CN113546049A

CN113546049A - Flexible pill medicine adhesive and flexible pill prepared by using same

Info

Publication number: CN113546049A
Application number: CN202110485920.7A
Authority: CN
Inventors: 张仕林; 葛秋平; 刘莉; 尚秘; 毛松; 刘娅; 吴劲勇
Original assignee: Guiyang Dechangxiang Pharmaceutical Co ltd; Hanfang Pharma Co ltd
Current assignee: Guizhou Dechangxiang Pharmaceutical Co.,Ltd.
Priority date: 2021-04-30
Filing date: 2021-04-30
Publication date: 2021-10-26
Anticipated expiration: 2041-04-30
Also published as: CN113546049B

Abstract

The invention discloses a flexible pill medicament adhesive and a flexible pill prepared from the adhesive. The adhesive consists of glycerol and medicinal carboxymethyl cellulose salt. The soft pill prepared by the adhesive changes the hardness of the existing concentrated pill, so that the iron pill is changed into an elastic soft pill; improving the disintegration time limit of the original concentrated pill and shortening the disintegration time; the drying process is reduced, the moisture content can be effectively ensured, the efficiency is improved, and the medicine storage is facilitated; removing the coating, and reducing the use of auxiliary materials for coating; and is safe and non-toxic; the adhesive composition is mainly applied to water pills, water-honeyed pills, concentrated pills, small honeyed pills and large honeyed pills, and compared with pills prepared from traditional auxiliary materials, the pills prepared by the invention have the beneficial effect of higher volatile substance content.

Description

Flexible pill medicine adhesive and flexible pill prepared by using same

Technical Field

The invention relates to a flexible pill medicament adhesive, in particular to a flexible pill prepared by using the adhesive.

Background

The pill refers to a spherical or sphere-like solid preparation prepared from raw material medicaments and appropriate auxiliary materials, and the traditional pills comprise honeyed pills, water-honeyed pills, paste pills, wax pills, concentrated pills and the like. Honeyed pill is prepared from fine powder of decoction pieces by mixing with refined honey as binder; the water-honeyed pill is prepared from decoction pieces by mixing with Mel and water as binder; the watered pill is prepared from decoction pieces fine powder with water (or yellow wine, vinegar, diluted medicinal liquid, sugar solution, and aqueous solution containing refined honey less than 5% according to preparation method) as binder; the paste pill is prepared from decoction pieces fine powder with rice flour, rice paste or flour paste as binder; the concentrated pill is prepared by extracting decoction pieces or part of decoction pieces, concentrating, mixing with appropriate adjuvant or fine powder of other decoction pieces, and making into pill with water, refined honey or refined honey and water as binder. Generally, honeyed pills are prepared from whole powder, the ratio of the added adhesive (refined honey) to the medicinal powder is at least 1:2, the ratio of large honeyed pills is even close to 1:1, the refined honey contains high sucrose and maltose originally, and the honeyed pills are not suitable for being taken by diabetics, and the quality problems of cracking or slow disintegration of the pills and the like can occur in the storage process of water-paste pills or concentrated pills prepared by the traditional adhesive.

Disclosure of Invention

The invention aims to provide a flexible pill medicine adhesive and a flexible pill prepared by using the adhesive. The invention changes the hardness of the prior concentrated pill, so that the iron pill is changed into an elastic flexible pill; the disintegration time limit of the existing concentrated pill is improved, and the disintegration time is shortened; the drying process is reduced, the moisture content can be effectively ensured, the efficiency is improved, and the medicine storage is facilitated; removing the coating, and reducing the use of auxiliary materials for coating; and is safe and non-toxic; the adhesive composition is mainly applied to water pills, water-honeyed pills, concentrated pills, small honeyed pills and large honeyed pills, and compared with pills prepared from traditional auxiliary materials, the soft pills prepared by the invention have higher volatile substance content.

The technical scheme of the invention is as follows:

a flexible pill medicine adhesive is composed of glycerol and medicinal carboxymethyl cellulose salt, wherein the weight ratio of the glycerol to the medicinal carboxymethyl cellulose salt is 100: 1-15.

Specifically, the soft pill medicine adhesive comprises 100 parts by weight of glycerin and 2.5-10 parts by weight of medicinal carboxymethyl cellulose salt.

More specifically, the soft pill medicine adhesive comprises 100 parts by weight of glycerin and 2.5-7.66 parts by weight of medicinal carboxymethyl cellulose salt.

The pharmaceutically acceptable carboxymethyl cellulose salt includes: sodium carboxymethyl cellulose or calcium carboxymethyl cellulose.

The soft pill is added with medicine extract powder or medicinal powder accounting for 50-80% of the total weight of the prepared medicines.

Specifically, the soft pill is added with medicine extract powder or medicinal powder accounting for 55-75% of the total weight of the prepared medicines.

More specifically, the soft pill is added with medicinal extract powder or medicinal powder accounting for 60-70% of the total weight of the prepared medicines.

The flexible pill is prepared by:

(1) putting glycerol into a container, adding medicinal carboxymethyl cellulose salt, stirring, sealing, and heating until the carboxymethyl cellulose salt is completely swelled to obtain adhesive;

(2) preparation of the pill: adding adhesive into the medicinal extract powder or medicinal powder, mixing, and making into pill.

