Fresh panax notoginseng enteric-coated tablet and preparation method thereof

Abstract

The application discloses a fresh panax notoginseng enteric-coated tablet and a preparation method thereof. The fresh panax notoginseng enteric-coated tablet comprises fresh panax notoginseng extract and excipients. The fresh panax notoginseng extract is extracted from the dug panax notoginseng root without drying treatment and comprises panax notoginseng saponins, panax notoginseng element and panax notoginseng polysaccharide. The excipients are excipients and coating film components. The preparation method comprises the following steps: fresh panax notoginseng extract extraction, fresh panax notoginseng extract tablet core preparation, fresh panax notoginseng extract tablet core coating, and fresh panax notoginseng extract extraction, which comprises fresh panax notoginseng cleaning, weighing, wet crushing, solid-liquid separation, alcohol precipitation, polysaccharide separation, vacuum drying, dry granulation, tablet pressing and coating. The fresh panax notoginseng raw material is directly extracted, so that the active components are not destroyed due to heating in the drying process of panax notoginseng medicinal materials and the risk of mold growth of the dried panax notoginseng medicinal materials is avoided. The wet crushing extraction method is adopted, so that the heat-sensitive components are not destroyed in the process of extracting the active components of panax notoginseng by heating, and the panax notoginseng extract, panax notoginseng saponins, panax notoginseng element and panax notoginseng polysaccharide have good biological activity. The enteric coating avoids the decomposition of the drug under the acidic condition of the stomach and improves the bioavailability of the active components in the body.

Description

Technical Field

[0001] This invention relates to traditional Chinese medicine preparation technology, and in particular to a fresh Panax notoginseng enteric-coated tablet and its preparation method. Background Technology

[0002] Ancient people have already explained that Panax notoginseng has both blood-activating and hemostatic effects.

[0003] The properties and channels of Panax notoginseng: sweet, slightly bitter, warm, enters the liver and stomach channels;

[0004] Functions and indications: "It disperses blood stasis and stops bleeding, reduces swelling and relieves pain, and is used for hemoptysis, hematemesis, epistaxis, hematochezia, metrorrhagia, and traumatic bleeding."

[0005] The main components of Panax notoginseng include saponins, flavonoids, volatile oils, amino acids, polysaccharides, and notoginsenosides [National Pharmacopoeia Commission. Pharmacopoeia of the People's Republic of China (Part I) [M]. Beijing: China Medical Science and Technology Press, 2015: 11].

[0006] Pharmacological studies have shown that Panax notoginseng has a dual pharmacological effect, with good hemostatic effect on the one hand and blood-activating and stasis-removing effect on the other [Yang Zhigang et al., Effects of Panax notoginseng on the blood system and cardiovascular system [J]. Chinese Journal of Veterinary Drugs, 2008, 42(3): 46].

[0007] Panax notoginseng powder has the effects of significantly reducing platelet activity, inhibiting platelet adhesion and aggregation, anti-thrombosis, and improving microcirculation. Compared with the antithrombotic mechanism and efficacy of aspirin, aspirin cannot inhibit platelet aggregation induced by two or more agglutinating agents and cannot inhibit all pathways of platelet aggregation. In comparison, the antithrombotic mechanism of Panax notoginseng powder is more comprehensive [Wan Xiaoqing. Comparison of antithrombotic mechanism and efficacy of Panax notoginseng powder and aspirin [J]. Journal of Integrated Traditional and Western Medicine on Cardiovascular and Cerebrovascular Diseases, 2009, 7(5): 604-605].

[0008] The main components of Panax notoginseng that promote blood circulation and remove blood stasis are Panax notoginseng saponins [Huang Jiawen et al., Screening of active components of Panax notoginseng for hemostasis and blood circulation [J] Journal of Yunnan University of Traditional Chinese Medicine, 2018, 41(6)12-18]

[0009] Panax notoginseng saponins can inhibit platelet aggregation, reduce whole blood viscosity, inhibit platelet activation and aggregation, significantly reduce myocardial ischemia, improve myocardial microcirculation, scavenge oxygen free radicals, inhibit lipid peroxidation and stabilize nerve cells; Panax notoginseng saponins, quercetin and other saponins can promote the occurrence of coagulation process, shorten the coagulation time after bleeding and promote the generation of thrombin; they are often used for the prevention and treatment of coronary heart disease, angina pectoris and cerebrovascular diseases [Zhou Chen et al., Functions and chemical components of Panax notoginseng [J] Practical Journal of Traditional Chinese Medicine Internal Medicine 2018, 32(8)4-7].

[0010] Panax notoginseng amino acid has significant hemostatic activity and is considered to be the main effective component of Panax notoginseng for hemostasis [Ding Yongsheng, Research on Quality Evaluation of Panax notoginseng Based on Blood-Activating Spectrum Effect [D] Beijing University of Chinese Medicine 2020]

[0011] The content of notoginseng in Panax notoginseng was determined to be 0.87% using an automatic amino acid analyzer [Lu Qi et al., Isolation, Identification and Content Determination of Hemostatic Components in Panax notoginseng [J], Chinese Traditional and Herbal Drugs, 1988, (9) 34-35].

[0012] Compared with tranexamic acid, dencichine not only stops bleeding faster, but also requires a much smaller dose. 100mg of tranexamic acid shortens bleeding time by 30s, while 1mg of dencichine shortens it by 5min [Zhao Guoqiang et al., Dencichine, a hemostatic component of Panax notoginseng [J] Chinese Traditional and Herbal Drugs 1986, 17(6) 34-35].

[0013] Experimental observations on the effects of Panax notoginseng saponins on platelet function and thrombosis in animals revealed that Panax notoginseng saponins can significantly inhibit collagen, arachidonic acid (AA), and adenosine diphosphate (ADP)-induced platelet aggregation in rats and rabbits, and inhibit experimental thrombosis in rats [Su Ya et al., Effects of Panax notoginseng saponins on platelet function and thrombosis in animals [J] Chinese Traditional and Herbal Drugs, 1996, 27(11)666]. These studies provide strong evidence for the application of Panax notoginseng in anti-anginal pectoral pain and thrombosis treatment.

[0014] Panax notoginseng, quercetin, etc. can all promote the occurrence of coagulation process, shorten the coagulation time after bleeding, promote the generation of thrombin, thereby constricting local blood vessels and increasing platelet count [Wang Mingyue. A case of upper gastrointestinal bleeding caused by blister beetle poisoning treated with Panax notoginseng powder after taking Zhibai Dihuang Decoction [J] Journal of Traditional Chinese Medicine, 1984, 12(5): cover 4].

[0015] Notoginsenoside is considered the main component responsible for the hemostatic effect of Panax notoginseng [Li Lin et al., Study on the in vitro transdermal permeability characteristics of notoginsenoside [J]. Chinese Traditional and Herbal Drugs, 2015, 46(17): 2563-2567]. Notoginsenoside not only has significant hemostatic effects but also neuroprotective, anti-inflammatory, and effects in reducing diabetic and renal damage [Yang Lingjuan et al., High-performance liquid chromatography detection of notoginsenoside and its isomers in Panax notoginseng [J]. Chinese Medicinal Herbs, 2015, 38(02): 311-314].

[0016] The effective hemostatic component of Panax notoginseng is notoginsenoside, which is easily destroyed by heat. Therefore, Panax notoginseng should be used raw. [Tang Can et al., Optimization of preparation process of solid ring capsules [J] Chinese patent medicine 2001, 23(2)84-87].

[0017] Panax notoginseng amino acid has significant hemostatic activity and is considered to be the main effective component of Panax notoginseng for hemostasis [Ding Yongsheng, Study on quality evaluation of Panax notoginseng based on blood-activating spectrum effect [D] Beijing University of Chinese Medicine 2020].

