American ginseng and turmeric buccal tablet candy with chemical liver injury auxiliary protection function and preparation method of American ginseng and turmeric buccal tablet candy

Abstract

The invention discloses an American ginseng and turmeric buccal tablet candy with a chemical liver injury auxiliary protection function and a preparation method of the American ginseng and turmeric buccal tablet candy. The American ginseng and turmeric buccal tablet candy is prepared from American ginseng, turmeric powder, edible glucose powder and edible starch as raw materials and sodium carboxymethyl cellulose and magnesium stearate as auxiliary materials. The radix panacis quinquefolii and rhizoma curcumae longae powder is prepared from the following raw and auxiliary materials in parts by weight: 125 to 170 parts of radix panacis quinquefolii, 460 to 750 parts of rhizoma curcumae longae powder, 590 to 780 parts of edible glucose powder, 15 to 20 parts of edible starch, 18 to 24 parts of magnesium stearate and 1.2 to 1.6 parts of sodium carboxymethyl cellulose. The American ginseng volatile oil and the turmeric are mixed by adopting a specific process, so that the fat solubility is increased, the absorption and utilization of curcumin in the turmeric are increased, the buccal tablet candy is prepared into a buccal tablet candy form, and the buccal tablet candy is rapidly absorbed into blood through oral mucosa blood vessels and sublingual capillary vessels, so that the first-pass effect of gastrointestinal tracts is avoided, and the health-care effect of the product is exerted.

Description

Technical Field

[0001] The invention belongs to the field of traditional Chinese medicine, and specifically relates to an American ginseng and turmeric oral tablet candy (tablet candy) with auxiliary protection function for chemical liver damage and a preparation method thereof. Background Art

[0002] 1. The protective function of American ginseng against chemical liver damage is mainly reflected in the following aspects: 1.1. Antioxidant effect The saponin components in American ginseng have significant antioxidant effects. These antioxidants can remove free radicals in the body and reduce oxidative stress damage to the liver, thereby protecting the liver from damage by chemical substances. By improving the liver's antioxidant capacity, American ginseng helps maintain the normal physiological functions of the liver.

[0003] 1.2. Inhibition of lipid peroxidation The active ingredients in American ginseng can inhibit the lipid peroxidation process and reduce the production of peroxidation products in the liver. This effect helps to reduce lipid peroxidation damage to the liver, protect the integrity of the liver cell membrane, and thus maintain the normal structure and function of the liver.

[0004] 1.3. Improve inflammatory response Chemical liver damage is often accompanied by the occurrence of inflammatory response. Certain components in American ginseng can inhibit the release of inflammatory factors and reduce the inflammatory response of the liver, thereby helping to alleviate liver inflammation and damage caused by chemical liver damage.

[0005] 1.4. Promote liver detoxification metabolism American ginseng has the function of promoting liver detoxification metabolism. By enhancing the liver's detoxification ability, American ginseng helps accelerate the metabolism and excretion of toxic substances in the body, thereby reducing the damage of chemical substances to the liver. This effect is of great significance for the prevention and treatment of chemical liver damage.

[0006] 1.5. Experimental research Experimental studies have shown that total saponins of American ginseng can effectively antagonize acute liver damage in mice caused by certain chemicals (such as acetaminophen) by restoring the activity of the body's antioxidant enzymes, inhibiting lipid peroxidation, improving inflammatory responses, and resisting cell apoptosis and necrosis. These experimental results further confirm the protective effect of American ginseng against chemical liver damage.

[0007] 2. Turmeric has a significant protective function against chemical liver damage, which is mainly due to its rich active ingredient curcumin.

[0008] 2.1. Main effects of curcumin 2.1.1. Antioxidant effect: As a powerful natural antioxidant, curcumin can increase the activity and content of antioxidant enzymes (such as superoxide dismutase, glutathione peroxidase and glutathione reductase) in the liver.

[0009] By scavenging free radicals and reducing oxidative stress, curcumin can protect liver cells from oxidative damage, thereby maintaining normal liver function.

[0010] 2.1.2. Anti-inflammatory effect: Liver disease is often accompanied by inflammatory responses, and curcumin can intervene and inhibit the key inflammatory signaling pathways in this process. By reducing the inflammatory state of the liver, curcumin helps reduce the risk of liver damage.

[0011] 2.1.3. Anti-fibrosis effect: Liver fibrosis is a response of the liver to chronic damage. Long-term existence will gradually lead to loss of liver function. Curcumin can block this process through various mechanisms, including inhibiting the activation and proliferation of hepatic stellate cells, promoting their apoptosis, reducing the level of oxidative stress in liver tissue, and reducing collagen synthesis and extracellular matrix deposition.

[0012] 2.2. Experimental and clinical studies on the protection of turmeric against chemical liver damage 2.2.1. Experimental research: Using experimental methods such as liver cancer cell transplantation models and chemical-induced acute or chronic liver injury models, it was found that curcumin can significantly reduce serum transaminase levels, improve liver function, and promote the repair and regeneration of liver cells; pathological examination showed that curcumin can reduce liver tissue inflammation and fibrosis and improve liver structure.

[0013] 2.2.2. Clinical research: Some clinical trials have also verified the protective effects of turmeric and its extracts (such as turmeric capsules) against chemical liver damage. These studies usually adopt a randomized controlled trial design to evaluate the therapeutic effect of turmeric by comparing serum transaminase levels, liver function indicators, and symptom improvement between the turmeric treatment group and the control group.

[0014] 3. Turmeric swallowing and edible gastrointestinal absorption defects Curcumin in turmeric has poor water solubility and low bioavailability in vivo. After oral administration, most of it is rapidly metabolized in the gastrointestinal tract to generate reduced products and then excreted from the body, which to a certain extent limits the clinical application of curcumin. References "Effects of chitosan modification on the stability and antioxidant activity of liposome-encapsulated curcumin" Wang Xiaoyong, Yan Jialei, Proceedings of the 15th Conference on Colloid and Interface Chemistry of the Chinese Chemical Society, Section 5.

