CN113425696B - Effervescent preparation of compound oral rehydration salt and preparation process and application thereof - Google Patents

Effervescent preparation of compound oral rehydration salt and preparation process and application thereof Download PDF

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CN113425696B
CN113425696B CN202110749591.2A CN202110749591A CN113425696B CN 113425696 B CN113425696 B CN 113425696B CN 202110749591 A CN202110749591 A CN 202110749591A CN 113425696 B CN113425696 B CN 113425696B
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parts
effervescent
granules
preparation
montmorillonite
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CN113425696A (en
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李小清
蒋雅红
顾珽
李玉柱
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Lingyao Biotechnology Shanghai Co ltd
Shanghai Yaoda Biotechnology Co ltd
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Lingyao Biotechnology Shanghai Co ltd
Shanghai Yaoda Biotechnology Co ltd
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Abstract

The invention discloses an effervescent preparation of compound oral rehydration salt, a preparation process and application thereof, which comprises the following steps of,the effervescent preparation comprises 30-90% of main drug composition of rehydration salt, probiotics and modified montmorillonite coated particles and 10-70% of pharmaceutically acceptable effervescent auxiliary materials; wherein the probiotic is 10 6 ‑10 10 CFU/g, the effervescent auxiliary material comprises an acid source and an alkali source. The compound oral rehydration salt effervescent preparation combines the rehydration salt, the probiotics and the modified montmorillonite coated particles for use, and after the oral rehydration salt and the probiotics have corresponding curative effects and effects, the montmorillonite generates mucous membrane adhesion and plays a role in continuously protecting gastrointestinal tracts, thereby effectively overcoming the side effects caused by the combined administration of the rehydration salt, the montmorillonite and other medicinal preparations; can effectively treat and relieve symptoms of acute and severe patients who need the quick response of the medicine in time, is particularly suitable for children, old people and patients who have difficulty in taking pills, and is convenient to carry and use.

Description

Effervescent preparation of compound oral rehydration salt and preparation process and application thereof
Technical Field
The invention belongs to the technical field of medicinal preparations, relates to an oral liquid salt, and particularly relates to an effervescent preparation of a compound oral rehydration salt, and a preparation process and application thereof.
Background
The oral rehydration salt is one of the first-choice medicaments recommended by the world health organization for treating diarrhea and dehydration, the oral therapy clinically used for treating and preventing dehydration caused by various reasons is oral rehydration, and the early oral rehydration can play a relatively obvious curative effect on maintenance treatment of non-severe dehydration and severe dehydration, and the effective rate is more than 95%. The traditional diarrhea treatment, especially for children patients, has the disadvantages of complex operation, large amount of liquid consumption, salty taste of the rehydration salt, and possibly poor clinical compliance and prolonged treatment time due to the fact that at least two preparations are involved in the use process. The common powder has the defects of easy moisture absorption, enhanced chemical activity of medicinal components, easy loss, easy oxidation and the like in the using process.
Montmorillonite is a common medicine for clinical intestinal diseases at present, and is popular because the medicine is derived from pure natural minerals, has remarkable effect, high safety and low toxic and side effects. The montmorillonite can form a layer of protective film on the surface of the intestinal mucosa, so that the intestinal mucosa is prevented from being further damaged, and the diarrhea symptom can be well improved. However, the montmorillonite only plays a role in relieving and assisting treatment, and clinically, other medicines for treating diarrhea need to be taken simultaneously when the montmorillonite is used for treating diarrhea, so that the diarrhea symptoms can be better improved.
Published patent CN110292582A discloses an ellagic acid montmorillonite effervescent agent and a preparation method thereof, which provide the stability and solubility of ellagic acid through processing the ellagic acid, equivalently increase the dosage of the single effervescent tablet, and solve the problems that the solid ellagic acid dispersion and the montmorillonite preparation have bitter taste and influence on taking. Ellagic acid in the effervescent preparation has antibacterial effect, and in the preparation process, after mixing acid source and alkali source, 5% PVP absolute ethanol solution is added for granulation.
Published patent CN101272986A discloses a boron fertilizer effervescent granule and a preparation method thereof, which uses mixed acid of organic acid and inorganic acid to modify montmorillonite to obtain modified calcium-based montmorillonite, modified sodium calcium-based montmorillonite, modified hydrogen-based montmorillonite, modified magnesium-based montmorillonite or modified sodium-based montmorillonite, and prepares the modified montmorillonite coating granule into an effervescent agent.
Patent publication CN109260256A discloses an effervescent granule for infantile diarrhea, which can significantly improve the flowability, adhesiveness and hygroscopicity of the material by adding sodium bicarbonate and citric acid as effervescent disintegrant, adding tagatose and soluble starch as filler, and using a small amount of montmorillonite and aerosil as anti-caking agent, lubricant, etc. The infantile diarrhea effervescent granule is prepared from infantile diarrhea relieving, and montmorillonite is used as anticaking agent, and has slow clinical effect, short treatment effect on gastrointestinal tract, and need improvement.
In addition, published patent CN108853138A discloses an oral rehydration salt effervescent tablet and a preparation method thereof, wherein the rehydration salt is prepared into an effervescent preparation by adopting a flash flow processing mode, the oral rehydration salt effervescent tablet generates carbon dioxide when meeting water, so that the tablet is rapidly disintegrated into small pieces, the contained medicinal components can be rapidly dissolved, and the tablet can be used for effectively treating and relieving symptoms of acute and severe patients requiring rapid onset of action of the medicament in time, and the process is characterized in that the tablet is directly tableted after mixing raw and auxiliary materials.
Although prior patents CN110292582A, CN101272986A, CN109260256A, CN108853138A and the like disclose a scheme of preparing montmorillonite into an effervescent agent and a technical scheme of preparing rehydration salt into an effervescent agent. In practical application, however, for a specific patient with diarrhea and dehydration, the rehydration salt, the montmorillonite and other pharmaceutical preparations need to be taken together, but the rehydration salt, the montmorillonite and other pharmaceutical preparations are taken together, so that certain side effects are inevitably generated, and are mainly influenced by the montmorillonite, because montmorillonite particles attach to intestinal tracts to form a protective film, the gastrointestinal absorption capacity is poor, the water, salt and sugar in the gastrointestinal tracts are emptied and absorbed, and the absorption of other preparations is inhibited, which shows that the gastrointestinal tracts are difficult to tolerate the oral rehydration and other pharmaceutical preparations, abdominal distension, vomiting and diarrhea are possibly caused, and even serious consequences are caused, and the absorption of the rehydration salt and other preparations is seriously influenced.
At present, in order to reduce the side effect of simultaneous taking of the rehydration salt, the montmorillonite and other medicinal preparations, the common taking method is to take the rehydration salt, the medicinal preparations and the montmorillonite at intervals, but the discomfort of a patient is inevitably increased by taking the rehydration salt, the medicinal preparations and the montmorillonite for a plurality of times, and the joint treatment effect of the medicaments is reduced to a certain extent by taking the rehydration salt, the montmorillonite and other medicinal preparations at intervals, so that the pain of the patient is delayed, and the pain of the patient is increased.
Disclosure of Invention
The invention provides a compound oral rehydration salt effervescent preparation which simplifies the taking mode and has good curative effect on diarrhea, and a preparation process and application thereof, aiming at overcoming the defects of complicated taking procedure, large amount of liquid drinking, poor taste and great side effect when a plurality of traditional medicines are taken together.
In order to achieve the purpose, the invention adopts the following technical scheme:
the invention provides an effervescent preparation of compound oral rehydration salt, which comprises the rehydration salt, probiotics and modified montmorillonite coated particles in percentage by mass30-90% of the main medicine composition and 10-70% of pharmaceutically acceptable effervescent auxiliary materials; wherein the probiotic is 10 6 -10 10 CFU/g, the effervescent auxiliary material comprises an acid source and an alkali source.
Furthermore, the effervescent preparation of the compound oral rehydration salt comprises 39.9-79.9% of the main medicine composition of the rehydration salt, probiotics and modified montmorillonite coated particles and the balance of pharmaceutically acceptable effervescent auxiliary materials by mass percentage.
