Chewable tablet containing ginseng, codonopsis pilosula and radix glehniae and preparation method of chewable tablet

Abstract

The invention provides a ginseng, codonopsis pilosula and radix glehniae chewable tablet capable of improving the immunity of a human body, and particularly relates to a chewable tablet containing ginseng, codonopsis pilosula and radix glehniae and a preparation method of the chewable tablet, the stability of a chewable tablet preparation is improved and the yield of a product is increased by optimizing the prescription composition and particularly controlling the selection and dosage of a filling agent in the chewable tablet; the waste of raw materials is reduced; the taste of the chewable tablet is improved by controlling the selection and dosage of the flavoring agent in the chewable tablet; besides, according to the preparation method of the chewable tablet, the product yield is improved by optimizing a raw material extraction process and an auxiliary material adding mode, and the chewable tablet is more suitable for industrial production.

Description

Technical Field

[0001] The invention belongs to the field of pharmaceutical preparations, and specifically relates to chewable tablets containing ginseng, codonopsis pilosula, and northern adenophora and a preparation method thereof, and in particular to a chewable tablet capable of improving human immunity and a preparation method thereof. Background Art

[0002] According to the survey, 60% of the middle-aged and elderly people in the country suffer from insomnia, dreaminess, difficulty falling asleep or daytime dozing, 62% suffer from backaches, 58% suffer from fatigue, and 48% suffer from bad temper or anxiety. These problems are often caused by the breakdown of their immune balance and low immunity. Low immunity provides opportunities for diseases and viruses to invade, seriously affecting the quality of life of individuals and bringing immeasurable burdens to families and society. Therefore, low immunity must be given enough attention. At present, the market for traditional Chinese medicine that helps to enhance the immune function of the human body is constantly expanding. In today's era of high-speed development, people's bodies and minds are more likely to feel tired. Whether it is physical fatigue or mental fatigue, people will show emotions such as irritability. These problems are ultimately caused by low immunity, so traditional Chinese medicine and health products that improve immunity are a must-have for many people today.

[0003] CN112430514A discloses a kind of anti-fatigue and immunity-enhancing medicinal wine and its preparation method, including: first ingredient: 3-6 parts of buffalo horn, 2-5 parts of deer antler, 4-7 parts of turtle shell, 1-3 parts of bezoar, 3-6 parts of earthworm, second ingredient: 2-6 parts of ginseng, 7-10 parts of ophiopogon, 4-9 parts of polygonatum, third ingredient: 6-9 parts of longan, 5-10 parts of gentian, 5-9 parts of wolfberry, 500-1000 parts of sorghum wine. The product fully extracts the effective ingredients of these medicinal materials through sorghum wine, so that the efficacy of each drug produces a synergistic effect, thereby playing the effect of invigorating the middle and replenishing qi, strengthening the body, but the invention does not consider the needs of people who are allergic to alcohol or people who are not used to the taste of alcohol, and a variety of precious ingredients / medicinal materials are used in the medicinal wine, which is costly and has low accessibility.

[0004] CN107375509B discloses a composition for improving immunity, characterized in that: expressed in parts by weight, the product is composed of 100-300 parts of raw edible fungus polysaccharide, 1500-3500 parts of honeysuckle extract, 280-480 parts of houttuynia cordata extract, 500-700 parts of dandelion extract, 500-1000 parts of ginseng extract and 60-90 parts of selenium-enriched edible fungus powder. It involves multiple extracts, each of which uses a different process flow, is time-consuming to prepare, and has low yield efficiency.

[0005] CN108065391A discloses a composition for improving immunity, which is composed of 26%-28% of Codonopsis pilosula, 12%-14% of deer medicine, 16%-18% of fenugreek, 15%-17% of lily, 14%-16% of oyster, and 11%-13% of Glehnia littoralis. The raw materials are extracted and powdered, mixed and granulated, and finally made into capsules for consumption. The product does not take into account people with dysphagia and is not convenient to use during travel.

[0006] Therefore, there is still a need to develop a product that is easy to carry, convenient to take, has a good taste, high stability, simple process, and is suitable for industrial production and can improve immunity, so as to effectively solve the above problems. Summary of the invention

[0007] The invention provides a chewable tablet containing ginseng, codonopsis pilosula and northern adenophora and a preparation method thereof.

[0008] This product uses ginseng, northern adenophora and codonopsis as raw materials to make chewable tablets with the function of improving immunity. The polysaccharides and saponins contained in the raw materials are the main ingredients of the product for enhancing immunity. The combination is reasonable, safe and effective.

[0009] Ginseng has always been called the "king of Chinese medicine". It has been recorded in the "Shennong's Herbal Classic" and listed as a top-grade product. It is believed that ginseng "mainly nourishes the five internal organs, stabilizes the spirit, stabilizes the soul, stops panic, removes evil spirits, improves eyesight, makes people happy and improves intelligence, and long-term use makes the body light and prolongs life". Zhang Zhongjing's "Treatise on Febrile Diseases" contains a total of 113 prescriptions, of which 21 are compatible with ginseng, and discusses that ginseng has the effects of "warming, nourishing, strengthening, strengthening essence, keeping warm, enhancing vision, and stabilizing the spirit". "Compendium of Materia Medica" records that "ginseng can cure all deficiency syndromes of men and women, fever and spontaneous sweating, dizziness and headache, nausea and vomiting, malaria, diarrhea and chronic dysentery, frequent urination, dripping, fatigue and internal injuries, stroke, heatstroke, fistula, vomiting blood, coughing up blood, bleeding, hematuria, hemorrhage, and various diseases before and after pregnancy." In modern Chinese medicine, ginseng is often used to replenish qi and rescue people from collapse, invigorate qi and restore pulse, nourish the heart and calm the mind, promote fluid production and quench thirst, nourish the lungs and calm asthma, strengthen the spleen and stop diarrhea, and expel toxins and heal sores.