[0018] The effective hemostatic component of Panax notoginseng is notoginsenoside, and the effective blood-activating component of Panax notoginseng is total saponins of Panax notoginseng [Sun Fengzhi, Research progress on the hemostatic and blood-activating effects of Panax notoginseng [J] Medical Research Journal 2013, 42(9)24-271.

[0019] It is known that Panax notoginseng contains both the hemostatic active ingredient notoginsenoside and the blood-activating active ingredient total saponins of Panax notoginseng. The blood-activating and hemostatic effects of the total extract of Panax notoginseng are related to the dosage. The hemostatic effect is more significant at low doses, while the blood-activating effect is more significant at medium and high doses, that is, the antithrombotic effect is stronger. The mechanism may be the inhibition of platelet aggregation. There is a certain dose-effect relationship between the dosage of Panax notoginseng and its hemostatic and blood-activating effects [Zhang Haiying et al. Experimental study on the hemostatic and antithrombotic effects of Panax notoginseng [J] Journal of Xinjiang Medical University, 2012, 35(4): 487-490].

[0020] Small doses of Panax notoginseng have a significant hemostatic effect; medium and large doses of Panax notoginseng have a significant antithrombotic effect [Luo Shijiang et al., Experimental observation on the hemostatic and antithrombotic effects of Panax notoginseng [J]. Journal of Guiyang University of Traditional Chinese Medicine, 2013, 35(1): 260-261].

[0021] Notoginsenoside is considered to be the main component of Panax notoginseng that exerts its hemostatic effect. Notoginsenoside not only has significant hemostatic effects, but also has neuroprotective, anti-inflammatory, diabetic damage relief, and kidney damage relief effects [Yang Lingjuan et al., HPLC detection of notoginsenoside and its isomers in Panax notoginseng [J] Chinese Medicinal Herbs, 2015, 38(02)311-314].

[0022] The effective hemostatic component of Panax notoginseng, notoginsenoside, is easily destroyed by heat [Tang Can, Optimization of the preparation process of solid ring capsules [J] Chinese Traditional and Pharmaceutical Products 2001, 23(2)].

[0023] The Pharmacopoeia specifies the dosage of Panax notoginseng tablets, with each tablet containing Panax notoginseng: (1) 0.5g for large tablets and (2) 0.25g for small tablets. It further specifies that large tablets contain ginsenoside R. g1 Ginsenoside R b1 The three items are: total saponins of Panax notoginseng R1, total saponins of Panax notoginseng ≥20mg, and small tablets contain total saponins of Panax notoginseng ≥10mg [Pharmacopoeia of the People's Republic of China (Part I) [S] Chemical Industry Press, 323].

[0024] According to literature, small doses of Panax notoginseng have a significant hemostatic effect, while medium and large doses have a significant antithrombotic effect. Existing preparations use Panax notoginseng raw materials, some dried and some baked. Dried Panax notoginseng is difficult to remove moldy parts, while baked Panax notoginseng undergoes inconsistent changes in heat-sensitive components due to different heating temperatures and durations. This results in varying hemostatic and antithrombotic effects among the different heat-affected components. Clinically, whether to administer medication for hemostasis or blood-activating purposes, and how to balance the dosage thresholds for hemostasis and blood-activating effects, makes accurate symptomatic medication difficult to control. This leads to uncertainty and even danger in clinical medication. Ensuring the consistency of the bioactivity of saponins, notoginsenosides, and polysaccharides in Panax notoginseng preparations is crucial. It directly relates to the correct dosage for clinical use, whether for hemostasis or blood-activating effects, and is an important factor in clinical disease prevention, treatment, and minimizing adverse reactions.

[0025] However, the existing processing techniques for Panax notoginseng raw materials and extraction processes for Panax notoginseng extracts, as recorded in the literature, are difficult to meet the above requirements.

[0026] Literature records three different drying methods; the content of Rg1 in Panax notoginseng slices was investigated; vacuum freeze-drying, vacuum drying and hot air drying; the experimental results showed that vacuum freeze-drying can better preserve the Rg1 content in Panax notoginseng slices, which is better than vacuum drying and hot air drying [Zhou Guoyan et al., Research on vacuum freeze-drying process of Panax notoginseng [J]. Chinese Traditional and Herbal Drugs, 2013(11): 2525-2528]. This indicates that Panax notoginseng saponin Rg1 is easily destroyed by heat.

[0027] Vacuum freeze-drying is carried out at very low temperatures, with thin air and low oxygen content, which effectively inhibits the biological, chemical or physical changes of active ingredients such as heat-sensitive saponins and notoginseng, and preserves their intrinsic components well. After being freshly cut, it is placed in a 40℃ forced-air oven for drying, but the drying time is still relatively long, and the loss of notoginseng and total sugar is still relatively large [Ma Ni et al., Effects of different drying methods on saponin content of Panax notoginseng slices [J] Specialty Products Research, 2010, 32((3)42).

[0028] During the drying process after Panax notoginseng slices are dried, the active ingredients are carried away by the migration of moisture, and even the internal components are salted out, resulting in a white appearance and loss of components such as Panax notoginseng saponins. The longer the drying time, the greater the loss [Guo Hui. Study on the drying characteristics and mass transfer model of Panax notoginseng in Yunnan [D] Kunming: Kunming University of Science and Technology, 2015].

[0029] Traditional processing of Panax notoginseng involves drying the whole roots directly in the sun or oven without washing them after harvesting. This method has significant drawbacks: First, the drying and dehydration process is lengthy, requiring large drying areas or baking workshops, which is time-consuming, labor-intensive, and space-consuming. Insufficient turning and drying can lead to mold growth. Second, not washing the roots before drying results in a large amount of soil adhering to the surface of the Panax notoginseng, leading to poor hygiene, inaccurate net weight, and the risk of excessive heavy metals and pesticide residues.

[0030] According to literature, in order to overcome the long dehydration time in the whole Panax notoginseng root drying process, it is adopted to dry the roots while they are fresh. Experiments show that different drying methods have different effects on the active ingredients of Panax notoginseng. The alcohol extract of freshly dried slices is 24.64%, the alcohol extract of freshly dried slices at 60℃ is 19.72%, and the alcohol extract of freeze-dried slices is 25.73%. The alcohol extract of freeze-dried slices is 30.4% higher than that of freshly dried slices at 60℃. The content of notoginsenosides is the highest after freeze-drying after fresh cutting, which is 18.39% higher than that of traditional whole root drying. Under the drying condition of 50℃, the total saponin content of freshly cut slices is 7.24% higher than that of traditional decoction piece production process [Liu Yong et al., Effect of fresh cutting processing on the drying rate and quality of Panax notoginseng medicinal materials [J] China Journal of Traditional Chinese Medicine 2019, 44(7) 1381-1392].

[0031] According to the literature, nine groups of fresh Panax notoginseng slices from different origins were prepared. After slicing, nine fresh samples of equal weight were collected from each group. The nine fresh Panax notoginseng samples of equal weight were dried in an oven at 40℃ to obtain dried Panax notoginseng. The content of Panax notoginseng saponins in each group was detected by high performance liquid chromatography. The results are listed in Table 1.

[0032] Table 1. Differences in the content of notoginseng saponins in three groups after drying fresh notoginseng from nine different origins.

[0033]

[0034]

[0035] [Ma Ni et al., Comparison of saponin content between fresh and dried Panax notoginseng [J]. Chinese Traditional and Herbal Drugs, 2004, 35(1)].