Further preferably, the effervescent preparation of the compound oral rehydration salt comprises 49.9-69.9% of main drug composition of the rehydration salt, probiotics and modified montmorillonite coated particles and the balance of pharmaceutically acceptable effervescent auxiliary material source by mass percent.
Further, the main medicine composition also comprises prebiotics according to the mass percentage of the effervescent preparation, and the prebiotics comprise the following components: 0.1-0.5% of prebiotics, 10.9-31.5% of rehydration salt and 19-58% of modified montmorillonite coating particles.
Further, the liquid supplementing salt comprises the following components in percentage by mass of the effervescent preparation: 2.6 to 7 percent of sodium chloride, 1.2 to 3 percent of potassium chloride, 1.6 to 3.5 percent of citric acid and 5.5 to 18 percent of anhydrous glucose.
Further, the modified montmorillonite coated particle comprises the following components in percentage by mass of the effervescent preparation: 11.2 to 34.5 percent of montmorillonite, 0.5 to 1.5 percent of sodium pyruvate, 0.1 to 0.5 percent of ethyl cellulose, 0.2 to 0.5 percent of chitosan, 0.5 to 1 percent of citric acid acetyl ethyl ester and 6.5 to 20 percent of PVP-K30.
Further preferably, the modified montmorillonite coated particle is prepared by the following method in percentage by mass:
firstly, montmorillonite micropowder in a formula ratio is prepared according to the mass ratio of 1: 5 dispersing in an acetone solution to form a solution A, and dissolving sodium pyruvate in pure ethanol according to the mass ratio of 1:2 to form a solution B;
adding the solution B into the solution A, adding ethyl cellulose in the formula ratio, uniformly stirring, ultrasonically dispersing for 15-20min, and drying in a spray dryer at the drying temperature of 60-65 ℃ to obtain modified primary coating micro powder;
finally, dissolving chitosan, acetyl triethyl citrate and PVP-K30 in the formula ratio by using 70-80% ethanol, then carrying out secondary coating on the primary coated micro powder, continuously drying after the coating is finished until the moisture is below 6%, and sieving by using a 100-mesh sieve to obtain the chitosan/triethyl citrate composite micro powder.
Further, according to the mass percentage, the montmorillonite is high-purity montmorillonite with the content of 95-100%, the particle size is 50-150 mu m, and the content of heavy metal (lead, mercury and arsenic) is less than 10 ppm.
Furthermore, the effervescent auxiliary materials are acceptable auxiliary materials in food, health products, special medical food or medicine processing, and at least comprise an acid source and an alkali source which form the effervescent agent.
Further, the effervescent auxiliary material comprises the following components in percentage by mass of the effervescent preparation: 1-10% of acid source, 1-10% of alkali source, 7-34% of filling agent, 0.5-8% of disintegrating agent, 0-2% of lubricating agent, 0-1% of flavoring agent and 0.5-5% of adhesive.
Further preferably, the acid source is one or more selected from citric acid, malic acid, tartaric acid and fumaric acid; the alkali source is selected from one or more of sodium bicarbonate, sodium carbonate, potassium bicarbonate and potassium carbonate.
More preferably, the alkali source is one or more of sodium bicarbonate and sodium carbonate.
Further preferably, the filler is selected from one or more of microcrystalline cellulose, xylitol, sorbitol, starch, mannitol, erythritol, sucrose, glucose, fructose, lactose, isomalt, maltodextrin, and maltitol;
the disintegrant is selected from one or more of sodium carboxymethyl starch, croscarmellose sodium and crospovidone;
the lubricant is selected from one or more of stearate, stearic acid, silicon dioxide, avocado oil, linseed oil, olive oil, glycerol and polyethylene glycol;
the flavoring agent is one or more selected from sucralose, stevioside, aspartame, AK sugar, edible essence and salt.
Further, the effervescent auxiliary material also comprises 5-10% of a binding agent, and the binding agent comprises one or a combination of more of hydroxypropyl methylcellulose, polyvinylpyrrolidone, sodium carboxymethyl starch, pregelatinized starch, maltodextrin and acacia.
Further, the probiotic comprises one or more of bifidobacterium, lactobacillus, streptococcus, enterococcus, saccharomyces, clostridium and bacillus.
Further preferably, the bifidobacterium comprises one or more of bifidobacterium longum, bifidobacterium breve, bifidobacterium animalis, bifidobacterium infantis, bifidobacterium bifidum, bifidobacterium lactis and bifidobacterium adolescentis;
the lactobacillus comprises one or more of lactobacillus helveticus, lactobacillus rhamnosus, lactobacillus acidophilus, lactobacillus plantarum, lactobacillus casei, lactobacillus paracasei, lactobacillus reuteri, lactobacillus salivarius, lactobacillus fermentum, lactobacillus gasseri, lactobacillus bulgaricus, lactobacillus delbrueckii subspecies lactis and lactobacillus johnsonii;
the streptococcus is streptococcus thermophilus; the enterococcus comprises one or two of enterococcus faecalis and enterococcus faecium;
the Saccharomyces is Saccharomyces boulardii; the clostridium is clostridium butyricum; the bacillus comprises one or more of bacillus subtilis, bacillus cereus and bacillus licheniformis.
Further preferably, the probiotics adopt bifidobacterium and lactobacillus, and the weight ratio of the bifidobacterium to the lactobacillus is (1-5): (5-15).
Further, the prebiotics of the effervescent preparation of the compound oral rehydration salt comprise one or more of inulin, polydextrose, fructo-oligosaccharide, galacto-oligosaccharide, xylo-oligosaccharide, stachyose, soybean oligosaccharide, breast milk oligosaccharide, isomalto-oligosaccharide, isomaltulose, trehalose and arabinose.
The second aspect of the invention is a preparation process of the effervescent preparation of the compound oral rehydration salt, which comprises the following steps:
(1) pretreatment: weighing the required raw and auxiliary materials according to the prescription amount, wherein all the raw and auxiliary materials pass through a 30-mesh standard sieve;
(2) and (3) granulating: according to the properties of raw and auxiliary materials, the preparation of acid granules and alkali granules is completed through a low-temperature dry pressing process, wherein the acid granules contain main medicine rehydration salt, and the alkali granules contain main medicine probiotics, prebiotics and montmorillonite; and preparing modified montmorillonite coated particles;
(3) straightening: sieving acid granules and alkali granules with 24 mesh and 80 mesh;
(4) total mixing: mixing the acid granules, the alkali granules and the lubricant to obtain mixed granules;
(5) and (4) carrying out effervescent granule or tabletting on the mixed granules obtained in the step (4) according to a conventional method to prepare effervescent tablets.
The third aspect of the invention provides application of the effervescent preparation of the compound oral rehydration salt in preparation of medicines, health products, special medical foods or foods for improving and treating diarrhea and/or gastrointestinal dysfunction.
The main medicine composition containing the rehydration salt, the probiotics and the montmorillonite provided by the invention adopts the rehydration salt, the probiotics and the montmorillonite in a specific proportion as main raw materials, and simultaneously adopts the combined action of a plurality of strains, and the strains have good effects on relieving or treating diarrhea. Wherein the species having a good effect on alleviating or treating diarrhea are Bifidobacterium and Lactobacillus. The bifidobacteria adhere to the surface of the epithelial cells of the intestinal tract and secrete the bacteroids, and meanwhile, the thickness of the lubricating liquid in the intestinal tract is increased, so that pathogenic bacteria are inhibited from invading the intestinal tract, and the intestinal tract diseases caused by the disturbance of an immune system are improved. The lactobacillus can inhibit the reproduction of putrefying bacteria and pathogenic bacteria in intestinal tract, reduce the content of blood ammonia and cholesterol in blood, and maintain the balance of flora in intestinal tract.
