CN111588775A - Belladonna extract and belladonna capsule compound preparation - Google Patents
Belladonna extract and belladonna capsule compound preparation Download PDFInfo
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Abstract
The invention relates to the technical field of medicines, in particular to a belladonna extract and belladonna capsule compound preparation; the method for extracting belladonna extract comprises the following steps: percolating belladonna coarse powder with ethanol solvent; concentrating the obtained percolate extract, washing with ethanol, and centrifuging to obtain supernatant; the solvent contains 0.1-0.3% of acid; the method further comprises the steps of adjusting the pH value of the supernatant to 3-4, purifying with macroporous resin (such as NKA-II type), and performing gradient elution with 80-95% and 65-75% ethanol solutions respectively. The extraction method provided by the invention can effectively reduce the content of chlorophyll and impurities in the belladonna extract and improve the quality of the belladonna extract. The invention also provides a belladonna capsule compound preparation containing the belladonna extract, and the stability of the preparation can be effectively improved by optimizing the components in the preparation and the preparation process.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to a belladonna extract and belladonna capsule compound preparation.
Background
The belladonna extract is mainly prepared from belladonna grass and has the main effects of treating gastric and duodenal ulcer, chronic gastritis and the like.
According to the Chinese pharmacopoeia (2010 edition: 397), the belladonna extract is prepared by the following steps: taking 1000g of belladonna coarse powder, using 85% ethanol as a solvent, soaking for 48 hours, slowly percolating at the speed of 1-3 ml per minute, collecting about 3000ml of primary percolate, preserving in another container, continuously percolating until alkaloid is completely percolated, and using the continuous percolate as the solvent for the next percolation; recovering ethanol from the primary percolate under reduced pressure at 60 deg.C, cooling to room temperature, separating chlorophyll, filtering, evaporating the filtrate at 60-70 deg.C to obtain soft extract, adding 10 times of ethanol, stirring, standing, collecting supernatant, recovering ethanol at 60 deg.C under reduced pressure, and concentrating to obtain belladonna extract. However, the above method has complicated process, and belladonna extract has the defects of low alkaloid extraction rate, long time consumption and large ethanol consumption.
CN104173578A discloses a belladonna extract preparation method, which comprises the following steps: reflux-extracting belladonna coarse powder with sulfuric acid water solution as solvent for three times, concentrating the extractive solution, adding inorganic base and 95% ethanol, standing, and collecting supernatant; neutralizing the supernatant with diluted acid, and concentrating under reduced pressure to obtain belladonna extract. However, the belladonna extract obtained by the method has more chlorophyll content and incomplete impurity removal.
CN1846752A discloses a preparation method of belladonna extract, which comprises the following steps: taking 1000g of belladonna grass primary powder, soaking the belladonna grass primary powder in 50-90% ethanol for 10-30 hours according to a percolation method under the item of extract, slowly percolating at the speed of 1-8 ml per hour, collecting 6000ml of filtrate, and recovering ethanol under reduced pressure to obtain a fluid extract; a water extraction step is also carried out after the alcohol extraction step; decocting the dregs in water for 1-4 times, wherein the water is added 2-10 times each time, the water decocting time is 1-3 hours respectively, filtering, combining the filtrates, and concentrating to the relative density of 1-1.4; then mixing with the fluid extract extracted by ethanol, and continuing to concentrate under reduced pressure to obtain thick paste. However, the belladonna extract obtained by the method has high chlorophyll content, low purity and incomplete impurity removal.
In view of the above, the present invention is particularly proposed.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides a belladonna extract extraction method, a belladonna extract obtained by the method and application of the belladonna extract.
The invention provides a method for extracting belladonna extractum, which is used for obviously improving the quality of the belladonna extractum.
In particular, the extraction method provided by the invention uses a solvent containing ethanol to carry out percolation extraction on belladonna coarse powder; concentrating the obtained percolate extract, washing with ethanol, and centrifuging to obtain supernatant; wherein the solvent contains 0.1-0.3% of acid; and adjusting the pH value of the supernatant to 3-4, purifying with macroporous resin, and performing gradient elution with 80-95% and 65-75% ethanol solutions respectively.
Preferably, the macroporous resin is NKA-II type macroporous resin.
In the prior art, belladonna extractum is extracted by adopting an 85% ethanol percolation method; however, the belladonna extract obtained by the 85% ethanol percolation method has high chlorophyll content, low purity and incomplete impurity removal. The invention has the unexpected discovery that when a proper amount of acid is added into the ethanol extraction solution, the chlorophyll and other impurities can be effectively prevented from dissolving out, but the alkaloid can be effectively promoted to dissolve out; namely, ethanol solution containing a proper amount of acid is used as the percolation extracting solution, so that the dissolution rate of chlorophyll and impurities can be reduced, and the dissolution rate of alkaloid can be improved.