In the step (1), the heating condition is that the mixture is heated for 4 to 10 hours at the temperature of between 60 and 105 ℃, and the mixture is stirred once every 0.5 to 2 hours.

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

the invention is prepared by weighing glycerol and medicinal carboxymethyl cellulose salt, such as sodium carboxymethyl cellulose or calcium carboxymethyl cellulose, according to the proportion of the components, adding the sodium carboxymethyl cellulose or calcium carboxymethyl cellulose into the glycerol at normal temperature, stirring uniformly to uniformly disperse the adhesive in the solvent, and heating for 4-8 hours (preferably 6 hours) under the condition of 50-120 ℃ (preferably 60-105 ℃) to fully swell the adhesive.

The flexible pill medicament adhesive provided by the invention is used for replacing refined honey in large honeyed pills to prepare a novel pill, so that the problem that the pill is not beneficial to being taken by a diabetic patient due to high sugar content is solved, and meanwhile, the quality control of volatile medicaments in the pill can be improved, and the test data of the six-ingredient rehmannia pills and the wolfberry-chrysanthemum rehmannia pills are shown. The flexible pill (children's rejuvenation pill) prepared by the flexible pill medicine adhesive solves the problems of hardness, slow disintegration and difficult absorption of the children's rejuvenation pill, and the prepared novel children's rejuvenation pill is relatively flexible and easy to disintegrate and absorb. The flexible pill prepared by the adhesive can solve the problem of cracking of the gynecological reconstruction pill in the storage process, and improves the product quality.

The adhesive composition is mainly applied to water pills, water-honeyed pills, concentrated pills, small honeyed pills and large honeyed pills, and compared with pills prepared from traditional auxiliary materials, the pills prepared by the invention have higher volatile substance content.

The applicant applies the preparation technology of the soft pills to the gynecological reconstruction pills, the children rejuvenation pills, the six-ingredient rehmannia pills, the medlar-chrysanthemum rehmannia pills, the storax pills and the Zhibai-rehmannia pills, and obtains remarkable effects. In order to research/verify the technical scheme and the beneficial effects of the invention, the inventor conducts a large number of tests, and partial tests are recorded as follows:

the following are the relevant data of the screening test and orthogonal test of the soft pill medicament adhesive and the relevant data of the new preparation method of the children's Huichun pill.

1. Screening of pharmaceutical adjuvant types

The purpose of the test is as follows: screening out proper auxiliary material solvent and adhesive and finding out proper, safe and suitable collocation combination.

The test method comprises the following steps: through the retrieval and analysis of the properties of different pharmaceutic adjuvants, the following solvents are preliminarily screened out, and the solvents and the adhesive are mixed according to a certain proportion.

(1) Glycerol;

(2) tween 80;

(3) propylene glycol;

(4) phenoxyethanol;

(5) polyethylene glycol 400;

screening out several adhesives:

(1) sodium carboxymethylcellulose;

(2) calcium carboxymethylcellulose;

(3) methyl cellulose;

(4) carbomer;

(5) gum arabic powder;

(6) gelatin;

mixing adhesive and solvent uniformly, wherein the proportion of the adhesive is 3%, heating for a certain time at 90 ℃ (the heating aims at shortening the swelling time) to make the adhesive completely swell, measuring the viscosity of the adhesive or adding paste powder to make pills to ensure that the pills can be made smoothly, ensuring that the pills can be completely swelled under a certain condition, achieving the effect of combining the adhesive, observing whether a container has precipitation or delamination, observing whether particles which are not swelled exist on the container wall, and observing whether the two particles have swelling phenomenon or the proportion of the swelling of the adhesive.

Weighing a certain weight of glycerin on a one percent balance, weighing a certain weight of adhesive, adding the adhesive into the glycerin, uniformly stirring to uniformly disperse the adhesive in a solvent, and heating in a stable oven to accelerate the swelling process. Pelleting and checking mixture and viscosity.

Test 1:

test 2:

test 3:

test 4:

test 5:

test 6:

test 7:

test 8:

test 9:

test 10:

according to the fact that the preliminary experiment is a single-factor experiment, it is determined that the factors which have great influence on the pelleting process, the product appearance and the properties during the preparation of the composition agent comprise an adhesive A: percentage of glycerin; the heating temperature of the composition agent B; c combination heating time, therefore 3-factor 3 horizontal quadrature test was designed.

The experimental design was as follows:

and (4) experimental conclusion: the A3B3C2 has the best effect

Test results

The new pill has the advantages that:

1. the hardness of the original concentrated pill is changed, so that the iron pill is changed into an elastic flexible pill. Referring to fig. 153 and 154, the flexible pellets prepared using the present invention were tested to be 0.77kg compared to 3.89kg for the original process pellets (condensation pellets).

2. Improve the disintegration time limit of the original concentrated pill and shorten the disintegration time. The disintegration time of the soft pill prepared by the invention is 43min, compared with the prior art pill (concentrated pill) which is 105min, as shown in figure 155.

