Montmorillonite-containing tablet-shaped composition and preparation method thereof

Abstract

The invention discloses a montmorillonite-containing tablet-shaped composition and a preparation method thereof. The montmorillonite-containing tablet-shaped composition comprises the following components in percentage by weight: 50%-90% of montmorillonite, 2%-40% of a soluble auxiliary material, 0.5%-5% of a flavoring agent auxiliary material, 0.5%-1.5% of essence, 0.5%-1.5% of a lubricant and 5%-15% of purified water. Compared with the prior art, the traditional Chinese medicine composition has the advantages that the composition of auxiliary materials is simple, the use is safer and more convenient, and the traditional Chinese medicine composition can be taken by infants below 1 year old; the tablet is stable in quality, rapid in disintegration, uniform in dispersion, easy to master in dosage, convenient to transport and carry and relatively good in palatability; meanwhile, the preparation is prepared by adopting a traditional tabletting technology, and the method is simple, convenient to operate, low in production cost and suitable for industrial mass production.

Description

Technical Field

[0001] The invention relates to the technical field of biomedicine, in particular to a composition in the shape of montmorillonite tablets and a preparation method thereof. Background Art

[0002] Montmorillonite is a typical sandwich structure with strong adsorption and ion exchange capacity. In the formation of montmorillonite ore, due to external factors, the trivalent aluminum ions in some octahedral alumina are replaced by low-valent cations of calcium and magnesium, resulting in uneven distribution of charge. The basic layer is negatively charged, and the interlayer is positively charged. This uneven charge makes montmorillonite have a very strong electrostatic adsorption capacity. Montmorillonite powder has viscoplasticity in liquid medium, and the basic layers can slide open, increasing the mucosal coverage area of ​​montmorillonite powder, and the layers will not be scattered and separated, so that montmorillonite has continuity in mucosal coverage. The strong electrostatic adsorption capacity and viscoplasticity of montmorillonite can adsorb and remove a variety of viruses, bacteria and their toxins, improve the quality and quantity of digestive tract mucus, strengthen the function of mucosal barrier, promote the repair and regeneration of digestive tract epithelial cells, support normal flora, and ensure that the intestinal mucosa avoids the invasion of pathogenic bacteria and viruses, and maintains normal metabolic function.

[0003] The montmorillonite preparations currently on the market are mainly montmorillonite powders, which have a serious problem of flying after unpacking, which is not conducive to dividing the dose; they have a gritty and earthy smell when taken, have poor palatability, and poor patient compliance. Therefore, other dosage forms such as montmorillonite suspension, montmorillonite dispersible tablets, and montmorillonite granules have been developed on the market, but different dosage forms also have some disadvantages:

[0004] Montmorillonite suspension

[0005] The preparation process of montmorillonite suspension is disclosed in Chinese patent applications CN108721325A, CN109414407B and CN116077437A. A large amount of suspending agents are added to the prescriptions. Antibacterial agents are also added to CN108721325A and CN109414407B. Although CN116077437A adopts low-temperature heat sterilization combined with cold sterilization to replace preservatives, non-ionic polymer suspending agents are used in combination with low-temperature degassing dispersion to suspend montmorillonite, the preparation process is complicated and the production cost is high.

[0006] Montmorillonite Dispersible Tablets

[0007] Chinese patent application CN1698648A discloses a dispersible tablet of montmorillonite and its preparation process, which is composed of montmorillonite, a filler and a disintegrant. Chinese patent application CN104055793A discloses a dispersible tablet of iron-based montmorillonite and its preparation method, which is composed of an iron-based montmorillonite drug and excipients, wherein the excipients mainly include a filler, a disintegrant, a lubricant, and an adhesive, and an antioxidant is added to play an antioxidant role. Although the dispersible tablet can disintegrate quickly, the dosage is easy to control, and it is convenient to transport and carry, the preparation contains a large amount of water-insoluble excipients, the composition is complex, and its palatability is poor;

[0008] Montmorillonite particles

[0009] Chinese patent application CN112386607A discloses a method for preparing montmorillonite particles, which includes the following steps: a. weigh the following raw materials in proportion: montmorillonite 2800-3200g; sucrose 900-1100g; sucralose 5-12g; essence 15-25g; b. crush the sucrose and pass it through an 80-mesh sieve; c. mix the sucrose, montmorillonite, sucralose and essence evenly, and put them into a dry granulator for granulation; d. perform quality inspection on the obtained montmorillonite particles. A large amount of sucrose is used in the preparation of the particles, and it is not easy for children and diabetic patients to use this product; the dry granulation process has high requirements on equipment, is difficult, and has high production costs; and the redispersibility of the preparation is poor when the particles are taken. Summary of the invention

[0010] The technical problem to be solved by the present invention is to overcome the above technical defects and provide a composition and preparation method of a montmorillonite dry suspension (tablet type) for children for treating acute and chronic diarrhea and gastritis, which has scientific and reasonable material compatibility, simple preparation method, convenient administration, good patient compliance and good therapeutic effect. The medicament is not only convenient and safe to take, but also has low production process difficulty and low cost.