Although the addition of the acid can reduce the content of chlorophyll in the belladonna extract, the actual application shows that the control of the acid content also has an influence on the content of atropine sulfate (namely alkaloid), and particularly has a direct and effective influence on index components when the concentration is higher; for example, when the acid content is more than 1%, the content of atropine sulfate is reduced.
Preferably, the acid in the solvent is sulfuric acid or hydrochloric acid; 0.1 to 0.3 percent of sulfuric acid or hydrochloric acid is mixed into the ethanol, and the percolation extraction effect is particularly ideal (the properties of active ingredients and the like are not substantially influenced).
In addition, the invention further discovers that the specific form purification of the supernatant obtained by percolation extraction can specifically remove specific impurities of the final product (belladonna extractum). The invention also provides a specific feasible purification scheme, namely: adjusting the pH value of the supernatant of the obtained percolation extract to be acidic (specifically 3-4), purifying by NKA-II type macroporous resin, and performing gradient elution by ethanol solutions with different concentrations respectively, so that the contents of chlorophyll and other impurities in the belladonna extract can be effectively reduced, and the quality of the belladonna extract is improved; the content of impurities can be controlled to be not more than 15%.
Preferably, the gradient elution is sequentially carried out by 10-12 BV of ethanol solution with volume fraction of 80-95% and 65-75%; compared with the single concentration elution solvent, the ethanol solution with specific concentration is adopted for gradient elution, the purification effect is better, and the yield is basically unchanged.
Preferably, the purified sample loading amount is 7-9 BV; and after the purification is finished, further removing impurities by using 12-14 BV of deionized water to further ensure the subsequent adsorption purification (NKA-II type macroporous resin), and the effect is better.
Preferably, the particle size of the belladonna coarse powder is not more than 2.2mm, and the particularly suitable particle size is 1.5-2.0 mm; the belladonna coarse powder in the particle size range can be fully mixed and contacted with an acid-containing ethanol solution, so that the dissolution of chlorophyll and impurities is effectively reduced, and the dissolution of alkaloid is further improved. In some embodiments provided by the present invention, the particle size particularly has a significant inhibitory effect on the dissolution of chlorophyll.
As a preferable scheme of the invention, belladonna coarse powder is added into an ethanol solution containing 0.1-0.3% of acid and ultrasonically mixed for 3.5-4.5 h, and the ultrasonic power is controlled to be 550-650W. Compared with the prior art that belladonna grass coarse powder is added into ethanol solution for soaking, the ultrasonic treatment is introduced, so that the soaking time is greatly shortened (mostly 48 hours of soaking in the prior art), the combination state of active ingredients in the belladonna grass coarse powder can be unexpectedly and obviously changed (mainly ideal intervention on cell walls), and the full dissolution of alkaloid is promoted. In some embodiments provided by the invention, the ultrasonic process has an obvious promotion effect on the dissolution of the alkaloid (without destroying the structure of the medicinal composition) and no secondary pollutant is generated.
In the above preferred embodiment, the more desirable ultrasonic conditions are ultrasonic power 600W and ultrasonic time 4 h.
In the method provided by the invention, the dosage of the percolation extraction solvent comprises the dosage of the percolation extraction solvent related to the ultrasonic extraction and the dosage supplemented for ensuring enough percolation liquid (preferably 1000g coarse powder corresponding to 6000ml percolation liquid) in the percolation process.
Preferably, the centrifugation conditions are: carrying out percolation extraction on the ethanol-washed percolation extract at 5000-10000 rpm for 14-16 min; under the conditions, the impurities related to centrifugation can be more adsorbed on the solid matter, thereby facilitating the subsequent purification (NKA-II type macroporous resin).
For example, as an embodiment of the present invention, the method for extracting belladonna extract includes the following steps:
(1) adding belladonna coarse powder into an ethanol solution containing 0.1-0.3% of sulfuric acid or hydrochloric acid, and ultrasonically mixing for 3.5-4.5 hours under the conditions of 550-650W;
(2) percolating the belladonna grass coarse powder subjected to ultrasonic treatment by taking the ethanol solution containing 0.1-0.3% of sulfuric acid or hydrochloric acid as a percolation extraction solvent (the dosage of the percolation extraction solvent relative to the belladonna grass coarse powder is 5-7 ml/g), wherein the flow rate of percolation is 2-4 ml/min, and collecting percolate; concentrating the percolate under reduced pressure to obtain a first concentrated solution;
(3) filtering the first concentrated solution by using filter paper, and continuously concentrating under reduced pressure to obtain a second concentrated solution;
(4) adding 5 times of ethanol into the second concentrated solution, and centrifuging at 5000-10000 rpm for 14-16 min to obtain a supernatant;
(5) adjusting the pH value of the supernatant to 3-4, purifying with NKA-II type macroporous resin, wherein the sample loading amount is 7-9 BV, and removing impurities with 12-14 BV deionized water; and then gradient elution is carried out by using 10-12 BV of ethanol solution with volume fraction of 80-95% and 65-75%. Preferably, the first concentration under reduced pressure is carried out until the relative density is 1.03-1.10, especially 1.03.