3. The drying process is reduced, the moisture content can be effectively ensured, the efficiency is improved, and the medicine storage is facilitated, as shown in figure 156.

Sampling quantity: 33.3300g calculation procedure: 1.8/33.3300 × 100% ═ 5.40%.

4. The soft pill prepared by the invention can remove the coating and reduce the auxiliary materials used for coating.

In conclusion, the invention changes the hardness of the original concentrated pill, so that the iron pill is changed into the elastic flexible pill; improving the disintegration time limit of the original concentrated pill and shortening the disintegration time; the drying process is reduced, the moisture content can be effectively ensured, the efficiency is improved, and the medicine storage is facilitated; removing the coating, and reducing the use of auxiliary materials for coating; and is safe and non-toxic; the adhesive composition is mainly applied to water pills, water-honeyed pills, concentrated pills, small honeyed pills and large honeyed pills, and compared with pills prepared from traditional auxiliary materials, the pills prepared by the invention have the beneficial effect of higher volatile substance content.

Drawings

FIG. 1 is a graph showing the swelling of sodium carboxymethylcellulose in test 1 of the present invention;

FIG. 2 is a graph showing the swelling of sodium carboxymethylcellulose in test 1 of the present invention;

FIG. 3 is a diagram of the pelleting of glycerol + sodium carboxymethylcellulose in test 1 of the present invention;

FIG. 4 is a graph of the pelleting of glycerol + sodium carboxymethylcellulose in test 1 of the present invention;

FIG. 5 is a graph showing the swelling behavior of calcium carboxymethylcellulose in test 1 of the present invention;

FIG. 6 is a graph showing the swelling behavior of calcium carboxymethylcellulose in test 1 of the present invention;

FIG. 7 is a graph of the pelleting of glycerol + carboxymethylcellulose calcium for test 1 of the present invention;

FIG. 8 is a graph of the pelleting of glycerol + carboxymethylcellulose calcium of test 1 of the present invention;

FIG. 9 is a graph showing the swelling of gum arabic in test 1 of the present invention;

FIG. 10 is a graph showing the swelling of gum arabic in test 1 of the present invention;

FIG. 11 is a graph of the pelletization of gum arabic in experiment 1 of the present invention;

FIG. 12 is a graph of the pelletization of gum arabic in experiment 1 of the present invention;

FIG. 13 is a graph showing swelling of carboxymethyl cellulose in test 1 of the present invention;

FIG. 14 is a graph showing swelling of carboxymethyl cellulose in test 1 of the present invention;

FIG. 15 is a graph showing the swelling of carbomer 940 in test 1 of the present invention;

FIG. 16 is a graph showing the swelling of carbomer 940 in trial 1 of the present invention;

FIG. 17 is a graph of the pelleting of glycerol + carbomer 940 in test 1 of the present invention;

FIG. 18 is a graph of the pelleting of glycerol + carbomer 940 in test 1 of the present invention;

FIG. 19 is a graph showing the swelling of carbomer U20 in test 1 of the present invention;

FIG. 20 is a graph showing the swelling of gelatin in test 1 of the present invention;

FIG. 21 is a graph showing the swelling of gelatin in test 1 of the present invention;

FIG. 22 is a graph of the pelleting of gelatin in trial 1 of the present invention;

FIG. 23 is a graph of the pelleting of gelatin in trial 1 of the present invention;

FIG. 24 is a graph showing the swelling of sodium carboxymethylcellulose + glycerol in test 2 of the present invention;

FIG. 25 is a graph of sodium carboxymethylcellulose + glycerol pelleting in test 2 of the present invention;

FIG. 26 is a graph showing the swelling behavior of sodium carboxymethylcellulose + ethylene glycol phenyl ether in test 2 of the present invention;

FIG. 27 is a graph showing the swelling behavior of sodium carboxymethylcellulose + glyceryl triacetate in inventive test 2;

FIG. 28 is a graph showing the swelling of sodium carboxymethylcellulose + ethylene glycol in test 2 of the present invention;

FIG. 29 is a graph showing the swelling of sodium carboxymethylcellulose + ethylene glycol in test 2 of the present invention;

FIG. 30 is a plot of sodium carboxymethylcellulose + ethylene glycol pelleting in test 2 of the present invention;

FIG. 31 is a graph showing the swelling of sodium carboxymethylcellulose +1, 2-propanediol in test 2 of the present invention;

FIG. 32 is a graph showing the swelling of sodium carboxymethylcellulose +1, 2-propanediol in test 2 of the present invention;

FIG. 33 is a graph showing the swelling behavior of sodium carboxymethylcellulose + Tween 80 in test 2 of the present invention;

FIG. 34 is a graph showing the swelling of sodium carboxymethylcellulose + polyethylene glycol 400 in test 2 of the present invention;

FIG. 35 is a graph showing the swelling of sodium carboxymethylcellulose + polyethylene glycol 400 in test 2 of the present invention;

FIG. 36 is a graph showing the swelling behavior of calcium carboxymethylcellulose + glycerol in test 2 of the present invention;

FIG. 37 is a graph of the pelleting of calcium carboxymethylcellulose + glycerol in test 2 of the invention;