[0010] The shape of the Radix Adenophorae is slender, the texture is firm and dense; it tastes sweet, slightly bitter, and slightly cold. Sweetness replenishes yang, and slightly bitterness replenishes yin. It is not very bitter, but has a cold nature. It has a light and clear body and a light smell. It has a light and floating nature. It belongs to the lung and stomach meridians, so it is specialized in the middle and upper Jiao, the lungs and stomach, clearing the heat of the lungs and stomach, nourishing the yin of the lungs and stomach, and has a good function of invigorating qi. Modern research has shown that the Radix Adenophorae contains coumarin components, which have a pungent and dispersing effect, and has the characteristics of "unblocking without dryness, moisturizing without stagnation".

[0011] Codonopsis pilosula is a medicinal material included in the Chinese Pharmacopoeia. It is the dried root of Codonopsis pilosula, Codonopsis pilosula or Codonopsis pilosula of the Campanulaceae family. Codonopsis pilosula is mild in nature, sweet in taste, and enters the spleen and lung meridians. It has the effects of strengthening the spleen and lungs, nourishing blood and producing body fluid. It is often used for symptoms such as spleen and lung qi deficiency, poor appetite and fatigue, cough and asthma, qi and blood deficiency, sallow complexion, palpitations and shortness of breath, thirst due to loss of body fluid, and internal heat and thirst.

[0012] In the formula, ginseng tastes sweet, slightly bitter, and is neutral. It enters the spleen, lung, and heart meridians. It can greatly replenish vital energy, restore the pulse and consolidate the body, replenish the spleen and benefit the lungs, produce body fluids, and calm the mind. It is the first medicine for replenishing qi and is the main raw material in the formula. Codonopsis pilosula is sweet, neutral, and enters the spleen and lung meridians. It strengthens the spleen and benefits the lungs, nourishes blood and produces body fluids, and helps ginseng replenish qi, strengthen the spleen and benefit the lungs. Adenophora australis tastes sweet and slightly cold. It enters the lung and stomach meridians. It nourishes yin and clears the lungs, benefits the stomach and produces body fluids, and assists ginseng in replenishing lungs and producing body fluids. The combination of the raw materials in the formula can not only replenish qi and benefit the lungs, nourish blood and produce body fluids, but also nourish yin and strengthen the spleen, so that the tonic effect will not be too excessive, thereby better enhancing the body's immunity.

[0013] The present invention provides a method for preparing a chewable tablet containing ginseng, codonopsis pilosula and northern radix adenophorae, the preparation method comprising the following steps:

[0014] 1) Preparation of dry paste powder

[0015] Extract ginseng, codonopsis and northern ginseng with water, filter the extract, concentrate the filtrate into a thick paste, dry and grind to obtain a dry paste powder;

[0016] 2) Obtain mixed powder A

[0017] Mix the flavoring agent and filler a evenly to obtain mixed powder A;

[0018] 3) Granulation and tableting

[0019] Mix the mixed powder A, dry paste powder and filler b and granulate them. Add lubricant to the obtained granules, mix them evenly and press them into tablets.

[0020] Wherein, in step 1), 400-600 parts of ginseng, 400-600 parts of codonopsis, and 400-600 parts of northern adenophora are taken by weight; preferably, 440-550 parts of ginseng, 440-550 parts of codonopsis, and 440-550 parts of northern adenophora are taken; more preferably, 500 parts of ginseng, codonopsis, and northern adenophora are taken.

[0021] Specifically, in step 1), the amount of water added for water extraction of ginseng, codonopsis and northern ginseng is 8-14 times the amount, the extraction method is decoction, the number of extractions is 2-4 times, and the time for each extraction is 1-3 hours. Preferably, the number of water extractions is 2 times, 12 times the amount of water is added for the first extraction, and 10 times the amount of water is added for the second extraction. Each decoction is 1.5 hours. It is also preferred that the extracts obtained from each water extraction are filtered separately, and the filtrates are combined and concentrated.

[0022] Specifically, the number of concentrations in step 1) is twice. Preferably, the concentration is reduced pressure concentration (-0.06 to -0.08 MPa, 50 to 70°C). More preferably, the concentration operation is: the filtrate is concentrated for the first time to obtain a concentrated solution, the relative density of the concentrated solution is 1.05 to 1.10 (60°C), centrifuged, and the centrifuged solution is concentrated for the second time to obtain a thick paste, the relative density of the thick paste is 1.30 to 1.35 (60°C), and dried under reduced pressure (-0.06 to -0.10 MPa, 50 to 70°C) until dry, crushed, and passed through an 80-mesh sieve to obtain a dry paste powder.