Preferably, the second concentration under reduced pressure is carried out to a relative density of 1.20 to 1.30, especially 1.23.
The extraction method of the invention can well grasp the efficiency and quality of concentration, especially the removal effect of main relevant impurities including chlorophyll, by controlling the concentration degree.
In the present invention, the relative density is measured at a temperature of about 60 ℃ basically, unless otherwise specified.
As an embodiment of the present invention, the extraction method may further include step (6):
and (3) concentrating the eluent obtained after gradient elution under reduced pressure to obtain belladonna thick paste, preferably concentrating under reduced pressure to control the relative density of the belladonna thick paste to be 1.20-1.30.
Or, as another embodiment of the present invention, the extraction method may further include step (7):
adding a filling agent into the belladonna thick paste obtained in the step (6) to prepare the belladonna extract;
preferably, the content of atropine sulfate in the belladonna extract is not lower than 9.7 mg/g;
the filler may be selected from common pharmaceutically acceptable filler materials known in the art, and particularly preferably is corn starch.
That is to say, the belladonna extract can be belladonna thick paste (the relative density is generally 1.20-1.30) obtained by eluting in the step (5) and then concentrating the eluent under reduced pressure; optionally, a filler, such as belladonna extract obtained by adding corn starch, can be further added into the belladonna extract.
After the filler is added into the belladonna thick paste, the belladonna extract shows obvious advantages in dissolution performance, particularly stability in the process of preparing a preparation, and further contributes to ensuring the quality of the preparation.
The extraction method provided by the invention has the advantages of simple process, high extraction efficiency, less loss of active ingredients and significantly higher content of atropine than that of the prior art.
The invention also provides the belladonna extract prepared by the preparation method, and the quality of the extract is obviously improved compared with the existing product whether the extract is independently used as a finished product or is further prepared into a preparation (such as a belladonna capsule compound preparation and the like).
The invention also provides a belladonna capsule compound preparation which contains the belladonna extract.
Preferably, the belladonna extract accounts for 0.16-0.40% of the total mass of the belladonna capsule compound preparation, and the proper content ensures that the preparation is more convenient to apply and meets the clinical dosage requirement.
The belladonna capsule compound preparation can be prepared by taking the belladonna extract as an active ingredient according to common pharmaceutical common knowledge (such as adding sodium bicarbonate, a filling agent, a moisture-proof agent and the like), and the invention is not further limited for common preparation means.
However, considering that the dissolution performance, stability and the like of the belladonna capsule compound preparation are closely related to an auxiliary material system, and the performance is the core index of the preparation quality, the invention repeatedly searches and optimizes the prescription of the preparation.
Preferably, the belladonna capsule compound preparation further comprises sodium bicarbonate, corn starch and silicon dioxide.
As a known technique, sodium bicarbonate can neutralize gastric acid, raise pH, reduce pepsin activity, resist acid and relieve pain, and thus it is widely used in drugs for treating gastric diseases; however, formulations containing sodium bicarbonate tend to decompose upon moisture absorption, resulting in poor formulation stability. In addition, the known belladonna capsule compound preparation has more outstanding defects in material uniformity and dissolution rate. The belladonna capsule compound preparation provided by the invention selects corn starch and silicon dioxide as a filling agent and a moisture-proof agent respectively, so that the problems can be obviously and effectively solved.
Specifically, the dosage ratio of the belladonna extract to the sodium bicarbonate is preferably 1-2: 280-300 parts of;
preferably, the dosage ratio of the sodium bicarbonate to the silicon dioxide is 280-300: 10-13;
preferably, the dosage ratio of the silicon dioxide to the corn starch is 10-13: 270 to 280.
The belladonna extract is more ideally distributed and combined in preparation materials by selecting and optimizing the core auxiliary materials, so that better guarantee is provided for the subsequent preparation process.
As a preferred technical scheme of the invention, the belladonna capsule compound preparation comprises the following components in parts by weight:
under the weight portion ratio, the components can be synergized, so that the problems of decomposition after moisture absorption, uneven materials and the like of the preparation are effectively solved.
Further preferably, the disintegrant is sodium starch glycolate.