FIG. 38 is a graph showing the swelling of gelatin + polyethylene glycol 400 in test 2 of the present invention;

FIG. 39 is a graph showing the swelling of gelatin + polyethylene glycol 400 in test 2 of the present invention;

FIG. 40 is a graph showing the swelling of carbomer 940+ polyethylene glycol 400 in test 2 of the present invention;

FIG. 41 is a graph of the pelleting of carbomer 940+ polyethylene glycol 400 in test 2 of the invention;

FIG. 42 is a graph showing the swelling behavior of calcium carboxymethylcellulose + ethylene glycol in test 2 of the present invention;

FIG. 43 is a graph showing the swelling behavior of calcium carboxymethylcellulose + ethylene glycol in test 2 of the present invention;

FIG. 44 is a graph of the calcium carboxymethylcellulose + ethylene glycol pelleting profile of inventive run 2;

FIG. 45 is a graph showing the swelling behavior of sodium carboxymethylcellulose + water in test 2 of the present invention;

FIG. 46 is a graph showing the swelling behavior of sodium carboxymethylcellulose + water in test 2 of the present invention;

FIG. 47 is a drawing of the pelleting of sodium carboxymethylcellulose + water in test 2 of the invention;

FIG. 48 is a graph showing the swelling behavior of gelatin + water in test 2 of the present invention;

FIG. 49 is a graph showing the swelling of gelatin + water in test 2 of the present invention;

FIG. 50 is a graph of gelatin + water pelleting in experiment 2 of the present invention;

FIG. 51 is a graph of gelatin + water pelleting in experiment 2 of the present invention;

FIG. 52 is a graph of pure glycerol pelleting in test 2 of the present invention;

FIG. 53 is a graph of pure glycerol pelleting in test 2 of the present invention;

FIG. 54 is a graph of the present invention at room temperature addition in experiment 3;

FIG. 55 is a graph of the present invention after swelling at room temperature for 6 hours of addition in test 3;

FIG. 56 is a graph of the present invention at 40 ℃ addition in test 3;

FIG. 57 is a graph of the present invention after swelling at 40 ℃ for 6 hours after addition;

FIG. 58 is a graph of the present invention at 60 ℃ addition in test 3;

FIG. 59 is a graph showing swelling at 60 ℃ for 6 hours in test 3 of the present invention;

FIG. 60 is a graph of the present invention at 90 ℃ addition in test 3;

FIG. 61 is a graph of the present invention after swelling at 90 ℃ for 6 hours after addition;

FIG. 62 is a graph showing swelling at 2 hours in test 4 of the present invention;

FIG. 63 is a graph showing swelling at 4h in test 4 of the present invention;

FIG. 64 is a graph showing swelling at 4 hours in test 4 of the present invention;

FIG. 65 is a graph showing swelling at 6 hours in test 4 of the present invention;

FIG. 66 is a graph showing swelling at 8 hours in test 4 of the present invention;

FIG. 67 is a graph showing swelling at 10 hours in test 4 of the present invention;

FIG. 68 is a graph showing swelling at 16h in test 4 of the present invention;

FIG. 69 is a graph showing swelling at 16h in test 4 of the present invention;

FIG. 70 is a graph showing the heating time at 60 ℃ for 2 hours in test 5 of the present invention;

FIG. 71 is a graph of heating time at 60 ℃ for 6 hours in inventive test 5;

FIG. 72 is a graph of heating time at 75 ℃ for 2 hours in test 5 of the present invention;

FIG. 73 is a graph of heating time at 75 ℃ for 6 hours in test 5 of the present invention;

FIG. 74 is a graph of heating time at 90 ℃ for 2 hours in test 5 of the present invention;

FIG. 75 is a graph of 90 ℃ heating time 6 hours for test 5 of the present invention;

FIG. 76 is a graph of heating time at 105 ℃ for 2 hours in inventive test 5;

FIG. 77 is a graph showing the heating time at 105 ℃ for 6 hours in test 5 of the present invention;

FIG. 78 shows the CMC-Na: test plots for 1.5%, 2.0%, 2.5%, 3.0%, 3.5% glycerol;

FIG. 79 is a CMC-Na: test pattern with 3.0% glycerol;

FIG. 80 is a CMC-Na: test pattern with 4.0% glycerol;

FIG. 81 is a CMC-Na: test pattern with 5.0% glycerol;

FIG. 82 is a CMC-Na: test pattern with 5.0% glycerol;

FIG. 83 is a CMC-Na: test pattern for 7.66% glycerol;

FIG. 84 is a CMC-Na: the glycerol content is 7.66 percent;

FIG. 85 shows the CMC-Na ratio in inventive run 6: test pattern with 10.0% glycerol;

FIG. 86 is a CMC-Na: test pattern with 10.0% glycerol;

FIG. 87 is a CMC-Na: the pill making condition with 10.0% of glycerin is shown in the figure;

FIG. 88 is a photograph of pellets of this invention with an adjuvant ratio of 20.13% in test 7;

FIG. 89 is a photograph of pellets of trial 7 of the present invention having an adjuvant ratio of 20.13%;