[0036] Table 2. Differences in the content of three saponins between fresh and dried Panax notoginseng.

[0037] <![CDATA[R g1 %]]> <![CDATA[R b1 %]]> <![CDATA[R1%]]> <![CDATA[R g1 +R b1 +R1(%)]]> Fresh Panax notoginseng 3.35 3.28 1.12 7.95 Dried Panax notoginseng 2.64 2.16 0.69 5.49 Loss after drying 21.1％ 34.1％ 38.4％％ 30.9％

[0038] [Gao Mingju, Comparison of the content of fresh Panax notoginseng, dried Panax notoginseng and active Panax notoginseng saponins [J] Ginseng Research 2003(2)25-26]

[0039] Using fresh Panax notoginseng as raw material, 1000g of washed fresh Panax notoginseng was chopped and ground with 15L of purified water to achieve cell wall disruption. Three batches of experimental samples were used to extract 29.96g, 30.08g and 29.91g of total Panax notoginseng saponins respectively, with a transfer rate of 90.02% [Qian Rugui et al., Research on the process of extracting total Panax notoginseng saponins and starch from fresh Panax notoginseng [J] Ginseng Research 2021(5)44-48]. 1000g of fresh Panax notoginseng was converted to 250g of dried Panax notoginseng. According to the Pharmacopoeia [Pharmacopoeia of the People's Republic of China (Part I) [S] Chemical Industry Press, 11] Panax notoginseng slices contain R g1 % and R b1 The three items, % and R1%, indicate that the total saponins are ≥5.0%.

[0040] According to the literature, the moisture content of 3-year-old plants harvested in December is 74.93%, and the moisture content of 1-month-old plants is 75.0%; the moisture content of 4-year-old plants harvested in December is 79.91%, and the moisture content of 1-month-old plants is 76.19% [Wang Qingyuan, Discussion on the drying mechanism of Panax notoginseng [J] Agricultural Mechanization Research 2007(6)25-33].

[0041] Experiments using non-heating grinding and extraction methods have shown that the total saponin yield extracted from fresh Panax notoginseng is 20% higher than the standard in the Pharmacopoeia.

[0042] The 2010 edition of the Chinese Pharmacopoeia includes 61 traditional Chinese medicine preparations containing Panax notoginseng. Among them, 41 are made by directly pulverizing into fine powder and adding directly to the medicine, while 18 are made by decoction, reflux, soaking, and alcohol extraction [Shi Jiaping et al. Analysis of dosage forms and processes of traditional Chinese medicine preparations containing Panax notoginseng in the 2010 edition of the Chinese Pharmacopoeia [J]. Today's Pharmacy, 2012, 22(7): 392-394].

[0043] Among the 61 traditional Chinese medicine preparations containing Panax notoginseng, whether they were pulverized into fine powder and added directly to the medicine, or whether they were prepared by decoction, reflux, soaking, or alcohol extraction, the heating process could not avoid the destruction of the active ingredients of Panax notoginseng. In addition, the active ingredients contained in Panax notoginseng were destroyed to varying degrees when different heating and drying methods were used in the drying process.

[0044] The following reactions may occur during the heating process of Panax notoginseng saponins: ① Hydrolysis causing glycosyl desorption: Heating can promote the breakage of glycosidic bonds between glycosyl groups and aglycones in saponin molecules, leading to glycosyl desorption and thus reducing the activity of saponins. ② Changes in aglycone structure: The aglycone may undergo hydrolysis during heating, resulting in structural changes and affecting its biological activity. ③ Oxidation reaction: Some aglycones in saponins contain multiple hydroxyl groups, which are easily oxidized during heating to form new compounds, thereby altering the properties of saponins. ④ Ring cleavage: Under high-temperature conditions, the cyclic structure in saponin molecules may cleave, leading to a complete change in molecular structure. ⑤ Molecular rearrangement: During the heating process, the high temperature and thermal density of the part in direct contact with the heat transfer wall can cause rearrangement within the saponin molecule, forming new isomers. These newly formed isomers may not have the original biological activity. ⑥ Polymerization reaction: Under high temperatures, saponin molecules may undergo polymerization reactions to form high molecular weight polymers, which can lead to reduced solubility and bioavailability. ⑦ Maillard reaction: During heating, saponins may also undergo a Maillard reaction with reducing sugars to produce brown substances and a series of complex compounds, which alters the stability and activity of the saponins.

[0045] To maintain the stability and bioactivity of Panax notoginseng saponins, raw Panax notoginseng should be treated at a lower temperature or by avoiding heating methods, or when extracting Panax notoginseng extracts; avoid prolonged exposure to high temperature and oxygen-containing environments.

[0046] Panax notoginseng medicinal material is prepared according to the Chinese Pharmacopoeia [National Pharmacopoeia Commission, Chinese Pharmacopoeia, Part I [S], Chemical Industry Press, 2000, 636] to obtain the coarsest powder (passing through a No. 1 sieve), coarse powder (passing through a No. 3 sieve), and medium powder (passing through a No. 4 sieve).

[0047] Table 3. Saponins R in Panax notoginseng raw materials and extracts from materials with different degrees of powdering b1 R g1 R b1 +R b1 content(%)

[0048] Serial Number sample Rb1 / % Rg1 / % Rb1+Rg1 / % 1 medicinal materials 4.6886 4.9488 9.6374 2 Coarsest grade (passes through No. 1 sieve) 4.6167 5.0428 9.6595 3 Coarse powder (passed through a No. 3 sieve) 4.3756 5.3756 9.512 4 All-purpose flour (passed through a No. 4 sieve) 1.9426 4.6106 6.5532

[0049] [Zhang Hanzhong, Effect of Panax notoginseng powder fineness on drug component extraction rate [J] Chinese Journal of Hospital Pharmacy 2004, 24(11)719].

[0050] The data in the table shows that the finer the particle size, the more saponin components are destroyed. This is because the pulverization of solid materials requires pressure at any point within the solid to cause shape change, exceeding the limit value under uniaxial pressure, at which point the solid material yields. Alternatively, the maximum shear force must reach the limit under uniaxial stress, causing yielding failure in the solid material particles. Although the energy consumed in solid deformation is related to the properties of the solid material, most of the energy is converted into heat. The work required for solid pulverization is 100 to 1000 times higher than the work required for yielding failure. Since dried Panax notoginseng has a hard, dense structure and high impact toughness, the yielding failure process requires even more work, leading to rapid heat accumulation and a rapid temperature rise. When subjected to pulverization impact, the Panax notoginseng root blocks quickly reach high temperatures, destroying the active ingredients contained within. This suggests that the current practice of directly pulverizing Panax notoginseng into fine powder for medicinal use (currently found in 41 traditional Chinese medicine preparations) requires improvement. Summary of the Invention

[0051] This invention addresses the shortcomings of existing technologies by proposing a method to avoid the destruction of active ingredients caused by heating during the drying process of Panax notoginseng, the risk of mold growth due to sun drying, and the damage to heat-sensitive components during the extraction of active ingredients from Panax notoginseng using heating methods. It also improves the method of using powdered Panax notoginseng to avoid the destruction of active ingredients during the pulverization process. Furthermore, to prevent the hydrolysis of certain active ingredients in Panax notoginseng by gastric acid, especially the glycosidic bonds of saponins, which could lead to saponin decomposition and loss of its original biological activity, this invention provides an enteric-coated tablet of fresh Panax notoginseng coated with an enteric-coating material and its preparation method.

[0052] The technical solution for realizing the present invention of a fresh Panax notoginseng enteric-coated tablet includes the composition of the fresh Panax notoginseng enteric-coated tablet and its preparation method;

[0053] The fresh Panax notoginseng enteric-coated tablets are composed of fresh Panax notoginseng extract and excipients.