The invention also provides a preparation method of the belladonna capsule compound preparation, which comprises the following steps:
(1) mixing belladonna extract and vanillin to obtain a mixture I;
(2) mixing the liquid paraffin and the corn starch, and sieving the mixture through a sieve of 60-70 meshes to obtain a mixture II;
(3) mixing the mixture I and the mixture II to obtain a mixture III;
(4) and mixing the mixture III with sodium bicarbonate, a disintegrating agent and silicon dioxide.
The invention discovers that stable and non-different mouthfeel can be ensured by mixing the belladonna extract and the vanillin firstly; then mixing the liquid paraffin with the corn starch to ensure that the product has stable properties; and (3) mixing the mixture I in the step (1) with the mixture II in the step (2), and then mixing with sodium bicarbonate, a disintegrating agent and silicon dioxide, so that the mouthfeel can be fully ensured, and the product properties are prevented from being changed differently.
That is to say, the belladonna capsule compound preparation prepared according to the steps has the advantages that the active ingredients can be distributed in the medicine in a better form, the stability is better (moisture absorption and decomposition are not easy) and the dissolution performance is excellent.
Preferably, in the step (4), the mixing is carried out in a batch mixer for 15-25 min.
Preferably, the preparation method of the belladonna capsule compound preparation further comprises the step of packaging; specifically, the method comprises the following steps: filling the mixture obtained in the step (4) into capsules by using a capsule filling machine, and controlling the filling amount to be 0.6g per capsule; and (4) carrying out bubble cap, packaging the product in an aluminum plastic aluminum package mode, and pressing the product according to the packaging specification of 12 granules/plate.
The invention adopts the packaging form of aluminum-plastic-aluminum during aluminum molding, and compared with the conventional aluminum-plastic packaging, the moisture absorption condition of the preparation is more effectively prevented.
Compared with the known preparation, the belladonna capsule compound preparation prepared by the invention has obvious advantages in stability and curative effect, can be used for treating various symptoms of stomach diseases, and has extremely high clinical application value.
Detailed Description
The following examples are intended to illustrate the invention but are not intended to limit the scope of the invention.
EXAMPLE 1 belladonna extract
This example provides a belladonna extract, which is extracted by the following method:
(1) pulverizing 1000g belladonna grass into coarse powder (particle size is about 2.0 mm), adding the coarse powder into ethanol solution (percolation extraction solvent, about 3000ml, the same below) containing 0.1% sulfuric acid, and ultrasonic mixing at 600W for 4 hr;
(2) percolating the belladonna grass coarse powder after ultrasonic treatment (taking ethanol solution containing 0.1% sulfuric acid in the step 1 as a percolation extraction solvent, and supplementing insufficient parts), wherein the flow rate of percolation is 3ml/min, and collecting 6000ml of percolate; concentrating the percolate under reduced pressure (the temperature is controlled below 60 deg.C, and the specific gravity is 1.03) to obtain a first concentrated solution;
(3) filtering the first concentrated solution with filter paper to remove chlorophyll, and continuing concentrating under reduced pressure (the temperature is controlled below 60 ℃, the specific gravity is 1.25) to obtain a second concentrated solution;
(4) adding 5 times volume of ethanol into the second concentrated solution, centrifuging at 6000rpm for 15min, and collecting supernatant;
(5) adjusting the pH value of the supernatant to 3, then carrying out sample loading, selecting NKA-II type macroporous resin for purification, wherein the sample loading amount is 8BV, removing impurities by using 13BV deionized water after purification, then respectively carrying out gradient elution by using 10BV ethanol solution with volume fraction of 80% and 65%, and collecting all eluates;
(6) mixing all eluates, and concentrating under reduced pressure (at a temperature below 60 deg.C and a specific gravity of 1.2) to obtain 123.5ml thick paste; detecting that the content of atropine sulfate in the thick paste is 24.3mg/ml, and compared with the content of atropine sulfate before purification (supernatant), the content of atropine sulfate is improved by 3.2 times; detecting that the chlorophyll content in the soft extract is reduced by 83.4% compared with that in the raw material (the concentration of chlorophyll in the soft extract is 2.3 mg/ml);
(7) according to the content detection result, adding 200g of corn starch { so that each 1g of belladonna extract contains alkaloid (calculated by atropine sulfate) which is not less than 9.7mg }, and drying to obtain extract;
(8) pulverizing the dried extract with a pulverizer, and mixing the pulverized medicinal powder with a batch mixer to obtain belladonna extract 280 g.