[0023] The present application uses 10-12 times the amount of water to extract the raw material drug extract, which consumes a large amount of water. The extract contains a large amount of polysaccharides and saponins with high viscosity and poor air permeability, which directly leads to long drying time, high drying temperature, and easy pitting of the finished product after drying. Therefore, the present application does not use spray drying to avoid sticking to the wall and serious loss of yield. The present application preferably uses two-step reduced pressure concentration to a relative density of 1.30-1.35 (60°C), and then reduces pressure to dry. The use of vacuum drying not only reduces the loss of raw materials, but also makes the extract powder crisp and fragile, and then passes through an 80-mesh sieve to avoid spots and pitting when pressing the tablets. In addition, the active ingredients of the present application are polysaccharides and saponin components, especially saponin components, which will produce a large amount of foam during the vacuum concentration process and are easy to rush out of the rotary evaporator and the condenser. Therefore, the present application is concentrated in two steps. The first step is to concentrate into a clear paste, reduce water, centrifuge to reduce foam, and also remove a small amount of fat-soluble components. The second step is to concentrate to the required relative density, avoiding the yield loss caused by a large amount of foam rushing out of the rotary evaporator during the vacuum concentration process. The vacuum concentration is performed twice and the appropriate concentration density is set to ensure that the subsequent drying time will not be too long, and the concentration density will not be too large, making it difficult to transfer and causing excessive losses.

[0024] Specifically, in step 2), the filler a is selected from lactose and microcrystalline cellulose, and in step 3), the filler b is selected from lactose, microcrystalline cellulose, and β-cyclodextrin, and the filler a and the filler b are the same or different, and the total amount of the filler is 600 to 1100 parts by weight, preferably 650 to 900 parts;

[0025] Preferably, filler a is lactose, and filler b is β-cyclodextrin. By weight, lactose is preferably 150 to 700 parts, more preferably 200 to 500 parts, and most preferably 250 to 400 parts; β-cyclodextrin is preferably 300 to 500 parts, more preferably 350 to 450 parts, and most preferably 400 parts. When the chewable tablet filler is lactose and β-cyclodextrin in the preferred amount, the obtained chewable tablet has a certain hardness and brittleness, and is easier to granulate.

[0026] Specifically, the flavoring agent in step 2) is selected from one or more of stevioside, aspartame, sucralose, citric acid, malic acid, tartaric acid, lactic acid, and acetic acid, preferably a combination of sucralose and anhydrous citric acid; by weight, 0.1 to 0.6 parts of sucralose and 5 to 15 parts of anhydrous citric acid, preferably 0.3 to 0.4 parts of sucralose and 6 to 12 parts of anhydrous citric acid, more preferably 0.36 parts of sucralose and 9 parts of anhydrous citric acid. When the chewable tablet takes an appropriate amount of sucralose and anhydrous citric acid as flavoring agents, the resulting tablet has a better taste, suitable sweetness and sourness, can well cover the bitterness brought by the raw materials, and improve the taste.

[0027] Specifically, the process of obtaining the mixed powder A in step 2) is to first take sucralose and an equal amount of anhydrous citric acid, mix them evenly, then add an equal amount of anhydrous citric acid to the above mixture, mix them evenly, and increase the amount by multiples until the mixture is mixed with the anhydrous citric acid, and then add an equal amount of lactose to the mixture, mix them evenly, and increase the amount by multiples until the mixture is mixed with the lactose, to obtain the mixed powder A; preferably, the filler and the flavoring agent are crushed before mixing and passed through an 80-mesh sieve; more preferably, the mixing means is to pass through an 80-mesh sieve manually for more than 2 times, preferably 3 times.

[0028] In step 2), sucralose and anhydrous citric acid are first added in equal amounts and mixed evenly, and then the mixture and lactose are added in equal amounts and mixed evenly to obtain mixed powder A. This allows the three auxiliary materials in the mixed powder to be highly uniform, ensuring the consistency of the taste of the final chewable tablet preparation and avoiding local bitterness.

[0029] Specifically, in step 3), the mixed powder A, the dry paste powder and the β-cyclodextrin are mixed evenly, and then the soft material is made with 85% ethanol, granulated with 20 mesh, dried at 60°C, and the obtained dry granules are added with a lubricant, mixed evenly and tableted; preferably, after the above drying operation, the dry granules are granulated with 18 mesh and then mixed with the lubricant. Experiments have shown that the granulation is neither sticky nor loose when the soft material is made with 85% ethanol, granulated with 20 mesh, dried at 60°C, and granulated with 18 mesh, and the granulation is high in yield and good in particle size.

[0030] Specifically, the lubricant described in step 3) is selected from one or more of magnesium stearate, talc, hydrogenated vegetable oil, and stearic acid, preferably magnesium stearate; preferably, by weight, the lubricant is 1 to 10 parts, preferably 5 to 10 parts, and more preferably 6 parts.

[0031] Specifically, the preparation method further includes a coating step. Preferably, a film coating agent of a formula ratio is used to coat the plain tablet obtained in step 3), and the coating weight increases by 2% to 4%. More preferably, the coating operation is to add 70% ethanol to the coating agent to prepare a coating solution with a solid content of 12%, and the plain tablet obtained in step 3) is put into a coating machine for coating, and the coating weight increases by 2% to 4%, preferably 2%. The film coating agent is recorded by weight, preferably 25 to 35 parts, and more preferably 30 parts. After the plain tablet in step 3) is subjected to the coating operation, the surface of the tablet is smooth and the coating layer is uniform. Conventional test results show that the properties and weight differences of the film-coated tablets meet conventional production requirements.

[0032] In another aspect, the present invention provides a chewable tablet obtained by the above preparation method. The chewable tablet is easy to take, has a good taste, is highly stable, can enhance human immunity, and has an efficient and stable preparation process, which is suitable for industrial production.