FIG. 90 is a photograph of pellets of trial 7 of the present invention having an excipient ratio of 25.24%;

FIG. 91 is a photograph of pellets of trial 7 of the present invention having an excipient ratio of 25.24%;

FIG. 92 is a photograph of pellets of the invention with an adjuvant ratio of 30.35% in test 7;

FIG. 93 is a photograph of pellets of the invention from trial 7 with an adjuvant ratio of 30.35%;

FIG. 94 is a photograph of pellets of this invention with an adjuvant ratio of 35.30% in test 7;

FIG. 95 is a photograph of pellets of the present invention at an adjuvant ratio of 35.30% in test 7;

FIG. 96 is a photograph of pellets of trial 7 of the present invention having an excipient ratio of 40.20%;

FIG. 97 is a photograph of pellets of trial 7 of the present invention having an excipient ratio of 40.20%;

FIG. 98 is a graph of cream powder + glycerin of trial 8 of the present invention;

FIG. 99 is a graph of paste powder + glycerin + CMC-Na in trial 8 of the present invention;

FIG. 100 is a diagram of soft mass of paste powder + glycerin + CMC-Na in test 8 of the present invention;

FIG. 101 is a press pellet of paste powder + glycerin + CMC-Na of trial 8 of the present invention;

FIG. 102 is a graph of paste powder + CMC-Na in test 8 of the present invention;

FIG. 103 is a graph of paste powder + CMC-Na + glycerol in trial 8 of the present invention;

FIG. 104 is a diagram of the soft mass of paste powder + CMC-Na + glycerin in test 8 of the present invention;

FIG. 105 is a press pellet of paste powder + CMC-Na + glycerin of trial 8 of the present invention;

FIG. 106 is a graph of cream powder + glycerin of test 8 of the present invention;

FIG. 107 is a graph of paste powder + glycerin + CMC-Na in trial 8 of the present invention;

FIG. 108 is a graph of the paste powder + glycerin + CMC-Na90 heated at 6 hours in test 8 of the present invention;

FIG. 109 is a graph of paste powder + CMC-Na in test 8 of the present invention;

FIG. 110 is a graph of paste powder + CMC-Na + glycerol in test 8 of the present invention;

FIG. 111 is a graph of the paste powder + CMC-Na + glycerin heated at 90 ℃ for 6 hours in test 8 of the present invention;

FIG. 112 is a graph of CMC-Na + glycerol in test 8 of the present invention;

FIG. 113 is a graph of CMC-Na + glycerol + paste powder in test 8 of the present invention;

FIG. 114 is a diagram of the soft mass of CMC-Na + glycerol + paste powder in test 8 of the present invention;

FIG. 115 is a pellet plot of CMC-Na + glycerol + paste powder from inventive run 8;

FIG. 116 is a graph of CMC-Na + glycerol (heated at 90 ℃ for 6 hours) in test 8 of the present invention;

FIG. 117 is a drawing showing the pelletization of CMC-Na + glycerol (heated at 90 ℃ C. for 6 hours) + paste powder in test 8 of the present invention;

FIG. 118 is a graph of 80 mesh in trial 9 of the present invention;

FIG. 119 is a graph of 80 mesh in trial 9 of the present invention;

FIG. 120 is a graph of 100 of the present invention in experiment 9;

FIG. 121 is a graph of 100 mesh in experiment 9 of the present invention;

FIG. 122 is a graph of 120 mesh in experiment 9 of the present invention;

FIG. 123 is a graph of 120 mesh in experiment 9 of the present invention;

FIG. 124 is a graph of 80, 100 and 120 mesh in experiment 9 of the present invention;

FIG. 125 is a diagram showing the swollen state of the adhesive No. 1 in the test 10 of the present invention;

FIG. 126 is a view showing a swollen state of an adhesive No. 1 in test 10 of the present invention;

FIG. 127 is a view showing a swollen state of an adhesive No. 2 in test 10 of the present invention;

FIG. 128 is a drawing of a series 2 pellet form of trial 10 of the present invention;

FIG. 129 is a diagram showing the swollen state of the adhesive No. 3 in test 10 of the present invention;

FIG. 130 is a view showing a swollen state of an adhesive No. 3 in test 10 of the present invention;

FIG. 131 is a drawing of a series 3 pellet formulation of test 10 of the present invention;

FIG. 132 is a view showing a swollen state of an adhesive No. 4 in test 10 of the present invention;

FIG. 133 is a view showing a swollen state of an adhesive No. 4 in test 10 of the present invention;

FIG. 134 is a drawing of run No. 4 pelletization of test 10 of the present invention;

FIG. 135 is a view showing a swollen state of an adhesive No. 5 in test 10 of the present invention;

FIG. 136 is a view showing a swollen state of an adhesive No. 5 in test 10 of the present invention;

FIG. 137 is a drawing of trial number 5 pellets of the present invention run 10;

FIG. 138 is a view showing a swollen state of an adhesive No. 6 in test 10 of the present invention;

FIG. 139 is a diagram showing a swollen state of an adhesive No. 6 in test 10 of the present invention;

FIG. 140 is a drawing of a series 6 pellet form of test 10 of the present invention;