Example 2 belladonna extract
This example provides a belladonna extract, which is extracted by the following method:
(1) pulverizing 1000g belladonna grass into coarse powder (particle size is about 2.0 mm), adding the coarse powder into ethanol solution (percolation extraction solvent) containing 0.1% hydrochloric acid, and ultrasonic mixing at 600W for 4 hr;
(2) percolating the belladonna grass coarse powder after ultrasonic treatment (taking ethanol solution containing 0.1% hydrochloric acid in the step 1 as a percolation extraction solvent, and supplementing insufficient parts), wherein the flow rate of percolation is 3ml/min, and collecting 6000ml of percolate; concentrating the percolate under reduced pressure (the temperature is controlled below 60 deg.C, and the specific gravity is 1.03) to obtain a first concentrated solution;
(3) filtering the first concentrated solution with filter paper to remove chlorophyll, and continuing concentrating under reduced pressure (the temperature is controlled below 60 ℃, the specific gravity is 1.23) to obtain a second concentrated solution;
(4) adding 5 times volume of ethanol into the second concentrated solution, centrifuging at 8000rpm for 15min, and collecting supernatant;
(5) adjusting the pH value of the supernatant to 3.5, then carrying out sample loading, selecting NKA-II type macroporous resin for purification, wherein the sample loading amount is 8BV, removing impurities by using 13BV deionized water, then respectively carrying out gradient elution by using 11BV ethanol solution with volume fraction of 80% and 65%, and collecting all eluates;
(6) mixing all eluates, and concentrating under reduced pressure (the temperature is controlled below 60 deg.C, and the specific gravity is 1.2) to obtain 132.3ml thick paste; detecting that the content of atropine sulfate in the thick paste is 27.6mg/ml, and compared with the content of atropine sulfate before purification (supernatant), the content of atropine sulfate is improved by 3.8 times; detecting that the chlorophyll content in the soft extract is reduced by 81.8% compared with that in the raw material (the concentration of chlorophyll in the soft extract is 2.6 mg/ml);
(7) according to the content detection result, adding 200g of corn starch { so that each 1g of belladonna extract contains alkaloid (calculated by atropine sulfate) which is not less than 9.7mg }, and drying to obtain extract;
(8) pulverizing the dried extract with a pulverizer, and mixing the pulverized medicinal powder with a batch mixer to obtain belladonna extract 280 g.
EXAMPLE 3 belladonna extract
This example provides a belladonna extract, which is extracted by the following method:
(1) pulverizing 1000g belladonna grass into coarse powder (particle size is about 2.0 mm), adding the coarse powder into ethanol solution (percolation extraction solvent) containing 0.3% hydrochloric acid, and ultrasonic mixing at 600W for 4 hr;
(2) percolating the belladonna grass coarse powder after ultrasonic treatment (taking ethanol solution containing 0.3% hydrochloric acid in the step 1 as a percolation extraction solvent, and supplementing insufficient parts), wherein the flow rate of percolation is 3ml/min, and collecting 6000ml of percolate; concentrating the percolate under reduced pressure (the temperature is controlled below 60 deg.C, and the specific gravity is 1.03) to obtain a first concentrated solution;
(3) filtering the first concentrated solution with filter paper to remove chlorophyll, and continuing concentrating under reduced pressure (the temperature is controlled below 60 ℃, the specific gravity is 1.22) to obtain a second concentrated solution;
(4) adding 5 times volume of ethanol into the second concentrated solution, centrifuging at 6000rpm for 15min, and collecting supernatant;
(5) adjusting the pH value of the supernatant to 3.5, then carrying out sample loading, selecting NKA-II type macroporous resin for purification, wherein the sample loading amount is 8BV, removing impurities by using 13BV deionized water, then respectively carrying out gradient elution by using 85% and 70% ethanol solution with the volume fraction of 12BV, and collecting all eluates;
(6) mixing all eluates, and concentrating under reduced pressure (temperature controlled below 60 deg.C, specific gravity 1.2) to obtain 138.3ml soft extract; detecting that the content of atropine sulfate in the thick paste is 28.3mg/ml, and compared with the content of atropine sulfate before purification (supernatant), the content of atropine sulfate is improved by 3.8 times; detecting that the chlorophyll content in the soft extract is reduced by 82.7% (the concentration of chlorophyll in the soft extract is 2.5 mg/ml);
(7) according to the content detection result, adding 200g of corn starch { so that each 1g of belladonna extract contains alkaloid (calculated by atropine sulfate) which is not less than 9.7mg }, and drying to obtain extract;
(8) pulverizing the dried extract with a pulverizer, and mixing the pulverized medicinal powder with a batch mixer to obtain belladonna extract 280 g.
