CN107582954B - Zhenhuang stomach tablet and preparation method thereof - Google Patents
Zhenhuang stomach tablet and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a Zhenhuang stomach tablet and a preparation process thereof. The Zhenhuangwei tablet comprises the following raw materials: the composition comprises fructus amomi, camphor tree seeds, elecampane, pseudo-ginseng, rheum officinale, rhizoma acori graminei, calcium carbonate, calcined concha arcae, rhizoma bletillae, nacreous layer powder, polyethylene glycol, microcrystalline cellulose, light magnesium oxide, a synergist and a flavoring agent, wherein the synergist comprises alginic acid and a gelatin derivative in a mass ratio of (0.2-1) to 1, and the gelatin derivative is a carboxylated or anhydrized gelatin derivative. The supercritical fluid technology is used for effectively extracting partial traditional Chinese medicine raw materials, and the hot-melt granulation technology is combined for preparing granules and tabletting, so that the prepared tablets are smooth in appearance, good in hardness, low in friability, small in tablet weight difference, uniform in content, stable in quality, and capable of remarkably improving the moisture absorption resistance of the Zhenhuang stomach tablets and improving the stability of the medicine.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a Zhenhuang stomach tablet and a preparation method thereof.
Background
The Zhenhuangwei tablet is prepared by using pearl layer powder, bletilla striata, camphor tree seed, pseudo-ginseng, rhubarb, concha arcae (calcined), costus root, calcium carbonate, amomum fruit and grassleaf sweelflag rhizome as active ingredients and adding a certain amount of auxiliary materials, has the functions of strengthening stomach with fragrance, promoting qi circulation, relieving pain, stopping bleeding and promoting granulation, and is used for treating epigastric pain, anorexia and acid regurgitation caused by qi stagnation, blood stasis and damp turbidity obstruction, and chronic gastritis with the symptoms.
In the prior art, the traditional Chinese medicine components in the formula of the Zhenhuang stomach tablet are effectively extracted by the processes of water extraction, water extraction and alcohol precipitation, impregnation, reflux extraction and the like, then are mixed with proper auxiliary materials, and are prepared by a wet granulation and tabletting method. However, the traditional Chinese medicine extract contains a large amount of functional oil components, and the drying temperature for preparing the extract by a wet granulation tabletting method has great influence on the effective components of the medicine, so that the medicine effect is reduced or impurities are increased. In addition, the Zhenhuang stomach tablet contains calcined concha arcae, pearl layer powder and calcium carbonate, and has poor fluidity and compressibility, so that the prepared tablet has larger weight difference and even has pockmarked holes on the surface.
On the other hand, the traditional Chinese medicine tablet is easy to absorb moisture, the traditional Chinese medicine tablet without coating is very easy to absorb moisture in the air and wet during long-term storage, the disintegration and the absorption of the tablet are influenced, and meanwhile, the content of components of the tablet containing volatile components is reduced after long-term storage. Therefore, there is a need to develop a new preparation process of Zhenhuang stomach tablet to improve the quality of Zhenhuang stomach tablet and improve the stability of Zhenhuang stomach tablet, so as to satisfy clinical application.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a Zhenhuang stomach tablet and a preparation method thereof, wherein the tablet obtained has uniform content, good in-vitro dissolution behavior and better storage stability without coating treatment.
Specifically, the invention realizes the above purpose by the following technical scheme:
the Zhenhuang stomach tablet comprises the following raw materials in parts by weight: 250-350 parts of fructus amomi, 500-700 parts of camphor tree seeds, 500-700 parts of costustoot, 500-700 parts of pseudo-ginseng, 500-700 parts of rheum officinale, 500-700 parts of rhizoma acori graminei, 1000-2000 parts of calcium carbonate, 100-200 parts of calcined concha arcae, 1000-2000 parts of rhizoma bletillae, 1000-2000 parts of pearl layer powder, 500-1000 parts of polyethylene glycol, 1000-2000 parts of microcrystalline cellulose, 300-500 parts of light magnesium oxide, 3000-6000 parts of a synergist and 500-700 parts of a flavoring agent.
Preferably, the Zhenhuang stomach tablet comprises the following raw materials in parts by weight: 310 parts of fructus amomi, 625 parts of camphor tree seeds, 625 parts of costustoot, 625 parts of pseudo-ginseng, 625 parts of rhubarb, 625 parts of grassleaf sweelflag rhizome, 1500 parts of calcium carbonate, 180 parts of calcined concha arcae, 1250 parts of common bletilla pseudobulb, 1500 parts of pearl layer powder, 800 parts of polyethylene glycol, 1500 parts of microcrystalline cellulose, 400 parts of light magnesium oxide, 5000 parts of synergist and 600 parts of flavoring agent.