FIG. 141 is a view showing a swollen state of an adhesive No. 7 in test 10 of the present invention;

FIG. 142 is a view showing a swollen state of an adhesive No. 7 in test 10 of the present invention;

FIG. 143 is a drawing of a series 7 pellet formulation of test 10 of the present invention;

FIG. 144 is a diagram showing a swollen state of an adhesive No. 8 in test 10 of the present invention;

FIG. 145 is a view showing a swollen state of an adhesive No. 8 in test 10 of the present invention;

FIG. 146 is a drawing of trial 10 of the present invention numbered 8 as a pellet;

FIG. 147 is a view showing a swollen state of an adhesive No. 9 in test 10 of the present invention;

FIG. 148 is a view showing a swollen state of an adhesive No. 9 in test 10 of the present invention;

FIG. 149 is a drawing of a series 9 pellet form of trial 10 of the present invention;

FIG. 150 is a view showing a swollen state of an adhesive No. 10 in test 10 of the present invention;

FIG. 151 is a drawing showing the swollen state of the adhesive No. 10 in test 10 of the present invention;

FIG. 152 is a drawing of a series 10 pellet form of trial 10 of the present invention;

fig. 153 is a graph of the hardness of a flexible pellet made using the present invention in test demonstration of the present invention-advantage 1 of the new pellet;

FIG. 154 is a graph of the hardness of the original process pellet (concentrated pellet) as tested for proof of the invention-advantage 1 of the new pellet;

FIG. 155 is a graph of the present invention trial demonstrating disintegration in advantage 2 of the new pellet; (left: flexible pill; right: original concentrated pill)

Fig. 156 is a graph of the moisture content in advantage 3 of the present invention test demonstration-new pellet.

Detailed Description

The invention is further illustrated by the following figures and examples, which are not to be construed as limiting the invention.

Example 1. A gynecological reconstruction pill-soft pill is prepared by the following steps:

(1) paste powder mixture: weighing 65.14g of wine angelica sinensis, 66.14g of vinegar-processed rhizoma cyperi, 43.43g of radix paeoniae alba, 21.71g of prepared rehmannia root, 10.86g of donkey-hide gelatin, 65.14g of poria cocos, 21.71g of codonopsis pilosula, 21.71g of astragalus membranaceus, 32.57g of Chinese yam, 16.28g of bighead atractylodes rhizome, 43.43g of wine-processed glossy privet fruit, 32.57g of vinegar-processed tortoise shell, 21.71g of dogwood, 21.71g of teasel root, 21.71g of salt eucommia ulmoides, 10.86g of cistanche, 16.28g of raspberry, 5.43g of cornu cervi degelatinatum, 43.43g of ligusticum wallichii, 21.71g of salvia miltiorrhiza, 16.28g of achyranthes bidentata, 21.71g of motherwort, 16.28g of corydalis tuber, 5.43g of crisp panax notoginseng, 43.43g of vinegar-processed folium artemisiae argyi, 21.71g of fennel, 21.71g of ligusticum sinensis, 21.71g of cuttlebone 32.57g, 7g of spicebush, 7g of sauted sanguisorba officinalis, 3543 g of radix polygalae, 32.57g of radix gentianae, 3543 g of prepared radix gentianae, 3586 g of prepared radix rehmanniae praeparatae, 3645 g of radix rehmanniae praeparata, 32.57g of honey-fried radix rehmanniae praeparata, 3627.80 g of radix rehmanniae praeparata, 3627 g of honey-fried radix rehmanniae praeparata, 3.32 g of honey-fried radix polygalae, 3526 g of radix rehmanniae preparata, 3627 g of honey-fried radix rehmanniae praeparata, 3.32 g of honey-fried radix polygalae, 3g of honey-fried radix polygalae, 3.35 g of honey-fried radix rehmanniae praeparata, 3g of honey-fried radix et radix polygalae, 3.71 g of honey-fried radix et radix polygalae, 3g of honey-fried radix polygalae, 3.32 g of honey-fried radix et radix salviae, 3g of honey-fried radix et radix polygalae, 3g of radix et radix salviae, 3g of radix salviae officinalis, 3.32 g of radix et radix salviae officinalis, 3g of honey-fried radix salviae miltiorrhizae, 3.35 g of radix et radix salviae officinalis, 3g of radix salviae miltiorrhizae, 3g of radix et radix salviae officinalis, 3.27 g of radix et radix salviae miltiorrhizae, 3g of honey-fried radix et rhizoma, 3g of honey-fried radix et radix salviae miltiorrhizae, 3.27 g of honey-fried radix et radix salviae miltiorrhizae, 3g of radix salviae sinensis, 3.35 g of radix et radix salviae miltiorrhizae, 3g of radix et radix salviae sinensis, 3.7 g of honey-fried radix et radix salviae miltiorrhizae, 3g of honey-fried radix et rhizoma, 3g of honey-fried radix et rhizoma, 3.27 g of honey-fried radix salviae miltiorrhizae, 3.32 g of honey-fried radix salviae miltiorrhizae, decocting Cistanchis herba, Achyranthis radix and cortex Lycii in water twice, each for two hours, mixing decoctions, filtering, and concentrating the filtrate to obtain concentrated solution; melting colla Corii Asini in appropriate amount of water, mixing with the above concentrated solution, concentrating to obtain fluid extract with relative density of 1.10 at 80 deg.C, pulverizing the rest thirty-three materials, sieving with 100 mesh sieve to obtain fine powder, and mixing the fluid extract and fine powder to obtain paste powder mixture;

