CN105497161B

CN105497161B - Bezoar soft capsule for detoxifying

Info

Publication number: CN105497161B
Application number: CN201610045197.XA
Authority: CN
Inventors: 陈铎; 王俊峰; 王爱荣
Original assignee: Beijing Kangerfu Pharmaceutical Co Ltd
Current assignee: Beijing Kangerfu Pharmaceutical Co Ltd
Priority date: 2016-01-22
Filing date: 2016-01-22
Publication date: 2019-12-17
Anticipated expiration: 2036-01-22
Also published as: CN105497161A

Abstract

The invention relates to a bezoar detoxicating soft capsule with high bioavailability, stable quality and no leakage, which comprises contents and a soft capsule shell. The soft capsule according to the present invention, wherein the soft capsule shell comprises gelatin, plasticizer, and water in a ratio of 1: 1: 0.6, the plasticizer is selected from one or more of glycerol and sorbitol. Preferably glycerol and sorbitol, in a weight ratio of 1: 1.

Description

Bezoar soft capsule for detoxifying

Technical Field

The invention relates to a bezoar soft capsule for detoxifying.

Background

The bezoar detoxicating soft capsule is well documented in pharmacopoeia, the prescription is 2.5g of artificial bezoar, 25g of realgar, 100g of gypsum, 100g of rhubarb, 75g of scutellaria, 50g of balloonflower root, 12.5g of borneol and 25g of liquorice, the eight ingredients are ground into fine powder except the artificial bezoar; refining Realgar with water to obtain fine powder; pulverizing radix et rhizoma Rhei into fine powder; decocting the rest four materials with water twice for 2 hr each time, mixing decoctions, filtering, concentrating the filtrate to obtain soft extract, adding radix et rhizoma Rhei and Realgar powder, drying, adding artificial bezoar, Borneolum Syntheticum and soybean oil, mixing, and making into capsule of 1000 granules. Can clear away heat and toxic material. Can be used for treating excessive fire-heat, sore throat, gingival swelling and pain, aphtha of the mouth and tongue, and conjunctival congestion and swelling and pain.

However, as the soft capsule is known to be cross-linked during use or leaked after long-term storage, the applicant has solved the technical problems of easy leakage and slow disintegration of the soft capsule through a large number of experiments by adjusting the content ratio and the capsule shell composition.

disclosure of Invention

The invention aims to provide a bezoar detoxicating soft capsule with high bioavailability, stable quality and no leakage, which comprises contents and a soft capsule shell.

the soft capsule according to the present invention, wherein the soft capsule shell comprises gelatin, water, and a plasticizer in a ratio of 1: 1: 0.6, the plasticizer is selected from one or more of glycerol and sorbitol. Preferably glycerol and sorbitol, in a weight ratio of 1: 1.

Preparation of the contents:

batch 60 ten thousand prescriptions:

Taking four traditional Chinese medicine decoction pieces of scutellaria baicalensis, platycodon grandiflorum, liquorice and gypsum in specified quantity, and carrying out water extraction: putting the weighed scutellaria baicalensis, platycodon grandiflorum, liquorice and gypsum into a multifunctional extraction tank, adding 10 times (W/L) of drinking water of the medicinal materials, heating to slightly boil, keeping the steam pressure at 0.02-0.04MPa, decocting for 2 hours, filtering the decoction through a 100-mesh sieve, and pumping the filtrate into a storage tank; the extraction tank was further charged with 8 times (W/L). Heating drinking water to slightly boil, keeping steam pressure at 0.02-0.04MPa, decocting for 2 hr, filtering decoction with 100 mesh sieve, pumping filtrate into storage tank, and mixing with the above decoction. Double-effect concentration: pumping the decoction in the storage tank into a double-effect energy-saving concentration tank under reduced pressure, closing a feed valve, and carrying out double-effect concentration at a first-effect concentration temperature of 65-80 ℃, a first-effect evaporation chamber vacuum degree of 0.02-0.06 MPa, a second-effect concentration temperature of 50-70 ℃ and a second-effect evaporation chamber vacuum degree of 0.05-0.08 MPa until the relative density of the extract is 1.10-1.15(65 ℃); and (3) vacuum concentration: and pumping the extractum subjected to double-effect concentration into a vacuum concentration tank by using vacuum from the double-effect concentration tank for vacuum concentration, wherein the vacuum degree is controlled to be 0.01-0.08 Mpa, the concentration temperature is 50-70 ℃, and the extractum is concentrated until the relative density of the extractum is 1.35-1.40(50 ℃).