The probiotics inhibit the proliferation of harmful bacteria by competing with the harmful bacteria for oxygen, nutrition and colonization sites, thereby changing the balance of intestinal flora and purifying the intestinal environment. Has effects of regulating, preventing and treating diseases by antioxidant, anti-variation, physiological activity, and immunostimulation. The probiotic strains with synergistic effect are mainly streptococcus thermophilus, saccharomyces boulardii, enterococcus, bacillus and clostridium. The streptococcus thermophilus has tolerance to gastric acid and bile salt in a human body, can directly reach the far end of a small intestine, has an inhibition effect on intestinal pathogenic bacteria, and has a good synergistic effect on lactobacillus. The saccharomyces boulardii can secrete a protease of 54kDa, and the protease can degrade toxins secreted by part of intestinal pathogens, inhibit the combination of the toxins and cell receptors, and reduce the harmfulness of the pathogens. The bacillus subtilis can rapidly consume free oxygen in the intestinal tract, provide a low-oxygen environment for the intestinal tract, and promote the growth of beneficial anaerobic bacteria in the intestinal tract, thereby indirectly inhibiting the growth of other pathogenic bacteria. The clostridium butyricum can tolerate gastric acid, so that the clostridium butyricum enters intestinal tracts, secretes important nutrient substance butyric acid which is beneficial to regeneration and repair of intestinal mucosa, can promote growth of intestinal beneficial bacteria such as bifidobacterium and the like, inhibit growth of intestinal harmful bacteria such as shigella dysenteriae and the like, restore intestinal flora balance, reduce generation of intestinal toxins such as amine, ammonia, indole and the like and poison on the intestinal mucosa, and restore intestinal immune function.
The oral rehydration salt mainly comprises one or more of sodium chloride, sodium bicarbonate, potassium chloride, sodium citrate and anhydrous glucose. The oral rehydration salt has the functions of supplementing liquid and preventing or treating water electrolyte disorder, and is usually used for diarrhea patients. The rehydration salt mainly comprises glucose, sodium chloride, potassium chloride and sodium bicarbonate, can prevent and correct acid-base balance disorder, and can be used for treating diarrhea. Sodium ions and potassium ions are necessary for maintaining a constant osmotic pressure in the body, which is necessary for life, and sodium and potassium in the body are lost too much, which causes low sodium syndrome or low potassium syndrome. The product can be used for supplementing sodium, potassium and body fluid, and regulating balance of water and electrolyte.
Montmorillonite has a lamellar structure and non-uniform charge distribution, is an intestinal mucosa protective agent, can be attached to intestinal mucosa parts after being taken orally, has strong covering and protecting capability on digestive tract mucosa, repairs and improves the defense function of a mucosa barrier on attack factors, and has the effects of balancing normal flora and locally relieving pain; meanwhile, the montmorillonite also has strong fixing and inhibiting effects on viruses and germs in the digestive tract and toxins, gases and the like generated by the viruses and germs, so that the pathogenic effects of the viruses and germs are lost.
The effervescent preparation of the compound oral rehydration salt is also added with an acid source, an alkali source, a filling agent, a disintegrating agent, a lubricating agent and auxiliary materials which are acceptable in the production of foods, health-care products, special medical foods or medicines such as flavoring agents. The filler and the flavoring agent improve the taste of the product, and cover the salty taste of the product without influencing the nutrition and functional value of the product. The pharmaceutically acceptable adjuvants can be added with the above materials, and also can be added with some materials helpful for treating diarrhea.
In addition, the modified montmorillonite coated particles treated by the specific process are the montmorillonite raw material, so that the side effects caused by the combined administration of rehydration salt, montmorillonite and other medicinal preparations are effectively overcome. Specifically, the micronized particles are prepared by modifying montmorillonite with sodium pyruvate and a film-forming agent, namely ethyl cellulose, and the pyruvate has the functions of resisting acid, inflammation and oxidation, so that local acidosis, inflammatory damage and peroxidation damage of intestinal tissues during intestinal ischemia and fluid infusion (reperfusion) can be effectively relieved, the intestinal environment for absorption of the glucose-electrolyte oral liquid is improved, and the absorption effect of the oral liquid can be further improved. And then performing secondary inclusion on the modified montmorillonite micronized particles by adopting chitosan, acetyl triethyl citrate and PVP-K30 to form a slow release layer on the surfaces of the montmorillonite micronized particles, so as to play a role in delaying the release onset time of the montmorillonite.
In conclusion, the compound oral rehydration salt effervescent preparation provided by the invention treats diarrhea by oral rehydration salt rehydration and prevention or treatment of water electrolyte disorder, changes intestinal flora balance by probiotics, improves short diarrhea conditions, shortens course of disease, and generates a covering and protecting effect on digestive tract mucous membrane by montmorillonite, and the three components are jointly used, so that the aims of synergistic effect of curative effect, treatment effect improvement and medication compliance can be achieved. Meanwhile, due to the gastric mucosa protection effect of the montmorillonite, the absorption of other medicines can be influenced, the process features that a secondary coating technology is introduced, the montmorillonite is modified and then subjected to micro-powder coating to prepare montmorillonite micro-powder particles, the release onset time of the montmorillonite is delayed, and after the oral rehydration salt and the probiotics play corresponding curative effects and effects, the montmorillonite generates mucosa adhesion and plays a continuous protection effect on the gastrointestinal tract.
By adopting the technical scheme, compared with the prior art, the invention has the following technical effects:
(1) when the rehydration salt, the probiotics and the montmorillonite are used in a combined manner, the rehydration salt can adjust water and electrolyte in intestinal tracts to balance the water and the electrolyte, can ensure the supply of salt and water to the organism of a diarrhea patient in a short time, and simultaneously intakes a certain amount of probiotics to achieve the purpose of preventing and correcting dehydration;
(2) the montmorillonite is modified by adopting a secondary coating technology and then subjected to micro-powder coating to prepare montmorillonite micro-powder particles, so that the release onset time of the montmorillonite is delayed, after the oral rehydration salt and probiotics play corresponding curative effects and effects, the montmorillonite generates mucous membrane adhesion and plays a continuous protection role on gastrointestinal tracts, and the side effect caused by the combined administration of the rehydration salt, the montmorillonite and other pharmaceutical preparations is effectively overcome;
(3) prebiotics are adopted to promote the colonization and proliferation of probiotics in vivo, so that the balance of intestinal microorganisms is regulated by the probiotics, the intestinal function is improved, the immunity is improved, and beneficial ingredients are released or the activity of pathogenic bacteria is resisted to quickly relieve or treat diarrhea;
(4) the effervescent preparation of the compound oral rehydration salt adopts an effervescent preparation mode, the effervescent preparation not only generates carbon dioxide when meeting water, so that the tablet can be rapidly cracked into small fragments, the contained medicinal components can be rapidly dissolved, and the compound oral rehydration salt can effectively treat and relieve symptoms of acute and severe patients needing rapid drug effect in time, is particularly suitable for children, old people and patients who have difficulty in taking pills, and is convenient to carry and use.
Detailed Description
The present invention will be described in detail and specifically with reference to the following examples to facilitate better understanding of the present invention, but the following examples do not limit the scope of the present invention.
Example 1
Formula of effervescent preparation of compound oral rehydration salt
The effervescent preparation of the compound oral rehydration salt comprises probiotics of 1 multiplied by 10 9 CFU/g, 0.1 part of prebiotics, 10.9 parts of rehydration salt, 58 parts of modified montmorillonite coated particles and 31 parts of effervescent auxiliary materials. Specifically, the following components are included;
comprises a liquid supplementing salt component: 2.6 parts of sodium chloride, 1.2 parts of potassium chloride, 1.6 parts of citric acid and 5.5 parts of anhydrous glucose.
Comprises the following components of modified montmorillonite coating particles: 34.5 parts of montmorillonite, 1.5 parts of sodium pyruvate, 0.5 part of ethyl cellulose, 0.5 part of chitosan, 1 part of citric acid acetyl ethyl ester and 20 parts of PVP-K30.
Comprises the following effervescent auxiliary material components: 5 parts of acid source, 5 parts of alkali source, 14 parts of filler, 2.7 parts of disintegrating agent, 2 parts of lubricant, 0.1 part of flavoring agent and 2.2 parts of adhesive.