Furthermore, the synergist is formed by alginic acid and a gelatin derivative in a mass ratio of (0.2-1): 1, wherein the gelatin derivative is a carboxylated or anhydrized gelatin derivative.
Preferably, the synergist is alginic acid and a gelatin derivative in a mass ratio of 0.5: 1.
Further, the preparation of the gelatin derivative comprises the following steps:
(1) dissolving organic acid or anhydride in water to obtain 2% (m/m) solution, adding 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, and stirring to dissolve completely;
(2) and (2) adding water into gelatin, heating to 60 ℃ to completely dissolve the gelatin to obtain a gelatin solution with the concentration of 10% (m/m), dropwise adding the solution prepared in the step (1) under the condition of keeping the temperature and stirring, reacting for 60-120 min, and then carrying out vacuum drying to obtain the carboxylated or anhydride gelatin derivative.
The mass ratio of the gelatin to the organic acid or the acid anhydride in the preparation of the gelatin derivative is 1: 0.05-0.2, preferably 1: 0.1.
The addition amount of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 0.01-0.1% (m/m) of the addition amount of the organic acid or the anhydride.
Further, the organic acid is at least one of citric acid, malic acid, citric acid, maleic acid and oxalic acid;
the anhydride is at least one of acetic anhydride, maleic anhydride and succinic anhydride.
Preferably, the organic acid is maleic acid, and the anhydride is maleic anhydride.
Furthermore, the flavoring agent is composed of sucrose powder, sodium cyclamate and vanillin according to the mass ratio of 1 (0.05-0.1) to (0.001-0.006).
Preferably, the flavoring agent is composed of sucrose powder, sodium cyclamate and vanillin according to the mass ratio of 1:0.05: 0.005.
Further, the polyethylene glycol is at least one of polyethylene glycol PEG4000, polyethylene glycol PEG6000, polyethylene glycol PEG8000, polyethylene glycol PEG10000 and polyethylene glycol PEG 20000.
In the preparation process of the Zhenhuang stomach tablet, the supercritical fluid technology is adopted to effectively extract partial traditional Chinese medicine raw materials, and the hot melting granulation technology is combined to prepare the particles and carry out tabletting, so that the whole preparation process does not need to use water or organic solvent, the drug hydrolysis and organic solvent residue can be avoided, the drying step is avoided, the stability of the drug is improved, the energy and the time are saved, the one-step granulation is realized, and the production period is greatly shortened.
Specifically, the preparation process of the Zhenhuang stomach tablet comprises the following steps:
(1) crushing fructus amomi, camphor tree seeds and elecampane into coarse powder, mixing, placing the coarse powder in a supercritical carbon dioxide extraction device, adding ethanol with the volume fraction of 70-90% and the weight of 30-50% of the coarse powder, regulating the flow of carbon dioxide to be 15-20L/h, the extraction pressure to be 15-35 MPa, the extraction temperature to be 40-60 ℃, the extraction time to be 1.5-2 h, and carrying out reduced pressure separation to obtain a supercritical extract;
(2) respectively crushing pseudo-ginseng, rheum officinale, rhizoma acori graminei, bletilla striata, calcined concha arcae, pearl layer powder and calcium carbonate, and sieving with a 100-120-mesh sieve for later use;
(3) mixing 60-80% (m/m) of the pearl layer powder treated in the step (2) and calcium carbonate with the supercritical extract obtained in the step (1), uniformly mixing, adding half of polyethylene glycol, synergist and flavoring agent according to the formula amount, uniformly mixing, heating to 60-70 ℃, keeping the temperature for 15-20 min after reaching a preset temperature, cooling at room temperature, and finishing granules to obtain granules A for later use;
(4) mixing 20-40% (m/m) of the pearl layer powder and calcium carbonate treated in the step (2) with the pseudo-ginseng, the rheum officinale, the rhizoma acori graminei, the bletilla striata and the calcined concha arcae treated in the step (2), adding half of the rest of polyethylene glycol, the synergist and the flavoring agent, heating to 60-70 ℃, keeping the temperature for 15-20 min after reaching a preset temperature, cooling at room temperature, and finishing granules to obtain granules B for later use;
(5) and (4) uniformly mixing the granules A and B obtained in the steps (3) and (4), adding light magnesium oxide and microcrystalline cellulose, uniformly mixing, and tabletting to obtain the Zhenhuang stomach tablet.