[0033] Specifically, the present invention provides a chewable tablet comprising ginseng, codonopsis and northern adenophora, wherein the main raw materials of the chewable tablet are ginseng, codonopsis and northern adenophora, and the preferred range of ginseng: codonopsis: northern adenophora is 1-1.5:1-1.5:1-1.5 by weight ratio, and more preferably, ginseng: codonopsis: northern adenophora = 1:1:1; in terms of weight parts, the preferred range of the raw materials ginseng, codonopsis and northern adenophora is 400-600 parts, more preferably, 440-550 parts, and most preferably, the weight parts of ginseng: codonopsis: northern adenophora are 500 parts: 500 parts: 500 parts, and the raw materials need to be prepared through the above-mentioned water extraction-filtration-concentration-centrifugation-drying to obtain a dry paste powder, and then other auxiliary materials are added to obtain a chewable tablet.

[0034] Preferably, the present invention provides a chewable tablet comprising ginseng, codonopsis pilosula, and northern radix adenophorae, wherein the chewable tablet comprises:

[0035]

[0036] Further preferably, the chewable tablet composition comprises:

[0037]

[0038] More preferably, the chewable tablet contains 250-400 parts of lactose and 400 parts of β-cyclodextrin.

[0039] The present invention also provides the use of the chewable tablet in preparing a product for enhancing human immunity.

[0040] Beneficial effects of the present invention:

[0041] The present invention provides a chewable tablet containing ginseng, codonopsis and northern ginseng and a preparation method thereof, and improves the stability of the chewable tablet preparation by optimizing the auxiliary materials and the dosage thereof and selecting the preparation process, improves the taste of the product, increases the yield of the product, and reduces the waste of raw materials; the present invention prepares three-ginseng chewable tablets that can improve the human immune function, and the indicators such as hardness, brittleness, and appearance meet the national standards, and the product yield is high, the method is easy to operate, and is suitable for industrialized scale-up production. On the other hand, the present invention prepares the three ginsengs into chewable tablets by optimizing the auxiliary materials and proportions, which are more convenient to take, and are particularly suitable for the elderly, people with dysphagia or poor gastrointestinal function, and can be taken normally even in the case of water shortage; at the same time, because the surface area of ​​the chewable tablet is increased, it is more conducive to absorption in the body, which helps to improve the human immunity. DETAILED DESCRIPTION

[0042] The present invention will be described in detail below in conjunction with specific implementations, but the scope of the present invention is not limited thereto.

[0043] In the following specific examples, unless otherwise specified, the reagents and instruments used are commonly used reagents and instruments in the field and can be obtained commercially; the methods used are conventional methods in the field, and those skilled in the art can know how to specifically implement the methods and achieve corresponding results based on the contents of the examples.

[0044] Preparation of dry paste powder:

[0045] Weigh 500g of ginseng, northern adenophora and codonopsis respectively, add water and boil twice, each time for 1.5 hours, add 12 times of water for the first time, and add 10 times of water for the second time, filter, and combine the filtrates; concentrate the filtrate under reduced pressure (-0.06~-0.08MPa, 50~70℃) to a concentrated solution with a relative density of 1.05~1.10 (60℃), centrifuge, and continue to concentrate the centrifuge under reduced pressure (-0.06~-0.08MPa, 50~70℃) to a fluid extract with a relative density of 1.30~1.35 (60℃); dry under reduced pressure (-0.06~-0.10MPa, 50~70℃) until dry, crush, and pass through an 80-mesh sieve to obtain a dry paste powder;

[0046] Examples 1 to 14

[0047] Weigh dry paste powder, maltodextrin, lactose, β-cyclodextrin, microcrystalline cellulose and corn starch according to the amounts in Table 1. Each auxiliary material needs to be crushed and passed through an 80-mesh sieve. Then, mix in a mixer according to the amount prescribed in the table for 30 minutes, make a soft material with 85% ethanol, granulate with 20 mesh, dry at 60°C (the moisture content of the granules is controlled below 5%), granulate with 18 mesh, and press into tablets.

[0048] Table 1

[0049]

[0050] Continued

[0051]

[0052] Chewable tablets require a certain hardness and brittleness of the tablet core. Therefore, the tablet core hardness, brittleness, and difficulty of tableting are used as evaluation indicators. The test results of the prescriptions of each embodiment are shown in Table 2 below:

[0053] Table 2

[0054]

[0055]

[0056] The above results show that when the filler is an appropriate amount of lactose, microcrystalline cellulose, and a combination of them with β-cyclodextrin, granulation is easier, the obtained granules are uniform, have good compressibility, moderate hardness, qualified friability, and the tablet surface is smooth and beautiful; among them, when the filler is 40g β-cyclodextrin and 25.65g lactose, the tablet friability unqualified rate is the lowest (0.18%), and the utilization rate of raw materials and auxiliary materials is the highest.

[0057] Examples 15-17

[0058] The dry paste powder was prepared according to the above process, and 523 g of dry paste powder was obtained. Then 400 g of β-cyclodextrin, 9 g of anhydrous citric acid, 0.36 g of sucralose, and 267.64 g of lactose were taken, totaling 1200 g.

[0059] Each auxiliary material needs to be crushed and passed through an 80-mesh sieve. Then, sucralose and an equal amount of anhydrous citric acid are manually passed through an 80-mesh sieve for 3 times to mix evenly. Then, an equal amount of anhydrous citric acid as the above mixture is added, manually sieved for 3 times to mix evenly, and the amount is increased by multiples until the mixture is completely mixed with the anhydrous citric acid. Then, an equal amount of lactose is added to the mixture, manually sieved for 3 times to mix evenly, and the amount is increased by multiples until the mixture is completely mixed with the lactose, to obtain a mixed powder A of the three.