Wherein, the prebiotics adopts xylo-oligosaccharide, the alkali source adopts sodium bicarbonate, the adhesive adopts hydroxypropyl methylcellulose, the disintegrating agent adopts croscarmellose sodium, the filling agent adopts xylitol, and the flavoring agent adopts aspartame and orange essence.
The prescription raw materials with the specific formula ratio are divided into four parts, namely an acid granule formula, an alkali granule formula, modified montmorillonite coated particles and a lubricant according to the preparation process of the effervescent preparation, and the effervescent preparation specifically comprises the following components:
a: the formula of the acid granules is 20 parts:
2.6 parts of sodium chloride, 1.2 parts of potassium chloride, 6.6 parts of citric acid, 5.5 parts of anhydrous glucose, 1.75 parts of hydroxypropyl methylcellulose, 2.3 parts of croscarmellose sodium and 0.05 part of aspartame;
b: the alkali particle formula is 20 parts:
probiotic bacteria (equivalent to viable count addition of 1 × 10 9 CFU/g), xylo-oligosaccharide 0.1 part, sodium bicarbonate 5 parts, hydroxypropyl methylcellulose 0.45 part, croscarmellose sodium 0.4 part, xylitol 14 parts, and orange essence 0.05 part;
c: 58 parts of modified montmorillonite coating particles;
d: lubricant: and 2 parts of magnesium stearate.
(II) the preparation process comprises the following steps:
(1) pretreatment: passing all the raw and auxiliary materials through a 30-mesh standard sieve for later use;
(2) granulating: acid granulation: mixing the raw materials and auxiliary materials according to the prescription amount, and granulating by low-temperature dry pressing; alkali granulation: mixing the raw materials and auxiliary materials according to the prescription amount, and granulating by low-temperature dry pressing; modified montmorillonite coated particle: mixing the raw materials and the auxiliary materials according to the prescription amount, and preparing by adopting a micro powder coating process;
(3) straightening: granulating the acid granules and the alkali granules after dry pressing, and sieving the granules through 24 meshes and 80 meshes;
(4) total mixing: mixing the acid granules, the alkali granules, the modified montmorillonite coated granules and the lubricant;
(5) making into tablet by conventional method.
(III) examining indexes:
appearance: the particles should be dry, uniform, consistent in color and luster, and free of moisture absorption, softening, deliquescence and the like;
granularity: sieving the total mixed particles in a pharmacopoeia sieve for 3min, wherein the total amount of the powder which can not pass through a No. 2 sieve and can pass through a No. 6 sieve is not more than 8 parts;
loss on drying: detecting the total mixed granules according to a pharmacopoeia method, wherein the total mixed granules can not exceed 2.0%;
solubility: the test article is taken and heated with 200ml of water, and the effervescent granules can generate carbon dioxide gas immediately when contacting with water and are in an effervescent state.
Release time and content of montmorillonite: the content of the aqueous solution of the product is detected at different time points by adopting a blue absorption method-spectrophotometry, the solution does not adsorb methylene blue at the beginning, an adsorption phenomenon appears after 15min, the modified montmorillonite coated particle begins to release to take effect after 15min, and the content is detected after 30min, so that the content meets the requirement of the formula ratio content.
Example 2
Formula of effervescent preparation of compound oral rehydration salt
The effervescent preparation of the compound oral rehydration salt comprises probiotics of 1 multiplied by 10 9 CFU/g, 0.5 part of prebiotics, 15.9 parts of rehydration salt, 48 parts of modified montmorillonite coated particles and 35.6 parts of effervescent auxiliary materials. Specifically, the following components are included;
comprises a liquid supplementing salt component: 4.5 parts of sodium chloride, 3 parts of potassium chloride, 2.3 parts of citric acid and 6.1 parts of anhydrous glucose.
Comprises the following components of modified montmorillonite coating particles: 30 parts of montmorillonite, 1 part of sodium pyruvate, 0.5 part of ethyl cellulose, 0.5 part of chitosan, 1 part of acetyl ethyl citrate and 15 parts of PVP-K30.
Comprises the following effervescent auxiliary material components: 6 parts of acid source, 6 parts of alkali source, 16 parts of filler, 3.3 parts of disintegrating agent, 2 parts of lubricant, 0.1 part of flavoring agent and 2.2 parts of adhesive.
Wherein, the prebiotics adopts xylo-oligosaccharide, the alkali source adopts sodium bicarbonate, the adhesive adopts hydroxypropyl methylcellulose, the disintegrating agent adopts croscarmellose sodium, the filling agent adopts xylitol, and the flavoring agent adopts aspartame and orange essence.
The prescription raw materials with the specific formula ratio are divided into four parts, namely an acid granule formula, an alkali granule formula, modified montmorillonite coated particles and a lubricant according to the preparation process of the effervescent preparation, and the effervescent preparation specifically comprises the following components:
a: the formula of the acid granules is 25 parts:
4.5 parts of sodium chloride, 3 parts of potassium chloride, 8.3 parts of citric acid, 6.1 parts of anhydrous glucose, 1.75 parts of hydroxypropyl methyl cellulose, 1.3 parts of cross-linked sodium carboxymethyl cellulose and 0.05 part of aspartame;
b: the alkali granule formula is 25 parts:
probiotic (equivalent to viable count addition amount of 1 × 10) 9 ) 0.5 part of xylo-oligosaccharide, 6 parts of sodium bicarbonate, 0.45 part of hydroxypropyl methyl cellulose, 2 parts of croscarmellose sodium, 16 parts of xylitol and 0.05 part of orange essence;
c: 48 parts of modified montmorillonite coating particles;
d: lubricant: and 2 parts of magnesium stearate.
(II) the preparation process comprises the following steps:
(1) pretreatment: passing all the raw and auxiliary materials through a 30-mesh standard sieve for later use;
(2) granulating: acid granulation: mixing the raw materials and auxiliary materials according to the prescription amount, and granulating by low-temperature dry pressing; alkali granulation: mixing the raw materials and auxiliary materials according to the prescription amount, and granulating by low-temperature dry pressing; modified montmorillonite coated particle: mixing the raw materials and the auxiliary materials according to the prescription amount, and preparing by adopting a micro powder coating process;
(3) straightening: granulating the dry-pressed acid granules and alkali granules, and sieving through 24 meshes and 80 meshes;
(4) total mixing: mixing the acid granules, the alkali granules, the modified montmorillonite coated granules and the lubricant;
(5) making into tablet by conventional method.
(III) examining indexes:
appearance: the particles should be dry, uniform, consistent in color and luster, and free of moisture absorption, softening, deliquescence and the like;
granularity: sieving the total mixed particles in a pharmacopoeia sieve for 3min, wherein the total amount of the powder which can not pass through a No. 2 sieve and can pass through a No. 6 sieve is not more than 8 parts;
loss on drying: detecting the total mixed granules according to a pharmacopoeia method, wherein the total mixed granules can not exceed 2.0%;
solubility: the test article is taken, 200ml of hot water is added, and the effervescent granules immediately generate carbon dioxide when contacting water and are in an effervescent state.
Release time and content of montmorillonite: the content of the aqueous solution of the product is detected at different time points by adopting a blue absorption method-spectrophotometry, the solution does not adsorb methylene blue at the beginning, an adsorption phenomenon appears after 15min, the modified montmorillonite coated particle begins to release to take effect after 15min, and the content is detected after 30min, so that the content meets the requirement of the formula ratio content.
Example 3
Formula of effervescent preparation of compound oral rehydration salt
The compound oral rehydration salt effervescenceThe preparation comprises probiotic 1 × 10 9 CFU/g, 0.5 part of prebiotics, 20.9 parts of rehydration salt, 39 parts of modified montmorillonite coated particles and 39.6 parts of effervescent auxiliary materials. Specifically, the following components are included;
comprises a liquid supplementing salt component: 6.5 parts of sodium chloride, 2.5 parts of potassium chloride, 2.8 parts of citric acid and 8.1 parts of anhydrous glucose.