[0015] Chemical structure, release rate, and low solubility in gastrointestinal fluid are key factors limiting the bioaccessibility of curcumin. Since the early 1980s, scholars have conducted extensive research on the bioavailability of curcumin in rat models. According to research reports, after oral administration of 400 mg of curcumin to rats, only trace amounts (less than 5 μg / mL) of curcumin remained in the portal vein blood within 15 min to 24 h. In addition, it was found that after oral administration of 3.6 g of curcumin, the maximum content of curcumin in plasma was 11.1 nmol / L 1 h after administration. No curcumin was found in the plasma of patients who received lower doses of curcumin. References: "Research Progress on the Construction and Functional Application of Curcumin Membrane Delivery System" Zhou Arong, Lin Yilin, Qiu Jianqing, Zeng Shaoxiao*, Lin Shaoling*, Food Science, 266 2020, Vol.41, No.07. Summary of the invention

[0016] In order to overcome the defect of gastrointestinal absorption disorder when turmeric is swallowed and eaten, the purpose of the present invention is to provide a ginseng and turmeric oral compressed tablet candy (lozenge) with auxiliary protection function against chemical liver damage. The volatile oil of ginseng is mixed with turmeric by a specific process, which increases the fat solubility and the absorption and utilization of curcumin in turmeric, and is quickly absorbed into the blood through the oral mucosal blood vessels and sublingual capillaries, thereby avoiding the first-pass effect of the gastrointestinal tract, thereby exerting the health care effect of the product.

[0017] To achieve the above object, the present invention adopts the following technical solutions: A kind of American ginseng and turmeric oral tablet candy (tablet) with auxiliary protection function for chemical liver damage, which is composed of American ginseng, turmeric powder, edible glucose powder, edible starch as raw materials, and sodium carboxymethyl cellulose and magnesium stearate as auxiliary materials. In parts by weight, the amount of raw and auxiliary materials used is: 125-170 parts of American ginseng, 460-750 parts of turmeric powder, 590-780 parts of edible glucose powder, 15-20 parts of edible starch, 18-24 parts of magnesium stearate, and 1.2-1.6 parts of sodium carboxymethyl cellulose. Preferably, the mass ratio of turmeric powder to American ginseng is 3:1-5:1.

[0018] 1. Quality requirements for raw and auxiliary materials 1.1. American Ginseng Should comply with the requirements of Green Food Ginseng and American Ginseng (NY / T 1043) 1.2. Turmeric powder Should comply with the requirements of the National Food Safety Standard for Food Additive Turmeric (GB 1886.60) 1.3. Edible glucose powder Should comply with the requirements of Edible Glucose (GB / T 20880) 1.4. Edible starch Should comply with the requirements of the National Food Safety Standard Edible Starch (GB 31637) 1.5. Sodium carboxymethyl cellulose Should comply with the requirements of the National Food Safety Standard Food Additive Sodium Carboxymethyl Cellulose (GB 1886.232) 1.6. Magnesium stearate Should comply with the requirements of the National Food Safety Standard Food Additive Magnesium Stearate (GB 1886.91) The preparation method of the American ginseng and turmeric oral tablet candy (tablet) comprises the following steps: 1. American ginseng extract 1.1. Cleaning, drying and crushing Take the formulated amount of American ginseng and wash it three times with running drinking water to remove impurities. Dry the washed American ginseng in a thermal circulation oven at 60°C to 65°C. After natural cooling, crush the American ginseng into 10-mesh coarse powder for later use.

[0019] 1.2. Volatile oil extraction Take the crude powder of American ginseng, put it into a multi-functional extraction tank, and steam distill it for about 2-2.5 hours. Collect the distillate and separate the upper volatile oil for later use.

[0020] 1.3. Percolation extraction and concentration The distilled ginseng powder was stirred and moistened with 2 times the weight of 70wt% edible ethanol solution, and then sealed for 24 hours. Then, 13 times the weight of 70wt% edible ethanol solution was added to start percolation, and the percolation liquid flow rate was controlled at 230-270ml / min.

[0021] The percolate is concentrated into a thick paste with a relative density of 1.25-1.30 (measured at 60°C-65°C) using a single-effect vacuum decompression concentrator and then stored in a freezer (0-4°C) for later use, wherein the steam pressure is 0.06-0.1Mpa and the vacuum pressure is -0.04--0.08Mpa.

[0022] 2. Granulation 2.1. Pretreatment of turmeric powder and American ginseng volatile oil Slowly add American ginseng volatile oil to the turmeric powder while stirring, stir for 5 to 10 minutes, scrape the powder through a 20-mesh sieve of a swing granulator, and set aside.

[0023] 2.2. Crushing and sieving Grind edible glucose powder, edible starch and magnesium stearate into 100 mesh powders respectively for later use.

[0024] 2.3. Preparation of adhesive Take the prescribed amount of sodium carboxymethyl cellulose and disperse it overnight with 6 times the weight of 95wt% edible ethanol solution one day in advance, then add appropriate amount of purified water to prepare a 2.5-3.0wt% solution.

[0025] 2.4. Mixing and granulation Premix edible glucose powder and edible starch in a high-speed mixing granulator for 6 to 10 minutes, slowly add American ginseng paste under slow stirring, and continue stirring for 5 minutes; slowly add sodium carboxymethyl cellulose solution under fast stirring, and continue stirring for 5 minutes, pour the prepared wet granules into a boiling dryer, boil and dry at 70 to 80°C, and control the moisture content to 3wt% to 5wt%.

[0026] 2.5. Granulation and total mixing The dry granules were sieved with a 16-mesh sieve, magnesium stearate and turmeric powder were added, and the mixture was mixed in a three-dimensional motion mixer for 15 minutes.

