CN114010613B - Enteric coated preparation of liushen pills and preparation method thereof - Google Patents

Enteric coated preparation of liushen pills and preparation method thereof Download PDF

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CN114010613B
CN114010613B CN202111319302.1A CN202111319302A CN114010613B CN 114010613 B CN114010613 B CN 114010613B CN 202111319302 A CN202111319302 A CN 202111319302A CN 114010613 B CN114010613 B CN 114010613B
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liushen
enteric
pill
preparation
liushen pill
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CN114010613A (en
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潘耀宗
王恒斌
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Leiyunshang Pharmaceutical Group Co ltd
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Leiyunshang Pharmaceutical Group Co ltd
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Abstract

The invention provides a Liushen pill enteric-coated preparation. The enteric coated preparation of the Liushen pill comprises: the Liushen pill comprises a Liushen pill body and a coating, wherein the coating is coated on the surface of the Liushen pill body, and the coating contains a film forming agent which is disintegrated in an environment with the pH value of 6.0-8.0. The Liushen pill enteric-coated preparation has good compliance, avoids the stimulation effect of the Liushen pill on gastric mucosa, effectively reduces the incidence rate of adverse reactions of the Liushen pill, and has better anti-inflammatory and analgesic effects.

Description

Enteric coated preparation of liushen pills and preparation method thereof
Technical Field
The invention belongs to the field of medicines, and particularly relates to a Liushen pill enteric-coated preparation and a preparation method thereof.
Background
Liushen pill is a famous heat-clearing, detoxifying and sore-throat-relieving medicine, and is made up by using six Chinese medicinal materials of artificial musk and others. The LIUSHEN pill has effects of clearing away heat and toxic materials, relieving inflammation, and relieving pain. Can be used for treating scarlet fever, sore throat, single or double tonsillitis, infantile heat furuncle, carbuncle, furuncle, mammary abscess, back pain, and innominate swelling and pain. In addition, has good treatment effect on herpes zoster, phlebitis, leukemia, digestive tract tumor and mastitis.
However, some patients have adverse reactions such as nausea and vomiting after taking liushen pills, so that it is necessary to develop a novel preparation based on liushen pills, reduce irritation and improve compliance of patients after taking liushen pills.
Disclosure of Invention
The present application is based on the discovery and recognition by the inventors of the following facts and problems:
the Liushen pills have adverse reactions such as nausea and vomiting, and after patients take the Liushen pills, a large amount of medicines are intensively released in the stomach to stimulate gastric mucosa, so that the adverse reactions such as nausea and vomiting are caused after the patients take the Liushen pills.
The present invention is directed to solving, at least to some extent, one of the technical problems in the related art. To this end, in a first aspect of the invention, an enteric formulation is presented. According to an embodiment of the present invention, the enteric formulation comprises: the Liushen pill comprises a Liushen pill body and a coating, wherein the coating is coated on the surface of the Liushen pill body, and the coating contains a film forming agent, and the film forming agent comprises at least one selected from the following components: cellulose acetate phthalate, acrylic resins, hydroxypropylmethylcellulose phthalate and polyvinyl alcohol acetate phthalate.
The invention aims to solve the problems that patients are easy to cause adverse reactions due to stimulation on gastric mucosa when taking Liushen pills, and the like, and obtains a special Liushen pill enteric preparation.
The Liushen pill enteric-coated preparation provided by the embodiment of the invention can avoid stimulation of a medicament to gastric mucosa, delay the absorption time of the medicament, achieve the purpose of positioning and releasing small intestine, improve the compliance and increase the effect of local treatment.
According to an embodiment of the present invention, the enteric preparation of liushen pills described above may further have at least one of the following additional technical features:
according to an embodiment of the present invention, the film forming agent is an acrylic resin. According to the Liushen pill enteric-coated preparation provided by the embodiment of the invention, when the acrylic resin is used as the film forming agent, the Liushen pill is low in dissolution amount in hydrochloric acid and high in dissolution amount in a nitrate buffer solution, so that the Liushen pill is low in dissolution amount in gastric juice and high in dissolution amount in intestinal juice, is most suitable for being used as the film forming agent of the Liushen pill enteric-coated preparation, ensures low dissolution rate of the Liushen pill in gastric juice, is dissolved and released in intestinal tracts and exerts a drug effect.