In the formula of the Zhenhuang stomach tablet, a certain amount of light magnesium oxide is added, and the mixture of alginic acid and gelatin derivatives is used as a synergist, so that the flowability and the compressibility of the tablet in the preparation process can be obviously improved, and the prepared tablet has better performance, smooth appearance, better hardness, lower friability, less weight difference and uniform content.
Specifically, in the hot-melt granulation process, the medicine and the auxiliary materials are mixed in a molecular dispersion mode in a molten state through heating, shearing, mixing and other modes to form a mixture, and simultaneously, under the synergistic action of alginic acid, a layer of film is formed on the surface of the formed mixture by the carboxylated or acid-anhydride gelatin derivative, so that the formation of particles with higher sphericity is promoted, the flowability of the particles is improved, the hygroscopicity of the particles is inhibited, the stability is improved, and meanwhile, the bitter taste of the traditional Chinese medicine components can be masked to a certain degree, and the compliance is improved. In addition, the alginic acid can prevent the delayed dissolution of the filmed particles, promote the dissolution of the medicine, keep better dissolution and improve the bioavailability.
On the other hand, the addition of the light magnesium oxide can obviously improve the stability of the effective components of the traditional Chinese medicine tablet and prevent the oily components of the traditional Chinese medicine from losing in the long-term storage process. Meanwhile, the magnesium element in the light magnesium oxide can be combined with the carboxyl in the carboxylated or anhydride gelatin derivative, so that the light magnesium oxide is uniformly dispersed on the surface of the gelatin derivative filmed particles, the flowability and the dispersibility of the particles are further improved, and the problems of fine powder accumulation and increased tablet weight difference caused by the fact that a large amount of lubricant or filler is required to be added in order to overcome the poor flowability and the poor compressibility of the traditional Chinese medicine raw materials in the preparation process of the traditional Chinese medicine tablet are solved.
Compared with the conventional preparation method which adopts the steps of mixing all active ingredients with auxiliary materials, then granulating the mixture by wetting, and tabletting the mixture to prepare the tablet, in the preparation process of the Zhenhuang stomach tablet, the problems of poor flowability and compressibility of the calcined concha arcae, pearl layer powder and calcium carbonate three ingredients can be solved by reasonably distributing the active ingredients, respectively granulating the active ingredients and then carrying out mixed tabletting, the phenomenon of uneven mixing caused by large amount of traditional Chinese medicine raw material powder is avoided, the tablet weight difference of the Zhenhuang stomach tablet is obviously reduced, the dissolution effect is improved, and the synergistic effect of the ingredients is fully exerted.
In the research process, the inventor finds that extracts obtained by extracting fructus amomi, camphor tree seeds and costustoot by supercritical carbon dioxide are uniformly mixed with a large amount of pearl layer powder and calcium carbonate in a prescription, and half of polyethylene glycol, synergist and flavoring agent in the prescription, and then hot-melt granulation is carried out; mixing Notoginseng radix, radix et rhizoma Rhei, rhizoma Acori Graminei, rhizoma Bletillae, Concha arcae preparata, Margarita powder, calcium carbonate, polyethylene glycol, synergist and correctant, and granulating; finally, the prepared particles are added with a proper amount of light magnesium oxide and microcrystalline cellulose to be uniformly mixed and tabletted to obtain the Zhenhuang stomach tablet which has better content uniformity and in-vitro dissolution performance, stable quality, better storage stability without coating and unexpected technical effect.
Compared with the prior art, the invention has the advantages that:
(1) compared with a wet granulation and tabletting method, the prepared Zhenhuang stomach tablet has the advantages of smooth appearance, good hardness, low friability, small tablet weight difference, uniform content, good in-vitro dissolution behavior, stable quality, simple preparation process, low energy consumption, no solvent residue, no other impurities introduced in the whole process, and easiness in realizing continuous production, and the moisture absorption resistance of the Zhenhuang stomach tablet is obviously improved and the stability of a medicament is improved under the condition of no coating.