[0054] The fresh Panax notoginseng extract is an extract obtained from harvested Panax notoginseng root tubers without drying treatment, and includes Panax notoginseng saponins, Panax notoginseng glycosides, and Panax notoginseng polysaccharides.

[0055] The excipients mentioned are excipients and coating film components;

[0056] The excipients include sodium carboxymethyl starch, magnesium stearate, and microcrystalline cellulose;

[0057] Among them, sodium carboxymethyl starch has strong water absorption and swelling properties, and can quickly swell in cold water, causing the tablets to swell and disintegrate after absorbing water;

[0058] The magnesium stearate is used as a lubricant for tableted powders, to prevent sticking, to improve powder flow, and to improve tableting processability.

[0059] The microcrystalline cellulose, as an adsorbent and disintegrant, can achieve a synergistic disintegrant effect when used in combination with sodium carboxymethyl starch.

[0060] The excipients and the fresh Panax notoginseng extract are mixed evenly to prepare the tablet core;

[0061] The coating film includes Group A coating film and Group B coating film, which are enteric coatings;

[0062] The coating film is prepared by coating the excipient and the fresh Panax notoginseng extract evenly to form the outer surface of the tablet core; so that the fresh Panax notoginseng enteric tablets do not dissolve in gastric solution, but dissolve and release the fresh Panax notoginseng extract inside the coating film after entering the duodenum;

[0063] The enteric coating coating of the tablet core prepared by uniformly mixing the fresh Panax notoginseng extract avoids the decomposition of Panax notoginseng saponins, Panax notoginseng polysaccharides in the acidic environment of the stomach, thereby improving the bioavailability of the active ingredients in the body.

[0064] The A-group coating film is hydroxypropyl methylcellulose phthalate, abbreviated as (HPMCP);

[0065] The B-group coating film is composed of acrylic resin, Tween-80, castor oil, polyethylene glycol 6000, and 95% ethanol.

[0066] The fresh Panax notoginseng enteric-coated tablets are prepared by the following steps;

[0067] Step 1: Extraction of fresh Panax notoginseng extract; Step 2: Preparation of fresh Panax notoginseng extract into slices; Step 3: Coating of fresh Panax notoginseng extract slices.

[0068] Step 1: Extraction steps of the fresh Panax notoginseng extract:

[0069] Step 1: Wash the fresh Panax notoginseng;

[0070] The cleaning of fresh Panax notoginseng involves spraying water to remove dirt from the surface of the fresh Panax notoginseng, air-drying to remove water, and then air-drying to dry the surface moisture adhering to the sprayed water.

[0071] Step 2: Weigh and calculate the dry weight;

[0072] Weigh the fresh Panax notoginseng from step one and convert it to dried Panax notoginseng. According to the literature, the moisture content of Panax notoginseng harvested in December after 3 years of growth is 74.93% and that harvested in January is 75.0%; the moisture content of Panax notoginseng harvested in December after 4 years of growth is 79.91% and that harvested in January is 76.19%. Calculate the actual weight of the dried Panax notoginseng after washing.

[0073] Step 3: Wet grinding;

[0074] Fresh Panax notoginseng was soaked in a solvent and sheared using a high-speed shearing machine. After shearing, the particle size of the fresh Panax notoginseng was ≤0.855mm, and it passed through a 20-mesh sieve. The solvent contained a mixture of 75% ethanol and distilled water, and the ratio of the dry weight of the fresh Panax notoginseng root to the solvent was 1:15 (w / w). The moisture content of the fresh Panax notoginseng was included in the distilled water. The operating temperature of the wet pulverization process was ≤30℃. During the wet pulverization process, the fresh Panax notoginseng was sheared by a high-speed shearing machine. The shearing force broke the fresh Panax notoginseng, and the high-speed shearing was accompanied by extrusion pressure, forming a juicing effect. As the size of the sheared fresh Panax notoginseng particles decreased, more of the Panax notoginseng tissue was exposed to contact with the solvent, allowing the soluble components in the fresh Panax notoginseng to diffuse into the solvent. The extrusion pressure caused the fresh Panax notoginseng tissue to deform and its volume to change alternately, and the soluble components inside the fresh Panax notoginseng diffused into the solvent under the extrusion pressure. Finally, the soluble components in the fresh Panax notoginseng were fully dissolved in the solvent, and the fibers in the fresh Panax notoginseng tissue became the residue. The wet pulverization extraction process is a heat-free operation, with the operating temperature controlled at ≤35℃. This process replaces the heating and cooking process, avoiding the destruction of heat-sensitive components caused by heating and cooking. Among them, 75% ethanol not only acts as a solvent, but also inhibits microbial growth and sterilizes. The wet pulverization process reduces the particle size of fresh Panax notoginseng to ≤0.855mm, which passes through a 20-mesh sieve to obtain a solid-liquid mixture (1).

[0075] Step 4: Solid-liquid separation. The solid-liquid mixture (1) after wet grinding is separated by a centrifuge or plate and frame filter. The filtrate A and the residue a are collected.

[0076] Step 5: Wet pulverization of the dregs;

[0077] The dregs a were soaked in a solvent and sheared with a high-speed shearing machine. After shearing, the particle size of the fresh Panax notoginseng granules was ≤0.55mm. They passed through a 30-mesh sieve. The solvent contained a mixture of 75% ethanol and distilled water. The ratio of dregs a to the solvent was 1:5 (w / w). The operating temperature of the wet pulverization process was ≤30℃. A solid-liquid mixture (2) was obtained by passing through a 30-mesh sieve.

[0078] Step 6: Solid-liquid separation. The solid-liquid mixture (2) obtained from wet pulverization in step 5 is separated into solid and liquid mixtures using a centrifuge or plate and frame filter. The filtrate A1 is collected, and the residue is discarded.

[0079] Step 7: Negative pressure distillation concentration; Combine filtrate A and filtrate A1, and evaporate under negative pressure at a temperature of 35℃~40℃ and an absolute pressure of 500pa~1000pa; concentrate the filtrate to a thick paste with a specific gravity of 1.0~1.05;

[0080] The aforementioned negative pressure distillation concentration aims to reduce evaporation pressure, achieving concentration at a lower evaporation temperature. Lowering the evaporation temperature and operating in a negative pressure environment with lower oxygen content reduces or avoids oxidation and thermal damage to the fresh Panax notoginseng components during the distillation concentration process. The negative pressure distillation concentration utilizes a negative pressure still, which includes a vacuum system, a wall-scraping and stirring system, a heating and temperature control system, and a cold trap condensation system. The vacuum system maintains a negative pressure environment for distillation concentration. The wall-scraping and stirring system continuously scrapes and agitates the filtrate, constantly replacing the heat exchange interface. The heating and temperature control system maintains the evaporation temperature. The cold trap condensation system captures and recovers the evaporated ethanol vapor.

[0081] Step 7: Alcohol precipitation;

[0082] The starch, polysaccharides, gums, pectin, mucilage, proteins, and tannins in the thick paste are precipitated, while the supernatant containing notoginsenosides and notoginsenosides forms a solution. The alcohol content is 70-75%. The alcohol precipitation temperature is 4-6℃.

[0083] The alcohol precipitation process shall be carried out as follows:

[0084] Step 7.1: Pour the thick paste into the alcohol precipitation tank;

[0085] Step 7.2: Slowly add 95% ethanol to the alcohol precipitation tank and mix with the thick paste to prepare the alcohol precipitation solution;

[0086] Step 7.3: Cooling down;

[0087] The cooling process is a gradient cooling, with the cooling rate controlled at 1℃ / 20min, reducing the temperature to 5℃±1℃. This gradient cooling allows starch, gum, pectin, mucilage, protein, tannins, and polysaccharides in the solution to precipitate in an orderly manner, thereby increasing the yield of fresh Panax notoginseng extract.