[0027] 2.6. Tablet pressing The above materials were tableted using a ZP-35B rotary tablet press, and the tablet weight range was controlled within 1.20 to 1.25 g.

[0028] 2.7. Packaging The qualified tablets are packaged with PVC sheets / aluminum foil and medicinal composite films, with 12 tablets per plate.

[0029] Advantages of the Invention ① The oral mucosal epithelium is composed of multiple layers of flat epithelial cells. Only the tongue surface and lips are keratinized. There are many blood vessels distributed in the oral mucosa, forming a large vascular network in the inner layer of the mucosa, which provides a rich vascular pathway for the absorption of curcumin in turmeric. ② The abundant capillaries under the tongue allow curcumin in turmeric to enter the blood circulation faster.

[0030] ③ The oral mucosal epithelial cell membrane is composed of liposomes, so fat-soluble active substances such as curcumin can easily penetrate.

[0031] ④ Oral absorption avoids the first-pass effect of the gastrointestinal tract, and prevents most of the drug from being rapidly metabolized in the gastrointestinal tract to produce reduced products and then excreted from the body after oral administration, thereby improving bioavailability by holding the drug in the mouth.

[0032] ⑤ Synergistic effect of ginseng and turmeric: 1. Enhance Antioxidant Capacity Both American ginseng and turmeric have antioxidant effects. Using them together can further enhance the antioxidant capacity, better eliminate free radicals, and reduce the damage of oxidative stress to the liver.

[0033] 2. Synergistic anti-inflammatory effect Both have anti-inflammatory effects, and their combined use can more effectively inhibit the liver's inflammatory response and reduce the liver's inflammatory state.

[0034] 3. Promote liver cell regeneration and repair: American ginseng can promote the regeneration of liver cells, while turmeric can protect liver cells from damage. The combination of the two can better promote the repair and regeneration of liver tissue. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 The microscopic examination results of the solvent control group are shown in Figure 2. Figure 2 CCl 4 Microscopic examination results of the control group; Figure 3 These are the microscopic results of the low-dose group; Figure 4 This is the microscopic examination result of the medium-dose group; Figure 5 These are the microscopic examination results of the high-dose group. DETAILED DESCRIPTION

[0036] A kind of American ginseng and turmeric oral tablet candy (tablet) with auxiliary protection function for chemical liver damage, which is composed of American ginseng, turmeric powder, edible glucose powder, edible starch as raw materials, and sodium carboxymethyl cellulose and magnesium stearate as auxiliary materials. In parts by weight, the amount of raw materials and auxiliary materials used is: 125-170 parts of American ginseng, 460-750 parts of turmeric powder, 590-780 parts of edible glucose powder, 15-20 parts of edible starch, 18-24 parts of magnesium stearate, and 1.2-1.6 parts of sodium carboxymethyl cellulose.

[0037] Formulation optimization screening test 1. Recipe classification 1.1. Overview In TCM, chemical liver injury falls into the category of liver and gallbladder damp-heat and asthenia, with clinical manifestations including flank pain, fatigue, abdominal distension, nausea, vomiting, poor appetite, aversion to oil, yellow urine, jaundice of sclera and skin, bitter taste in the mouth, dry throat, etc.

[0038] American ginseng can nourish qi and yin, clear away heat and promote the production of body fluids. It is used for qi and yin deficiency, deficiency heat and fatigue, cough, asthma, sputum and blood, internal heat and thirst, dry mouth and throat. The dosage is 3-6g. Turmeric has the function of breaking blood and promoting qi, relieving pain by promoting menstruation. It is used for chest and flank pain, chest obstruction and heart pain, dysmenorrhea, amenorrhea, masses, rheumatic shoulder and arm pain, and swelling and pain caused by falls. The dosage is 3-10g. Formulation 1: 1 part by weight of turmeric; Formulation 2: 1 part by weight of American ginseng; Formulation 3: 1 part by weight of turmeric, 2 parts by weight of American ginseng; Formulation 4: 1 part by weight of turmeric, 1 part by weight of American ginseng; Formulation 5: 2 parts by weight of turmeric, 1 part by weight of American ginseng; Formulation 6: 3 parts by weight of turmeric, 1 part by weight of American ginseng; Formulation 7: 4 parts by weight of turmeric, 1 part by weight of American ginseng; Formulation 8: 5 parts by weight of turmeric, 1 part by weight of American ginseng; Formulation 9: 6 parts by weight of turmeric and 1 part by weight of American ginseng.

[0039] 2. Test sample preparation The materials were crushed into fine powder according to the mass ratio and then pressed into 1.2 g / tablet.

[0040] 3. Subjects Patients with chemical liver injury whose clinical manifestations included flank pain, fatigue, abdominal distension, nausea, vomiting, poor appetite, aversion to oil, yellow urine, yellow sclera and skin, bitter taste in the mouth, and dry throat were selected.

[0041] 4. Dosage and time of consumption Each person takes 2 tablets 3 times a day, sublingually, for 15 consecutive days as a course of treatment. During this period, the people maintain their original living and eating habits.

[0042] 5. Determination of improvement of chemical liver injury symptoms Improve the symptoms of flank pain, fatigue, abdominal distension, nausea, vomiting, poor appetite, aversion to oil, yellow urine, yellow sclera and skin, bitter taste in the mouth, and dry throat in patients with chemical liver injury. No improvement is marked as “-”, improvement is marked as “+”, obvious improvement is marked as “++”, and significant improvement is marked as “+++”.

[0043] 6 Test results 6.1 General There were 60 volunteers at the beginning of the trial, and 9 were lost to follow-up at the end of the trial. There were 36 males and 15 females with an average age of 45.3 years.