(2) According to the formula of the Zhenhuang stomach tablet, a certain amount of light magnesium oxide is added, and the mixture of alginic acid and the gelatin derivative is used as a synergist, so that the gelatin derivative forms a film layer on the surface of particles, and the light magnesium oxide is further combined, so that the flowability and the dispersibility of the particles are improved, the tablet weight difference after tabletting is reduced, and the content uniformity is improved.
Detailed Description
The present invention will be further described below by way of specific embodiments, but the present invention is not limited to only the following examples.
EXAMPLE 1 preparation of gelatin derivatives
| Group of | Composition (I) |
| Group A | Gelatin 100g and maleic acid 10g |
| Group B | Gelatin 100g and maleic anhydride 10g |
Preparation steps of group A:
(1) dissolving 10g of maleic acid in water to prepare a solution with the concentration of 2% (m/m), adding 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, and stirring until the solution is completely dissolved for later use, wherein the adding amount of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 0.1% (m/m) of the adding amount of the maleic acid;
(2) taking 100g of gelatin, adding water, heating to 60 ℃ to completely dissolve the gelatin to obtain a gelatin solution with the concentration of 10% (m/m), dropwise adding the solution prepared in the step (1) under the condition of keeping the temperature and stirring, reacting for 80min, and then carrying out vacuum drying to obtain the maleated gelatin derivative.
The preparation procedure for group B was similar to that of group a.
EXAMPLES 2-4 AND COMPARATIVE EXAMPLES 1-7 preparation of ZHENHUANGWEI tablet
Examples 2 to 4The composition of the Zhenhuang stomach tablet is shown in the following table:
comparative examples 1 to 5The composition of the Zhenhuang stomach tablet is shown in the following table:
comparative examples 6 to 7The composition of the Zhenhuang stomach tablet is shown in the following table:
example 2Preparation of Zhenhuang stomach tablet
(1) Crushing fructus amomi, camphor tree seeds and elecampane into coarse powder, mixing, placing the coarse powder in a supercritical carbon dioxide extraction device, adding ethanol with volume fraction of 75 percent accounting for 45 percent of the weight of the coarse powder, regulating and controlling the flow of carbon dioxide to be 20L/h, the extraction pressure to be 35MPa, the extraction temperature to be 50 ℃, the extraction time to be 2h, and carrying out reduced pressure separation to obtain a supercritical extract;
(2) respectively pulverizing Notoginseng radix, radix et rhizoma Rhei, rhizoma Acori Graminei, rhizoma Bletillae, Concha arcae preparata, Margarita layer powder, and calcium carbonate, and sieving with 100 mesh sieve;
(3) taking 75% (m/m) of the nacreous layer powder treated in the step (2), calcium carbonate and the supercritical extract obtained in the step (1), uniformly mixing, adding half of polyethylene glycol, synergist and flavoring agent according to the formula amount, uniformly mixing, heating to 65 ℃, keeping the temperature for 15min after reaching the preset temperature, cooling at room temperature, and finishing granules to obtain granules A for later use;
(4) mixing 25% (m/m) of the nacreous layer powder and calcium carbonate treated in step (2) with the Notoginseng radix, radix et rhizoma Rhei, rhizoma Acori Graminei, rhizoma Bletillae and Concha arcae preparata treated in step (2), adding half of the rest polyethylene glycol, synergist and correctant, heating to 65 deg.C, maintaining the temperature for 15min after reaching the predetermined temperature, cooling at room temperature, and grading to obtain granule B;
(5) and (4) uniformly mixing the granules A and B obtained in the steps (3) and (4), adding light magnesium oxide and microcrystalline cellulose, uniformly mixing, and tabletting to obtain the Zhenhuang stomach tablet.
Examples 3 and 4 preparation of Zhenhuang stomach tablets reference example 2.
Comparative examples 1-5 preparation of a Zhenhuang stomach tablet reference example 2 is shown.
Comparative example 6Preparing the Zhenhuang stomach tablet:
(1) crushing fructus amomi, camphor tree seeds and elecampane into coarse powder, mixing, placing the coarse powder in a supercritical carbon dioxide extraction device, adding ethanol with volume fraction of 75 percent accounting for 45 percent of the weight of the coarse powder, regulating and controlling the flow of carbon dioxide to be 20L/h, the extraction pressure to be 35MPa, the extraction temperature to be 50 ℃, the extraction time to be 2h, and carrying out reduced pressure separation to obtain a supercritical extract;
(2) respectively pulverizing Notoginseng radix, radix et rhizoma Rhei, rhizoma Acori Graminei, rhizoma Bletillae, Concha arcae preparata, Margarita layer powder, and calcium carbonate, sieving with 100 mesh sieve, mixing, adding the supercritical extract obtained in step (1), polyethylene glycol, synergist and correctant, mixing, heating to 65 deg.C, keeping the temperature for 15min after reaching a predetermined temperature, cooling at room temperature, and grading;
(3) and (3) adding light magnesium oxide and microcrystalline cellulose into the granules obtained in the step (2), uniformly mixing, and tabletting to obtain the Zhenhuang stomach tablet.