Taking prescribed amount of rhubarb powder and realgar powder, and sieving with a No. 9 sieve (200 meshes). Mixing Realgar powder and radix et rhizoma Rhei powder by equivalent gradual addition method, adding into jacketed pan, slowly adding the extract under stirring, and mixing the extract with the mixture of Realgar and radix et rhizoma Rhei fine powder for 20 min.

and (3) drying: and (3) putting the mixed extract into a clean stainless steel disc of a square vacuum drier, and drying in the square vacuum drier, wherein the vacuum degree is controlled as follows in the drying process: 0.02-0.08 MPa, and controlling the drying temperature to be: drying for 24 hours at the temperature of 60-75 ℃, wherein the water content of the dry paste is required to be less than or equal to 5.0 percent

Crushing the dry paste: pulverizing the dry extract into fine powder with 100 mesh sieve, and packaging the pulverized dry extract powder with double-layer medicinal low density polyethylene bag.

Preparing a capsule material:

Taking 150.00 kg of gelatin, 150.00 kg of purified water and 90.00 kg of glycerin

Dissolving gelatin in a water bath type gelatin dissolving tank according to gelatin, purified water and glycerol ratio of 1: 0.6. And in the gelatin melting process, stirring when the temperature is raised to 65-70 ℃ (the temperature is kept at 65-70 ℃ during stirring), vacuumizing when gelatin is completely dissolved, controlling the vacuum degree at 0.01-0.09 Mpa, vacuumizing for 30 minutes, opening a gelatin outlet valve, filtering the melted gelatin solution through a 80-mesh sieve, putting the gelatin solution into a gelatin heat-insulating barrel, preserving the heat at 60-70 ℃, standing, and standing for at least 4 hours for use (standby).

The liquid medicine stirring paddle is installed on the equipment, and the equipment feeding system is connected with the liquid medicine heat-preserving container through the pneumatic diaphragm pump. And (3) taking gelatin liquid, installing the gelatin box on equipment, and connecting the gelatin heat-insulating barrel with the gelatin box of the equipment by using a gelatin pipeline. Adjusting the temperature of the gelatin box and the heating sleeve to be 60-65 ℃, adjusting the temperature of the left rubber wheel and the right rubber wheel to be less than or equal to 15 ℃, adjusting the thickness of the rubber to be 0.75-0.80mm, adjusting the temperature of the spraying body to be 38-42 ℃, adjusting the loading, wherein the weight of each pressed particle (containing the rubber) is 0.58-0.65g, the loading of each particle is 0.36-0.44g, and starting production after the particle is qualified;

Pelleting: in the process of pelleting, 10 capsules are taken every 30 minutes to check the average capsule weight, the weight (including capsule skin) of each capsule after pelleting is 0.58-0.65g, the loading amount of each capsule is 0.36-0.44g, and the soft capsules are shaped in a rotating cage after pelleting.