(2) adhesive: putting 100g of glycerol into a container, adding 4g of sodium carboxymethylcellulose, uniformly stirring, sealing, heating the container at 90 ℃ for 6 hours, and stirring once every 1.5 hours to prepare an adhesive for later use;

(3) gynecological reconstruction pill-soft pill: and (3) adding 35% of the adhesive in the step (2) into the paste powder mixture in the step (1), uniformly mixing, and making into pills.

Example 2. A preparation method of a gynecological reconstruction pill comprises the following steps:

(1) a paste powder mixture was prepared as described in example 1;

(2) adhesive: adding 100g of glycerol into a container, adding 15g of carboxymethylcellulose calcium, uniformly stirring, sealing, heating the container at 105 ℃ for 4-5 hours until the carboxymethylcellulose calcium is completely swelled, and stirring once every 0.5 hour to prepare an adhesive for later use;

(3) gynecological reconstruction pill-soft pill: adding binder 50% of the total amount of the prepared medicinal materials into the paste powder mixture, mixing, and making into pill.

Example 3. A method for preparing a pill of six ingredients with rehmannia, namely a soft pill, comprises the following steps:

(1) powder: according to the prescription of the pill of six ingredients with rehmannia, 160g of prepared rehmannia root, 80g of wine-processed cornus, 60g of tree peony bark, 80g of Chinese yam, 60g of tuckahoe and 60g of alisma orientale, crushing, sieving and uniformly mixing to obtain medicinal powder;

(2) adhesive: according to the weight ratio, 100g of glycerol is put into a container, then 5g of calcium carboxymethylcellulose is added, the mixture is uniformly stirred and heated for 5 to 6 hours at the temperature of 95 ℃ until the calcium carboxymethylcellulose is completely swelled, and the adhesive is obtained;

(3) pill of six ingredients with rehmannia: adding binder 40% of the total amount of the prepared medicinal materials into the medicinal powder mixture, mixing, and making into pill.

Example 4. A preparation method of Qiju Dihuang Wan-Soft pill comprises the following steps:

(1) powder: according to the weight ratio, 40 parts of medlar, 40 parts of chrysanthemum, 160 parts of prepared rehmannia root, 80 parts of wine dogwood fruit, 60 parts of tree peony bark, 80 parts of Chinese yam, 60 parts of tuckahoe and 60 parts of alisma orientale are taken; pulverizing the Chinese medicinal materials, sieving, and mixing to obtain medicinal powder;

(2) preparation of the adhesive: adding 100g of glycerol into a container, adding 4g of carboxymethylcellulose calcium, stirring uniformly, sealing, heating at 70-80 ℃ for 9-10 hours until the carboxymethylcellulose calcium is completely swelled, and stirring once every 2 hours to prepare an adhesive for later use;

(3) preparation of the pill: adding binder in an amount of 28% of the total amount of the prepared medicinal materials, mixing, and making into pill.

Example 5. A preparation method of a flexible rejuvenation pill for children comprises the following steps:

(1) paste powder mixture: taking 25 parts of coptis chinensis, 50 parts of buffalo horn concentrated powder, 25 parts of antelope horn, 25 parts of calcined chinese cabbage, 25 parts of fermented soybean, 50 parts of folium isatidis, 50 parts of schizonepeta, 50 parts of notopterygium root, 50 parts of kudzu root, 50 parts of rehmannia, 50 parts of caulis clematidis armandii, 50 parts of red paeony root, 50 parts of scutellaria baicalensis, 75 parts of radix peucedani, 75 parts of radix scrophulariae, 75 parts of platycodon grandiflorum, 37.5 parts of radix bupleuri, 37.5 parts of cacumen tamaricis, 20 parts of rhizoma cimicifugae and 75 parts of fried burdock; pulverizing cornu Saigae Tataricae into fine powder, and mixing with pulvis Cornus Bubali Concentratus to obtain mixture A; pulverizing 2/3 of the rest materials into fine powder, sieving with 80 mesh sieve, mixing the above fine powder with the above QINGGAO to obtain paste powder mixture;

(2) preparation of the adhesive: adding 100g of glycerol into a container, adding 4g of sodium carboxymethylcellulose, stirring uniformly, sealing, heating at 105 ℃ for 4 hours until the sodium carboxymethylcellulose is completely swelled, and stirring once every 2 hours to obtain an adhesive for later use;

(3) preparation of the pill: adding binder 29% of the total amount of the prepared medicinal materials into the medicinal powder, mixing, and making into pill.