[0011] In order to solve the above problems, the technical solution of the present invention is: a composition in the shape of montmorillonite tablets, calculated by content percentage: the suspension contains 50%-90% montmorillonite, 2%-40% soluble excipients, 0.5%-5% flavoring excipients, 0.5%-1.5% flavors, 0.5%-1.5% lubricants and 5%-15% purified water.

[0012] Further: the montmorillonite content is preferably 70-85%.

[0013] Further: the soluble auxiliary material is preferably mannitol, which can be one or more of soluble auxiliary materials such as sorbitol, xylitol, glucose, sucrose, etc., and the dosage is preferably 10-14%.

[0014] Furthermore: the flavoring auxiliary material is preferably a combination of a sweetener sucralose and an acidulant citric acid, and can also be one or more of other sweeteners such as acesulfame potassium, saccharin sodium, aspartame or other edible acids such as malic acid, lactic acid, tartaric acid, etc. The amount of the acidulant is preferably 0.3-2.5%, and the amount of the sweetener is 0.2-2.5%.

[0015] Further: the flavor can be selected from strawberry flavor, citrus flavor, peach flavor, preferably strawberry flavor which is easily accepted by children, and the preferred dosage is 0.8-1.5%.

[0016] Furthermore: the lubricant can be selected from one or more of the commonly used lubricants for tablets, such as magnesium stearate, talc, and stearic acid, and the amount used is preferably 0.8-1.5%.

[0017] Furthermore: the purified water is used as a wetting agent and a binder, and can prevent tablets from cracking during placement. The preferred amount is 7-12%.

[0018] Furthermore: 75-85% of montmorillonite, 11-13% of mannitol, 0.3-0.4% of sucralose, 1.8-2.2% of citric acid, 0.9-1.1% of strawberry flavor, 0.9-1.1% of magnesium stearate and 7-9% of purified water.

[0019] A method for preparing a composition in the form of montmorillonite tablets, comprising the following preparation method:

[0020] Step 1: Pass the above raw materials through a 80-100 mesh sieve;

[0021] Step 2: premix the above raw materials and add the weighed soluble auxiliary materials and montmorillonite into a wet mixing granulator, and the order of adding materials is: part of montmorillonite (1 / 2 of the total content of montmorillonite), soluble auxiliary materials, part of montmorillonite (1 / 2 of the total content of montmorillonite);

[0022] Step 3: Granulation, first prepare the wetting agent, weigh the prescribed amount of purified water into a clean stainless steel barrel, add the weighed flavoring agent (such as sucralose, citric acid) into the purified water, stir to dissolve, and set aside, add slurry: turn on the wet granulator at speed I stirring and speed I cutting state, add the wetting agent to the montmorillonite premixed powder by atomization, after the wetting agent is completely added, mix for 90-240s and stop, take samples, and use a rapid moisture meter to measure the moisture content of the particles (7% to 12%), and discharge the material after it is qualified;

[0023] Step 4: Granulation: Install an 80-mesh stainless steel screen on the swing granulator, and use the swing granulator to granulate the wet granules. The wet granules should have uniform particle size.

[0024] Step 5: Whole granulation and total mixing. Add the prescribed amount of strawberry essence to the granules after whole granulation and put them into the mixer for mixing for 3-5 minutes. Then add the prescribed amount of magnesium stearate and mix for 3-5 minutes. After mixing, take samples and control the moisture range: 7% to 12%. Discharge the materials after they are qualified and open the discharge port to discharge the materials.

[0025] Step 6: Take the montmorillonite dry suspension granules that have passed the inspection, install the appropriate punch and die, add the granules into the barrel of the tablet press, calculate the theoretical tablet weight according to the total mixed granule content, adjust the tablet weight and pressure, test the pressure, check the appearance, weight difference, hardness, and friability, and then start tableting;

[0026] Step 7: The inner packaging adopts the ordinary tablet packaging form, medicinal aluminum foil + PVC, and the outer packaging adopts polyester / aluminum / polyethylene medicinal composite bag packaging, and then packed into boxes.

[0027] Further: the total montmorillonite content in step 2 is equal to the montmorillonite content required to be added.