Selecting pills: the temperature is 18-26 ℃, and the relative humidity is below 65%;

Airing the pills: uniformly spreading the pressed soft capsule on a stainless steel screen mesh for drying, turning over once every 2 hours in the drying process, checking that the hardness of the soft capsule is proper, and then putting the soft capsule into a drying rotary cage for drying and washing pills;

Drying and washing pills: adding a special mercerized towel (wetted by 75% ethanol) into each cage of soft capsules, simultaneously opening the air blower, changing the mercerized towel once every 30 minutes, and visually observing the brightness and no oil stain of the soft capsules, namely cleaning the soft capsules, wherein the soft capsules have certain hardness and no adhesion phenomenon.

Selecting pills: each disk of soft capsules is placed on a workbench, and unqualified soft capsules with oil leakage, abnormal shape, insufficient loading amount and the like are picked out.

Aluminum plastic: 12 granules are filled in each plate, the upper plate is heated to 125-130 ℃, the lower plate is heated to 125-130 ℃, the temperature of a heat sealing roller is 195-205 ℃, the blanking speed is 20-60Hz, and the pressing is tight.

Example 1: screening of soft capsule material formula

Putting gelatin, glycerol and water in a water bath gelatin melting tank according to a certain proportion, heating and dissolving in a water bath at 85-90 ℃, stirring for 2h, vacuumizing and degassing, keeping the temperature at 50-60 ℃ and standing overnight, pressing the gelatin capsule the next day, drying, observing the appearance and physical properties of the soft capsule for three months, and observing the appearance and physical properties of the soft capsule, wherein the results are shown in table 1:

TABLE 1 selection of Soft Capsule materials

example 2

the soft capsule shell comprises the following components in parts by weight: selecting capsule materials 1-3 in Table 1, respectively, selecting capsule shells 1-3 in Table 1, adding soybean oil to total amount of 250.00kg and 230.00kg to obtain soft capsule, respectively corresponding to test products 4-9, and adding capsule materials of 100g gelatin, 60g glycerol, 100g water and soybean oil to total amount of 250.00kg (test product 4); the capsule wall material was 100g of gelatin, 60g of glycerin, 100g of water and soybean oil to a total of 230.00kg of contents (test article 5); capsule wall material 100g gelatin, 60g sorbitol, 100g water and soybean oil to a total of 250.00kg contents (test article 6); capsule wall material 100g gelatin, 60g sorbitol, 100g water and soybean oil to total 230.00kg of contents (test article 7); the capsule wall was 100g of gelatin, 30g of glycerin, 30g of sorbitol, 100g of water and soybean oil to a total of 250.00kg of contents (test article 8), and the capsule wall was 100g of gelatin, 30g of glycerin, 30g of sorbitol, 100g of water and soybean oil to a total of 230.00kg of contents (test article 9).

The 9 soft capsules obtained above were sealed with a lid in a high density polyethylene bottle (50 capsules per bottle per formulation, 100 capsules per formulation were used for each formulation), and after standing in a constant temperature and humidity apparatus at 40 ℃ and 75% relative humidity for 10 months, the number of leaks in the soft capsules obtained in different formulations was checked, and the number of leaks was divided by 100 capsules per formulation to obtain a leak rate (%) (the leak rate can be represented by R), and the results are shown in table 2:

TABLE 2

Example 3 accelerated test

The test method comprises the following steps: the test products 1 to 3 and the commercial bezoar detoxicating soft capsule in example 2 were placed in a constant temperature box with 40 ℃ and 75% relative humidity, samples were taken at different time periods, and the disintegration time was determined according to the regulations in the first related monograph of the Chinese pharmacopoeia, 2010 edition, and the results are shown in Table 3:

TABLE 3 accelerated test

Day 0

1 month

2 months old

3 months old

4 months old

For 5 months

6 months old

7 months old

Test article 1

8 minutes

9 minutes

10 minutes

11 minutes

12 minutes

test article 2

8 minutes

9 minutes

10 minutes

11 minutes

12 minutes

Test article 3

8 minutes

9 minutes

10 minutes

Is commercially available

8 minutes

9 minutes

10 minutes

11 minutes

12 minutes

14 minutes

16 minutes

The result shows that the soft capsule prepared by the method is qualified in disintegration and high in bioavailability.