The preparation process of comparative example 6 was compared with that of example 2 except that granulation was not separately performed
And (6) tabletting.
Comparative example 7Preparing the Zhenhuang stomach tablet: (Wet granulation tableting method)
(1) Crushing fructus amomi, camphor tree seeds and elecampane into coarse powder, mixing, placing the coarse powder in a supercritical carbon dioxide extraction device, adding ethanol with volume fraction of 75 percent accounting for 45 percent of the weight of the coarse powder, regulating and controlling the flow of carbon dioxide to be 20L/h, the extraction pressure to be 35MPa, the extraction temperature to be 50 ℃, the extraction time to be 2h, and carrying out reduced pressure separation to obtain a supercritical extract;
(2) respectively pulverizing Notoginseng radix, radix et rhizoma Rhei, rhizoma Acori Graminei, rhizoma Bletillae, Concha arcae preparata, Margarita powder, and calcium carbonate, sieving with 100 mesh sieve, mixing, adding the supercritical extract obtained in step (1), microcrystalline cellulose, polyvidone K90 and correctant, mixing, making soft mass with purified water, drying in oven at 60 deg.C, grading, mixing with crospovidone and magnesium stearate, and tabletting to obtain ZHENHUANGWEI tablet.
Test example I, influence of different formulations and preparation processes on preparation of Zhenhuang stomach tablet particles
The yields of the granule preparations in the preparation of the Zhenhuang stomach tablets of examples 2 to 4 and comparative examples 1 to 7, respectively, were examined, and the results are shown in Table 1 below.
TABLE 1 influence of different preparation processes on the preparation of Zhenhuang Weipian granule
| Group of | Easy granulation | Particle yield (%) |
| Example 2 | Easy, uniform particles | 96.4 |
| Example 3 | Easy, uniform particles | 95.6 |
| Example 4 | Easy, uniform particles | 95.2 |
| Comparative example 1 | Easy and uniform granules | 90.4 |
| Comparative example 2 | Easy and uniform granules | 91.0 |
| Comparative example 3 | Difficult to be bonded into a mass | 52.0 |
| Comparative example 4 | Easy, uniform particles | 94.2 |
| Comparative example 5 | Difficult to be bonded into a mass | 50.4 |
| Comparative example 6 | Excessive fine powder | 82.0 |
| Comparative example 7 | Difficult to be bonded into a mass | 51.8 |
As can be seen from table 1 above, the formula and the preparation process of the zhenhuang stomach tablet provided by embodiments 2 to 4 of the present invention are suitable, the granule preparation is easy, the obtained granule is uniform, and the yield is high, which can reach 95.2 to 96.4%. As can be seen from comparative examples 1 to 5, the change of the prescription has a great influence on the preparation of the yield of the particles, and the combination of alginic acid and the gelatin derivative is used as a synergist to be matched with light magnesium oxide, which is beneficial to improving the yield of the particles. As can be seen from comparative examples 6 and 7, the yield of the granules in the preparation of the Chinese medicinal tablet can not be improved by adopting the conventional one-step granulation, tabletting process or wet granulation process of the materials, which is favorable for improving the yield of the granules.
Test example II quality test of Zhenhuang stomach tablet
The Zhenhuang stomach tablets obtained in examples 2 to 4 and comparative examples 1 to 7 were subjected to the examination of appearance, hardness, friability, tablet weight difference, disintegration time period, respectively, and the results are shown in Table 2 below.
TABLE 2 measurement results of appearance, hardness, friability, tablet weight difference and disintegration time limit of Zhenhuang stomach tablet
As can be seen from the above Table 2, the Zhenhuang stomach tablets prepared in the examples 2-4 of the present invention have smooth surfaces, proper hardness, a weight loss of 0.2% in friability test, no cracking, and a weight difference less than + -2%, which is significantly better than the Zhenhuang stomach tablets prepared in the comparative examples 1-7.