[0028] The advantages of the present invention compared with the prior art are:

[0029] 1. The composition in the form of montmorillonite tablets of the present invention has stable quality (water content is low at 7% to 12%), rapid disintegration (disintegration time is 20s to 60s) and uniform dispersion, a particle size equivalent to that of a powder, no gritty feeling or earthy smell, and better palatability.

[0030] The use of water-soluble excipients in the prescription can quickly open up the water channels inside the tablet. In addition, the water absorption and expansion characteristics of montmorillonite allow water to quickly enter the tablet and quickly disintegrate and disperse. The particle size is strictly controlled during the granulation process to reduce the gritty feeling in the mouth.

[0031] The prescription composition comprises montmorillonite, soluble auxiliary materials, flavoring agents (sweeteners and acidulants), essences, lubricants, and purified water. Less auxiliary materials are used to achieve the best taste. When treating diarrhea, the composition can be dispersed into a suspension with water externally and then taken orally, or dispersed into a suspension with water in the oral cavity and then swallowed; it can also be chewed or held in the mouth without drinking water.

[0032] 2. Easy to divide the dose, convenient to transport and carry; according to the usage and dosage, when children aged 2 years and below take 1g of montmorillonite each time, the dose is more accurate and more convenient to take (children aged 2 years and above can chew it, and infants under 2 years old can take it with a small amount of water). This product is in the form of a 1g tablet, and the user does not need to divide the dose again; the preparation is packaged in ordinary tablets, which is more convenient to transport and carry.

[0033] 3. The process preparation method is simple, easy to operate, and has low production cost, which is suitable for large-scale industrial production. This product adopts conventional tablet preparation technology, strictly controls the amount of binder / wetting agent (water) added, and does not need to be dried after granulation. The whole granules can be directly mixed and tableted. DETAILED DESCRIPTION

[0034] In order to make the contents of the present invention more clearly understood, the technical solutions in the embodiments of the present invention will be clearly and completely described below in combination with the embodiments of the present invention.

[0035] A composition in the form of montmorillonite tablets, calculated by percentage: the suspension contains 50%-90% montmorillonite, 2%-40% soluble auxiliary materials, 0.5%-5% flavoring auxiliary materials, 0.5%-1.5% flavor, 0.5%-1.5% lubricant and 5%-15% purified water.

[0036] The montmorillonite content is preferably 70-85%, and the soluble auxiliary material is preferably mannitol, which can be one or more soluble auxiliary materials such as sorbitol, xylitol, glucose, sucrose, etc., and the dosage is preferably 10-14%.

[0037] The flavoring auxiliary material is preferably a combination of a sweetener sucralose and an acidulant citric acid, and may also be one or more of other sweeteners such as acesulfame potassium, saccharin sodium, aspartame or other edible acids such as malic acid, lactic acid, tartaric acid, etc. The amount of the acidulant is preferably 0.3-2.5%, and the amount of the sweetener is 0.2-2.5%.

[0038] The flavor can be powdered flavors such as strawberry flavor, citrus flavor, peach flavor, etc., preferably strawberry flavor that is easily accepted by children, and the preferred dosage is 0.8-1.5%.

[0039] The lubricant can be selected from one or more of the commonly used lubricants for tablets, such as magnesium stearate, talc, and stearic acid, and the amount used is preferably 0.8-1.5%.

[0040] The purified water is used as a wetting agent and a binder, and can also prevent tablets from cracking during placement. The preferred amount is 7-12%.

[0041] The prescription can include 75-85% montmorillonite, 11-13% mannitol, 0.3-0.4% sucralose, 1.8-2.2% citric acid, 0.9-1.1% strawberry flavor, 0.9-1.1% magnesium stearate and 7-9% purified water.

[0042] A method for preparing a composition in the form of montmorillonite tablets, comprising the following preparation method:

[0043] Step 1: Pass the above raw materials through a 80-100 mesh sieve;

[0044] Step 2: premix the above raw materials and add the weighed mannitol and montmorillonite into a wet mixing granulator in the following order: montmorillonite (1 / 2 of the total amount), mannitol, and montmorillonite (1 / 2 of the total amount);

[0045] Step 3: Granulation, first prepare the wetting agent, weigh the prescribed amount of purified water into a clean stainless steel barrel, add the weighed sucralose and citric acid into the purified water, stir to dissolve, and set aside, add slurry: turn on the wet granulator at speed I stirring and speed I cutting state, add the wetting agent to the mixed powder of montmorillonite and mannitol by atomization, after the wetting agent is completely added, mix for 120s and stop, take samples, and measure the moisture content of the particles (7% to 12%) with a rapid moisture meter, and discharge the material after passing the test. The wetting agent in step 3 is added by atomization;