[0088] Step 7.4: Settling: The settling process involves maintaining a constant temperature of 5℃±1℃ for 24 hours. During the settling process, the precipitate fully settles, forming a supernatant.

[0089] Step 7.5: Take the supernatant; the supernatant contains notoginseng saponins and notoginseng extract; the precipitate contains notoginseng polysaccharides, collect supernatant B1 and precipitate C1;

[0090] Step 8: Separate Panax notoginseng polysaccharides;

[0091] The separation process of Panax notoginseng polysaccharides is carried out as follows:

[0092] Step 8.1: Dilution;

[0093] Add 5 times the volume of distilled water to precipitate C1, stir thoroughly at 70℃ to prepare water precipitation solution;

[0094] Step 8.2: Ultrafiltration;

[0095] The ultrafiltration process involves ultrafiltration of a 70°C aqueous solution using a 100kDa ultrafiltration membrane, maintaining the filtration temperature at 65°C–70°C, and removing molecules with molecular weights >10×10⁻⁶. 4 Impurities; yielded ultrafiltrate B2 containing Panax notoginseng polysaccharides;

[0096] Step 9: Vacuum drying;

[0097] The vacuum drying process involves combining the supernatant B1 and the ultrafiltrate B2, evaporating and recovering the ethanol, and evaporating some of the water to obtain a dried crystalline powder containing notoginseng saponins, notoginsenosides, and notoginseng polysaccharides, namely, the fresh notoginseng extract D.

[0098] The vacuum drying described herein is a vacuum drying equipment equipped with a vacuum pump, temperature control heating, stirring function, and condensation recovery system. The temperature control during the vacuum drying operation is 45℃~50℃, and the absolute pressure is 100pa~1500pa; wherein, the ethanol condensation recovery stage operates at a temperature of 50℃ and an absolute pressure of 1000~1500pa.

[0099] During the dehydration stage, the operating temperature was 45℃ and the absolute pressure was 100 Pa to 500 Pa. The vacuum drying environment, with its thin air and low oxygen content, prevented the oxidation and denaturation of notoginseng saponins, notoginsenosides, and notoginseng polysaccharides, effectively preserving their biological activity. Vacuum drying was performed until the moisture content (D) of the fresh notoginseng extract was ≤3%.

[0100] Step 2: Preparation of slice cores from fresh Panax notoginseng extract:

[0101] Step 1: Ingredient Preparation

[0102] The ingredients are the fresh Panax notoginseng extract and the excipients in a specific ratio.

[0103] As listed in Table 4

[0104] Table 4. Ratio of Fresh Panax notoginseng Extract to Excipients

[0105] name Fresh Panax notoginseng extract D microcrystalline cellulose Sodium carboxymethyl starch magnesium stearate Percentage (w / w)% 49.5 49.4 0.7 0.3

[0106] Step II Mixing:

[0107] The mixing process involves thoroughly and uniformly mixing the ingredients listed in Table 1 using a powder mixer.

[0108] Step III: Dry Granulation

[0109] The dry granulation process involves compressing the mixture from step II into flakes using dry roller pressing technology, followed by crushing, granulation, and sieving to produce ≤30 mesh granules, and then collecting fresh Panax notoginseng extract to fill the granules.

[0110] Step IV: Tableting; Tableting is performed using a tablet press to obtain fresh Panax notoginseng extract tablet cores;

[0111] Step 3: Coating of fresh Panax notoginseng extract cores; the coating process is as follows:

[0112] Step a: Prepare the coating solution;

[0113] The coating solution preparation includes a coating solution for preparing group A coating films and a coating solution for preparing group B coating films.

[0114] The coating solution for the Group A coating film includes hydroxypropyl methylcellulose phthalate, abbreviated as (HPMCP);

[0115] The coating solution for the B-group coating film includes acrylic resin, Tween-80, castor oil, and polyethylene glycol 6000;

[0116] The composition and preparation steps of the coating film and coating solution of Group A;

[0117] The hydroxypropyl methylcellulose phthalate (HPMCP) is a high-performance enteric coating film component. Based on its dissolution pH, it can be divided into HP55 and HP50 types. HP55 requires a pH of 5.5 to dissolve, while HP50 requires a pH of 6.0. The pH of the upper to lower part of the human duodenum is 5.0 to 6.0. Therefore, HPCP coating, whether HP55 or HP50, is an enteric coating film that can dissolve in the upper part of the duodenum.

[0118] The coating solution consists of: HPMCP 2%–9%; ethanol 45.5%–49%; acetone 45.5%–49%.

[0119] The optimization of the composition ratio of the coating liquid in group A:

[0120] When HPMCP < 2%, the coating film is too thin and it is difficult to form a complete film; when HPMCP > 9%, the coating solution is too viscous, resulting in uneven coating film thickness.

[0121] The coating solution composition of Group A coating films is listed in Table 5.

[0122] Table 5A Composition and Ratio of Coating Solution for Group A Coating Film

[0123] name HPMCP 95% ethanol acetone Percentage (w / w)% 5％ 47.5％ 47.5％

[0124] The coating solution for the group A coating film is prepared according to the following steps:

[0125] Step s1, Sol;

[0126] The sol is prepared by adding 5% HPMCP, 47.5% ethanol, and 47.5% acetone to a stirred sol container, stirring, and heating to 65°C to melt the HPMCP completely.

[0127] Step s2: Degassing;

[0128] The degassing process involves turning on the vacuum equipment of the stirring sol tank after HPMCP has been fully dissolved to remove gas from the HPMCP solution, thus preventing the formation of bubbles or pores in the coating film during the coating process.

[0129] Step s3: Collect the coating solution of group A;

[0130] The composition and preparation steps of the B-group coating film and the coating solution;

[0131] The coating solution comprises: acrylic resin; Tween-80, castor oil, and polyethylene glycol 6000; wherein the acrylic resin includes acrylic resin II and acrylic resin III.

[0132] The acrylic resin II described is an anionic methacrylic acid copolymer, insoluble in gastric juice but soluble in intestinal juice. It is mainly used as a coating for enteric-coated oral tablets, capsules, pills, and granules. It can also be used in the manufacture of capsules, films, etc., to regulate the drug release site, and commonly uses 85-95% ethanol as a solvent.

[0133] Acrylic resin II and acrylic resin III are soluble in ethanol and methanol, but insoluble in water and acids. Acrylic resin II dissolves at pH 6.0 and acrylic resin III at pH 6.5 and above, respectively. Most enteric-coated formulations currently use a mixture of acrylic resin II and acrylic resin III for coating. Acrylic resin II has the advantages of high solids content and low viscosity, making it less prone to tablet sticking and pan adhesion, resulting in uniform coating and a smooth coating layer. Acrylic resin III easily forms a film with good surface gloss, but it is prone to sticking. In practical applications, mixing acrylic resin II and acrylic resin III in an appropriate ratio can overcome the disadvantage of easy sticking while maintaining the advantages of easy film formation and good surface gloss. Adjusting the ratio of the two can also adjust the solubility at different pH values. Acrylic resins are enzyme-resistant and have low drug permeability. The process involves preparing a coating solution using acrylic resin II and acrylic resin III in an appropriate ratio, and then coating the tablet cores using a coating device.

[0134] Adding an appropriate amount of plasticizer can improve the toughness of the coating film. The plasticizer includes one of triethyl citrate and polyethylene glycol 6000.