Comprises the following components of modified montmorillonite coating particles: 24 parts of montmorillonite, 0.5 part of sodium pyruvate, 0.5 part of ethyl cellulose, 0.5 part of chitosan, 0.5 part of acetyl ethyl citrate and 13 parts of PVP-K30.
Comprises the following effervescent auxiliary material components: 7 parts of acid source, 7 parts of alkali source, 19 parts of filler, 3.3 parts of disintegrating agent, 1 part of lubricant, 0.1 part of flavoring agent and 2.2 parts of adhesive.
Wherein, the prebiotics adopts xylo-oligosaccharide, the alkali source adopts sodium bicarbonate, the adhesive adopts hydroxypropyl methylcellulose, the disintegrating agent adopts croscarmellose sodium, the filling agent adopts xylitol, and the flavoring agent adopts aspartame and orange essence.
The prescription raw materials with the specific formula ratio are divided into four parts, namely an acid granule formula, an alkali granule formula, modified montmorillonite coated particles and a lubricant according to the preparation process of the effervescent preparation, and the effervescent preparation specifically comprises the following components:
a: the formula of the acid granules is 30 parts:
6.5 parts of sodium chloride, 2.5 parts of potassium chloride, 9.8 parts of citric acid, 8.1 parts of anhydrous glucose, 1.2 parts of hydroxypropyl methylcellulose, 0.85 part of cross-linked sodium carboxymethylcellulose and 0.05 part of aspartame;
b: 30 parts of alkali particle formula:
probiotic (equivalent to viable count addition amount of 1 × 10) 9 ) 0.5 part of xylo-oligosaccharide, 7 parts of sodium bicarbonate, 1 part of hydroxypropyl methyl cellulose, 2.45 parts of croscarmellose sodium, 19 parts of xylitol and 0.05 part of orange essence;
c: 39 parts of modified montmorillonite coating particles;
d: lubricant: and 1 part of magnesium stearate.
(II) the preparation process comprises the following steps:
(1) pretreatment: passing all the raw and auxiliary materials through a 30-mesh standard sieve for later use;
(2) and (3) granulating: acid granulation: mixing the raw materials and the auxiliary materials according to the prescription amount, and performing low-temperature dry pressing to complete granulation; alkali granulation: mixing the raw materials and the auxiliary materials according to the prescription amount, and performing low-temperature dry pressing to complete granulation; modified montmorillonite coated particle: mixing the raw materials and the auxiliary materials according to the prescription amount, and preparing by adopting a micro powder coating process;
(3) straightening: granulating the acid granules and the alkali granules after dry pressing, and sieving the granules through 24 meshes and 80 meshes;
(4) total mixing: mixing the acid granules, the alkali granules, the modified montmorillonite coated granules and the lubricant;
(5) making into granule by conventional method.
(III) examining indexes:
appearance: the particles should be dry, uniform, consistent in color and luster, and free of moisture absorption, softening, deliquescence and the like;
granularity: sieving the total mixed granules in a pharmacopeia sieve for 3min, wherein the total powder which can not pass through a No. 2 sieve and can pass through a No. 6 sieve is not more than 8 parts;
loss on drying: detecting the total mixed granules according to a pharmacopoeia method, wherein the total mixed granules can not exceed 2.0%;
solubility: the test article is taken and heated with 200ml of water, and the effervescent granules can generate carbon dioxide gas immediately when contacting with water and are in an effervescent state.
Release time and content of montmorillonite: the content detection of the product water solution at different time points is carried out by adopting a blue absorption method-spectrophotometry, the solution does not adsorb methylene blue at the beginning, the adsorption phenomenon appears after 10min, the modified montmorillonite coated particle starts to release after 10min to take effect, and the content is detected after 30min to meet the content requirement of the prescription proportion.
Example 4
Formula of effervescent preparation of compound oral rehydration salt
The effervescent preparation of the compound oral rehydration salt comprises probiotics of 1 multiplied by 10 9 CFU/g, 1 part of prebiotics, 25.9 parts of rehydration salt, 29 parts of modified montmorillonite coated particles and 44.1 parts of effervescent auxiliary materials. Specifically, the following components are included;
comprises a liquid supplementing salt component: 6.5 parts of sodium chloride, 2.5 parts of potassium chloride, 3 parts of citric acid and 12.9 parts of anhydrous glucose.
Comprises the following components of modified montmorillonite coating particles: 20 parts of montmorillonite, 0.5 part of sodium pyruvate, 0.3 part of ethyl cellulose, 0.2 part of chitosan, 0.5 part of citric acid acetyl ethyl ester and 7.5 parts of PVP-K30.
Comprises the following effervescent auxiliary material components: acid source, 7 parts of 8 parts of alkali source, 22.5 parts of filler, 3.3 parts of disintegrating agent, 1 part of lubricant, 0.1 part of flavoring agent and 2.2 parts of adhesive.
Wherein, the prebiotics adopts xylo-oligosaccharide, the alkali source adopts sodium bicarbonate, the adhesive adopts hydroxypropyl methylcellulose, the disintegrating agent adopts croscarmellose sodium, the filling agent adopts xylitol, and the flavoring agent adopts aspartame and orange essence.
The prescription raw materials with the specific formula ratio are divided into four parts, namely an acid granule formula, an alkali granule formula, modified montmorillonite coated particles and a lubricant according to the preparation process of the effervescent preparation, and the effervescent preparation specifically comprises the following components:
a: the formula of the acid granules comprises 35 parts:
6.5 parts of sodium chloride, 2.5 parts of potassium chloride, 10 parts of citric acid, 12.9 parts of anhydrous glucose, 1.0 part of hydroxypropyl methylcellulose, 1.05 parts of cross-linked sodium carboxymethyl cellulose and 0.05 part of aspartame;
b: the alkali particle formula comprises 35 parts:
probiotic (equivalent to viable count addition amount of 1 × 10) 9 ) 1 part of xylo-oligosaccharide, 8 parts of sodium bicarbonate, 1.2 parts of hydroxypropyl methyl cellulose, 2.25 parts of croscarmellose sodium, 22.5 parts of xylitol and 0.05 part of orange essence;
c: 29 parts of modified montmorillonite coating particles;
d: lubricant: and 1 part of magnesium stearate.
(II) the preparation process comprises the following steps:
(1) pretreatment: passing all the raw and auxiliary materials through a 30-mesh standard sieve for later use;
(2) and (3) granulating: acid granulation: mixing the raw materials and auxiliary materials according to the prescription amount, and granulating by low-temperature dry pressing; alkali granulation: mixing the raw materials and auxiliary materials according to the prescription amount, and granulating by low-temperature dry pressing; modified montmorillonite coated particle: mixing the raw materials and the auxiliary materials according to the prescription amount, and preparing by adopting a micro powder coating process;
(3) straightening: granulating the dry-pressed acid granules and alkali granules, and sieving through 24 meshes and 80 meshes;
(4) total mixing: mixing the acid granules, the alkali granules, the modified montmorillonite coated granules and the lubricant;
(5) making into tablet by conventional method.
(III) examining indexes:
appearance: the particles should be dry, uniform, consistent in color and luster, and free of moisture absorption, softening, deliquescence and the like;
granularity: sieving the total mixed particles in a pharmacopoeia sieve for 3min, wherein the total amount of the powder which can not pass through a No. 2 sieve and can pass through a No. 6 sieve is not more than 8 parts;
loss on drying: detecting the total mixed granules according to a pharmacopoeia method, wherein the total mixed granules can not exceed 2.0%;
solubility: taking a test article, adding 200ml of hot water, wherein the effervescent granules immediately generate carbon dioxide when contacting water and are in an effervescent state;
release time and content of montmorillonite: the content of the aqueous solution of the product is detected at different time points by adopting a blue absorption method-spectrophotometry, the solution does not adsorb methylene blue at the beginning, an adsorption phenomenon appears after 10min, the modified montmorillonite coated particle begins to release to take effect after 10min, and the content is detected after 30min, so that the content meets the requirement of the formula ratio content.