Example 6. A preparation method of a flexible rejuvenation pill for children comprises the following steps:

(1) paste powder mixture: prepared according to the method of example 5;

(2) preparation of the adhesive: adding 100g of glycerol into a container, adding 10g of carboxymethylcellulose calcium, stirring uniformly, sealing, heating at 95 ℃ for 6 hours until the carboxymethylcellulose calcium is completely swelled, and stirring once every 1 hour to obtain an adhesive for later use;

(3) preparation of the pill: adding adhesive in an amount of 30% of the total amount of the prepared medicinal materials into the medicinal powder, mixing, and making into pill.

Example 7. A preparation method of Qijudihuang pills comprises the following steps:

Example 8. A preparation method of Qijudihuang pills comprises the following steps:

(1) powder: preparing a powder as described in example 7;

(2) preparation of the adhesive: adding 100g of glycerol into a container, adding 7g of carboxymethylcellulose calcium, stirring uniformly, sealing, heating at 90-95 ℃ for 5-6 hours until the carboxymethylcellulose calcium is completely swelled, and stirring once every 1.5 hours to prepare an adhesive for later use;

(3) preparation of the pill: adding binder accounting for 25% of the total amount of the prepared medicine into the medicinal powder, mixing uniformly, and making into pills.

Example 9. A preparation method of storax pills comprises the following steps:

(1) mixing the medicines: weighing 50g of storax, 100g of benzoin, 50g of borneol, 200g of buffalo horn concentrated powder, 75g of artificial musk, 100g of sandalwood, 100g of agilawood, 100g of clove, 100g of rhizoma cyperi, 100g of elecampane, 100g of prepared frankincense, 100g of long pepper, 100g of bighead atractylodes rhizome, 100g of myrobalan meat and 100g of cinnabar according to the weight components, and refining cinnabar into fine powder by water except the storax, the artificial musk, the borneol and the buffalo horn concentrated powder; pulverizing the rest materials into fine powder; respectively grinding Moschus, Borneolum Syntheticum, and pulvis Cornus Bubali Concentratus into fine powder, mixing with above powder, grinding, sieving, and mixing to obtain mixed medicinal powder; stewing storax to obtain mixed medicinal powder;

(2) preparation of the adhesive: adding 100g of glycerol into a container, adding 4.15g of sodium carboxymethylcellulose, stirring uniformly, sealing, heating at 90 ℃ for 7 hours until the sodium carboxymethylcellulose is completely swelled, and stirring once every 1 hour to prepare an adhesive for later use;

(3) preparation of the pill: adding adhesive in an amount which is 38 percent of the mixed medicinal powder into the medicinal powder, uniformly mixing, and making into pills.

Example 10. A preparation method of Zhibai Dihuang Wan is prepared according to the following steps:

(1) powder: weighing 40g of rhizoma anemarrhenae, 40g of cortex phellodendri, 160g of prepared rehmannia root, 80g of dogwood (prepared), 60g of moutan bark, 80g of Chinese yam, 60g of poria cocos and 60g of rhizoma alismatis according to weight components, crushing, sieving and uniformly mixing to obtain medicinal powder;

(2) preparation of the adhesive: adding 100g of glycerol into a container, adding 4.16g of sodium carboxymethylcellulose, stirring uniformly, sealing, heating at 105 ℃ for 4 hours until the sodium carboxymethylcellulose is completely swelled, and stirring once every 0.5 hour to obtain an adhesive for later use;

(3) preparation of the pill: adding adhesive in the amount of 32% of the total amount of the prepared medicinal materials, mixing, and making into pill.

Claims

1. The flexible pill medicine adhesive is characterized in that: the adhesive consists of glycerol and medicinal carboxymethyl cellulose salt, wherein the weight ratio of the glycerol to the medicinal carboxymethyl cellulose salt is 100: 1-15.

2. The pliable pill drug adhesive of claim 1, wherein: the weight ratio of glycerin to medicinal carboxymethyl cellulose salt is 100: 2.5-10.

3. The pliable pill drug adhesive of claim 1, wherein: according to the weight ratio, glycerin and medicinal carboxymethyl cellulose salt are 100: 2.5-7.66.

4. The pliable pill drug binder of any one of claims 1-3 wherein: the pharmaceutically acceptable carboxymethyl cellulose salt includes: sodium carboxymethyl cellulose or calcium carboxymethyl cellulose.

5. Flexible pellets made with the binder of any of claims 1 to 3, characterized in that: the soft pill is added with medicine extract powder or medicinal powder accounting for 50-80% of the total weight of the prepared medicines.

6. A flexible pellet formulation with the binder of claim 5 wherein: the soft pill is added with medicine extract powder or medicinal powder accounting for 55-75% of the total weight of the prepared medicines.

7. A flexible pellet formulation with the adhesive of claim 6 wherein: the soft pill is added with medicinal extract powder or medicinal powder accounting for 60-70% of the total weight of the prepared medicines.

8. A flexible pellet formulation formed with the binder of any one of claims 5 to 7 wherein: the flexible pill is prepared by:

9. A flexible pellet formulation with the adhesive of claim 8 wherein: in the step (1), the heating condition is heating at 60-105 ℃ for 4-10 hours.

10. A flexible pellet formulation with the adhesive of claim 8 wherein: in the step (1), the stirring is carried out once every 0.5-2 hours during the heating.