Claims

1. A detoxicating soft capsule of bezoar is characterized in that: the soft capsule shell is prepared from gelatin, water and a plasticizer according to the proportion of 1: 1: 0.6, and the plasticizer is glycerol and sorbitol, and the weight ratio of the glycerol to the sorbitol is 1: 1, the content is bezoar detoxification fluid extract; the bezoar detoxicating fluid extract comprises the following components by 60 ten thousand pills: extracting dry extract powder, Borneolum 7.50kg, artificial bezoar 1.50kg, and soybean oil to total amount of 240.00kg,

The extracted dry paste powder is prepared according to the following method:

Baikal skullcap root 45.00Kg platycodon root 30.00Kg licorice root 15.00Kg

Gypsum Fibrosum 60.00Kg Realgar 15.00Kg radix Et rhizoma Rhei 60.00Kg

Taking four traditional Chinese medicine decoction pieces of scutellaria baicalensis, platycodon grandiflorum, liquorice and gypsum, and carrying out water extraction: putting the weighed scutellaria baicalensis, platycodon grandiflorum, liquorice and gypsum into a multifunctional extraction tank, adding drinking water with the volume 10 times of the weight of the medicinal materials, heating to slightly boil, keeping the steam pressure at 0.02-0.04MPa, decocting for 2 hours, filtering the decoction through a 100-mesh sieve, and pumping the filtrate into a storage tank; adding drinking water with a volume 8 times of the mass of the medicinal materials into the extraction tank, heating to slightly boil, keeping the steam pressure at 0.02-0.04MPa, decocting for 2 hours, filtering the decoction through a 100-mesh sieve, pumping the filtrate into a storage tank, and combining the filtrate with the last decoction for later use; double-effect concentration: the decoction in the storage tank is pumped into a double-effect energy-saving concentration tank under reduced pressure, a feed valve is closed, double-effect concentration is carried out, the temperature of first-effect concentration is 65-80 ℃, the vacuum degree of a first-effect evaporation chamber is controlled to be 0.02-0.06 MPa, the temperature of second-effect concentration is 50-70 ℃, the vacuum degree of a second-effect evaporation chamber is controlled to be 0.05-0.08 MPa, and the liquid medicine is concentrated until the relative density of the extract is 1.10-1.15 below 65 ℃; and (3) vacuum concentration: pumping the extractum subjected to double-effect concentration into a vacuum concentration tank by using vacuum from the double-effect concentration tank for vacuum concentration, controlling the vacuum degree to be 0.01-0.08 Mpa and the concentration temperature to be 50-70 ℃, and concentrating until the relative density of the extractum is 1.35-1.40 at 50 ℃;

Sieving radix Et rhizoma Rhei powder and Realgar powder with No. 9 sieve; mixing Realgar powder and radix et rhizoma Rhei powder by equivalent gradual addition method, adding into jacketed pan, slowly adding the extract under stirring, and mixing the extract with the mixture of Realgar and radix et rhizoma Rhei fine powder for 20 min;

And (3) drying: and (3) putting the mixed extract into a clean stainless steel disc of a square vacuum drier, and drying in the square vacuum drier, wherein the vacuum degree is controlled as follows in the drying process: 0.02-0.08 MPa, and controlling the drying temperature to be: drying for 24 hours at the temperature of 60-75 ℃, wherein the water content of the dry paste is required to be less than or equal to 5.0 percent;

Crushing the dry paste: pulverizing the dry extract into fine powder, sieving with 100 mesh sieve, and packaging the pulverized dry extract powder with double-layer medicinal low density polyethylene bag.

2. The use of the soft capsule of claim 1 in the preparation of a medicament for treating excessive internal heat, sore throat, gingival swelling and pain, aphtha of the mouth and tongue, and conjunctival congestion and swelling and pain.