[0044] 6.2 Test results Table 1 Improvement of symptoms of chemical liver injury 6.3 Conclusion Turmeric: American ginseng = 3:1~5:1 is the ideal ratio. This ratio can effectively improve the symptoms of chemical liver injury such as side pain, fatigue, abdominal distension, nausea, vomiting, poor appetite, aversion to oil, yellow urine, jaundice of sclera and skin, bitter taste in the mouth, dry throat, etc. in patients with chemical liver injury, especially for the symptoms of poor appetite, abdominal distension, side pain, nausea, vomiting, aversion to oil, yellow urine, jaundice of sclera and skin in patients with chemical liver injury, and can significantly improve the patients' mental state and quality of life.

[0045] Process screening and human bioavailability testing 1. Process 1 (process in which American ginseng volatile oil is not collected separately) 1.1. Formulation Calculated by weight, the amount of raw and auxiliary materials used is: 130 parts of American ginseng, 520 parts of turmeric powder, 650 parts of edible glucose powder, 18 parts of edible starch, 20 parts of magnesium stearate, and 1.4 parts of sodium carboxymethyl cellulose.

[0046] 1.2. American ginseng extract 1.2.1. Cleaning, drying and crushing Take the formulated amount of American ginseng and wash it three times with running drinking water to remove impurities. Dry the washed American ginseng in a thermal circulation oven at 63°C. After natural cooling, crush the American ginseng into 10-mesh coarse powder for later use.

[0047] 1.2.2. Percolation extraction and concentration After the American ginseng crude powder was stirred and moistened with 2 times the weight of 70wt% edible ethanol solution and sealed for 24 hours, 13 times the weight of ginseng powder was added with 70wt% edible ethanol solution to start percolation, and the percolation liquid flow rate was controlled at 250ml / min.

[0048] The percolate is concentrated into a thick paste with a relative density of 1.28 (60°C) using a single-effect vacuum decompression concentrator to recover ethanol and is then stored in a freezer (0-4°C) for later use. The steam pressure is 0.06-0.1Mpa and the vacuum pressure is -0.04-0.08Mpa.

[0049] 1.3. Granulation 1.3.1. Crushing and sieving Grind edible glucose powder, edible starch and magnesium stearate into 100 mesh powders respectively for later use.

[0050] 1.3.2. Preparation of adhesive Take the prescribed amount of sodium carboxymethyl cellulose and disperse it overnight with 6 times the amount of 95wt% edible ethanol solution one day in advance, then add appropriate amount of purified water to prepare a 2.5wt% solution.

[0051] 1.3.3. Mixing and granulation Premix edible glucose powder and edible starch in a high-speed mixing granulator for 6 minutes, slowly add American ginseng paste under slow stirring, and continue stirring for 5 minutes; slowly add sodium carboxymethyl cellulose solution under fast stirring, and continue stirring for 5 minutes, pour the prepared wet granules into a boiling dryer, boil and dry at 70-80°C, and control the moisture content to 3wt%.

[0052] 1.3.4. Granulation and total mixing The dry granules were sieved with a 16-mesh sieve, magnesium stearate and turmeric powder were added, and the mixture was mixed in a three-dimensional motion mixer for 15 minutes.

[0053] 1.3.5. Tablet pressing The above materials were tableted using a ZP-35B rotary tablet press, and the tablet weight range was controlled within 1.20 to 1.25 g.

[0054] 1.3.6. Packaging The qualified tablets are packaged with PVC sheets / aluminum foil and medicinal composite films, with 12 tablets per plate.

[0055] 2. Process 2 (Separate collection process of American ginseng volatile oil) 2.1. Formulation Calculated by weight, the amount of raw and auxiliary materials used is: 130 parts of American ginseng, 520 parts of turmeric powder, 650 parts of edible glucose powder, 18 parts of edible starch, 20 parts of magnesium stearate, and 1.4 parts of sodium carboxymethyl cellulose.

[0056] 2.2. American ginseng extraction 2.2.1. Cleaning, drying and crushing Take the formulated amount of American ginseng and wash it three times with running drinking water to remove impurities. Dry the washed American ginseng in a thermal circulation oven at 63°C. After natural cooling, crush the American ginseng into 10-mesh coarse powder for later use.

[0057] 2.2.2. Volatile oil extraction Take the crude powder of American ginseng, put it into a multifunctional extraction tank, pass steam distillation, extract for 2.0 hours, collect the distillate, separate the upper volatile oil, and set aside.

[0058] 2.2.3. Percolation extraction and concentration The distilled ginseng powder was stirred and moistened with 2 times the weight of 70wt% edible ethanol solution, and then sealed for 24 hours. Then, 13 times the weight of 70wt% edible ethanol solution was added to start percolation, and the percolation liquid flow rate was controlled at 250ml / min.

[0059] The percolate is concentrated into a thick paste with a relative density of 1.28 (60°C) using a single-effect vacuum decompression concentrator to recover ethanol and is then stored in a freezer (0-4°C) for later use. The steam pressure is 0.06-0.1Mpa and the vacuum pressure is -0.04-0.08Mpa.

[0060] 2.3. Granulation 2.3.1. Pretreatment of turmeric powder and American ginseng volatile oil Slowly add American ginseng volatile oil to the turmeric powder while stirring, stir for 5 minutes, and use a 20-mesh sieve of a swing granulator to scrape the powder for later use. 2.3.2. Crushing and sieving Grind edible glucose powder, edible starch and magnesium stearate into 100 mesh powders respectively for later use.

[0061] 2.3.3. Preparation of adhesive Take the prescribed amount of sodium carboxymethyl cellulose and disperse it overnight with 6 times the amount of 95wt% edible ethanol solution one day in advance, then add appropriate amount of purified water to prepare a 2.5wt% solution.

[0062] 2.3.4. Mixing and granulation Premix edible glucose powder and edible starch in a high-speed mixing granulator for 6 minutes, slowly add American ginseng paste under slow stirring, and continue stirring for 5 minutes; slowly add sodium carboxymethyl cellulose solution under fast stirring, and continue stirring for 5 minutes, pour the prepared wet granules into a boiling dryer, boil and dry at 70-80°C, and control the moisture content to 3wt%.