As can be seen from comparative example 1, the tablet prepared by replacing the light magnesium oxide of the present invention with magnesium stearate had a rough surface, slightly increased hardness and friability, a large difference in tablet weight, and a slightly prolonged disintegration time, which may be associated with the presence of steric hindrance of fatty acid in magnesium stearate, so that magnesium ions could not be bonded to carboxyl groups in the carboxylated gelatin derivative and could not be uniformly dispersed on the surface of the filmed granules. As can be seen from comparative example 2, substituting gelatin for the carboxylated gelatin derivative of the present invention produced tablets having occasional rough surfaces on the surface, slightly increased hardness and friability, large difference in tablet weight, and slightly prolonged disintegration time, which may be associated with the inability of conventional gelatin to bind light magnesium oxide and to disperse light magnesium oxide uniformly on the surface of the filmed granules. From comparative example 3, it can be seen that alginic acid alone is used as a synergist, and the obtained tablet has short disintegration time, but occasionally pitted surface on the surface, reduced hardness, and cracked pieces, and the difference of tablet weight is greatly and obviously increased, which indicates that alginic acid can improve the dissolution performance of the tablet to a certain extent, but cannot improve the dispersibility and flowability of the tablet material. As can be seen from comparative example 4, the tablet prepared by using the carboxylated gelatin derivative alone as the synergist has smooth surface and insignificant change of hardness, but has increased friability, increased difference of tablet weight and prolonged disintegration time, which indicates that the lack of alginic acid has a certain synergistic effect on the formation of a thin film layer on the surface of the particles by the carboxylated gelatin derivative, which can promote the formation of particles with higher degree of sphericity, improve the flowability of the particles and improve the dissolution performance of the thin film particles. As can be seen from comparative example 5, the tablet lacks the synergist, and the prepared tablet has a pitted surface on the surface, reduced hardness, increased friability, obvious tablet weight difference and prolonged disintegration time, indicating that the synergist consisting of alginic acid and a carboxylated gelatin derivative has an important influence on the quality of the Zhenhuang stomach tablet. As can be seen from comparative examples 6 and 7, the materials in the formula are directly granulated and tabletted at one time or the wet granulation and tabletted process is adopted to prepare the tablet, the prepared tablet has poor quality, the appearance of the tablet is rough, the hardness is reduced, the friability is increased, the tablet weight difference is increased and the disintegration time is prolonged, which shows that the preparation difficulty caused by the large amount of the raw materials of the traditional Chinese medicine in the prescription of the stomach tablet with the conventional wet granulation and tabletted process or the traditional material one-time granulation and tabletted process cannot be effectively solved.
Test example III test of moisture absorption Properties of Zhenhuang stomach tablet
The glass dryer with supersaturated sodium chloride solution at the bottom was placed in a thermostat at 40 ℃ for 5h at a relative humidity of 75% in the dryer. The Zhenhuang stomach tablets prepared in examples 2 to 4 and comparative examples 1 to 7 were placed in flat weighing bottles having a constant weight, 10 tablets for each example, and after being accurately weighed, the tablets were placed in a desiccator, stored at 40 ℃, and weighed after 10 hours, and the moisture absorption percentage of the Zhenhuang stomach tablets was calculated by measuring the weight before and after moisture absorption, and the results are shown in Table 3 below.
TABLE 3 moisture resistance measurement results of Zhenhuang stomach tablet prepared from each group
As can be seen from the above table, the Zhenhuang stomach tablet prepared in the embodiment 2-4 of the present invention has better moisture resistance, the tablet appearance is round and round, the moisture absorption percentage is 2.88-3.15%, and the moisture resistance is significantly better than that of the Zhenhuang stomach tablet prepared in the comparative example 1-7, when the tablet is stored for 10 hours under the condition that the relative humidity is 75% and the temperature is 40 ℃. As can be seen from comparative examples 3 and 5, the Zhenhuang stomach tablet prepared by the formula without the gelatin derivative or the synergist has poor moisture resistance and obviously increased moisture absorption percentage which are respectively 9.80% and 12.25%, which shows that the gelatin derivative can effectively inhibit the absorbability of the tablet and improve the stability. As can be seen from comparative example 6, the tablets prepared by directly granulating the materials in the formulation at one time still have round appearance, but have certain hygroscopicity, and the absorption percentage is increased to 9.80%, which indicates that the one-time granulation can not effectively thin the surface of the granules, and finally the tablets still have hygroscopicity. As can be seen from comparative example 7, the tablet prepared by the wet granulation tableting process was the worst moisture resistance of the Zhenhuang stomach tablet, the tablet was loose and melted, and the moisture absorption percentage was 13.60%, indicating that the wet granulation tableting could not effectively inhibit the moisture absorption performance of the Zhenhuang stomach tablet without coating.