[0046] Step 4: Granulation: Install an 80-mesh stainless steel screen on the swing granulator, and use the swing granulator to granulate the wet granules. The wet granules should have uniform particle size. The mesh number of the granules sieved in step 4 should be ≥80 mesh standard sieve;

[0047] Step 5: Blend the whole granules. Add the prescribed amount of strawberry essence to the granules after granulation and put them into the mixer for 5 minutes. Then add the prescribed amount of magnesium stearate and mix for 3 minutes. Take samples after mixing to control the moisture range: 7% to 12%. Discharge the materials after they are qualified. Open the discharge port to discharge the materials. The moisture content of the total mixed granules in step 5 should be controlled at 7% to 12%;

[0048] Step 6: Take the montmorillonite dry suspension granules that have passed the inspection, install appropriate punches and dies, add the granules into the barrel of the tablet press, calculate the theoretical tablet weight according to the total mixed particle content, adjust the tablet weight and pressure, test the pressure, check the appearance, weight difference, hardness, and friability, and start tableting after passing the test. The punch die is strawberry-shaped;

[0049] Step 7: The inner packaging adopts the ordinary tablet packaging form, medicinal aluminum foil + PVC, and the outer packaging adopts polyester / aluminum / polyethylene medicinal composite bag packaging, and then packed into boxes.

[0050] Furthermore, during the tableting process in step 6, the average tablet weight and hardness are checked and recorded every 30 minutes, and 20 tablets are sampled every 30 minutes to check and record the weight of each tablet (the allowable range of tablet weight: ±4%, the allowable range of hardness: 6-15 kgf).

[0051] In specific use, Example 1 and Example 2 are selected for supplementary explanation. Example 1 is 50% montmorillonite, 38% mannitol, 1.2% citric acid, 0.3% sucralose, 0.5% strawberry powder flavor, 0.5% magnesium stearate and 9.5% purified water. The above preparation method is used to prepare tablets with smooth and delicate texture, uniform color, no cracks, no sticking, and no loose tablets. The average tablet weight is ±4% of the tablet weight, the weight difference is ±4%, the friability is ≤1%, and the hardness is 6 to 15 kgf.

[0052] Example 2 is 90% montmorillonite, 2% mannitol, 1.6% citric acid, 0.4% sucralose, 0.5% strawberry powder flavor, 0.5% magnesium stearate and 5% purified water. The above preparation method is used to prepare tablets with smooth and delicate texture, uniform color, no cracks, no sticking, and no loose tablets. The average tablet weight is ±4% of the tablet weight, the weight difference is ±4%, the friability is ≤1%, and the hardness is 6 to 15 kgf.

[0053] Mannitol is mainly used as a diluent because it has a negative heat of solution, a sweet taste, and a refreshing feel.

[0054] Citric acid, also known as citric acid, is an edible acid that can stimulate the secretion of saliva in the mouth and accelerate the softening and dispersion of this product.

[0055] Sucralose: commonly known as sucralose, is a high-intensity sweetener with high stability. Its sweetness duration and aftertaste are very close to sucrose. It has a diluting effect on sour and salty tastes, a masking effect on astringent, bitter, alcoholic tastes, and a synergistic effect on spicy and milky tastes. It does not participate in metabolism in the human body, is not absorbed by the human body, and has a zero calorie value. It is an ideal sweetener for diabetics. In addition, sucralose has an anti-caries effect. Therefore, the addition of sucralose can be used for diabetics and children.

[0056] Purified water: The amount of purified water used was determined through process research. The tablets produced have good formability and all test indicators meet the quality standards. If the amount of water is increased, the granules will be larger and there will be a gritty feeling when taking the tablets; if the amount of water is less, the tablets will easily break and will be difficult to produce and transport.

[0057] The sweet and sour taste combination of citric acid and sucralose is the best, and mannitol adds a refreshing feeling.

[0058] In the specific operation process, there is the following comparative process. In comparative example 1, the ingredients mainly include 40% montmorillonite, 50% mannitol, 1.2% citric acid, 0.3% sucralose, 0.5% strawberry powder flavor, 0.5% magnesium stearate and 7.5% purified water. Under the same preparation process, the tablets of the present invention with the same ingredient ratio are larger, with more auxiliary materials and high cost. During the storage process, there will be a problem of cracking. The specific cracking situation is cracking.

[0059] The present invention and its implementation methods are described above, and such description is not restrictive. In short, if a person skilled in the art is inspired by it and, without departing from the purpose of the invention, designs structures and embodiments similar to the technical solution without creativity, they should all fall within the protection scope of the present invention.