[0060] Mixed powder A, dry paste powder and β-cyclodextrin were placed in a mixer and mixed for 30 minutes, then divided into 3 equal parts, 400 g each, and soft materials were prepared using different wetting agents, 20 mesh granules were made, dried at 60°C (the moisture content of the granules was controlled below 5%), and 18 mesh granules were granulated. The results are shown in the following table:

[0061] Table 3

[0062]

[0063] This product is a mixed powder obtained by water extraction of ginseng, northern adenophora, and codonopsis pilosula and mixed with auxiliary materials. It has high viscosity. In order to reduce the viscosity of the extract and facilitate preparation, ethanol of different concentrations is selected as a wetting agent for granulation. The difficulty of granulation and particle yield are used as evaluation indicators to select the wetting agent.

[0064] The test results show that 85% ethanol and 90% ethanol are easier to granulate and have higher granule yields. However, the granules produced by 85% ethanol have a better particle size, while the granules produced by 90% ethanol are loose. Therefore, 85% ethanol is selected as the wetting agent for this product to make soft material.

[0065] Examples 18-21

[0066] Prepare dry paste powder according to the above method, and examine the flavoring agent and dosage according to Table 4 below.

[0067] The flavor correctives need to be crushed and passed through an 80-mesh sieve in advance. After the materials in the table are evenly mixed, they are made into a soft material with 85% ethanol, granulated with 20 mesh, dried at 60°C (the moisture content of the granules is controlled below 5%), granulated with 18 mesh, dried, and tableted. The taste of the chewable tablets is used as an indicator for investigation. The results of the investigation are shown in the table below.

[0068] Table 4

[0069]

[0070] Taste evaluation: Referring to GB / T39625-2020, taste descriptors and evaluation criteria were established based on the taste characteristics of Sanshen chewable tablets (see Table 5). The evaluation indicators were descriptors such as moderate sweetness and sourness, and the taste quality of chewable tablets was analyzed using qualitative description methods. A food taste evaluation team composed of 10 food professionals conducted a taste test on Sanshen chewable tablets. During the test, the mouth was rinsed continuously (with purified water until the mouth was almost tasteless), and the next sample test was conducted after an interval of 10 minutes to eliminate the influence of residual taste in the mouth on the evaluation results. If there was a difference in the results, the taste of the majority was taken as the final result.

[0071] Table 5.

[0072]

[0073] In the present invention, ginseng, northern radix adenophorae and codonopsis are the main raw materials, and the prepared dry paste powder has obvious bitterness, so a sweetener is added to improve the taste, but the sweetness is bland and the taste is not rich enough when the sweetener is simply added. A sour agent can be used in combination to significantly improve its flavor and mask the bitterness. The sucralose in the above embodiment has high sweetness, pure sweetness, high safety, and has a masking effect on unpleasant tastes such as astringency and bitterness. It is one of the most excellent functional sweeteners at present, and anhydrous citric acid is the most widely used sour agent, with a soft and refreshing sour taste, and the highest sour feeling is reached when entering the mouth, but the aftertaste lasts for a short time, which can alleviate the mellow sour taste.

[0074] The above results show that the chewable tablets obtained by using anhydrous citric acid and sucralose as flavoring agents in Example 20 have the best taste, with appropriate sweet and sour taste, and its taste was unanimously recognized by the evaluation team members; Example 21 increases the amount of the two, and the sweet and sour taste is more obvious, and the taste is second.

[0075] Embodiment 22

[0076]

[0077] According to the above method, 500g of ginseng, codonopsis and northern adenophora were weighed to prepare dry paste powder, and 375g of dry paste powder was obtained this time. Lactose is used as a dosage regulator. Under the premise of ensuring that the total amount of dry paste powder and excipients is 1200g, the dosage can be calculated to be 379.64g. Weigh the prescribed amount of lactose, β-cyclodextrin, anhydrous citric acid, and sucralose, crush them through an 80-mesh sieve respectively, and set aside; magnesium stearate is passed through an 80-mesh sieve and set aside.

[0078] Take sucralose and an equal amount of anhydrous citric acid and manually pass through an 80-mesh sieve 3 times to mix evenly, then add an equal amount of anhydrous citric acid to the mixture and manually sieve 3 times to mix evenly, increase the amount by multiples until the mixture is mixed with the anhydrous citric acid, then add an equal amount of lactose to the mixture and manually sieve 3 times to mix evenly, increase the amount by multiples until the mixture is mixed with the lactose, and obtain mixed powder A; take mixed powder A, dry paste powder and β-cyclodextrin and place them in a mixer and mix for 30 minutes, use 85% ethanol to make a soft material, granulate with 20 mesh, dry at 60°C (the moisture content of the particles is controlled to be below 5%), and granulate with 18 mesh; add the prescribed amount of magnesium stearate to the dry particles and mix evenly to obtain a total mixture; take the above total mixture, press the tablets, and control the tablet weight to 1.18g / tablet. Take the prescribed amount of film coating agent, add 70% ethanol to make a coating solution with a solid content of 12%, put the plain tablets into the coating machine for coating, and the coating weight increases by about 2%.