[0063] 2.3.5. Granulation and total mixing The dry granules were sieved with a 16-mesh sieve, magnesium stearate and turmeric powder were added, and the mixture was mixed in a three-dimensional motion mixer for 15 minutes.

[0064] 2.3.6. Tabletting The above materials were tableted using a ZP-35B rotary tablet press, and the tablet weight range was controlled within 1.20 to 1.25 g.

[0065] 2.3.7. Packaging The qualified tablets are packaged with PVC sheets / aluminum foil and medicinal composite films, with 12 tablets per plate.

[0066] 3. Human biological interest rate test 3.1. Test conclusion In this study, HPLC-MS was used to determine the concentrations of curcumin and its derivatives in plasma at different times after 19 healthy male volunteers took American ginseng and turmeric oral tablets (6 tablets, 1.2 g / tablet) with a curcumin content of 156 mg (calculated as total curcumin) or American ginseng and turmeric oral tablets (6 tablets, 1.2 g / tablet) with a curcumin content of 154 mg (calculated as total curcumin) by taking American ginseng and turmeric oral tablets (6 tablets, 1.2 g / tablet) with a curcumin content of 156 mg (calculated as total curcumin) by chewing and swallowing American ginseng and turmeric oral tablets (6 tablets, 1.2 g / tablet, chewed and swallowed at one time) in each healthy male volunteer. The plasma concentration-time curve was plotted, and the pharmacokinetic parameters were obtained. The trapezoidal method was used to calculate the AUC value, and the semi-logarithmic plotting method was used to calculate t from the concentration at the end of the elimination phase. 1 / 2 .

[0067] The concentration of curcumin and its derivatives in plasma was determined by HPLC-MS. Endogenous substances in plasma did not interfere with sample determination. The linear range of the standard curve was 2.2-1076 ng / ml, the lower limit of quantification was 2.2 ng / ml, and the extraction recovery was 67.0%-70.8%. The intra-batch and inter-batch precision and accuracy were in compliance with relevant regulations and met the requirements for biological sample analysis.

[0068] The bioavailability (F) of 19 subjects calculated by Winnonlin 5.2.1 software compared the American ginseng and turmeric oral compressed candy taken by buccal process 2, the American ginseng and turmeric oral compressed candy taken by buccal process 1, and the American ginseng and turmeric oral compressed candy taken by chewing and swallowing process 2 are shown in Table 2.

[0069] Table 2 Comparison of bioavailability of oral and swallowed products in 19 subjects The relative bioavailability F of curcumin in the product of Process 1 taken orally compared with that in the product of Process 2 taken orally is 5500%; the relative bioavailability F of curcumin in the product of Process 2 taken orally compared with that in the product of Process 2 taken orally is 9000%. Since the volatile oil of American ginseng is mixed with turmeric in the product of Process 2, the fat solubility is increased, and the absorption and utilization of curcumin in turmeric is increased.

[0070] 3.2 Experimental examples 3.2.1. Blood drug concentration data of volunteer No. 1 after taking the drug 3.2.2. Blood drug concentration data of volunteer No. 2 after taking the drug 3.2.3. Blood drug concentration data of volunteer No. 3 after taking the drug In order to make the contents of the present invention easier to understand, the technical solution of the present invention is further described below in conjunction with specific implementation methods, but the present invention is not limited thereto.

[0071] Example 1 1. Weighing: According to weight ratio, 125 parts of American ginseng, 460 parts of turmeric powder, 590 parts of edible glucose powder, 15 parts of edible starch, 18 parts of magnesium stearate and 1.2 parts of sodium carboxymethyl cellulose were weighed respectively.

[0072] 2. American ginseng extract 2.1. Cleaning, drying and crushing Take the formulated amount of American ginseng and wash it three times with running drinking water to remove impurities. Dry the washed American ginseng in a thermal circulation oven at 60°C. After natural cooling, crush the American ginseng into 10-mesh coarse powder for later use.

[0073] 2.2. Volatile oil extraction Take the crude powder of American ginseng, put it into a multifunctional extraction tank, pass steam distillation, extract for 2.0 hours, collect the distillate, separate the upper volatile oil, and set aside.

[0074] 2.3. Percolation extraction and concentration The distilled ginseng powder was stirred and moistened with 2 times the weight of 70wt% edible ethanol solution, and then sealed for 24 hours. Then, 13 times the weight of 70wt% edible ethanol solution was added to start percolation, and the percolation liquid flow rate was controlled at 235ml / min.

[0075] The percolate is concentrated into a thick paste with a relative density of 1.26 (60°C) using a single-effect vacuum decompression concentrator to recover ethanol and then stored in a freezer (0-4°C) for later use. The steam pressure is 0.06-0.08Mpa and the vacuum pressure is -0.04--0.06Mpa. 3. Granulation 3.1. Pretreatment of turmeric powder and American ginseng volatile oil Slowly add American ginseng volatile oil to the turmeric powder while stirring, stir for 5 minutes, scrape the powder through a 20-mesh sieve of a swing granulator, and set aside.

[0076] 3.2. Crushing and sieving Grind edible glucose powder, edible starch and magnesium stearate into 100 mesh powders respectively for later use.

[0077] 3.3. Preparation of adhesive Take the prescribed amount of sodium carboxymethyl cellulose and disperse it overnight with 6 times the amount of 95wt% edible ethanol solution one day in advance, then add appropriate amount of purified water to prepare a 2.8wt% solution.

[0078] 3.4. Mixing and granulation Premix edible glucose powder and edible starch in a high-speed mixing granulator for 6 minutes, slowly add American ginseng paste under slow stirring, and continue stirring for 5 minutes; slowly add sodium carboxymethyl cellulose solution under fast stirring, and continue stirring for 5 minutes, pour the prepared wet granules into a boiling dryer, boil and dry at 75-78°C, and the moisture content of the granules is 3.5wt%.

