Production process of discodendron slice

Abstract

The application provides a production process of Panlongqi tablets and relates to the fields of traditional Chinese medicine compositions and traditional Chinese medicine preparations. The production process comprises the following steps: grinding and screening Radix Aconiti Lateralis, Radix Aconiti Kusnezoffii and Radix Aconiti Praeparatae, adding 12-14 times of water, soaking for 25-35 min, decocting for 2-3 h, adding 8-10 times of water for the second time, decocting for 1-2 h, adding 4-5 times of water for the third time, decocting for 1-2 h, filtering, and concentrating to obtain extract; grinding and screening the remaining medicinal materials to obtain coarse materials; activating and drying the coarse materials; adding a composite enzyme, adjusting pH, ultrasonic extraction, and vacuum reducing pressure concentration to obtain extract; refining the extract by using a macroporous adsorption resin column chromatography; adding mannitol, isomalt, tert-butylhydroquinone and magnesium stearate, spray drying, tabletting, sugar coating, and obtaining Panlongqi tablets. The Panlongqi tablets prepared by the application have the effects of activating blood and resolving stasis, dispelling wind and dampness, and relieving swelling and pain, and have very high stability, and are suitable for industrial popularization.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine compositions and preparations, specifically to a production process for Panlongqi tablets. Background Technology

[0002] Panlongqi tablets are a medication used to treat rheumatic diseases. They are characterized by their ability to reduce swelling and pain, dispel wind and dampness, improve blood circulation, and promote wound repair. While possessing the anti-inflammatory, analgesic, wind-dispelling, dampness-removing, swelling-reducing, and anti-exudation effects of Western medicine hormones, Panlongqi tablets do not have hormone-like side effects. They are safe, effective, and can be taken long-term without drug resistance or dependence.

[0003] Panlongqi tablets are a compound preparation composed of 29 Chinese herbal medicines. The traditional production process of Panlongqi tablets is as follows: First, the following medicinal materials are needed: Panlongqi, Zhuangjindan, Chuanwu, Shengcaowu, Danggui, Duzhong, Qingwaqi, Zhuzishen, Qinjiu, Muxiang, Zusima, Luoshiteng, Tiebangchui, Honghua, Wujiapi, Niuxi, Baimaoqi, Guoshanlong, Caowu, Laoshuqi, Zhizhuliao, Honghua, Moyao, Zhugenqi, Valerian, Yangjiaoqi, Shenjincao, Danshen, Balima, Ruxiang, and Chonglou. Of the above twenty-nine ingredients, excluding *Zusima*, *Zhugenqi*, *Baimaoqi*, *Guoshanlong*, *Yangjiaoqi*, *Luoshiteng*, *Valeriana*, and *Shenjincao*, the remaining twenty-one ingredients are pulverized into a fine powder, sieved, and mixed evenly. The coarse powder, along with eight other ingredients including *Zusima*, is decocted twice with water, each time for 2 hours. The decoctions are combined, filtered, and concentrated to an extract with a relative density of 1.20 (60℃). This extract is mixed with the fine powder, and appropriate amounts of starch and sucrose powder are added, mixed well, granulated, dried, and pressed into 3000 tablets, which are then sugar-coated. The product has the drawbacks of a complex formula (29 ingredients), crude processing, large dosage, and difficulty in quality control. Therefore, the secondary development of Panlongqi tablets has strong market potential and prospects.

[0004] Chinese Patent CN 113350320 A discloses a Panlongqi compound poultice with blood-activating, stasis-removing, anti-inflammatory, and analgesic properties and its preparation method. The Panlongqi compound poultice is prepared by combining 29 kinds of traditional Chinese medicines from Panlongqi tablets with a humectant (glycerin, butylene glycol or polyethylene glycol), a binder (sodium polyacrylate or kaolin), a transdermal penetration enhancer (azone, oleic acid or a mixture of azone and oleic acid), and a thickener (sodium alginate, sodium carboxymethyl cellulose or sodium hydroxyethyl cellulose).

[0005] Traditional Chinese medicine (TCM) herbs are complex in composition, making it difficult to fully extract their active ingredients using traditional methods. Furthermore, high temperatures can damage heat-sensitive components, significantly reducing the efficacy of the medicine. For example, decoction and reflux extraction are currently the most common methods for extracting TCM herbs. Decoction involves heating the solvent to its boiling point, causing it to boil continuously, intensifying the thermal motion of the herb molecules, increasing solubility, and accelerating diffusion, thus achieving extraction. Reflux extraction generates a large amount of hot steam when the solvent reaches its boiling point. This steam condenses under the action of a condensation system and returns to the extraction system, where it is immersed in fresh solvent, allowing the active ingredients to diffuse continuously into the extraction solvent. However, the high temperatures involved in decoction and reflux extraction can decompose and destroy heat-sensitive components. For TCM herbs containing large amounts of starch, mucilage, and other polysaccharides, heating increases the solubility of impurities, affecting the filtration rate. Another method is ultrasonic extraction, which uses high-frequency mechanical waves with a frequency range of 15-60 kHz to extract the active ingredients from TCM raw materials. Compared with conventional extraction methods, ultrasonic extraction has the advantages of shorter extraction time, no need for heating, higher content of active ingredients, and lower cost. However, ultrasonic extractors are noisy during operation and have limited extraction capacity, making them unsuitable for large-scale production.

[0006] Based on the above problems, developing a suitable extraction method and production process for Panlongqi tablets is a key research focus and direction for researchers in this field. This invention provides a production process for Panlongqi tablets, which, through pulverization, activation, extraction, granulation, purification, and optimization of parameters during the production process, yields a Panlongqi tablet with high stability, high quality, and good efficacy. Summary of the Invention

[0007] To address the aforementioned problems, this invention provides a production process for Panlongqi tablets. First, the raw materials are pulverized, then activated, extracted, and purified using macroporous adsorption resin column chromatography, resulting in Panlongqi tablets with higher stability and better efficacy.