According to an embodiment of the invention, the coating further comprises at least one of an antistatic agent and a plasticizer. According to the Liushen pill preparation provided by the embodiment of the invention, the coating can be softer and is beneficial to stretching and shaping by using a proper amount of plasticizer.
According to an embodiment of the invention, the antistatic agent is sodium lauryl sulfate. According to the Liushen pill preparation provided by the embodiment of the invention, sodium dodecyl sulfate is used as an antistatic agent, so that the preparation of a coating is facilitated, and the coating is wrapped on the surface of the Liushen pill to form the Liushen pill enteric preparation, so that the stability of the Liushen pill is improved.
According to an embodiment of the invention, the plasticizer comprises at least one selected from the group consisting of: bis (2-ethylhexyl) sebacate, dioctyl adipate, dibutyl sebacate, di-n-butyl adipate and dibutyl phthalate, preferably dibutyl phthalate. According to the embodiment of the invention, the plasticizer can make the coating softer and beneficial to stretching, is beneficial to shaping of the coating, and enables the coating to be uniformly coated on the surface of the Liushen pill to delay drug absorption.
According to the embodiment of the invention, the mass ratio of the Liushen pills to the coating is (10-95): (95-10).
According to the embodiment of the invention, the mass ratio of the Liushen pills to the coating is (20-80): (80-20).
According to the Liushen pill enteric-coated preparation disclosed by the embodiment of the invention, by adopting the components and the mass ratio range of the Liushen pills to the coating, the weight gain of the coating is 5-15 mg/cm 2 The release does not occur in an environment with a pH value of 1 for 2 hours, the release does not occur in an environment with a pH value of 2-6.8 for 2 hours, and the release is rapid in an environment with a pH value of 7.8-8.0. The pH of intestinal fluid is in a weakly alkaline environment, and the Liushen pill enteric preparation prepared by adopting the proportion can avoid the concentrated release of the Liushen pill in acidic gastric juice, reduce the stimulation to gastric mucosa and further avoid the adverse reaction of patients.
Preferably, the mass ratio of the Liushen pills to the coating is (70-85): (30 to 15). The inventor finds that the Liushen pill enteric-coated preparation prepared by adopting the proportion not only can ensure that the Liushen pill is positioned in the small intestine to release, but also can improve the anti-inflammatory and analgesic effects of the medicine, and compared with the Liushen pill, the Liushen pill enteric-coated preparation prepared by adopting the proportion has better anti-inflammatory and analgesic effects.
According to an embodiment of the invention, in said coating, the mass ratio of said film-forming agent, said antistatic agent and said plasticizer is (10 to 80): (1-10): (2-10); preferably, the mass ratio of the film forming agent to the antistatic agent to the plasticizer is (10-20) to (2-5) to (3-5). According to the embodiment of the invention, the coating prepared by adopting the proportion has good ductility and stretchability, is beneficial to matching the shape and size of the Liushen pill, is coated on the surface of the Liushen pill, ensures that the Liushen pill is not released for a proper time in an acid environment, is beneficial to slowly releasing the Liushen pill in a weak alkaline environment of small intestinal juice, avoids the stimulation of the medicine to the intestines and stomach of a patient, and reduces adverse reactions.
According to the embodiment of the invention, the mass ratio of the Liushen pills to the film forming agent, the antistatic agent and the plasticizer is (10-90): (10-80): (1-10): (2-10); preferably, the mass ratio of the Liushen pill to the film forming agent to the antistatic agent to the plasticizer is (70-85) to (10-20) to (2-5) to (3-5); more preferably, the mass ratio of the Liushen pill, the film forming agent, the antistatic agent and the plasticizer is 85.
According to an embodiment of the present invention, the mass ratio of the liushen pill, the film-forming agent, the antistatic agent and the plasticizer is 10: 5; or the mass ratio of the Liushen pill, the film-forming agent, the antistatic agent and the plasticizer is 30; or the Liushen pill, the film forming agent, the antistatic agent and the plasticizer have the mass ratio of 50; or the mass ratio of the Liushen pill, the film-forming agent, the antistatic agent and the plasticizer is 70; or the Liushen pill, the film forming agent, the antistatic agent and the plasticizer have the mass ratio of 85.