[0079] The chewable tablets obtained by the above method have a brown film-coated tablet appearance, are complete and smooth, have a uniform color, have a suitable hardness, have no peculiar smell, and have no foreign impurities visible to the naked eye. After being placed at 38°C and 75% relative humidity for 3 months, the appearance is still smooth and complete, with a uniform color, and there is no change observed by the naked eye.

[0080] Embodiment 23-25:

[0081] Weigh the amounts of ginseng, northern adenophora and codonopsis as shown in Table 6, add water and boil twice, each time for 1.5 hours, add 12 times the amount of water for the first time, and add 10 times the amount of water for the second time, filter, and combine the filtrates; the filtrate is concentrated under reduced pressure (-0.06 to -0.08 MPa, 50 to 70°C) to a concentrated solution with a relative density of 1.05 to 1.10 (60°C), centrifuged at high speed, and the centrifuged liquid is further concentrated under reduced pressure (-0.06 to -0.08 MPa, 50 to 70°C) to a fluid extract with a relative density of 1.30 to 1.35 (60°C); dry under reduced pressure (-0.06 to -0.10 MPa, 50 to 70°C) until dry, crush, and pass through an 80-mesh sieve to obtain a dry paste powder.

[0082] Lactose, β-cyclodextrin, anhydrous citric acid and sucralose were respectively pulverized and passed through a 80-mesh sieve for later use; magnesium stearate was passed through a 80-mesh sieve for later use.

[0083] Take sucralose and an equal amount of anhydrous citric acid, manually pass through an 80-mesh sieve 3 times to mix evenly, then add an equal amount of anhydrous citric acid to the mixture, manually sieve 3 times to mix evenly, increase the amount by multiples until the mixture is mixed with the anhydrous citric acid, then add an equal amount of lactose to the mixture, manually sieve 3 times to mix evenly, increase the amount by multiples until the mixture is mixed with the lactose, to obtain mixed powder A.

[0084] Mixed powder A, dry paste powder and β-cyclodextrin were placed in a mixer and mixed for 30 minutes. 85% ethanol was used to make a soft material, 20 mesh granules were made, dried at 60°C (the moisture content of the granules was controlled below 5%), and 18 mesh granules were made. The prescribed amount of magnesium stearate was evenly added to the dry granules to obtain a total mixture.

[0085] The above total mixture was taken and tableted, and the tablet weight was controlled to be 1.18 g / tablet.

[0086] Take a film coating agent in a formula ratio, add 70% ethanol to prepare a coating solution with a solid content of 12%, put the plain tablets into a coating machine for coating, and the coating weight gain is about 2%.

[0087] As shown in Table 6 below, three batches were scaled up for production, with production feed amounts of 20,000 tablets, 10,000 tablets, and 10,000 tablets (1.2 g / tablet) respectively, and actual yield and yield rate were examined.

[0088] Table 6.

[0089]

[0090]

[0091] *Actual weighing weight

[0092] The above test results show that three batches of pilot production were carried out according to the determined process conditions, and the results had good parallelism, high actual yield rate and less waste of raw materials, indicating that the determined prescription and process are stable and feasible and suitable for industrial production.

[0093] Main pharmacodynamic experiments of the Sanshen chewable tablets of the present invention:

[0094] In order to prove that the health food of the present invention helps to improve immunity, a drug efficacy experiment was carried out using the three ginseng chewable tablets (1.2 g / tablet) prepared in Example 23 of the present invention.

[0095] 1. Experimental animals:

[0096] BALB / c female SPF mice were selected, with a body weight range of 20±2g, bred by the China Food and Drug Administration. The license number is SCXK (Beijing) 2014-0013.

[0097] Maintenance feed was purchased from Beijing Keao Xieli Feed Co., Ltd., license number SCXK (Beijing) 2014-0010.

[0098] According to the experimental requirements, each experimental project group was randomly divided into four groups: control group, low-dose, medium-dose, and high-dose, with 15 mice in each group.

[0099] 2. Dose selection and test substance administration method:

[0100] After the mice were adapted to feeding for 3 days, they were continuously gavaged with the test substance. The recommended human dose of the test substance is 4.8g / day, which is equivalent to a recommended daily dose of 0.08g per kilogram of body weight based on an adult weighing 60kg. The test substance was prepared at a gavage dose of 10mL / kg.BW for animals. Mice in the high, medium and low dose groups were given 2.4g / kg.BW, 0.8g / kg.BW and 0.4 / kg.BW of the test substance, respectively, which were equivalent to 30, 10 and 5 times the recommended human dose, respectively. The control group was given distilled water. After 30 days of continuous gavage, the animals were killed and various immune indicators were measured.

[0101] 3. Methods and Results

[0102] 3.1 Determination of organ / body weight ratio

[0103] The mice were weighed and then killed, and the spleen and thymus were taken out, the fascia was removed, the blood stains on the surface of the organs were absorbed with filter paper, and the weights were weighed to calculate the spleen / body weight ratio and thymus / body weight ratio.