Example 5
Formula of effervescent preparation of compound oral rehydration salt
The effervescent preparation of the compound oral rehydration salt comprises probiotics of 1 multiplied by 10 9 CFU/g, 0.5 part of prebiotics, 10.9 parts of rehydration salt, 48 parts of modified montmorillonite coated particles and 40.6 parts of effervescent auxiliary materials. Specifically, the following components are included;
comprises a fluid infusion salt component: 2.6 parts of sodium chloride, 1.2 parts of potassium chloride, 1.6 parts of citric acid and 5.5 parts of anhydrous glucose.
Comprises the following components of modified montmorillonite coating particles: 30 parts of montmorillonite, 1 part of sodium pyruvate, 0.5 part of ethyl cellulose, 0.5 part of chitosan, 1 part of acetyl ethyl citrate and 15 parts of PVP-K30.
Comprises the following effervescent auxiliary material components: 7 parts of acid source, 7 parts of alkali source, 19 parts of filler, 3.3 parts of disintegrating agent, 2 parts of lubricant, 0.1 part of flavoring agent and 2.2 parts of adhesive.
Wherein, the prebiotics adopts xylo-oligosaccharide, the alkali source adopts sodium bicarbonate, the adhesive adopts hydroxypropyl methylcellulose, the disintegrating agent adopts croscarmellose sodium, the filling agent adopts xylitol, and the flavoring agent adopts aspartame and orange essence.
The prescription raw materials with the specific formula ratio are divided into four parts, namely an acid granule formula, an alkali granule formula, modified montmorillonite coated particles and a lubricant according to the preparation process of the effervescent preparation, and the effervescent preparation specifically comprises the following components:
a: the formula of the acid granules is 20 parts:
2.6 parts of sodium chloride, 1.2 parts of potassium chloride, 7.6 parts of citric acid, 5.5 parts of anhydrous glucose, 1.0 part of hydroxypropyl methylcellulose, 1.05 parts of cross-linked sodium carboxymethylcellulose and 0.05 part of aspartame;
b: 30 parts of alkali particle formula:
probiotic bacteria (equivalent to viable count addition of 2X 10) 9 ) 0.5 part of xylo-oligosaccharide, 7 parts of sodium bicarbonate, 1.2 parts of hydroxypropyl methyl cellulose, 2.25 parts of croscarmellose sodium, 19 parts of xylitol and 0.05 part of orange essence;
c: 48 parts of modified montmorillonite coating particles;
d: lubricant: and 2 parts of magnesium stearate.
(II) the preparation process comprises the following steps:
(1) pretreatment: passing all the raw and auxiliary materials through a 30-mesh standard sieve for later use;
(2) and (3) granulating: acid granulation: mixing the raw materials and the auxiliary materials according to the prescription amount, and performing low-temperature dry pressing to complete granulation; alkali granulation: mixing the raw materials and the auxiliary materials according to the prescription amount, and performing low-temperature dry pressing to complete granulation; modified montmorillonite coated granule is prepared by mixing the raw materials and auxiliary materials according to the prescription amount and adopting a micro powder coating process;
preparing;
(3) straightening: granulating the dry-pressed acid granules and alkali granules, and sieving through 24 meshes and 80 meshes;
(4) total mixing: mixing the acid granules, the alkali granules, the modified montmorillonite coated granules and the lubricant;
(5) making into granule by conventional method.
(III) examining indexes:
appearance: the particles should be dry, uniform, consistent in color and luster, and free of moisture absorption, softening, deliquescence and the like;
granularity: sieving the total mixed particles in a pharmacopoeia sieve for 3min, wherein the total amount of the powder which can not pass through a No. 2 sieve and can pass through a No. 6 sieve is not more than 8 parts;
loss on drying: detecting the total mixed granules according to a pharmacopoeia method, wherein the total mixed granules can not exceed 2.0%;
solubility: the test article is taken and heated with 200ml of water, and the effervescent granules can generate carbon dioxide gas immediately when contacting with water and are in an effervescent state.
Release time and content of montmorillonite: the content of the aqueous solution of the product is detected at different time points by adopting a blue absorption method-spectrophotometry, the solution does not adsorb methylene blue at the beginning, an adsorption phenomenon appears after 15min, the modified montmorillonite coated particle begins to release to take effect after 15min, and the content is detected after 30min, so that the content meets the requirement of the formula ratio content.
Example 6
Formula of effervescent preparation of compound oral rehydration salt
The effervescent preparation of the compound oral rehydration salt comprises probiotics of 1 multiplied by 10 9 CFU/g, 0.5 part of prebiotics, 20.9 parts of rehydration salt, 48 parts of modified montmorillonite coated particles and 30.6 parts of effervescent auxiliary materials. Specifically, the following components are included;
comprises a fluid infusion salt component: 6 parts of sodium chloride, 3 parts of potassium chloride, 3.3 parts of citric acid and 8.6 parts of anhydrous glucose.
Comprises the following components of modified montmorillonite coating particles: 30 parts of montmorillonite, 1 part of sodium pyruvate, 0.5 part of ethyl cellulose, 0.5 part of chitosan, 1 part of acetyl ethyl citrate and 15 parts of PVP-K30.
Comprises the following effervescent auxiliary material components: 5 parts of acid source, 5 parts of alkali source, 14 parts of filler, 2.3 parts of disintegrating agent, 2 parts of lubricant, 0.1 part of flavoring agent and 2.2 parts of adhesive.
Wherein, the prebiotics adopts xylo-oligosaccharide, the alkali source adopts sodium bicarbonate, the adhesive adopts hydroxypropyl methylcellulose, the disintegrating agent adopts croscarmellose sodium, the filling agent adopts xylitol, and the flavoring agent adopts aspartame and orange essence.
The prescription raw materials with the specific formula ratio are divided into four parts, namely an acid granule formula, an alkali granule formula, modified montmorillonite coated particles and a lubricant according to the preparation process of the effervescent preparation, and the effervescent preparation specifically comprises the following components:
a: the formula of the acid granules is 30 parts:
6 parts of sodium chloride, 3 parts of potassium chloride, 8.3 parts of citric acid, 8.6 parts of anhydrous glucose, 2.0 parts of hydroxypropyl methyl cellulose, 2.05 parts of cross-linked sodium carboxymethyl cellulose and 0.05 part of aspartame;
b: the alkali particle formula is 20 parts:
probiotic bacteria (equivalent to viable count addition of 1 × 10 9 ) 0.5 part of xylo-oligosaccharide, 5 parts of sodium bicarbonate, 0.2 part of hydroxypropyl methyl cellulose, 0.25 part of cross-linked sodium carboxymethyl cellulose, 14 parts of xylitol and 0.05 part of orange essence;
c: 48 parts of modified montmorillonite coating particles;
d: lubricant: and 2 parts of magnesium stearate.
(II) the preparation process comprises the following steps:
(1) pretreatment: passing all the raw and auxiliary materials through a 30-mesh standard sieve for later use;
(2) granulating: acid granulation: mixing the raw materials and auxiliary materials according to the prescription amount, and granulating by low-temperature dry pressing; alkali granulation: mixing the raw materials and auxiliary materials according to the prescription amount, and granulating by low-temperature dry pressing; modified montmorillonite coated particle: mixing the raw materials and the auxiliary materials according to the prescription amount, and preparing by adopting a micro powder coating process;
(3) straightening: granulating the acid granules and the alkali granules after dry pressing, and sieving the granules through 24 meshes and 80 meshes;
(4) total mixing: mixing the acid granules, the alkali granules, the modified montmorillonite coated granules and the lubricant;
(5) making into tablet by conventional method.
(III) examining indexes:
appearance: the particles should be dry, uniform, consistent in color and luster, and free of moisture absorption, softening, deliquescence and the like;
granularity: sieving the total mixed particles in a pharmacopoeia sieve for 3min, wherein the total amount of the powder which can not pass through a No. 2 sieve and can pass through a No. 6 sieve is not more than 8 parts;
loss on drying: detecting the total mixed granules according to a pharmacopoeia method, wherein the total mixed granules can not exceed 2.0%.