The inventor finds that the Liushen pill enteric-coated preparation prepared by adopting the proportion not only can ensure that the Liushen pill is positioned in the small intestine to be released, but also can improve the anti-inflammatory and analgesic effects of the medicine, and compared with the Liushen pill, the Liushen pill enteric-coated preparation prepared by adopting the proportion has better anti-inflammatory and analgesic effects. In an anti-inflammatory analgesic effect experiment of a mouse, compared with the Liushen pill, the Liushen pill enteric-coated preparation prepared from 70; in addition, the Liushen pill enteric-coated preparation also has better pain relieving effect, the inhibition rate of the Liushen pill enteric-coated preparation on mouse writhing can reach 74.29% and 76.57% which are higher than 73.18% of Liushen pill, and simultaneously, the Liushen pill enteric-coated preparation in the proportion has stronger effect of inhibiting TNF-a and IL-6 which are far higher than that of the Liushen pill and aspirin.
According to an embodiment of the invention, the film forming agent disintegrates in an environment having a pH of 6.0 to 8.0.
In a second aspect of the invention, the invention proposes a method of preparing the enteric formulation proposed in the first aspect of the invention. According to an embodiment of the invention, the method comprises: 1) First mixing a solution containing a film-forming agent with the antistatic agent and the plasticizer to obtain a coating solution; 2) And secondly, mixing the coating solution with the Liushen pills, and aging the obtained mixed solution so as to obtain the Liushen pill enteric-coated preparation. The method provided by the embodiment of the invention is simple to operate, low in cost and convenient to operate, and the prepared Liushen pill enteric preparation is good in compliance, avoids the stimulation effect of Liushen pills on gastric mucosa, effectively reduces the incidence rate of adverse reactions of Liushen pills and has better anti-inflammatory and analgesic effects.
According to an embodiment of the present invention, the above method may further have at least one of the following additional technical features:
according to the embodiment of the invention, the second mixing is carried out in a spheronizer, wherein the speed of a rotary table is 100-140 r/min, the blowing frequency is 20-30 Hz, the air inlet temperature is 40-50 ℃, the atomizing pressure is 0.05-0.2 MPa, and the flow rate of a peristaltic pump is 4-8 mL/min; preferably, the speed of the rotary table is 120r/min, the blowing frequency is 25Hz, the air inlet temperature is 45 ℃, the atomizing pressure is 0.1MPa, and the flow rate of the peristaltic pump is 6mL/min. The method provided by the embodiment of the invention is simple to operate, low in cost and convenient to operate, and the prepared Liushen pill enteric preparation is good in compliance, avoids the stimulation of Liushen pills on gastric mucosa, effectively reduces the incidence rate of adverse reactions of Liushen pills and has better anti-inflammatory and analgesic effects.
In a third aspect, the invention provides the use of the enteric formulation of the first aspect, or the enteric formulation prepared by the method of the second aspect, in the manufacture of a medicament for the treatment of a disease. According to an embodiment of the present invention, the disease includes erysipelas, sore throat, single or double tonsillitis, infantile heat furuncle, carbuncle, furuncle, acute mastitis, back swelling, innominate swelling, herpes zoster, phlebitis, leukemia, digestive tract tumor, mastitis.
Additional aspects and advantages of the invention will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the invention.
Detailed Description
The following detailed description of embodiments of the invention is intended to be illustrative, but not limiting, of the invention.
Furthermore, the terms "first", "second" and "first" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one such feature. In the description of the present invention, "a plurality" means at least two, e.g., two, three, etc., unless explicitly specified otherwise.
The invention will now be described with reference to specific examples, which are intended to be illustrative only and not to be limiting in any way.