Example 4 belladonna extract
This example provides a belladonna extract, which is extracted by the following method:
(1) pulverizing 1000g belladonna grass into coarse powder (particle size is about 2.0 mm), adding the coarse powder into ethanol solution (percolation extraction solvent) containing 0.2% sulfuric acid, and ultrasonic mixing at 600W for 4 hr;
(2) percolating the belladonna grass coarse powder after ultrasonic treatment (taking ethanol solution containing 0.2% sulfuric acid in the step 1 as a percolation extraction solvent, and supplementing insufficient parts), wherein the flow rate of percolation is 3ml/min, and collecting 6000ml of percolate; concentrating the percolate under reduced pressure (the temperature is controlled below 60 deg.C, and the specific gravity is 1.03) to obtain a first concentrated solution;
(3) filtering the first concentrated solution with filter paper to remove chlorophyll, and continuing concentrating under reduced pressure (the temperature is controlled below 60 ℃, the specific gravity is 1.20) to obtain a second concentrated solution;
(4) adding 5 times volume of ethanol into the second concentrated solution, centrifuging at 7500rpm for 15min, and collecting supernatant;
(5) adjusting the pH value of the supernatant to 3.5, then carrying out sample loading, selecting NKA-II type macroporous resin for purification, wherein the sample loading amount is 8BV, removing impurities by using 13BV deionized water, then respectively carrying out gradient elution by using 85% and 70% ethanol solution with volume fraction of 12BV, and collecting all eluates;
(6) mixing all eluates, and concentrating under reduced pressure (at a temperature below 60 deg.C and a specific gravity of 1.2) to obtain 134.2ml soft extract; detecting that the content of atropine sulfate in the thick paste is 27.6mg/ml, and compared with the content of atropine sulfate before purification, the content of atropine sulfate in the thick paste is improved by 3.8 times; detecting that the chlorophyll content in the soft extract is reduced by 84.5% (the concentration of chlorophyll in the soft extract is 2.1 mg/ml);
(7) according to the content detection result, adding 200g of corn starch { so that each 1g of belladonna extract contains alkaloid (calculated by atropine sulfate) which is not less than 9.7mg }, and drying to obtain extract;
(8) pulverizing the dried extract with a pulverizer, and mixing the pulverized medicinal powder with a batch mixer to obtain belladonna extract 280 g.
EXAMPLE 5 belladonna Capsule Compound preparation
The embodiment provides a belladonna capsule compound preparation which comprises the following components in parts by weight:
the preparation method of the belladonna capsule compound preparation comprises the following steps:
(1) mixing belladonna extract and vanillin to obtain a mixture I;
(2) mixing the liquid paraffin and the corn starch, and sieving the mixture completely through a 65-mesh sieve to obtain a mixture II;
(3) mixing the mixture I and the mixture II to obtain a mixture III;
(4) sieving the mixture III with a 65-mesh sieve, and mixing the mixture III with sodium bicarbonate, sodium carboxymethyl starch and silicon dioxide in a batch mixer for 20 minutes;
(5) filling the mixture obtained in the step (4) into capsules by using a capsule filling machine, controlling the filling amount to be 0.6g per capsule, and polishing the capsules by using a polishing machine after filling;
(6) carrying out bubble cap on the capsule obtained in the step (5), packaging the capsule in an aluminum-plastic-aluminum packaging mode, and pressing the capsule into 12 capsules per plate according to the packaging specification;
(7) and (4) carrying out pillow wrapping on the medicine board obtained in the step (6) by using a moisture-proof bag coil stock (composite film), adding a bag of drying agent into each bag, and turning to outer packaging after pillow wrapping is finished.
EXAMPLE 6 belladonna Capsule Compound preparation
The embodiment provides a belladonna capsule compound preparation which comprises the following components in parts by weight:
the preparation method of the belladonna capsule compound preparation comprises the following steps:
(1) mixing belladonna extract and vanillin to obtain a mixture I;
(2) mixing the liquid paraffin and the corn starch, and sieving the mixture completely through a 65-mesh sieve to obtain a mixture II;
(3) mixing the mixture I and the mixture II to obtain a mixture III;
(4) sieving the mixture III with a 65-mesh sieve, and mixing the mixture III with sodium bicarbonate, sodium carboxymethyl starch and silicon dioxide in a batch mixer for 20 minutes;
(5) filling the mixture obtained in the step (4) into capsules by using a capsule filling machine, controlling the filling amount to be 0.6g per capsule, and polishing the capsules by using a polishing machine after filling;
(6) carrying out bubble cap on the capsule obtained in the step (5), packaging the capsule in an aluminum-plastic-aluminum packaging mode, and pressing the capsule into 12 capsules per plate according to the packaging specification;
(7) and (4) carrying out pillow wrapping on the medicine board obtained in the step (6) by using a moisture-proof bag coil stock (composite film), adding a bag of drying agent into each bag, and turning to outer packaging after pillow wrapping is finished.
