 μm or less, and add an ethanol-water solution (the mass percentage of ethanol is 90). %) Wet process soft material, the ratio of solution to ultrafine powder is 1.0:1 (by weight), after mixing, pre-assembled 30 mesh sieve, using extrusion speed 80r/min, extrusion force 0.9MPa Wet granules, wet granules are transferred into a hot air loop oven, set to a drying temperature of 85 ° C, dried for 2.5 hours to dry, and the whole granules are sieved to obtain a Sanqi broken wall preparation.

Example 10

Take the Sanqijing medicinal material and coarsely pulverize it to a coarse powder of about 100 mesh, and then pulverize it into ultrafine powder to 90% of the powder with a particle size of 35 μm or less, and add ethanol-water soluble solution. The liquid (70% by mass of ethanol) is made of wet process soft material. The ratio of solution to ultrafine powder is 0.7:1 (by weight). After mixing, pre-loaded with 20 mesh sieve, the extrusion speed is 90r/min. Wet granules with a pressing force of 0.6 MPa, wet particles transferred to a hot air loop wind box, set the drying temperature to 85 ° C, dry for 2.0 hours to dry, and the whole granules are sieved to obtain the Sanqi broken wall preparation.

Example 11

Take the Sanqijing medicinal material and coarsely pulverize it to about 100 mesh coarse powder, then pulverize it into ultrafine powder to 90% of the powder with particle size less than or equal to 35μm, and add ethanol-water solution (ethanol mass percentage is 75%) Wet process soft material, the ratio of solution to ultrafine powder is 1.0:1 (by weight). After mixing, pre-loaded with 20 mesh sieve, the extrusion speed is 70r/min, and the extrusion force is 0.95MPa. Wet granules, wet granules are transferred into the hot air circulation bellows, set the drying temperature to 85 ° C, dry for 2.0 hours to dry, and the whole granules are sieved to obtain the Sanqi broken wall preparation.

Example 12

Take the Sanqijing medicinal material and coarsely pulverize it to a coarse powder of about 100 mesh, and then pulverize it into ultrafine powder to 90% of the powder with a particle size of 35 μm or less, and add ethanol-water soluble solution. The liquid (60% by mass of ethanol) is made of wet process soft material. The ratio of solution to ultrafine powder is 0.6:1 (by weight). After mixing, pre-loaded with 20 mesh sieve, the extrusion speed is 105r/min. The pressing force is 1.1MPa to make wet particles, and the wet particles are transferred into the hot air loop wind box. The drying temperature is set at 85 ° C, dried for 2.0 hours to dry, and the whole grain is sieved to obtain the Sanqi broken wall preparation.

Example 13

Take the Sanqijing medicinal material and coarsely pulverize it to about 100 mesh coarse powder, then pulverize it into ultrafine powder to 90% of the powder with particle size less than or equal to 35μm, and add ethanol-water solution (ethanol mass percentage is 65%) Wet process soft material, the ratio of solution to ultrafine powder is 0.6:1 (by weight), after mixing, pre-installed 20 mesh sieve, select extrusion speed 45r/min, extrusion force 0.04MPa Wet granules, wet granules are transferred into the hot air circulation bellows, set the drying temperature to 85 ° C, dry for 2.0 hours to dry, and the whole granules are sieved to obtain the Sanqi broken wall preparation.

The finished products of the examples 1 to 7 were tested according to the quality standards of the finished products, 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.

Table 1

Further, the first three or seven broken wall preparations of Examples 1 to 7 and the Panax notoginseng ultrafine powder and the Sanqi conventional decoction pieces were used as the evaluation indexes for the traits, water and the total amount of ginsenoside Rg ₁ , Rb ₁ and R ₁ . They were all packaged in a sealed plastic bag and placed at a temperature of 40 ° C ± 2 ° C and a relative humidity of 75% ± 5% for 3 months to evaluate the stability of each formulation. The results are as follows:

In the following step, the advanced nature of the present invention is illustrated by an acute toxicity and efficacy comparison experiment. The Sanqi broken wall preparation prepared in Example 7 is compared with a conventional decoction piece.

First, acute toxicity test

40 Kunming mice, weighing 18-22 grams, half male and half female, were randomly divided into photo group (distilled water 0.4ml/10g mouse), Sanqi tablet group, Sanqi cut mouth group and Sanqi broken wall preparation group were given 1g/ml. The concentration of the original drug solution (for maximum concentration) 0.4ml/10g mouse.