[0079] 3.5. Granulation and mixing The dry granules were sieved with a 16-mesh sieve, magnesium stearate and turmeric powder were added, and the mixture was mixed in a three-dimensional motion mixer for 15 minutes.

[0080] 4. Tablet pressing The above materials were tableted using a ZP-35B rotary tablet press, and the tablet weight range was controlled between 1.20 and 1.23 g.

[0081] 5. Packaging The qualified tablets are packaged with PVC sheets / aluminum foil and medicinal composite films, with 12 tablets per plate.

[0082] Example 2 1. Weighing: According to the mass ratio, 170 parts of American ginseng, 750 parts of turmeric powder, 780 parts of edible glucose powder, 20 parts of edible starch, 24 parts of magnesium stearate and 1.6 parts of sodium carboxymethyl cellulose were weighed respectively.

[0083] 2. American ginseng extract 2.1. Cleaning, drying and crushing Take the formulated amount of American ginseng and wash it three times with running drinking water to remove impurities. Dry the washed American ginseng in a thermal circulation oven at 63°C. After natural cooling, crush the American ginseng into 10-mesh coarse powder for later use.

[0084] 2.2. Volatile oil extraction Take the crude powder of American ginseng, put it into a multi-functional extraction tank, pass steam distillation, extract for 2.1 hours, collect the distillate, separate the upper volatile oil, and set aside.

[0085] 2.3. Percolation extraction and concentration The distilled ginseng powder was stirred and moistened with 2 times the weight of 70wt% edible ethanol solution, and then sealed for 24 hours. Then, 13 times the weight of 70wt% edible ethanol solution was added to start percolation, and the percolation liquid flow rate was controlled at 250ml / min.

[0086] The percolate is concentrated into a thick paste with a relative density of 1.28 (60°C) using a single-effect vacuum decompression concentrator to recover ethanol and is then stored in a freezer (0-4°C) for later use. The steam pressure is 0.06-0.8Mpa and the vacuum pressure is -0.04-0.07Mpa.

[0087] 3. Granulation 3.1. Pretreatment of turmeric powder and American ginseng volatile oil Slowly add American ginseng volatile oil to the turmeric powder while stirring, stir for 9 minutes, scrape the powder through a 20-mesh sieve of a swing granulator, and set aside.

[0088] 3.2. Crushing and sieving Grind edible glucose powder, edible starch and magnesium stearate into 100 mesh powders respectively for later use.

[0089] 3.3. Preparation of adhesive Take the prescribed amount of sodium carboxymethyl cellulose and disperse it overnight with 6 times the amount of 95wt% edible ethanol solution one day in advance, then add appropriate amount of purified water to prepare a 2.6wt% solution.

[0090] 3.4. Mixing and granulation Premix edible glucose powder and edible starch in a high-speed mixing granulator for 7 minutes, slowly add American ginseng paste under slow stirring, and continue stirring for 5 minutes; slowly add sodium carboxymethyl cellulose solution under fast stirring, and continue stirring for 5 minutes, pour the prepared wet granules into a boiling dryer, boil and dry at 75-78°C, and the moisture content of the granules is 4.3wt%.

[0091] 3.5. Granulation and mixing The dry granules were sieved with a 16-mesh sieve, magnesium stearate and turmeric powder were added, and the mixture was mixed in a three-dimensional motion mixer for 15 minutes.

[0092] 4. Tablet pressing The above materials were tableted using a ZP-35B rotary tablet press, and the tablet weight range was controlled at 1.23 to 1.24 g.

[0093] 5. Packaging The qualified tablets are packaged with PVC sheets / aluminum foil and medicinal composite films, with 12 tablets per plate.

[0094] Example 3 1. Weighing: Weigh 150 parts of American ginseng, 600 parts of turmeric powder, 700 parts of edible glucose powder, 18 parts of edible starch, 22 parts of magnesium stearate and 1.4 parts of sodium carboxymethyl cellulose respectively according to the mass ratio.

[0095] 2. American ginseng extract 2.1. Cleaning, drying and crushing Take the formulated amount of American ginseng and wash it three times with running drinking water to remove impurities. Dry the washed American ginseng in a thermal circulation oven at 65°C. After natural cooling, crush the American ginseng into 10-mesh coarse powder for later use.

[0096] 2.2. Volatile oil extraction Take the crude powder of American ginseng, put it into a multi-functional extraction tank, pass steam distillation, extract for 2.2 hours, collect the distillate, separate the upper volatile oil, and set aside.

[0097] 2.3. Percolation extraction and concentration The distilled ginseng powder was stirred and moistened with 2 times the weight of 70wt% edible ethanol solution, and then sealed for 24 hours. Then, 13 times the weight of 70wt% edible ethanol solution was added to start percolation, and the percolation liquid flow rate was controlled at 260ml / min.

[0098] The percolate is concentrated into a thick paste with a relative density of 1.26 (65°C) using a single-effect vacuum decompression concentrator to recover ethanol and is then stored in a freezer (0-4°C) for later use. The steam pressure is 0.06-0.9Mpa and the vacuum pressure is -0.04-0.07Mpa.

[0099] 3. Granulation 3.1. Pretreatment of turmeric powder and American ginseng volatile oil Slowly add American ginseng volatile oil to the turmeric powder while stirring, stir for 8 minutes, scrape the powder through a 20-mesh sieve of a swing granulator, and set aside.

[0100] 3.2. Crushing and sieving Grind edible glucose powder, edible starch and magnesium stearate into 100 mesh powders respectively for later use.

[0101] 3.3. Preparation of adhesive Take the prescribed amount of sodium carboxymethyl cellulose and disperse it overnight with 6 times the amount of 95wt% edible ethanol solution one day in advance, then add appropriate amount of purified water to prepare a 2.8wt% solution.