[0135] Tween-80 is a solubilizer that enables oily substances and water to mix better. Its hydrophilic and lipophilic groups in its molecular structure can reduce surface tension, eliminate foam, and form a stable mixture. In this solution, it plays a role in solubilizing acrylic resin and polyethylene glycol 6000 and eliminating foam in the coating solution.

[0136] Castor oil has good compatibility and plasticizing properties with resins, rosin, shellac, etc., and plays a role in optimizing the film formation of the coating solution in this scheme.

[0137] The composition and formulation of the coating solution in group B are listed in Table 6.

[0138] Table 6. Composition of the coating solution in Group B (w / w)

[0139]

[0140] The coating solution for the B-group coating film is prepared according to the following steps:

[0141] Step t1, Sol;

[0142] The sol is prepared by adding acrylic resin II, acrylic resin III, Tween-80, castor oil, polyethylene glycol 6000, and 95% ethanol into a stirring melting tank, stirring, and heating to 65°C to fully dissolve acrylic resin II, acrylic resin III, and polyethylene glycol 6000, thereby making the components of the B-group coating solution homogeneous and uniform.

[0143] Step t2: Degassing;

[0144] The degassing process involves fully dissolving acrylic resin II, acrylic resin III, and polyethylene glycol 6000, ensuring the six materials are homogeneous. Then, the vacuum equipment in the stirring sol tank is activated to remove the gas trapped in the mixture of acrylic resin II, acrylic resin III, polyethylene glycol 6000, Tween-80, castor oil, and 95% ethanol. This process prevents the formation of air bubbles or pores in the coating film during the coating process.

[0145] Step t3: Collect the enteric coating solution of group B;

[0146] Step b: Coating of fresh Panax notoginseng extract cores

[0147] The aforementioned fresh Panax notoginseng extract core coating involves coating the fresh Panax notoginseng extract core with either the collected coating solution from group A or group B.

[0148] Step b, the coating of fresh Panax notoginseng extract cores, is performed as follows:

[0149] The fresh Panax notoginseng extract tablets are placed into a rotating coating pan. The hot air heating system of the coating pan is activated, and a spray pump sprays either Group A or Group B enteric coating solution onto the surface of the fresh Panax notoginseng extract tablets in the rotating coating pan. The fresh Panax notoginseng extract tablets tumble in the rotating coating pan, and each surface of the tumbling tablets is coated with either Group A or Group B coating solution. Under the blowing of the 37°C to 39°C hot air heating system of the coating pan, the film-forming components in the coating solution are fixed on the surface of the fresh Panax notoginseng extract tablets, and the liquid phase components in the coating solution evaporate upon heating. The fresh Panax notoginseng extract tablets are completely coated with an enteric coating, thus obtaining fresh Panax notoginseng enteric-coated tablets.

[0150] Positive effects of the present invention: Fresh Panax notoginseng enteric-coated tablets and their preparation method

[0151] ① Fresh Panax notoginseng raw materials are extracted directly, avoiding the destruction of active ingredients caused by heating during the drying process of Panax notoginseng, and avoiding the risk of mold growth in Panax notoginseng that occurs when dried by sun.

[0152] ② Wet pulverization extraction method is adopted to avoid the process of extracting active ingredients of Panax notoginseng by heating, which would destroy heat-sensitive components and keep the Panax notoginseng extracts, such as notoginsenosides, notoginsenosides and notoginseng polysaccharides, in good biological activity.

[0153] ③ Improve the preparation of medicinal powder by pulverization to avoid the drastic temperature rise during the pulverization process of Panax notoginseng, which would destroy the active ingredients of Panax notoginseng;

[0154] ④ Enteric coating prevents the drug from decomposing under acidic gastric conditions, thus improving the bioavailability of the active ingredient in the body. Detailed Implementation

[0155] The following details the embodiments.

[0156] Step 1: Extraction of fresh Panax notoginseng extract;

[0157] Step 2: Preparation of tablet cores from fresh Panax notoginseng extract;

[0158] Step 3: Coating of fresh Panax notoginseng extract into tablet cores;

[0159] The following details the steps described: Step 1: Extraction of fresh Panax notoginseng extract; Step 2: Preparation of fresh Panax notoginseng extract into slices; Step 3: Coating of fresh Panax notoginseng extract slices.

[0160] Step 1: Extraction of fresh Panax notoginseng extract;

[0161] Step 1: Wash the fresh Panax notoginseng;

[0162] The process for cleaning fresh Panax notoginseng involves taking 4500g of fresh Panax notoginseng harvested in 1 month from 3-year-old plants, using spray water washing to remove surface dirt, air showering to remove water, and then blowing dry the surface moisture adhering to the spray water in an air shower room.

[0163] Step 2: Weigh 4000g, and convert it to 1000g of dried product;

[0164] Weigh the fresh Panax notoginseng from step one and convert it to dried Panax notoginseng; according to the literature, the moisture content of Panax notoginseng harvested in December after 3 years of growth is 74.93%, and the moisture content of Panax notoginseng harvested in January is 75.0%; convert it to dried Panax notoginseng.

[0165] Step 3: Wet grinding;

[0166] Fresh Panax notoginseng was soaked in a solvent and then sheared using a high-speed shearing machine. After shearing, the particle size of the fresh Panax notoginseng was ≤0.855mm, and it passed through a 20-mesh sieve.

[0167] The solvent contains a mixture of 75% ethanol and distilled water. The ratio of the dry weight of fresh Panax notoginseng roots to the solvent is 1:15 (w / w). The water content of 4000g of fresh Panax notoginseng is 3000g, which is included in the distilled water. The distilled water consists of 11.845L of 95% ethanol and 0.158L of distilled water.

[0168] The operating temperature of the wet pulverization process is ≤30℃; a solid-liquid mixture (1) is obtained by passing through a 20-mesh sieve.

[0169] Step 4: Solid-liquid separation;

[0170] The solid-liquid mixture (1) after wet grinding was separated by a plate and frame filter, and the filtrate A10L and the residue a9kg were collected.

[0171] Step 5: Wet pulverization of the dregs;

[0172] The dregs a were soaked in 27L of solvent and sheared by a high-speed shearing machine. The particle size of the fresh Panax notoginseng after shearing was ≤0.55mm. The particles passed through a 30-mesh sieve. The solvent contained a mixture of 75% ethanol and distilled water. The ratio of dregs a to the solvent was 1:3 (w / w). The operating temperature of the wet pulverization process was ≤30℃. The solid-liquid mixture (2) was obtained by passing through a 30-mesh sieve.

[0173] Step Six: Solid-Liquid Separation;

[0174] The solid-liquid mixture (2) obtained by wet pulverization in step 5 is separated by a plate and frame filter. The filtrate A1 is collected to obtain 35L of filtrate, and the residue is discarded.

[0175] Step 7: Negative pressure distillation concentration;

[0176] Filtrates A and A1 were combined and evaporated under negative pressure at a temperature of 35℃ to 40℃ and an absolute pressure of 500 Pa to 1000 Pa. Ethanol was recovered simultaneously. The filtrate was concentrated to a thick paste with a specific gravity of 1.0 to 1.05, yielding 1.5 kg of thick paste. Ethanol was recovered simultaneously.

[0177] Step 7: Alcohol precipitation;

[0178] Prepare the alcohol precipitation solution to achieve an alcohol content of 75%. Precipitation temperature: 5℃ ± 1℃.