[0104] 3.2 Antibody-producing cell detection (Jerne modified pick method)

[0105] Take defibrinated sheep blood, wash it with saline for 3 times, and prepare 2% (v / v) SRBC with saline. Intraperitoneally inject 0.2mL into each mouse. After sensitization for 5 days, kill the mice by cervical dislocation, take the spleen, and prepare spleen cell suspension. The whole spleen cells are suspended in 8mL Hank's solution. After heating and dissolving 1% agarose, place it in a 45℃ water bath and mix it with an equal amount of 2 times Hank's solution. Dispense it into small test tubes, 0.5mL per tube, add 50uL SA buffer solution to prepare 10% (V / V) Mianyang red blood cell (SRBC) suspension, 20uL whole spleen cell suspension, mix quickly, pour it on a glass slide brushed with a thin layer of 0.5% agarose, make parallel slides, and put the glass slide horizontally on the glass slide rack. In a carbon dioxide incubator with 5% CO 2 , incubate at 37℃ for 1.5h, add 10-fold complement (guinea pig serum) diluted with SA solution into the groove of the slide rack, continue incubation for 1.5h, and count the number of hemolytic plaques. The number of plaques in the whole spleen is 400 (the proportion of spleen cells in the smear to the whole spleen cells) multiplied by the number of plaques counted on the slide.

[0106] 3.3 Experiment on phagocytosis of chicken red blood cells by mouse peritoneal macrophages (drop method)

[0107] Take defibrinated sheep blood, wash it with saline for 3 times, and prepare a 2% (V / V) Mianyang red blood cell (SRBC) suspension with saline. Intraperitoneally inject 0.2mL into each mouse. After sensitization for 4 days, kill the mice by cervical vertebral dislocation. Intraperitoneally inject 4mL of Hank's solution with calf serum, gently rub the abdomen, cut a small incision in the abdominal wall cavity, and wash out 2mL into a test tube. Take 0.5mL of washing solution and add it to a test tube with 0.5mL1% chicken red blood cells, and mix well. Use a syringe to absorb 0.5mL of the mixture and add it to the agar circle. Incubate for 15min, quickly wash it off with saline, fix it with methanol solution for 1min, Giemsa solution for 15min, and rinse with distilled water. Dry it and count it under a 40x microscope.

[0108] 3.4 Test data statistics:

[0109] The experimental data were entered into a computer, a database was established using EXCEL software, and statistical analysis was performed using SPSS19.0 software. If the variances of the groups were equal, one-way ANOVA was used, with α = 0.05 as the significance level, and the F value was calculated. <F 0.05 , it is concluded that there is no significant difference between the groups; if F ≥ F 0.05 , P ≤ 0.05, the pairwise comparison method between the means of multiple experimental groups and a control group was used for statistical analysis. If the variance homogeneity could not be met, the Welch correction was used.

[0110] 3.5 Result determination

[0111] 3.5.1 Effects on mouse body weight

[0112] As shown in Table 7, different doses of Sanshen chewable tablets were orally administered to mice for 30 days. According to statistical analysis, there were no significant differences in the initial body weight, final body weight, and weight gain between the dose groups and the control group (P>0.05).

[0113] Table 7. Initial body weight, final body weight and body weight gain of mice in each group

[0114]

[0115] 3.5.2 Effects on the organ / body weight ratio of mice

[0116] Table 8. Effects of Sanshen chewable tablets on the organ / body weight ratio of mice

[0117]

[0118] As shown in Table 8, different doses of the Sanshen chewable tablets of Example 23 of the present invention were continuously administered for 30 days. According to statistical analysis, there was no significant difference in spleen / body weight and thymus / body weight between the dose groups and the control group (P>0.05).

[0119] 3.5.3 Effects on humoral immune function indicators in mice

[0120] Table 9. Effects on antibody-producing cell assay results

[0121] Dosage group (g / kg.BW) Number of animals <![CDATA[Number of hemolytic plaques (×10 2 total spleen)]]> P-value 0.0 15 65.5±22.7 -- 0.4 15 154.4±36.6** 0.000 0.8 15 240.9±45.2** 0.000 2.4 15 340.1±42.6** 0.000

[0122] Note: **P<0.01 is extremely significant when compared with the control group.

[0123] As shown in Table 9, different doses of the Sanshen chewable tablets prepared in Example 23 were continuously administered for 30 days. According to statistical analysis, the number of hemolytic plaques in the low-, medium- and high-dose groups of mice were significantly higher than that in the control group (P<0.01).

[0124] 3.5.4 Effects on phagocytic function of mouse monocytes and macrophages

[0125] Table 10. Effect of Sanshen chewable tablets on phagocytosis of chicken red blood cells by mouse peritoneal macrophages

[0126]

[0127] Note: Compared with the control group, *P<0.05 is significant, **P<0.01 is extremely significant.

[0128] As can be seen from Table 10, after continuous administration of different doses of the Sanshen chewable tablets of Example 23 of the present invention for 30 days, the phagocytic percentage and phagocytic index of mice in the low, medium and high dose groups were significantly higher than those in the control group, with statistical differences (P<0.05, P<0.01).

[0129] So far, different doses of the three ginseng chewable tablets of Example 23 of the present invention were orally administered to mice in low, medium and high dose groups for 30 days. Compared with the control group, the antibody-producing cell detection and the mouse peritoneal macrophage phagocytosis of chicken red blood cells in each dose group showed statistically significant differences (P<0.05, P<0.01); there were no statistical differences in the mouse body weight, organ / body weight ratio, and serum hemolysin determination (P>0.05). The above results can determine that humoral immunity and mouse mononuclear macrophage phagocytosis are positive.

[0130] According to the results of the immunity enhancement function in the "Technical Specifications for Inspection and Evaluation of Health Foods - 2003 Edition", the above-mentioned three-ginseng chewable tablets are positive in animal tests for helping to enhance the immunity function, that is, the three-ginseng chewable tablets of the present application have the immunity enhancement function.