Example 1: selection of enteric layer Material
Respectively weighing the cellulose acetate phthalate, acrylic resin, hydroxypropyl methyl cellulose phthalate, polyvinyl alcohol acetate phthalate, polyvinyl alcohol phthalate and cellulose acetate trimellitate according to the formula amount as enteric layer materials, respectively taking the enteric layer materials as formulas 1-6, wherein the formula raw materials are shown in table 1, respectively adding absolute ethyl alcohol, magnetically stirring for 1h to dissolve, then adding sodium dodecyl sulfate and dibutyl phthalate, and filtering for later use. Placing the LIUSHEN pill in a spheronizer, setting the speed of a rotary table at 120r/min, the blowing frequency at 25Hz, the air inlet temperature at 45 ℃, the atomization pressure at 0.1MPa, the flow rate of a peristaltic pump at 6mL/min, and aging at 40 ℃ for 4h after coating. Determining the amount of the enteric pellets dissolved out in a phosphate buffer (simulated intestinal solution) with pH = 6.8; the elution amount in 0.1mol/L hydrochloric acid solution (simulated gastric juice) is shown in Table 2.
Table 1: prescription 1-6 proportion of raw materials (weight parts of each substance)
Figure BDA0003344937230000041
Figure BDA0003344937230000051
TABLE 2 dissolution results of enteric formulations
Figure BDA0003344937230000052
The results in Table 2 show that: the enteric layer is made of cellulose acetate phthalate, acrylic resin, hydroxypropyl methyl cellulose phthalate and polyvinyl alcohol acetate phthalate, and the effect is better, wherein the enteric layer is made of acrylic resin, and the effect is best. When polyvinyl alcohol phthalate and cellulose acetate trimellitate are used as enteric layer materials, the dissolution effect is general, and the enteric layer materials are not suitable for Liushen enteric preparations.
Example 2: preparation of enteric coated preparation
Liushen pill 10 weight portions
Acrylic resin 80 parts by weight
Sodium dodecyl sulfate 5 parts by weight
Dibutyl phthalate 5 parts by weight
The preparation method comprises the following steps:
1. preparing a coating solution: weighing acrylic resin according to the prescription amount, adding absolute ethyl alcohol, magnetically stirring for 1h to dissolve the acrylic resin, and adding sodium dodecyl sulfate and dibutyl phthalate. Filtering for later use.
2. Preparing a coated pellet: placing the LIUSHEN pill in a spheronizer, setting the speed of a rotary table at 120r/min, the blowing frequency at 25Hz, the air inlet temperature at 45 ℃, the atomization pressure at 0.1MPa, the flow rate of a peristaltic pump at 6mL/min, and aging at 40 ℃ for 4h after coating.
Example 3: preparation of enteric coated preparation
Liushen pill 30 weight portions
Acrylic resin 60 parts by weight
Sodium dodecyl sulfate 7 parts by weight
Dibutyl phthalate 3 parts by weight
The preparation method comprises the following steps:
1. preparing a coating solution: weighing acrylic resin according to the prescription amount, adding absolute ethyl alcohol, magnetically stirring for 1h to dissolve the acrylic resin, and adding sodium dodecyl sulfate and dibutyl phthalate. Filtering for later use.
2. Preparing a coated pellet: placing the LIUSHEN pill in a spheronizer, setting the speed of a rotary table at 120r/min, the blowing frequency at 25Hz, the air inlet temperature at 45 ℃, the atomization pressure at 0.1MPa, the flow rate of a peristaltic pump at 6mL/min, and aging at 40 ℃ for 4h after coating.
Example 4: preparation of enteric coated preparation
Liushen pill 50 weight portions
Acrylic resin 38 parts by weight
Sodium dodecyl sulfate 8 parts by weight
Dibutyl phthalate 4 weight parts
The preparation method comprises the following steps:
1. preparing a coating solution: weighing acrylic resin according to the prescription amount, adding absolute ethyl alcohol, magnetically stirring for 1h to dissolve the acrylic resin, and adding sodium dodecyl sulfate and dibutyl phthalate. Filtering for later use.
2. Preparing a coated pellet: placing the LIUSHEN pill in a spheronizer, setting the speed of a rotary table at 120r/min, the blowing frequency at 25Hz, the air inlet temperature at 45 ℃, the atomization pressure at 0.1MPa, the flow rate of a peristaltic pump at 6mL/min, and aging at 40 ℃ for 4h after coating.