[0102] 3.4. Mixing and granulation Premix edible glucose powder and edible starch in a high-speed mixing granulator for 7 minutes, slowly add American ginseng paste under slow stirring, and continue stirring for 5 minutes; slowly add sodium carboxymethyl cellulose solution under fast stirring, and continue stirring for 5 minutes, pour the prepared wet granules into a boiling dryer, boil and dry at 70-75°C, and the moisture content of the granules is 4.3wt%.

[0103] 3.5. Granulation and mixing The dry granules were sieved with a 16-mesh sieve, magnesium stearate and turmeric powder were added, and the mixture was mixed in a three-dimensional motion mixer for 15 minutes.

[0104] 4. Tablet pressing The above materials were tableted using a ZP-35B rotary tablet press, and the tablet weight range was controlled between 1.20 and 1.23 g.

[0105] 5. Packaging The qualified tablets are packaged with PVC sheets / aluminum foil and medicinal composite films, with 12 tablets per plate.

[0106] Animal test on the auxiliary protection function against chemical liver damage 1.1. Overview According to the Technical Specifications for Inspection and Evaluation of Health Foods (2003 Edition) and the State Administration for Market Regulation's "Interpretation of Issues Concerning the Announcement on Standardizing the Labeling of Functional Claims of Health Foods" (No. 23 of 2018), 27 types of health foods must undergo testing when declaring their functions (animal testing or human food testing or both). For health foods with auxiliary protective functions against chemical liver damage, only animal testing and evaluation are required. For this reason, this product has undergone animal function testing.

[0107] Materials and methods 1.2.1. Test substances Finished product of Example 3, specification: 1.2 g / tablet*12 plates / box, the recommended oral dosage for humans is 7.2 g / d per person (adult), calculated as 60 kg body weight for an adult, and the equivalent dosage is 120 mg / kg BW.

[0108] 1.2.2. Experimental animals: Sixty healthy adult male Kunming mice of SPF grade bred in the Experimental Animal Center of Guangxi Medical University were selected, with a body weight of 18 to 22 grams.

[0109] 1.2.3. Dose selection: Three groups were set up: low, medium and high, with doses of 0.6, 1.2 and 3.6 g / kg·BW (equivalent to 5, 10 and 30 times the recommended dose, respectively), and the concentrations were 30, 60 and 180 mg / mL, respectively. A solvent control group (distilled water) and CCl 4 Control group, CCl 4 The dose is 24 mg / kg·BW.

[0110] 1.3. Main instruments and reagents: Hitachi 7060C fully automatic biochemical analyzer, biological tissue automatic dehydration machine, biological tissue freezing embedding machine, Finesse 325 Paraffin slicer, fully automatic staining machine, BX-51 microscope.

[0111] Biochemical reagents were purchased from Shanghai Jiuqiang Biochemical Reagent Co., Ltd., and analytical grade CCl 4 It was purchased from Shanghai Changjiang Chemical Plant and prepared with soybean oil to 2.4 mg / mL.

[0112] 1.4. Experimental methods: The experiment was conducted according to the Technical Specifications for Inspection and Evaluation of Health Food (2003 edition) and the animal experimental protocol of carbon tetrachloride liver injury model.

[0113] 1.4.1. Specific experimental methods The experimental animals were randomly divided into solvent and CCl 4The animals in the control group and the low, medium and high dose groups were given the test substance by oral gavage every day. The solvent control group and CCl 4 The control group was given distilled water (20 ml / kg·BW by intragastric administration). The animals were weighed twice a week to adjust the dose of the test substance and were allowed to eat and drink freely for 30 days.

[0114] One day before the end of the experiment, the animals in each group were fasted for 16 h overnight and CCl 4 The animals in the group and each dose group were intragastrically administered with CCl at a rate of 0.01 mL / g·BW each time. 4 The solvent control group was given soybean oil, and the test groups were treated with CCl 4 After 4 hours of exposure, the test substance was continued to be administered. CCl 4 After 24 hours, the eyeballs were removed and blood was collected to separate the serum for determination of ALT and AST. At the same time, the animals were killed and the livers were removed for histopathological examination.

[0115] 1.5. Scoring Criteria Among all types of lesions, 0 points were assigned if the liver cells were roughly normal, 1 point was assigned if the diseased cells occupied 1 / 4 of the entire visual field, 2 points were assigned if they occupied 1 / 2 of the entire visual field, 3 points were assigned if they occupied 3 / 4 of the entire visual field, and 4 points were assigned if they occupied the entire visual field. The total score was the sum of the scores for watery degeneration, ballooning degeneration, fatty degeneration, and cytoplasmic condensation, plus twice the score for liver cell necrosis.

[0116] 1.6. Statistics Statistical analysis was performed using SPSS11.0 software package.

[0117] Results 1.7.1. Effects of the test substance on serum ALT and AST CCl 4 The ALT and AST levels of mice in the control group were higher than those in the solvent control group (F values ​​were 36.8 and 27.9, respectively, P < 0.05). The ALT and AST values ​​of each dose group of the sample were lower than those of CCl 4 ALT / AST values ​​and CCl in the control group, medium-dose group and high-dose group 4 There were significant differences compared with the control group (F values ​​were 10.20 and 9.8, P < 0.05), see Table 3.

[0118] Table 3 ALT and AST test results of mice in each group ( ) Note: With CCl 4 Compared with the positive control group, ∗P<0.05.

[0119] 1.7.2. Liver histopathological examination 1.7.2.1. Visual observation Solvent control group: The liver surface was smooth, bright red in color, and soft in texture.

[0120] CCl 4 Control group: The liver surface was granular, the color became lighter to earthy yellow, and the texture was slightly hard.

[0121] Each dose group: The liver surface had uniform fine particles, with a slightly yellow, dark brown or khaki color, and was soft or slightly hard.