EXAMPLE 7 belladonna Capsule Compound preparation
The embodiment provides a belladonna capsule compound preparation which comprises the following components in parts by weight:
the preparation method of the belladonna capsule compound preparation comprises the following steps:
(1) mixing belladonna extract and vanillin to obtain a mixture I;
(2) mixing the liquid paraffin and the corn starch, and sieving the mixture completely through a 65-mesh sieve to obtain a mixture II;
(3) mixing the mixture I and the mixture II to obtain a mixture III;
(4) sieving the mixture III with a 65-mesh sieve, and mixing the mixture III with sodium bicarbonate, sodium carboxymethyl starch and silicon dioxide in a batch mixer for 20 minutes;
(5) filling the mixture obtained in the step (4) into capsules by using a capsule filling machine, controlling the filling amount to be 0.6g per capsule, and polishing the capsules by using a polishing machine after filling;
(6) carrying out bubble cap on the capsule obtained in the step (5), packaging the capsule in an aluminum-plastic-aluminum packaging mode, and pressing the capsule into 12 capsules per plate according to the packaging specification;
(7) and (4) carrying out pillow wrapping on the medicine board obtained in the step (6) by using a moisture-proof bag coil stock (composite film), adding a bag of drying agent into each bag, and turning to outer packaging after pillow wrapping is finished.
EXAMPLE 8 belladonna Capsule Compound preparation
The embodiment provides a belladonna capsule compound preparation which comprises the following components in parts by weight:
the preparation method of the belladonna capsule compound preparation comprises the following steps:
(1) mixing belladonna extract and vanillin to obtain a mixture I;
(2) mixing the liquid paraffin and the corn starch, and sieving the mixture completely through a 65-mesh sieve to obtain a mixture II;
(3) mixing the mixture I and the mixture II to obtain a mixture III;
(4) sieving the mixture III with a 65-mesh sieve, and mixing the mixture III with sodium bicarbonate, sodium carboxymethyl starch and silicon dioxide in a batch mixer for 20 minutes;
(5) filling the mixture obtained in the step (4) into capsules by using a capsule filling machine, controlling the filling amount to be 0.6g per capsule, and polishing the capsules by using a polishing machine after filling;
(6) carrying out bubble cap on the capsule obtained in the step (5), packaging the capsule in an aluminum-plastic-aluminum packaging mode, and pressing the capsule into 12 capsules per plate according to the packaging specification;
(7) and (4) carrying out pillow wrapping on the medicine board obtained in the step (6) by using a moisture-proof bag coil stock (composite film), adding a bag of drying agent into each bag, and turning to outer packaging after pillow wrapping is finished.
Comparative example 1
This comparative example provides a belladonna extract which differs from example 1 only in that: ethanol solution containing 0.65% sulfuric acid was used as extraction solvent.
In the belladonna thick paste prepared in the example, the chlorophyll content is 2.1 mg/ml; the content of alkaloid (calculated by atropine sulfate) is 16.3 mg/ml.
According to the content detection result, adding 120g of corn starch { so that each 1g of belladonna extract contains alkaloid (calculated by atropine sulfate) which is not less than 9.7mg }, and drying to obtain extract; pulverizing the dried extract with a pulverizer, and mixing the pulverized medicinal powder with a batch mixer to obtain belladonna extract 187 g.
Comparative example 2
This comparative example provides a belladonna extract which differs from example 1 only in that: the purification mode is different, and specifically comprises the following steps: performing static adsorption by using NKA-II macroporous resin; the specific operation is as follows:
placing the supernatant and NKA-II type macroporous resin in the Erlenmeyer flask, wherein the volume ratio of the supernatant to the macroporous resin is 8: 1, standing still, standing for 12 hours, filtering macroporous resin, removing impurities by using 13BV of deionized water respectively, and then performing gradient elution by using 12BV of ethanol solution with volume fraction of 85% and 70%.
In the extract prepared in the embodiment, the chlorophyll content is 7.5 mg/ml; the content of alkaloid (calculated by atropine sulfate) is 12.6 mg/ml.
According to the content detection result, adding 120g of corn starch { so that each 1g of belladonna extract contains alkaloid (calculated by atropine sulfate) which is not less than 9.7mg }, and drying to obtain extract; pulverizing the dried extract with a pulverizer, and mixing the pulverized medicinal powder with a batch mixer to obtain belladonna extract 187 g.
Comparative example 3
This comparative example provides a belladonna extract which differs from example 1 only in that: in step (5) elution was performed with 80% volume fraction ethanol solution (single eluent).
In the extract prepared in the embodiment, the chlorophyll content is 8 mg/ml; the content of alkaloid (calculated by atropine sulfate) is 17.2 mg/ml.
According to the content detection result, adding 120g of corn starch { so that each 1g of belladonna extract contains alkaloid (calculated by atropine sulfate) which is not less than 9.7mg }, and drying to obtain extract; pulverizing the dried extract with a pulverizer, and mixing the pulverized medicinal powder with a batch mixer to obtain belladonna extract 187 g.