The results in Table 2 indicate that the maximum daily dose of Sanqi Tablet, Sanqi Shekou Decoction Tablet and Sanqi Broken Wall Preparation on mice was 120g/kg, and no significant acute toxicity was observed.

Second, pharmacodynamic comparison

There were 56 Kunming mice, half male and half female, randomly divided into 7 groups, 8 in each group. Divided into normal group (salt saline), Sanqi decoction group (62.5mg/kg), Sanqi Jiankou decoction group (62.5mg/kg), Sanqi broken wall preparation, etc. (62.5mg/kg), Sanqi The low-dose group (7.8mg/kg), the middle dose group (15.6mg/kg), and the high-dose group (31.25mg/kg) of the broken powder of Sanqi. In the broken wall preparation group, the preparation prepared in Example 7 was allowed to stand for 90 days, and then washed with warm water of about 60 ° C, and the supernatant was administered by intragastric administration.

The results in Table 3 show that the pharmacodynamic effect of the Sanqi broken wall preparation is better than that of the Sanqi conventional decoction pieces and the cut-off pieces, which is equivalent to 1/4 amount.

Claims (9)

A Sanqi broken wall preparation, which is obtained by breaking the wall and pulverizing to obtain ultrafine powder, adding an ethanol-water solution to a soft material, further extruding to obtain a wet granule, and drying to obtain a Sanqi broken wall preparation; wherein the superfine 90% or more of the particles in the powder have a particle diameter of 35 μm or less. The Sanqi broken wall preparation according to Item 1 of the patent application, wherein the mass percentage of ethanol in the ethanol-water solution is 30% to 90%. The Sanqi broken wall preparation according to Item 1 of the patent application, wherein the mass ratio of the ultrafine powder to the ethanol-water solution is 1:0.4 to 1.0. According to the Sanqi broken wall preparation according to claim 1, wherein when the mass percentage of ethanol is 30% to 39%, the ratio of the ultrafine powder to the ethanol-water solution is 1:0.4 to 0.45 by weight; When the mass percentage is 40%~49%, the ratio of ultrafine powder to ethanol-water solution is 1:0.4~0.45; when the mass percentage of ethanol is 50%~59%, the ratio of ultrafine powder to ethanol-water solution The weight is 1:0.4~0.6; when the mass percentage of ethanol is 60%~69%, the ratio of ultrafine powder to ethanol-water solution is 1:0.4~0.7 by weight; when the mass percentage of ethanol is 70%~79 When %, the ratio of ultrafine powder to ethanol-water solution is 1:0.4~0.8 by weight; when the mass percentage of ethanol is 80%~90%, the ratio of ultrafine powder to ethanol-water solution is 1:0.4 by weight. ~1.0. According to the Sanqi broken wall preparation according to Item 4 of the patent application, wherein when the mass percentage of ethanol is 30% to 39%, the ratio of ultrafine powder to ethanol-water solution is 1:0.4 by weight; when the mass percentage of ethanol is When 40%~49%, the ratio of ultrafine powder to ethanol-water solution is 1:0.45; when the mass percentage of ethanol is 50%~59%, the ratio of ultrafine powder to ethanol-water solution is 1:0.4~0.5; when the mass percentage of ethanol is 60%~69%, ultrafine powder and ethanol - the ratio of aqueous solution is 1:0.5~0.7 by weight; when the mass percentage of ethanol is 70%~79%, the ratio of ultrafine powder to ethanol-water solution is 1:0.6~0.8 by weight; when the mass percentage of ethanol is 80% When the ratio is from % to 90%, the ratio of the ultrafine powder to the ethanol-water solution is 1:0.6 to 0.9 by weight. The Sanqi broken wall preparation according to Item 1 of the patent application, wherein the Sanqi broken wall preparation has a bulk density of 0.35 g/ml to 0.75 g/ml. According to the Sanqi broken wall preparation described in the first paragraph of the patent application scope, the extrusion conditions are: wet granulation: the pre-loaded sieve mesh number is 10 mesh to 30 mesh, the pressing force is 0.05 Mpa~1 Mpa, and the rotational speed is 50 r. /min~100r/min. According to the Sanqi broken wall preparation described in Item 7 of the patent application, the extrusion conditions are: wet granulation: extrusion force 0.75Mpa~0.85Mpa, rotation speed 65r/min~75r/min. According to the Sanqi broken wall preparation described in the first paragraph of the patent application, wherein the wet particle size obtained by the extrusion is 20 mesh to 40 mesh, the drying temperature during drying is 45 ° C to 85 ° C, and the drying time is 0.5 hour. 2.5 hours.