[0122] 1.7.2.2. Microscopic examination The microscopic examination results of each group are as follows Figure 1-5 As shown: Solvent control group: The hepatic sinusoids were very clear and obvious, and the hepatic cords were neatly arranged and extended from the central vein. The hepatocytes had normal morphology and structure, with very clear cell boundaries and elasticity. The cytoplasm was thick, the cytoplasm was uniform, there were no vacuoles, and there was no obvious cell necrosis and tissue deformation.

[0123] CCl 4 Control group: The liver cells adhered together, the cells were in disorder, some of the cell nuclei dissolved, the hepatic cords and hepatic sinusoids disappeared, the cells were swollen and necrotic, the cytoplasm was sparse, and the pathological damage was very serious.

[0124] Each dosage group: ① From the low-dose group, it can be seen that the liver cells are still very chaotic, with sparse and swollen cytoplasm, compact cells, and large-area necrosis. No obvious hepatic cords were seen, but hepatic sinusoids gradually appeared from the central vein, and the cytopathic changes were alleviated.

[0125] ② In the medium-dose sections, the hepatic sinusoids are obvious, the hepatic cords gradually become clear, and they branch out from the central vein. The cells tend to be normal, and there are no obvious vacuoles in the cells. However, there are still chaotic and necrotic cells.

[0126] ③ From the high-dose group, it can be seen that the hepatic sinusoids are very obvious, the hepatic cords are fresh, the cells are basically normal, the cytoplasm is thick, and there are no lesions.

[0127] ④ Compared with the low-dose group, the recovery of liver cells in the high-dose group was particularly obvious. The liver cells returned to normal from the swollen and vacuolated state, the cells became regular, and clear boundaries appeared between the cells.

[0128] CCl 4 The liver cell necrosis and total score in the control group were higher than those in the solvent control group (F values ​​were 17.5 and 9.0, respectively, P < 0.05). The liver cell necrosis and total score in the medium and high dose groups were higher than those in the CCl 4 The control group was lower (F values ​​were 9.9 and 14.7, P < 0.05). The results are shown in Table 4.

[0129] Table 4 Results of liver histopathological examination of mice in each group ( ) Note: With CCl 4 Compared with the positive control group, ∗P<0.05 1.8 Result determination This formula process product can reduce CCl 4 The serum ALT and AST levels were increased, and the liver damage degree of the test group was lower than that of CCl 4 The control group showed that the product had a protective effect against chemical liver damage when taken orally.

[0130] The above description is only a preferred embodiment of the present invention. All equivalent changes and modifications made according to the scope of the patent application of the present invention should fall within the scope of the present invention.

Claims

1. A candy containing American ginseng and turmeric oral tablets with auxiliary protection function against chemical liver damage, characterized in that: The invention is prepared from American ginseng, turmeric powder, edible glucose powder and edible starch as raw materials, and sodium carboxymethyl cellulose and magnesium stearate as auxiliary materials. The raw and auxiliary materials are used in the following amounts by weight: 125-170 parts of American ginseng, 460-750 parts of turmeric powder, 590-780 parts of edible glucose powder, 15-20 parts of edible starch, 18-24 parts of magnesium stearate and 1.2-1.6 parts of sodium carboxymethyl cellulose.

2. The American ginseng and turmeric oral tablet candy according to claim 1, characterized in that: The mass ratio of turmeric powder to American ginseng is 3:1 to 5:

1.

3. The method for preparing the American ginseng and turmeric oral tablet candy according to claim 1 or 2, characterized in that: The following steps are involved:

1. American ginseng extract 1.

1. Cleaning, drying and crushing Take a formula amount of American ginseng and wash it with running drinking water to remove impurities, dry the washed American ginseng at 60℃~65℃, and crush the American ginseng into 10 mesh coarse powder after natural cooling for later use; 1.

2. Volatile oil extraction Take the crude powder of American ginseng, put it into an extraction tank, steam distill it, extract it for 2-2.5 hours, collect the distillate, separate the upper volatile oil, and set it aside; 1.

3. Percolation extraction and concentration After distillation, the ginseng powder was stirred and moistened with 2 times the weight of 70wt% edible ethanol solution and sealed for 24 hours, and then 13 times the weight of 70wt% edible ethanol solution was added to start percolation, and the percolation liquid flow rate was controlled at 230-270ml / min; The percolate is concentrated into a thick paste with a relative density of 1.25 to 1.30 by using a single-effect vacuum decompression concentrator to recover ethanol, and then stored at 0 to 4°C for later use, wherein the steam pressure is 0.06 to 0.1 MPa and the vacuum pressure is -0.04 to -0.08 MPa; 2. Granulation 2.

1. Pretreatment of turmeric powder and American ginseng volatile oil Slowly add American ginseng volatile oil to the turmeric powder while stirring, stir for 5 to 10 minutes, and use a 20-mesh sieve of a swing granulator to scrape the powder for later use; 2.

2. Crushing and sieving Grind edible glucose powder, edible starch and magnesium stearate into 100 mesh powders respectively for later use; 2.

3. Preparation of adhesive Take the prescribed amount of sodium carboxymethyl cellulose and disperse it overnight with 6 times the weight of 95wt% edible ethanol solution one day in advance, then add appropriate amount of purified water to make a 2.5-3.0wt% solution; 2.

4. Mixing and granulation Place edible glucose powder and edible starch in a high-speed mixing granulator for premixing for 6 to 10 minutes, add American ginseng paste, and continue stirring for 5 minutes; then add sodium carboxymethyl cellulose solution, continue stirring for 5 minutes, pour the prepared wet granules into a boiling dryer, boil and dry at 70 to 80°C, and control the moisture content to 3wt% to 5wt%; 2.

5. Granulation and total mixing The dry granules were sieved with a 16-mesh sieve, magnesium stearate and turmeric powder were added, and mixed in a three-dimensional motion mixer for 15 minutes; 2.

6. Press into tablets and package.

4. The preparation method according to claim 3, characterized in that: The relative density of the American ginseng paste in step 1.3 is measured at 60°C to 65°C.

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