Example 5: preparation of enteric coated preparation
Liushen pill 70 weight portions
Acrylic resin 20 parts by weight
Sodium dodecyl sulfate 5 parts by weight
Dibutyl phthalate 5 parts by weight
The preparation method comprises the following steps:
1. preparing a coating solution: weighing acrylic resin according to the prescription amount, adding absolute ethyl alcohol, magnetically stirring for 1h to dissolve the acrylic resin, and adding sodium dodecyl sulfate and dibutyl phthalate. Filtering for later use.
2. Preparing a coated pellet: placing the LIUSHEN pill in a spheronizer, setting the speed of a rotary table at 120r/min, the blowing frequency at 25Hz, the air inlet temperature at 45 ℃, the atomization pressure at 0.1MPa, the flow rate of a peristaltic pump at 6mL/min, and aging at 40 ℃ for 4h after coating.
Example 6: preparation of enteric coated preparation
Liushen pill 85 weight portions
Acrylic resin 10 parts by weight
Sodium dodecyl sulfate 2 parts by weight
Dibutyl phthalate 3 parts by weight
The preparation method comprises the following steps:
1. preparing a coating solution: weighing acrylic resin according to the prescription amount, adding absolute ethyl alcohol, magnetically stirring for 1h to dissolve the acrylic resin, and adding sodium dodecyl sulfate and dibutyl phthalate. Filtering for later use.
2. Preparing a coated pellet: placing the LIUSHEN pill in a spheronizer, setting the speed of a rotary table at 120r/min, the blowing frequency at 25Hz, the air inlet temperature at 45 ℃, the atomization pressure at 0.1MPa, the flow rate of a peristaltic pump at 6mL/min, and aging at 40 ℃ for 4h after coating.
Example 7: research on treatment effect of Liushen pill enteric-coated preparation on H1N1 type influenza virus
Experimental rats with an initial mean body weight of 180 ± 5g were selected and randomly divided into 9 groups of 10 rats (male and female halves) each: blank control group, virus control group, experiment group of examples 2-6, liushen pill group and oseltamivir control group, wherein the administration concentration of the experiment group of examples 2-6 and Liushen pill group is calculated by equal amount of Liushen pills. The blank control group was not treated for viral infection, no drug was administered, and the other groups were fed normally, and rats were anesthetized with ether and infected with H1N1 virus by nasal drip, and the amount of infection per rat was 80. Mu.g. After confirmation of infection, no virus control group was administered; examples 2-6 experimental group, liu shen wan group and oseltamivir control group were administered by intragastric administration with the enteric preparation, liu shen wan and oseltamivir of examples 2-6, respectively, at a dose of 30 mg/kg/time twice a day. On day 5 after administration, each group of rats was sacrificed, their body weights were weighed with a precision balance, rats were dissected, lungs of the rats were taken, soaked in physiological saline, washed, water was sucked off with filter paper, lung weights were weighed, lung lesions were observed, and average lung index and lung lesion inhibition rate were calculated, and the results are shown in table 3.
Table 3: therapeutic effect of Liushen pill enteric-coated preparation on H1N1 type influenza virus
Figure BDA0003344937230000071
Figure BDA0003344937230000081
Note: lung lesion extent is measured as "+": 75< +++ <100, 50< +++ <75, 25< ++ <50,0< + < 25- > -indicating no lesion;
as can be seen from Table 3, the enteric preparations of LIUSHEN pill provided in examples 2-6 showed the best effect in examples 5 and 6, presumably due to the relationship between the weight gain and the release amount of the coating. Although the lung disease change inhibition effect of the Liushen pill group is the best in the test, the effect of the Liushen pill enteric-coated preparation provided by the examples 5 and 6 is basically similar to that of the Liushen pill group, and the treatment effect of the Liushen pill enteric-coated preparation provided by the examples 3 to 6 is better than that of the positive control oseltamivir group.