Claims

1. A composition in the form of montmorillonite tablets, characterized in that: Calculated by percentage, the suspension contains 50%-90% montmorillonite, 2%-40% soluble auxiliary materials, 0.5%-5% flavoring auxiliary materials, 0.5%-1.5% essence, 0.5%-1.5% lubricant and 5%-15% purified water.

2. The composition in the form of montmorillonite tablets according to claim 1, characterized in that: The montmorillonite content is preferably 70-85%.

3. The composition in the form of montmorillonite tablets according to claim 1, characterized in that: The soluble auxiliary material is preferably mannitol, which can be one or more of soluble auxiliary materials such as sorbitol, xylitol, glucose, sucrose, etc., and the dosage is preferably 10-14%.

4. The composition in the form of montmorillonite tablets according to claim 1, characterized in that: The flavoring auxiliary material is preferably a combination of a sweetener sucralose and an acidulant citric acid, and may also be one or more of other sweeteners such as acesulfame potassium, saccharin sodium, aspartame or other edible acids such as malic acid, lactic acid, tartaric acid, etc. The amount of the acidulant is preferably 0.3-2.5%, and the amount of the sweetener is 0.2-2.5%.

5. The composition in the form of montmorillonite tablets according to claim 1, characterized in that: The flavor can be selected from strawberry flavor, citrus flavor, peach flavor, preferably strawberry flavor which is easily accepted by children, and the preferred dosage is 0.8-1.5%.

6. The composition in the form of montmorillonite tablets according to claim 1, characterized in that: The lubricant can be selected from one or more of the commonly used lubricants for tablets, such as magnesium stearate, talc, and stearic acid, and the amount used is preferably 0.8-1.5%.

7. The composition in the form of montmorillonite tablets according to claim 1, characterized in that: The purified water is used as a wetting agent and a binder, and can also prevent tablets from cracking during placement. The preferred amount is 7-12%.

8. The composition in the form of montmorillonite tablets according to claim 1, characterized in that: The montmorillonite comprises 75-85%, mannitol 11-13%, sucralose 0.3-0.4%, citric acid 1.8-2.2%, strawberry flavor 0.9-1.1%, magnesium stearate 0.9-1.1% and purified water 7-9%.

9. The method for preparing a composition in the form of montmorillonite tablets according to claim 1, characterized in that: The invention comprises the following preparation methods: Step 1: Pass the above raw materials through a 80-100 mesh sieve; Step 2: premix the above raw materials and add the weighed soluble auxiliary materials and montmorillonite into a wet mixing granulator, and the order of adding materials is: part of montmorillonite (1 / 2 of the total content of montmorillonite), soluble auxiliary materials, part of montmorillonite (1 / 2 of the total content of montmorillonite); Step 3: Granulation, first prepare the wetting agent, weigh the prescribed amount of purified water into a clean stainless steel barrel, add the weighed flavoring agent (such as sucralose, citric acid) into the purified water, stir to dissolve, and set aside, add slurry: turn on the wet granulator at speed I stirring and speed I cutting state, add the wetting agent to the montmorillonite premixed powder by atomization, after the wetting agent is completely added, mix for 90-240s and stop, take samples, and use a rapid moisture meter to measure the moisture content of the particles (7% to 12%), and discharge the material after it is qualified; Step 4: Granulation: Install an 80-mesh stainless steel screen on the swing granulator, and use the swing granulator to granulate the wet granules. The granule size should be uniform. Step 5: Whole granulation and total mixing. Add the prescribed amount of strawberry essence to the granules after whole granulation and put them into the mixer for mixing for 3-5 minutes. Then add the prescribed amount of magnesium stearate and mix for 3-5 minutes. After mixing, take samples and control the moisture range: 7% to 12%. Discharge the materials after they are qualified and open the discharge port to discharge the materials. Step 6: Take the montmorillonite dry suspension granules that have passed the inspection, install the appropriate punch and die, add the granules into the barrel of the tablet press, calculate the theoretical tablet weight according to the total mixed granule content, adjust the tablet weight and pressure, test the pressure, check the appearance, weight difference, hardness, and friability, and then start tableting; Step 7: The inner packaging adopts the ordinary tablet packaging form, medicinal aluminum foil + PVC, and the outer packaging adopts polyester / aluminum / polyethylene medicinal composite bag packaging, and then packed into boxes.

10. The method for preparing a composition in the form of montmorillonite tablets according to claim 1, characterized in that: The total montmorillonite content described in step 2 is equal to the montmorillonite content required to be added.