[0179] The alcohol precipitation process shall be carried out as follows:

[0180] Step 7.1: Add 1.5 kg of the thick paste to the alcohol precipitation tank;

[0181] Step 7.2: Slowly add 5.63L of 95% ethanol to the alcohol precipitation tank and mix with the thick paste to prepare the alcohol precipitation solution;

[0182] Step 7.3: Cooling down;

[0183] The cooling process is a gradient cooling, with the cooling rate controlled at 1℃ / 20min, until the temperature is reduced to a constant 5℃±1℃ and allowed to stand. This gradient cooling allows the alcohol precipitate to precipitate in an orderly manner, thereby increasing the yield of fresh Panax notoginseng extract.

[0184] Step 7.4: Settling: The settling process involves maintaining a constant temperature of 5℃±1℃ for 24 hours. During the settling process, the precipitate fully settles, forming a supernatant.

[0185] Step 7.5: Take the supernatant; the supernatant contains notoginsenosides and notoginsenosides; the precipitate contains notoginseng polysaccharides. Collect supernatant B1 to obtain supernatant B1 5.8L and collect precipitate C1 to obtain precipitate C1 1.33L.

[0186] Step 8: Separate Panax notoginseng polysaccharides;

[0187] The separation process of Panax notoginseng polysaccharides is carried out as follows:

[0188] Step 8.1: Dilution;

[0189] Add 6.65 liters of distilled water to precipitate C1, stir thoroughly at 70°C to prepare the water-based precipitate solution;

[0190] Step 8.2: Ultrafiltration;

[0191] The ultrafiltration process involves ultrafiltration of a 70°C water-precipitated solution using a 100kDa ultrafiltration membrane at a filtration temperature maintained between 65°C and 70°C to remove impurities with a molecular weight >10×10⁴, resulting in an ultrafiltrate B25.5L containing Panax notoginseng polysaccharides. The filter residue is then discarded.

[0192] Step 9: Vacuum drying;

[0193] The supernatant B15.8L and ultrafiltrate B25.5L were combined and dried using a vacuum drying device. Ethanol was evaporated and condensed for recovery, and some of the water was evaporated to ensure that the water content of the fresh Panax notoginseng extract D was ≤3%. 200g of dried crystalline powder containing Panax notoginseng saponins, notoginsenosides, and Panax notoginseng polysaccharides was obtained.

[0194] The vacuum drying process is controlled at a temperature of 45℃~50℃ and an absolute pressure of 100pa~1500pa; the ethanol condensation and recovery stage is operated at a temperature of 50℃ and an absolute pressure of 1000~1500pa.

[0195] During the moisture removal operation, the operating temperature is 45℃ and the absolute pressure is 100pa~500pa.

[0196] Step 2: Preparation of tablet cores from fresh Panax notoginseng extract;

[0197] Step 1: Ingredient Preparation

[0198] The ingredients are prepared by mixing the fresh Panax notoginseng extract D with the excipient in a specific ratio.

[0199] As listed in Table 7

[0200] Table 7. Ratio of Fresh Panax notoginseng Extract to Excipients

[0201]

[0202]

[0203] Step II Mixing:

[0204] The mixing process involves thoroughly and uniformly mixing the ingredients listed in Table 1 using a powder mixer.

[0205] Step III: Dry Granulation

[0206] The dry granulation process involves compressing the mixture from step II into flakes using dry roller pressing technology, followed by crushing, granulation, and sieving to produce ≤30 mesh granules, and then collecting fresh Panax notoginseng extract to fill the granules.

[0207] Step IV: Tableting; tablets are produced using a tableting machine, yielding 1616 tablets of fresh Panax notoginseng extract, each weighing 0.25g.

[0208] Step 3: Coating of fresh Panax notoginseng extract into tablet cores;

[0209] The coating process is carried out according to the following steps:

[0210] Step a: Prepare the enteric coating solution;

[0211] The enteric coating solution is selected from group A coating film coating solutions;

[0212] The composition and preparation steps of the coating solution for the A-group coating film;

[0213] The composition of the coating solution for Group A coating films is listed in Table 8:

[0214] Table 8A Composition and Ratio of Coating Solution for Group A Coating Film

[0215] name HPMCP 95% ethanol acetone quantity 3.15g 37.6ml 37.8ml Percentage (w / w)% 5％ 47.5％ 47.5％

[0216] The preparation of the coating solution of group A is carried out according to the following steps:

[0217] Step s1, Sol;

[0218] The sol was prepared by first adding 3.15g of HPMCP and 37.6ml of ethanol to a stirred sol container and stirring to dissolve them; then adding 37.8ml of acetone to the stirred sol container and stirring to dissolve them. The mixture was then heated to 65°C to ensure that the HPMCP was fully dissolved.

[0219] Step s2: Degassing;

[0220] The degassing process involves fully dissolving HPMCP and then turning on the vacuum equipment in the stirring sol tank to remove gas from the HPMCP solution.

[0221] Step s3: Collect 75ml of coating solution from group A;

[0222] Step b: Coating of fresh Panax notoginseng extract cores

[0223] The aforementioned coating of fresh Panax notoginseng extract tablets involves coating the surface of the fresh Panax notoginseng extract tablets with the coating solution collected from group A.

[0224] Step b, the preparation is carried out as follows:

[0225] The fresh Panax notoginseng extract tablets are placed into a rotating coating pan. The hot air heating system of the coating pan is activated, and a spray pump sprays either Group A or Group B enteric coating solution onto the surface of the fresh Panax notoginseng extract tablets in the rotating coating pan. The fresh Panax notoginseng extract tablets tumble in the rotating coating pan, and each surface of the tumbling tablets is coated with the Group A coating solution. During the coating process, under the blowing of the 37°C to 39°C hot air heating system of the coating pan, the film-forming components in the coating solution are fixed on the surface of the tablets, and the liquid phase components in the coating solution evaporate upon heating. The fresh Panax notoginseng extract tablets are completely coated with an enteric coating, thus obtaining fresh Panax notoginseng enteric-coated tablets.

Claims

1. A fresh Panax notoginseng enteric-coated tablet, comprising fresh Panax notoginseng extract and excipients; The fresh Panax notoginseng extract is an extract obtained from harvested Panax notoginseng roots without drying treatment, and includes Panax notoginseng saponins, Panax notoginseng extract, and Panax notoginseng polysaccharides. The excipients mentioned are excipients and coating film components; The excipients include sodium carboxymethyl starch, magnesium stearate, and microcrystalline cellulose; The excipients are mixed evenly with the fresh Panax notoginseng extract to prepare the tablet core; The coating film is used to coat the outer surface of the tablet core prepared by uniformly mixing the excipient and the fresh Panax notoginseng extract. The coating film includes Group A coating film and Group B coating film, which are enteric coatings; The A-group coating film is hydroxypropyl methylcellulose phthalate, abbreviated as (HPMCP); The B-group coating film comprises acrylic resin, Tween-80, castor oil, polyethylene glycol 6000, and 95% ethanol.