Solubility: the test article is taken and heated with 200ml of water, and the effervescent granules can generate carbon dioxide gas immediately when contacting with water and are in an effervescent state.
Release time and content of montmorillonite: the content of the aqueous solution of the product is detected at different time points by adopting a blue absorption method-spectrophotometry, the solution does not adsorb methylene blue at the beginning, an adsorption phenomenon appears after 13min, the modified montmorillonite coated particle begins to release to take effect after 13min, and the content is detected after 30min, so that the content meets the requirement of the formula ratio content.
Example 7
Formula of effervescent preparation of compound oral rehydration salt
The effervescent preparation of the compound oral rehydration salt comprises probiotics 2 multiplied by 10 9 CFU/g, 0.5 part of prebiotics, 10.9 parts of rehydration salt, 39 parts of modified montmorillonite coated particles and 49.6 parts of effervescent auxiliary materials. Specifically, the following components are included;
comprises a fluid infusion salt component: 2.6 parts of sodium chloride, 1.2 parts of potassium chloride, 1.6 parts of citric acid and 5.5 parts of anhydrous glucose.
Comprises the following components of modified montmorillonite coating particles: 24 parts of montmorillonite, 0.5 part of sodium pyruvate, 0.5 part of ethyl cellulose, 0.5 part of chitosan, 0.5 part of acetyl ethyl citrate and 13 parts of PVP-K30.
Comprises the following effervescent auxiliary material components: 7 parts of acid source, 10 parts of alkali source, 22 parts of filler, 5.3 parts of disintegrating agent, 1 part of lubricant, 0.1 part of flavoring agent and 4.2 parts of adhesive.
Wherein, the prebiotics adopts xylo-oligosaccharide, the alkali source adopts sodium bicarbonate, the adhesive adopts hydroxypropyl methylcellulose, the disintegrating agent adopts croscarmellose sodium, the filling agent adopts xylitol, and the flavoring agent adopts aspartame and orange essence.
The prescription raw materials with the specific formula ratio are divided into four parts, namely an acid granule formula, an alkali granule formula, modified montmorillonite coated particles and a lubricant according to the preparation process of the effervescent preparation, and the effervescent preparation specifically comprises the following components:
a: the formula of the acid granules is 20 parts:
2.6 parts of sodium chloride, 1.2 parts of potassium chloride, 7.6 parts of citric acid, 5.5 parts of anhydrous glucose, 1.0 part of hydroxypropyl methylcellulose, 1.05 parts of cross-linked sodium carboxymethylcellulose and 0.05 part of aspartame;
b: the alkali particle formula comprises 40 parts:
probiotic bacteria (equivalent to viable count addition of 1 × 10 9 ) 0.5 part of xylo-oligosaccharide, 10 parts of sodium bicarbonate, 3.2 parts of hydroxypropyl methyl cellulose, 4.25 parts of croscarmellose sodium, 22 parts of xylitol and 0.05 part of sweet orange essence;
c: 39 parts of modified montmorillonite coating particles;
d: lubricant: and 1 part of magnesium stearate.
(II) the preparation process comprises the following steps:
(1) pretreatment: passing all the raw and auxiliary materials through a 30-mesh standard sieve for later use;
(2) and (3) granulating: acid granulation: mixing the raw materials and auxiliary materials according to the prescription amount, and granulating by low-temperature dry pressing; alkali granulation: mixing the raw materials and auxiliary materials according to the prescription amount, and granulating by low-temperature dry pressing; modified montmorillonite coated particle: mixing the raw materials and the auxiliary materials according to the prescription amount, and preparing by adopting a micro powder coating process;
(3) straightening: granulating the acid granules and the alkali granules after dry pressing, and sieving the granules through 24 meshes and 80 meshes;
(4) total mixing: mixing the acid granules, the alkali granules, the modified montmorillonite coated granules and the lubricant;
(5) making into granule by conventional method.
(III) examining indexes:
appearance: the particles should be dry, uniform, consistent in color and luster, and free of moisture absorption, softening, deliquescence and the like;
granularity: sieving the total mixed particles in a pharmacopoeia sieve for 3min, wherein the total amount of the powder which can not pass through a No. 2 sieve and can pass through a No. 6 sieve is not more than 8 parts;
loss on drying: detecting the total mixed granules according to a pharmacopoeia method, wherein the total mixed granules can not exceed 2.0%;
solubility: the test article is taken and heated with 200ml of water, and the effervescent granules can generate carbon dioxide gas immediately when contacting with water and are in an effervescent state.
Release time and content of montmorillonite: the content of the aqueous solution of the product is detected at different time points by adopting a blue absorption method-spectrophotometry, the solution does not adsorb methylene blue at the beginning, an adsorption phenomenon appears after 15min, the modified montmorillonite coated particle begins to release to take effect after 15min, and the content is detected after 30min, so that the content meets the requirement of the formula ratio content.
Example 8
Formula of effervescent preparation of compound oral rehydration salt
The effervescent preparation of the compound oral rehydration salt comprises probiotics of 1 multiplied by 10 9 CFU/g, 0.5 part of prebiotics, 30.9 parts of rehydration salt, 39 parts of modified montmorillonite coated particles and 29.6 parts of effervescent auxiliary materials. Specifically, the following components are included;
comprises a liquid supplementing salt component: 7 parts of sodium chloride, 3 parts of potassium chloride, 3.5 parts of citric acid and 17.4 parts of anhydrous glucose.
Comprises the following components of modified montmorillonite coating particles: 24 parts of montmorillonite, 0.5 part of sodium pyruvate, 0.5 part of ethyl cellulose, 0.5 part of chitosan, 0.5 part of acetyl ethyl citrate and 13 parts of PVP-K30.
Comprises the following effervescent auxiliary material components: 5 parts of acid source, 5 parts of alkali source, 14 parts of filler, 2.3 parts of disintegrating agent, 1 part of lubricant, 0.1 part of flavoring agent and 2.2 parts of adhesive.
Wherein, the prebiotics adopts xylo-oligosaccharide, the alkali source adopts sodium bicarbonate, the adhesive adopts hydroxypropyl methylcellulose, the disintegrating agent adopts croscarmellose sodium, the filling agent adopts xylitol, and the flavoring agent adopts aspartame and orange essence.
The prescription raw materials with the specific formula ratio are divided into four parts, namely an acid granule formula, an alkali granule formula, modified montmorillonite coated particles and a lubricant according to the preparation process of the effervescent preparation, and the effervescent preparation specifically comprises the following components:
a: 40 parts of an acid granule formula:
7 parts of sodium chloride, 3 parts of potassium chloride, 8.5 parts of citric acid, 17.4 parts of anhydrous glucose, 2.0 parts of hydroxypropyl methyl cellulose, 2.05 parts of cross-linked sodium carboxymethyl cellulose and 0.05 part of aspartame;
b: the alkali particle formula is 20 parts:
probiotic (equivalent to viable count addition amount of 1 × 10) 9 ) 0.5 part of xylo-oligosaccharide, 5 parts of sodium bicarbonate, 0.2 part of hydroxypropyl methyl cellulose, 0.25 part of cross-linked sodium carboxymethyl cellulose, 14 parts of xylitol and 0.05 part of orange essence;
c: 39 parts of modified montmorillonite coating particles;
d: lubricant: and 1 part of magnesium stearate.
(II) the preparation process comprises the following steps:
(1) pretreatment: passing all the raw and auxiliary materials through a 30-mesh standard sieve for later use;
(2) and (3) granulating: acid granulation: mixing the raw materials and auxiliary materials according to the prescription amount, and granulating by low-temperature dry pressing; alkali granulation: mixing the raw materials and auxiliary materials according to the prescription amount, and granulating by low-temperature dry pressing; preparing modified montmorillonite coated particles;
(3) straightening: granulating the acid granules and the alkali granules after dry pressing, and sieving the granules through 24 meshes and 80 meshes;
(4) total mixing: mixing the acid granules, the alkali granules, the modified montmorillonite coated granules and the lubricant;
(5) making into effervescent granule by conventional method.