Comparative example 4
The comparison example provides a belladonna capsule compound preparation, which is different from the belladonna capsule compound preparation in the formula of example 5: the method comprises the following specific steps:
test example 1
The experimental example compares the stability and dissolution performance of the belladonna capsule compound preparation prepared in example 5 and comparative example 4, and the specific experimental contents and results are as follows:
and (3) accelerated test: the samples were taken and placed under the conditions of 40 ℃ + -2 ℃ and 75% + -5% relative humidity for 6 months, and the samples were taken at 1 st, 2 nd, 3 rd and 6 th months respectively, and the results are shown in Table 1.
And (3) long-term test: samples were taken and placed at 25 ℃. + -. 2 ℃ under a relative humidity of 60%. + -. 10%, and were sampled at 3 rd, 6 th, 9 th, 12 th, 18 th and 24 th months, respectively, and the results are shown in Table 2.
Disintegration test: the basket containing the sample was immersed in the medium solution which had reached a temperature of 37. + -. 1 ℃ and the temperature of the medium solution was controlled to 37. + -. 1 ℃ and the apparatus was started, the time was recorded and disintegration was observed, the results are shown in Table 2.
Test subjects:
experimental groups: the product of example 5;
control group 1: comparative example 4 product;
control group 2: commercial belladonna capsule, national standard 61022880.
TABLE 1 accelerated test results
TABLE 2 Long-term test and disintegration test results
According to the test results, the quality of the obtained preparation is obviously improved (especially stability) compared with the known preparation by optimizing the active ingredients and the auxiliary material system.
Although the invention has been described in detail hereinabove by way of general description, specific embodiments and experiments, it will be apparent to those skilled in the art that many modifications and improvements can be made thereto based on the invention. Accordingly, such modifications and improvements are intended to be within the scope of the invention as claimed.
Claims (10)
1. A method for extracting belladonna extract comprises percolating belladonna coarse powder with ethanol-containing solvent; concentrating the obtained percolate extract, washing with ethanol, and centrifuging to obtain supernatant; the method is characterized in that: the solvent contains 0.1-0.3% of acid; the method further comprises the steps of adjusting the pH value of the supernatant to 3-4, purifying with macroporous resin, and performing gradient elution with 80-95% and 65-75% ethanol solutions respectively.
2. The extraction process according to claim 1, wherein the acid in the solvent is sulfuric acid or hydrochloric acid; and/or adding belladonna grass coarse powder into the solvent before percolation extraction, and ultrasonically mixing for 3.5-4.5 h, wherein the ultrasonic power is controlled to be 550-650W.
3. The extraction method according to claim 1 or 2, wherein the gradient elution is performed with 10-12 BV of 80-95% and 65-75% ethanol solution by volume respectively; and/or the purified sample loading amount is 7-9 BV.
4. The extraction method according to claim 1 or 2, further comprising: concentrating the eluate after gradient elution under reduced pressure to obtain belladonna soft extract; or adding filler into the belladonna soft extract to obtain belladonna extract;
preferably, the content of atropine sulfate in the belladonna extract is not lower than 9.7 mg/g; and/or the filler is corn starch.
5. A belladonna extract, which is obtained by the method of any one of claims 1 to 4.
6. A belladonna capsule compound preparation, which is characterized by comprising the belladonna extract of claim 5;
preferably, the belladonna extract accounts for 0.16-0.4% of the total mass of the belladonna capsule compound preparation.
7. The belladonna capsule compound preparation as claimed in claim 6, further comprising sodium bicarbonate, corn starch and silicon dioxide;
preferably, the dosage ratio of the belladonna extract to the sodium bicarbonate is 1-2: 280-300 parts of; and/or the dosage ratio of the sodium bicarbonate to the silicon dioxide is 280-300: 10-13; and/or the dosage ratio of the silicon dioxide to the corn starch is 10-13: 270 to 280.
8. The belladonna capsule compound preparation as claimed in claim 6 or 7, which is characterized by comprising the following components in parts by weight:
9. the belladonna capsule compound preparation as claimed in claim 8, wherein the disintegrant is carboxymethyl starch sodium.
10. A method of preparing the belladonna capsule compound preparation of any one of claims 6 to 9, which comprises the steps of:
(1) mixing belladonna extract and vanillin to obtain a mixture I;
(2) mixing the liquid paraffin and the corn starch, and sieving the mixture through a sieve of 60-70 meshes to obtain a mixture II;
(3) mixing the mixture I and the mixture II to obtain a mixture III;
(4) and mixing the mixture III with sodium bicarbonate, a disintegrating agent and silicon dioxide.
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