Example 8: experiment for inhibiting mouse ear swelling by Liushen pill enteric-coated preparation
Experimental mice with an initial average body weight of 25 ± 5g were selected and randomly divided into 8 groups of 10 mice (male and female halves) each, with the following: model control group, experiment group of examples 2-6, liushen pill group and aspirin control group, wherein the administration concentration of the experiment group of examples 2-6 and the liushen pill group is calculated by equivalent liushen pills. The medicine is administrated by gavage at a dose of 0.2mL/10g every day, 1 time/day, and continuously for 7 days. After 1h of last administration, 0.05mL of dimethylbenzene is uniformly smeared on two sides of the right ear of each group of mice to cause inflammation, the left ear of each group of mice is not smeared as a control, the cervical vertebra is removed after 30min to be killed, two ears of each group of mice are cut along the auricle of each group of mice, round ear pieces are punched at the same positions of the left ear and the right ear by a puncher with the diameter of 6mm, the round ear pieces are respectively weighed, the mass difference of the two ear pieces is used as the ear swelling degree, and the swelling inhibition rate is calculated.
SPSS 20.0 statistical package for data analysis to perform statistical processing and measurement of dataUsing mean. + -. Standard deviation
Figure BDA0003344937230000083
Showing that the comparison among the groups adopts one-factor analysis of variance, P<A difference of 0.05 is statistically significant. The results are shown in Table 3.
Table 4: liushen pill enteric-coated preparation for inhibiting mouse ear swelling
Figure BDA0003344937230000082
Figure BDA0003344937230000091
Note that P is <0.01 in comparison with model control group
As can be seen from Table 4, the enteric-coated preparations of LIUSHEN pill provided in examples 2-6 all have inhibitory effect on ear swelling of mice, wherein the sample of example 6 has the best effect, and the enteric-coated preparations of LIUSHEN pill provided in examples 5 and 6 have better effect than those of LIUSHEN pill group and positive control aspirin group. It is suggested that the Liushen pill enteric-coated preparation prepared by the methods of examples 5 and 6 has better effect of inhibiting mouse ear swelling than Liushen pills.
Example 9: research on analgesic effect of Liushen pill enteric-coated preparation on mice
Experimental mice with an initial average body weight of 25 ± 5g were selected and randomly divided into 8 groups of 10 mice (male and female halves) each, with the following: model control group, experiment group of examples 2-6, liushen pill group and aspirin control group, wherein the administration concentration of the experiment group of examples 2-6 and the liushen pill group is calculated by equivalent liushen pills. The medicine is administered by gavage at a dose of 0.2mL/10g for 1 time/day and 3 days continuously, and is fasted 12h before the last administration without water. After 30min of the last administration, the injection is subcutaneously injected by 0.2ml of 1% acetic acid solution, and the number of writhing of the mice within 10min is recorded after 30min, which is taken as the pain threshold index.
The statistical processing of data is carried out by SPSS 20.0 statistical package for data analysis, and the average value plus or minus standard deviation is used for measuring data
Figure BDA0003344937230000092
Showing that the comparison among the groups adopts one-factor analysis of variance, P<A difference of 0.05 is statistically significant. The results are shown in Table 5.
Table 5: research on analgesic effect of Liushen pill enteric-coated preparation on mice
Group of Number of times of body twisting Inhibition ratio (%)
Model comparison 33.25±2.54 -
Example 2 13.27±0.75* 60.09
Example 3 11.84±0.72* 64.38
Example 4 10.12±0.67* 69.57
Example 5 8.55±0.53* 74.29
Example 6 7.79±0.49* 76.57
Liushen pill 8.92±0.73* 73.18
Aspirin 9.16±0.81* 72.44
Note that P is <0.01 in comparison with model control group
As can be seen from Table 5, all of the enteric preparations of LIUSHEN pill provided in examples 2-6 have analgesic effect, wherein the enteric preparation provided in example 6 has the best effect, and the enteric preparations provided in examples 5 and 6 have better effect than those of LIUSHEN pill group and positive control aspirin group. It is suggested that the Liushen pill enteric-coated preparation prepared by the methods of the embodiments 5 and 6 has better analgesic effect than Liushen pills.
Example 10: research on TNF-a and IL-6 content inhibition of Liushen pill enteric-coated preparation
The concentration is 1X 10 5 Inoculating RAW264.7 mouse macrophage cell/mL into 6-well plate, adding complete medium containing 5mg/L LPS, placing at 37 deg.C, 5% 2 After incubation in the incubator for 24h, the old medium was discarded and washed 3 times with PBS. Respectively adding a model control group, an experimental group of examples 2-6, a Liushen pill group and an aspirin control group, continuously incubating for 18-24 h, collecting cell sap, centrifuging for 10min at 1000r/min, taking 200 mu L of supernatant, and detecting the contents of TNF-a and IL-6 by an ELISA method.