(III) examining indexes:
appearance: the particles should be dry, uniform, consistent in color and luster, and free of moisture absorption, softening, deliquescence and the like;
granularity: sieving the total mixed particles in a pharmacopoeia sieve for 3min, wherein the total amount of the powder which can not pass through a No. 2 sieve and can pass through a No. 6 sieve is not more than 8 parts;
loss on drying: detecting the total mixed particles according to a pharmacopeia method, wherein the total mixed particles are not more than 2.0%;
solubility: the test article is taken and heated with 200ml of water, and the effervescent granules can generate carbon dioxide gas immediately when contacting with water and are in an effervescent state.
Release time and content of montmorillonite: the content of the aqueous solution of the product is detected at different time points by adopting a blue absorption method-spectrophotometry, the solution does not adsorb methylene blue at the beginning, an adsorption phenomenon appears after 13min, which shows that the modified montmorillonite coated particles begin to release and take effect after 13min, and the content is detected after 30min, thus meeting the content requirement of the prescription.
Test experiments
Purpose of the experiment: analyzing the disintegration property and the stability of the effervescent preparation of the compound oral rehydration salt
The experimental method comprises the following steps:
referring to 2020 edition of Chinese pharmacopoeia, 0921 general rule disintegration time limit inspection method;
referring to national standard bentonite GB/T20973-2007, the content detection of different time points is carried out on the aqueous solution of the product by adopting a blue absorption method-spectrophotometry method;
referring to the 2020 edition of Chinese pharmacopoeia, the experimental principle of the stability guidance of raw material medicaments and preparations, the medicament preparation, the accelerated test, the storage for 6 months under the conditions of the temperature of 30 ℃ plus or minus 2 ℃ and the relative humidity of 65 percent plus or minus 5 percent;
subject: the effervescent preparation of the compound oral rehydration salt prepared in embodiments 1-8 of the invention;
the experimental results are as follows: as shown in the following table 1, the disintegration time limits of the examples 1-8 are respectively 4.5min, 3min, 2min, 1min, 3min, 2.5min and 4min, the disintegration speed is high and is less than 5min, and the requirements of the effervescent granules are met; meanwhile, through detection of the solution at different times, the modified montmorillonite coated particles in the embodiments 1-8 are not released within 15min, are released after 15min and are all released after 30min, so that the purpose of delaying release is achieved; all indexes in a stability investigation experiment have no obvious change, which shows that the effervescent granule has good stability.
TABLE 1 Experimental results of effervescent granules and effervescent tablets of compound oral rehydration salt
Figure 466392DEST_PATH_IMAGE001
According to the detection data, the oral rehydration salt probiotic effervescent preparation is prepared by keeping the activity of the original raw materials, the effervescent preparation generates carbon dioxide when meeting water, so that the medicine is quickly disintegrated, the contained medicinal components can be quickly dissolved, and the quick and heavy patients needing quick effect can be effectively treated and relieved symptoms in time; secondly, the preparation is especially suitable for children, the elderly and patients who have difficulty in taking pills, and is convenient to carry and use.
The embodiments of the present invention have been described in detail, but the embodiments are merely examples, and the present invention is not limited to the embodiments described above. Any equivalent modifications and substitutions to those skilled in the art are also within the scope of the present invention. Accordingly, equivalent changes and modifications made without departing from the spirit and scope of the present invention should be covered by the present invention.

Claims (3)

1. The effervescent preparation of the compound oral rehydration salt which can be taken with the pharmaceutical preparation simultaneously is characterized in that the effervescent preparation of the compound oral rehydration salt is prepared by 1 multiplied by 10 probiotics 9 CFU/g, 0.1 part of prebiotics, 10.9 parts of rehydration salt, 58 parts of modified montmorillonite coated particles and 31 parts of effervescent auxiliary materials:
the liquid supplementing salt comprises the following components: 2.6 parts of sodium chloride, 1.2 parts of potassium chloride, 1.6 parts of citric acid and 5.5 parts of anhydrous glucose;
the modified montmorillonite coated particle comprises the following components: 34.5 parts of montmorillonite, 1.5 parts of sodium pyruvate, 0.5 part of ethyl cellulose, 0.5 part of chitosan, 1 part of citric acid acetyl ethyl ester and 20 parts of PVP-K30;
the effervescent auxiliary material comprises the following components: 5 parts of acid source, 5 parts of alkali source, 14 parts of filler, 2.7 parts of disintegrating agent, 2 parts of lubricant, 0.1 part of flavoring agent and 2.2 parts of adhesive;
wherein the prebiotics is xylo-oligosaccharide, the alkali source is sodium bicarbonate, the binder is hydroxypropyl methylcellulose, the disintegrant is croscarmellose sodium, the filler is xylitol, and the flavoring agent is aspartame and orange essence;
the prescription raw materials of the formula ratio are divided into four parts, namely an acid granule formula, an alkali granule formula, a modified montmorillonite coated granule and a lubricant according to the preparation process of the effervescent preparation, and the formula comprises the following components:
a: the formula of the acid granules is 20 parts:
2.6 parts of sodium chloride, 1.2 parts of potassium chloride, 6.6 parts of citric acid, 5.5 parts of anhydrous glucose, 1.75 parts of hydroxypropyl methylcellulose, 2.3 parts of croscarmellose sodium and 0.05 part of aspartame;
b: the alkali particle formula is 20 parts:
equivalent to viable count of 1 × 10 9 CFU/g probiotics, 0.1 part of xylo-oligosaccharide, 5 parts of sodium bicarbonate, 0.45 part of hydroxypropyl methyl cellulose, 0.4 part of cross-linked sodium carboxymethyl cellulose, 14 parts of xylitol and 0.05 part of orange essence;
c: 58 parts of modified montmorillonite coating particles;
d: lubricant: 2 parts of magnesium stearate;
the effervescent preparation of the compound oral rehydration salt is prepared from the acid granule formula, the alkali granule formula, the modified montmorillonite coated granules and the lubricant by adopting the following processes:
(1) pretreatment: passing all the raw and auxiliary materials through a 30-mesh standard sieve for later use;
(2) granulating: acid granulation: mixing the raw materials and auxiliary materials according to the prescription amount, and granulating by low-temperature dry pressing; alkali granulation: mixing the raw materials and auxiliary materials according to the prescription amount, and granulating by low-temperature dry pressing; modified montmorillonite coated particle: mixing the raw materials and the auxiliary materials according to the prescription amount, and preparing by adopting a micro powder coating process;
(3) straightening: granulating the acid granules and the alkali granules after dry pressing, and sieving the granules through 24 meshes and 80 meshes;
(4) total mixing: mixing the acid granules, the alkali granules, the modified montmorillonite coated granules and the lubricant;
(5) making into tablet by conventional method;
wherein, the preparation method of the modified montmorillonite coated particle comprises the following steps:
firstly, montmorillonite micropowder in a formula ratio is prepared according to the mass ratio of 1: 5 dispersing in an acetone solution to form a solution A, and mixing sodium pyruvate according to a mass ratio of 1:2 dissolving in pure ethanol to form a solution B;
adding the solution B into the solution A, adding ethyl cellulose in a formula ratio, uniformly stirring, performing ultrasonic dispersion for 15-20min, and drying in a spray dryer at the drying temperature of 60-65 ℃ to obtain modified primary coating micro powder;
finally, dissolving the deacetylated derivatives chitosan, acetyl triethyl citrate and PVP-K30 in the formula ratio by using 70-80% ethanol, then carrying out secondary coating on the primary coated micro powder, continuously drying after coating, drying until the water content is below 6%, and sieving by using a 100-mesh sieve to obtain the chitosan/triethyl citrate composite micro powder.
2. The effervescent formulation of the combination oral rehydration salt of claim 1, wherein the probiotic comprises one or more of Bifidobacterium, Lactobacillus, Streptococcus, enterococcus, Saccharomyces, Clostridium, and Bacillus.
3. Use of an effervescent formulation of the compound oral rehydration salt of any of claims 1 to 2 in the manufacture of a medicament or health product for the amelioration of the treatment of diarrhea.
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