Test example four, Long-term test examination of Zhenhuang stomach tablet
The long-term stability test (25 ℃, 65% RH) was performed on each of the zhenhuang stomach tablets obtained in example 2 and comparative examples 1 to 7, and the results are shown in table 4 below.
Table 4 Long-term test investigation results of Zhenhuang stomach tablet prepared from each group
As can be seen from the above table, the Zhenhuang stomach tablet prepared in example 2 of the present invention has better stability, the microbial limit detection result meets the pharmacopoeia requirements after long-term storage for 12 months, and the number of bacteria is less than 104cfu/g, mold and yeast number < 102cfu/g, better moisture absorption resistance, and moisture absorption percentage only increased by 0.42 percent after long-term storage for 12 months, which shows that the Zhenhuang stomach tablet prepared by the formula and the process has good stability. It can be seen from comparative examples 1 to 5 that the change of the formulation ingredients has an important influence on the stability of the Zhenhuang stomach tablet, and the long-term storage stability of the tablet can be remarkably improved only when the synergist consisting of alginic acid and gelatin derivatives is used in combination with light magnesium oxide. As can be seen from comparative examples 6 and 7, the stability of the tablet cannot be improved by directly granulating and tabletting the materials in the formulation at one time by the conventional process, or by preparing the tablet by the wet granulation and tabletting process, and particularly the tablet prepared by the wet granulation and tabletting process has the worst stability. The results show that the Zhenhuang stomach tablet prepared by the formula and the process thereof still keeps better stability on the premise of no coating, and obtains unexpected technical effects.
The above is only a preferred embodiment of the present invention, and it should be noted that the above preferred embodiment should not be considered as limiting the present invention, and the protection scope of the present invention should be subject to the scope defined by the claims. It will be apparent to those skilled in the art that various modifications and adaptations can be made without departing from the spirit and scope of the invention, and these modifications and adaptations should be considered within the scope of the invention.
Claims (6)
1. The Zhenhuang stomach tablet is characterized by comprising the following raw materials in parts by weight: 250-350 parts of fructus amomi, 500-700 parts of camphor tree seeds, 500-700 parts of costustoot, 500-700 parts of pseudo-ginseng, 500-700 parts of rheum officinale, 500-700 parts of rhizoma acori graminei, 1000-2000 parts of calcium carbonate, 100-200 parts of calcined concha arcae, 1000-2000 parts of rhizoma bletillae, 1000-2000 parts of pearl layer powder, 500-1000 parts of polyethylene glycol, 1000-2000 parts of microcrystalline cellulose, 300-500 parts of light magnesium oxide, 3000-6000 parts of a synergist and 500-700 parts of a flavoring agent;
the synergist is composed of alginic acid and a gelatin derivative in a mass ratio of (0.2-1): 1, wherein the gelatin derivative is a carboxylated or anhydrized gelatin derivative;
the preparation of the gelatin derivative comprises the following steps:
(1) dissolving organic acid or anhydride in water to obtain 2% (m/m) solution, adding 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, and stirring to dissolve completely;
(2) taking gelatin, adding water, heating to 60 ℃ to completely dissolve the gelatin to obtain a gelatin solution with the concentration of 10% (m/m), dropwise adding the solution prepared in the step (1) under the condition of heat preservation and stirring, reacting for 60-120 min, and then carrying out vacuum drying to obtain a carboxylated or anhydrized gelatin derivative;
in the preparation of the gelatin derivative, the mass ratio of gelatin to organic acid or acid anhydride is 1: 0.05-0.2;
the addition amount of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 0.01-0.1% (m/m) of the addition amount of the organic acid or the anhydride;
the preparation method of the Zhenhuang stomach tablet comprises the following steps:
(1) crushing fructus amomi, camphor tree seeds and elecampane into coarse powder, mixing, placing the coarse powder in a supercritical carbon dioxide extraction device, adding ethanol with the volume fraction of 70-90% and the weight of 30-50% of the coarse powder, regulating the flow of carbon dioxide to be 15-20L/h, the extraction pressure to be 15-35 MPa, the extraction temperature to be 40-60 ℃, the extraction time to be 1.5-2 h, and carrying out reduced pressure separation to obtain a supercritical extract;
(2) respectively crushing pseudo-ginseng, rheum officinale, rhizoma acori graminei, bletilla striata, calcined concha arcae, pearl layer powder and calcium carbonate, and sieving with a 100-120-mesh sieve for later use;
(3) mixing 60-80% (m/m) of the pearl layer powder treated in the step (2) and calcium carbonate with the supercritical extract obtained in the step (1), uniformly mixing, adding half of polyethylene glycol, synergist and flavoring agent according to the formula amount, uniformly mixing, heating to 60-70 ℃, keeping the temperature for 15-20 min after reaching a preset temperature, cooling at room temperature, and finishing granules to obtain granules A for later use;
(4) mixing 20-40% (m/m) of the pearl layer powder and calcium carbonate treated in the step (2) with the pseudo-ginseng, the rheum officinale, the rhizoma acori graminei, the bletilla striata and the calcined concha arcae treated in the step (2), adding half of the rest of polyethylene glycol, the synergist and the flavoring agent, heating to 60-70 ℃, keeping the temperature for 15-20 min after reaching a preset temperature, cooling at room temperature, and finishing granules to obtain granules B for later use;
(5) and (4) uniformly mixing the granules A and B obtained in the steps (3) and (4), adding light magnesium oxide and microcrystalline cellulose, uniformly mixing, and tabletting to obtain the Zhenhuang stomach tablet.
2. The Zhenhuang stomach tablet of claim 1, wherein the tablet comprises the following raw materials in parts by weight: 310 parts of fructus amomi, 625 parts of camphor tree seeds, 625 parts of costustoot, 625 parts of pseudo-ginseng, 625 parts of rhubarb, 625 parts of grassleaf sweelflag rhizome, 1500 parts of calcium carbonate, 180 parts of calcined concha arcae, 1250 parts of common bletilla pseudobulb, 1500 parts of pearl layer powder, 800 parts of polyethylene glycol, 1500 parts of microcrystalline cellulose, 400 parts of light magnesium oxide, 5000 parts of synergist and 600 parts of flavoring agent.
3. The Zhenhuang gastric tablet as claimed in claim 1, wherein the synergist is alginic acid and gelatin derivative at a mass ratio of 0.5: 1.
4. The Zhenhuang stomach tablet of claim 1, wherein the organic acid is at least one of malic acid, citric acid, maleic acid, and oxalic acid; the anhydride is at least one of acetic anhydride, maleic anhydride and succinic anhydride.
5. The Zhenhuang stomach tablet of claim 1, wherein the flavoring agent is sucrose powder, sodium cyclamate and vanillin in a mass ratio of 1 (0.05-0.1) to (0.001-0.006).
6. The Zhenhuang Wei pian of claim 1, wherein the polyethylene glycol is at least one selected from polyethylene glycol PEG4000, polyethylene glycol PEG6000, polyethylene glycol PEG8000, polyethylene glycol PEG10000 and polyethylene glycol PEG 20000.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005007105A2 (en) * | 2003-07-10 | 2005-01-27 | Smithkline Beecham Corporation | Pharmaceutical compositions |
| CN102526593A (en) * | 2012-02-01 | 2012-07-04 | 广东一力集团制药有限公司 | Medicine composition for treating epigastric distending pain and chronic gastritis and preparing method |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005007105A2 (en) * | 2003-07-10 | 2005-01-27 | Smithkline Beecham Corporation | Pharmaceutical compositions |
| CN102526593A (en) * | 2012-02-01 | 2012-07-04 | 广东一力集团制药有限公司 | Medicine composition for treating epigastric distending pain and chronic gastritis and preparing method |
Non-Patent Citations (1)
| Title |
|---|
| 超临界CO2萃取木香挥发油的实验研究及数值模拟;宋应华等;《重庆工商大学学报( 自然科学版)》;20100630;第27 卷(第3 期);276-279,297 * |
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Address after: 526200, 88, Feng Shan Road, Sihui Town, Sihui City, Guangdong, Zhaoqing, Dongcheng District Patentee after: Yili Pharmaceutical Co.,Ltd. Address before: 526200, 88, Feng Shan Road, Sihui Town, Sihui City, Guangdong, Zhaoqing, Dongcheng District Patentee before: GUANGDONG YILI GROUP PHARMACEUTICAL Co.,Ltd. |