2. A method for preparing fresh Panax notoginseng enteric-coated tablets; comprising the following steps: Step 1: Extraction of fresh Panax notoginseng extract; Step 2: Preparation of slice cores from fresh Panax notoginseng extract; Step 3: Coating of fresh Panax notoginseng extract into tablet cores; The first step, the extraction of fresh Panax notoginseng extract: Step 1: Wash the fresh Panax notoginseng; The cleaning of fresh Panax notoginseng involves spraying water to remove dirt from the surface of the fresh Panax notoginseng, air-drying to remove water, and then air-drying to dry the surface moisture adhering to the sprayed water. Step 2: Weighing; Step 3: Wet grinding; The wet pulverization process involves soaking fresh Panax notoginseng in a solvent and shearing it using a high-speed shearing machine. After shearing, the particle size of the fresh Panax notoginseng is ≤0.855mm, and it passes through a 20-mesh sieve. The solvent is a mixture of 75% ethanol and distilled water; The ratio of the dry weight of fresh Panax notoginseng root to solvent is 1:15 (w / w); The operating temperature of the wet pulverization process is ≤30℃; the wet pulverization makes the particle size of fresh Panax notoginseng granules ≤0.855mm, and they pass through a 20-mesh sieve to obtain a solid-liquid mixture (1); Step 4: Solid-liquid separation. The solid-liquid mixture (1) after wet grinding is separated by a centrifuge or plate and frame filter. The filtrate A is collected and the residue a is collected. Step 5: Wet pulverization of the dregs; The dregs a were soaked in a solvent and sheared using a high-speed shearing machine. After shearing, the particle size of the fresh Panax notoginseng granules was ≤0.55mm and passed through a 30-mesh sieve. The solvent contains a mixture of 75% ethanol and distilled water, and the ratio of drug residue a to solvent is 1:5 (w / w); the operating temperature of the wet pulverization process is ≤30℃, and a solid-liquid mixture (2) is obtained; Step 6: Solid-liquid separation. The solid-liquid mixture (2) obtained from wet pulverization in step 5 is separated into solid and liquid mixtures using a centrifuge or plate and frame filter. The filtrate A1 is collected, and the residue is discarded. Step 7: Negative pressure distillation concentration; Combine filtrate A and filtrate A1, and evaporate under negative pressure at a temperature of 35℃~40℃ and an absolute pressure of 500pa~1000pa; concentrate the filtrate to a thick paste with a specific gravity of 1.0~1.05; Step 7: Alcohol precipitation; Adjust the thick paste to an alcohol content of 70-75% for alcohol precipitation. The alcohol precipitation temperature is 4-6℃. The alcohol precipitation process shall be carried out as follows: Step 7.1: Pour the thick paste into the alcohol precipitation tank; Step 7.2: Slowly add 95% ethanol to the alcohol precipitation tank and mix with the thick paste to prepare the alcohol precipitation solution; Step 7.3: Cooling down; The cooling process is a gradient cooling, with a temperature reduction of 1℃ / 20min, down to 5℃±1℃; Step 7.4: Settling: The settling process involves maintaining the alcohol precipitate at a constant temperature of 5℃±1℃ for 24 hours to form a supernatant. Step 7.5: Take the supernatant; the supernatant contains notoginseng saponins and notoginseng extract; the precipitate contains notoginseng polysaccharides, collect supernatant B1 and precipitate C1; Step 8: Separate Panax notoginseng polysaccharides; The separation process of Panax notoginseng polysaccharides is carried out as follows: Step 8.1: Dilution; Add 5 times the volume of distilled water to precipitate C1, stir thoroughly at 70℃ to prepare water precipitation solution; Step 8.2: Ultrafiltration; The ultrafiltration process involves ultrafiltration of a 70°C aqueous solution using a 100 kDa ultrafiltration membrane, maintaining the filtration temperature at 65°C–70°C, and removing molecules with molecular weights >10 × 10⁻⁶. 4 Impurities; yielded ultrafiltrate B2 containing Panax notoginseng polysaccharides; Step 9: Vacuum drying; The vacuum drying process involves feeding the supernatant B1 and ultrafiltrate B2 into a vacuum drying device, evaporating and recovering the ethanol, and evaporating some of the water to obtain a dried crystalline powder containing notoginseng saponins, notoginsenosides, and notoginseng polysaccharides, namely, the fresh notoginseng extract D. The vacuum drying described herein is a vacuum drying equipment that uses a matching vacuum pump, temperature control heating, stirring function, and condensation recovery system. The temperature control during the vacuum drying operation is 45℃~50℃, and the absolute pressure is 100pa~1500pa. Step 2: Preparation of slice cores from fresh Panax notoginseng extract: Step 1: Ingredient Preparation The ingredients are prepared by mixing the fresh Panax notoginseng extract D with the excipients in the specified proportions, as listed in Table 4. Table 4. Ratio of Fresh Panax notoginseng Extract to Excipients Step II Mixing: The mixing process involves using a powder mixer to thoroughly and evenly mix the ingredients listed in Table 4. Step III: Dry Granulation The dry granulation process involves compressing the mixture from step II into flakes using dry roller pressing technology, followed by crushing, granulation, and sieving to produce ≤30 mesh granules, and collecting fresh Panax notoginseng extract granules. Step IV: Tableting; Fresh Panax notoginseng extract granules are compressed into tablets using a tableting machine to obtain fresh Panax notoginseng extract tablet cores. Step 3: Coating the core of fresh Panax notoginseng extract slices; The coating process is carried out according to the following steps: Step a: Prepare the coating solution; The coating solution preparation includes a coating solution for preparing group A coating films and a coating solution for preparing group B coating films. The coating solution of the group A coating film includes hydroxypropyl methylcellulose phthalate, abbreviated as (HPMCP); The coating solution of the B-group coating film includes acrylic resin, Tween-80, castor oil, and polyethylene glycol 6000; The composition and preparation steps of the coating film and coating solution of Group A; The coating solution composition of Group A coating films is listed in Table 5. Table 5. Composition and ratio of coating solution for Group A coating film The coating solution for the group A coating film is prepared according to the following steps: Step s1, Sol; The sol is prepared by adding 5% HPMCP, 47.5% ethanol, and 47.5% acetone to a stirred sol container, stirring, and heating to 65°C to melt the HPMCP completely. Step s2: Degassing; The degassing process involves fully dissolving HPMCP and then turning on the vacuum equipment in the stirring sol tank to remove gas from the HPMCP solution. Step s3: Collect the coating solution of group A; The composition and preparation steps of the B-group coating film and the coating solution; The coating solution composition of group B coating films is listed in Table 6: Table 6. Composition of Group B coating solution (w / w) The coating solution for the B-group coating film is prepared according to the following steps: Step t1, Sol; The sol is prepared by adding acrylic resin II, acrylic resin III, Tween-80, castor oil, polyethylene glycol 6000, and 95% ethanol into a stirring melting tank, stirring, and heating to 65°C to fully dissolve acrylic resin II, acrylic resin III, and polyethylene glycol 6000, thereby making the components of the B-group coating solution homogeneous and uniform. Step t2: Degassing; The degassing process involves fully dissolving acrylic resin II, acrylic resin III, and polyethylene glycol 6000, ensuring that the six materials are homogeneous. Then, the vacuum equipment in the stirring sol tank is activated to remove the gases trapped in the mixture of acrylic resin II, acrylic resin III, polyethylene glycol 6000, Tween-80, castor oil, and 95% ethanol. Step t3: Collect the coating solution of group B; Step b: Coating of fresh Panax notoginseng extract cores The aforementioned fresh Panax notoginseng extract core coating involves coating the fresh Panax notoginseng extract core with either the collected coating solution from group A or group B. Step b is performed as follows: The fresh Panax notoginseng extract tablets are placed into a rotating coating pan. The hot air heating system of the coating pan is activated, and a spray pump sprays either Group A or Group B enteric coating solution onto the surface of the fresh Panax notoginseng extract tablets in the rotating coating pan. The fresh Panax notoginseng extract tablets tumble in the rotating coating pan, and each surface of the tumbling tablets is coated with either Group A or Group B coating solution. Under the blowing of the 37°C to 39°C hot air heating system of the coating pan, the film-forming components in the coating solution are fixed on the surface of the fresh Panax notoginseng extract tablets, and the liquid phase components in the coating solution evaporate upon heating. The fresh Panax notoginseng extract tablets are completely coated with an enteric coating, thus obtaining fresh Panax notoginseng enteric-coated tablets.

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