[0131] Although the present invention has described the above-mentioned implementation cases, it does not limit the patent protection scope of the present invention. Therefore, based on the innovative concept of the present invention, changes and modifications made to the implementation cases described herein, or equivalent structures or equivalent process changes made using the contents of the present invention specification, directly or indirectly applying the above technical solutions to other related technical fields are all included in the patent protection scope of the present invention.

Claims

1. A method for preparing a chewable tablet containing ginseng, codonopsis and northern ginseng, the method comprising the following steps: 1) Preparation of dry paste powder Extract ginseng, codonopsis and northern ginseng with water, filter the extract, concentrate the filtrate into a thick paste, dry and grind to obtain a dry paste powder; 2) Obtain mixed powder A Mix the flavoring agent and filler a evenly to obtain mixed powder A; 3) Granulation and tableting Mix the mixed powder A, dry paste powder and filler b and granulate them. Add lubricant to the obtained granules, mix them evenly and press them into tablets. in, In terms of weight, in step 1), 400-600 parts of ginseng, 400-600 parts of codonopsis, and 400-600 parts of northern adenophora are taken, preferably 440-550 parts of ginseng, 440-550 parts of codonopsis, and 440-550 parts of northern adenophora; In step 2), filler a is selected from lactose and microcrystalline cellulose, and in step 3), filler b is selected from lactose, microcrystalline cellulose, and β-cyclodextrin. The filler a and filler b are the same or different, and the total amount of filler is 600 to 1100 parts by weight, preferably 650 to 900 parts; Preferably, filler a is lactose, and filler b is β-cyclodextrin. By weight, lactose is 150 to 700 parts, and β-cyclodextrin is 300 to 500 parts. More preferably, lactose is 200 to 500 parts, and β-cyclodextrin is 350 to 450 parts. More preferably, the amount of each of ginseng, codonopsis pilosula and northern adenophora is 500 parts, the amount of lactose is 250-400 parts, and the amount of beta-cyclodextrin is 400 parts.

2. The preparation method according to claim 1, characterized in that The number of concentrations in step 1) is twice, preferably, the concentration is reduced pressure concentration, and more preferably, the concentration operation is: the filtrate is concentrated for the first time to obtain a concentrated solution, centrifuged, and the centrifuged solution is concentrated for the second time to obtain a thick paste, and the relative density of the thick paste is 1.30-1.35 (60°C); Preferably, the relative density of the concentrated solution obtained after the first concentration in step 1) is 1.05-1.10 (60° C.).

3. The preparation method according to any one of claims 1 or 2, characterized in that: In step 1), the amount of water added for water extraction of ginseng, codonopsis and northern ginseng is 8-14 times the amount, the extraction method is decoction, the number of extractions is 2-4 times, and the time for each extraction is 1-3 hours. Preferably, the number of water extractions is 2 times, 12 times the amount of water is added for the first extraction, and 10 times the amount of water is added for the second extraction. Each decoction is 1.5 hours. It is also preferred that the extracts obtained from each water extraction are filtered separately, and the filtrates are combined and concentrated.

4. The preparation method according to any one of claims 1 to 3, characterized in that: The flavoring agent in step 2) is selected from one or more of stevioside, aspartame, sucralose, citric acid, malic acid, tartaric acid, lactic acid, and acetic acid, preferably a combination of sucralose and anhydrous citric acid; In terms of weight, sucralose is 0.1-0.6 parts, and anhydrous citric acid is 5-15 parts. Preferably, sucralose is 0.3-0.4 parts, and anhydrous citric acid is 6-12 parts. More preferably, sucralose is 0.36 parts, and anhydrous citric acid is 9 parts.

5. The preparation method according to any one of claims 1 to 4, characterized in that: Step 2) The process of obtaining mixed powder A is to first take sucralose and an equal amount of anhydrous citric acid, mix them evenly, then add an equal amount of anhydrous citric acid to the above mixture, mix them evenly, and increase the amount by multiples until the mixture is completely mixed with the anhydrous citric acid, and then add an equal amount of lactose to the mixture, mix them evenly, and increase the amount by multiples until the mixture is completely mixed with the lactose, to obtain mixed powder A; Preferably, the filler and flavoring agent are crushed and passed through an 80-mesh sieve before mixing; More preferably, the mixing means is manually passing through an 80-mesh sieve for more than 2 times, preferably 3 times.

6. The preparation method according to any one of claims 1 to 5, characterized in that: In step 3), the mixed powder A, the dry paste powder and β-cyclodextrin are mixed evenly, and then a soft material is prepared using 85% ethanol, granulated into 20 mesh, and dried at 60° C. A lubricant is added to the obtained dry granules, mixed evenly, and then tableted; Preferably, after the drying operation, the dry granules are sized through 18 mesh and then mixed with a lubricant.

7. The preparation method according to any one of claims 1 to 6, characterized in that: The lubricant described in step 3) is selected from one or more of magnesium stearate, talc, hydrogenated vegetable oil, and stearic acid, preferably magnesium stearate; preferably, by weight, the lubricant is 1 to 10 parts, preferably 5 to 10 parts, and more preferably 6 parts.

8. The preparation method according to any one of claims 1 to 7, characterized in that: The method further comprises a coating step. Preferably, a film coating agent is used to coat the plain tablets obtained in step 3) in a formula ratio, and the coating weight gain is 2% to 4%.

9. A chewable tablet obtained by the preparation method according to any one of claims 1 to 8.

10. Use of the chewable tablet according to claim 9 in preparing a product for enhancing human immunity.

Images