The statistical processing of data is carried out by SPSS 20.0 statistical package for data analysis, and the average value plus or minus standard deviation is used for measuring data
Figure BDA0003344937230000101
Showing that the comparison among the groups adopts one-factor analysis of variance,P<a difference of 0.05 is statistically significant. The results are shown in Table 6.
TABLE 6 study on TNF-a and IL-6 content inhibition of enteric coated preparation of LIUSHEN pill
Group of TNF-a(ng/L) IL-6(ng/L)
Model comparison 7345.21±67.23 3256.78±45.97
Example 2 804.28±20.35* 376.41±12.82*
Example 3 591.36±17.51* 257.77±10.21*
Example 4 256.52±9.33* 179.09±7.39*
Example 5 105.42±4.89* 63.16±3.19*
Example 6 37.19±3.35* # 18.21±2.99* #
Liushen pill 223.57±11.13* 136.29±6.78*
Aspirin 249.31±12.14* 157.78±6.35*
Note: p x compared to model control group<0.01, P is compared with Liushen pill group and aspirin group # <0.05
As can be seen from Table 6, the enteric preparations of LIUSHEN pill provided in examples 2-6 all have the effect of inhibiting TNF-a and IL-6, wherein the enteric preparations of LIUSHEN pill provided in examples 5 and 6 have the best effect, and the samples of example 6 have significant difference (P < 0.05) in the effect of inhibiting TNF-a and IL-6 compared with the LIUSHEN pill group and the positive control aspirin group.
In the description herein, references to the description of the term "one embodiment," "some embodiments," "an example," "a specific example," or "some examples," etc., mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above are not necessarily intended to refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples. Moreover, various embodiments or examples and features of different embodiments or examples described in this specification can be combined and combined by one skilled in the art without contradiction.
Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention, and that variations, modifications, substitutions and alterations can be made to the above embodiments by those of ordinary skill in the art within the scope of the present invention.

Claims (6)

1. An enteric formulation, comprising: the Liushen pill comprises Liushen pills and a coating, wherein the coating is coated on the surface of the Liushen pills and contains a film forming agent, an antistatic agent and a plasticizer, the film forming agent is acrylic resin, the antistatic agent is sodium dodecyl sulfate, the plasticizer is dibutyl phthalate,
wherein the mass ratio of the Liushen pill, the film forming agent, the antistatic agent and the plasticizer is (70-85): 10-20): 2~5: 3~5.
2. The enteric formulation according to claim 1, wherein the film-forming agent disintegrates in an environment having a pH of 6.0 to 8.0.
3. A method of preparing the enteric formulation of claim 1 or 2, comprising:
1) First mixing a solution containing a film-forming agent with the antistatic agent and the plasticizer to obtain a coating solution;
2) And secondly, mixing the coating solution and the Liushen pills, and aging the obtained mixed solution so as to obtain the Liushen pill enteric-coated preparation.
4. The method according to claim 3, wherein the second mixing is carried out in a rolling machine, wherein the speed of a rotary table is 100 to 140r/min, the blowing frequency is 20 to 30Hz, the air inlet temperature is 40 to 50 ℃, the atomizing pressure is 0.05 to 0.2MPa, and the flow rate of a peristaltic pump is 4 to 8mL/min.
5. The method of claim 3, wherein the second mixing is performed in a spheronizer at a turntable speed of 120r/min, an air blast frequency of 25Hz, an air inlet temperature of 45 ℃, an atomization pressure of 0.1MPa, and a peristaltic pump flow rate of 6mL/min.
6. Use of the enteric preparation of claim 1 or 2, or the enteric preparation prepared by the method of any one of claims 3~5, in the preparation of a medicament for the treatment of a disease selected from erysipelas, sore throat, tonsillitis, furuncle, carbuncle, furuncle, mammary abscess, dorsal carbuncle, innominate swelling, herpes zoster, phlebitis, leukemia, digestive tract tumor, mastitis.
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