[0008] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0009] On the one hand, the present invention provides a production process for Panlong seven-piece tablets, comprising the following steps:

[0010] S1: Take Aconitum carmichaelii, Aconitum kusnezoffii, and Aconitum carmichaelii, crush and sieve them, add 12-14 times the amount of water, soak for 25-35 minutes, decoct for 2-3 hours, add 8-10 times the amount of water a second time, decoct for 1-2 hours, add 4-5 times the amount of water a third time, decoct for 1-2 hours, filter, and concentrate to obtain extract 1.

[0011] S2: Take Zhuangjin Dan, Du Zhong, Zhu Zi Shen, Hong Hua, Mo Yao, Ba Zhao Ma, Ru Xiang, Luo Shi Teng, Shen Jin Cao, Wu Jia Pi, Pan Long Qi, Dang Gui, Qing Hua Qi, Qin Jiao, Mu Xiang, Lao Shu Qi, Zhi Zhu Liao, Niu Xi, Dan Shen, Chong Lou, Zu Si Ma, Zhu Gen Qi, Bai Mao Qi, Guo Shan Long, Yang Jiao Qi, and Valerian, grind them into powder, sieve them, and obtain coarse material;

[0012] S3: The coarse material is activated and dried in a supercritical carbon dioxide environment;

[0013] S4: Add water to the activated crude material, add compound enzyme, adjust the pH to 5.5-6.5, extract with ultrasound at 55-60℃ for 2-3 hours, and concentrate under vacuum to obtain extract 2;

[0014] S5: Extract 1 and extract 2 were purified by macroporous adsorption resin column chromatography;

[0015] S6: Add the refined extract to mannitol, isomaltitol, tert-butylhydroquinone, and magnesium stearate, mix, spray dry, compress into tablets, and sugar-coat to obtain Panlongqi tablets.

[0016] Preferably, the Panlongqi tablets, by weight fraction, comprise the following components: Panlongqi 10-25g, Gentiana macrophylla 10-25g, Achyranthes bidentata 5-10g, Salvia miltiorrhiza 20-30g, Acanthopanax senticosus 10-25g, Valerian 5-10g, Ephedra sinica 5-10g, Smilax china 5-10g, Smilax china 5-10g, Angelica sinensis 30-50g, Paris polyphylla 20-30g, Aconitum carmichaelii 1-3g, Aconitum kusnezoffii 1-3 ... 3g, Iron Hammer 1-3g, Pearl Ginseng 1-3g, Trachelospermum jasminoides 5-10g, Goat Horn Seven 5-10g, Costus Root 5-10g, Frankincense 5-10g, Zusi Ma 1-3g, White Hair Seven 1-5g, Mouse Seven 1-5g, Eucommia ulmoides 10-25g, Safflower 5-10g, Strengthening Tendon Pill 1-5g, Myrrh 5-10g, Stretching Tendon Grass 1-5g, Pillar Polygonum Root 5-10g, and Bamboo Root Seven 5-10g.

[0017] More preferably, the Panlongqi tablets, by weight fraction, comprise the following components: Panlongqi 12g, Gentiana macrophylla 12g, Achyranthes bidentata 8g, Salvia miltiorrhiza 25g, Acanthopanax senticosus 12g, Valerian 8g, Ephedra sinica 8g, Smilax china 8g, Angelica sinensis 42g, Paris polyphylla 25g, Frog Qi 2g, Aconitum carmichaelii 2g, Aconitum kusnezoffii 2g, Cinnamomum cassia 2g, Codonopsis pilosula 2g, Trachelospermum jasminoides 8g, Angelica dahurica 8g, Aucklandia lappa 8g, Boswellia carterii 8g, Zousima aspergillum 2g, Prunus armeniaca 3g, Aconitum carmichaelii 3g, Eucommia ulmoides 12g, Carthamus tinctorius 8g, Zanthoxylum bungeanum 3g, Commiphora myrrha 8g, Lycopodium clavatum 1-5g, Polygonum cuspidatum 8g, and Phyllostachys edulis 8g.

[0018] Preferably, S1: Take Aconitum carmichaelii, Aconitum kusnezoffii, and Aconitum carmichaelii, crush and sieve them, add 10 times the amount of water, soak for 30 minutes, decoct for 2 hours, add 8 times the amount of water a second time, decoct for 1 hour, add 4 times the amount of water a third time, decoct for 1 hour, filter, and concentrate to obtain extract 1.

[0019] Preferably, the particle size of the coarse material in S2 can be 80-100 mesh; more preferably, the particle size of the coarse material in S2 can be 100 mesh.

[0020] Preferably, the activation temperature in S3 is 40-60℃, the pressure is 5-20 MPa, and the time is 20-30 min; more preferably, the activation temperature in S3 is 45℃, the pressure is 16 MPa, and the time is 20 min.

[0021] Preferably, the complex enzyme in S4 is selected from at least one of cellulase, α-glucosidase, mannanase, and Penicillium oxalate β-glucosidase; more preferably, the complex enzyme in S4 is selected from at least one of cellulase, mannanase, and Penicillium oxalate β-glucosidase; more preferably, the complex enzyme in S4 is cellulase, mannanase, and Penicillium oxalate β-glucosidase.

[0022] Preferably, the mass ratio of cellulase, mannanase and penicillium oxalate β-glucosidase in S4 is 2-4:1-2:1; more preferably, the mass ratio of cellulase, mannanase and penicillium oxalate β-glucosidase in S4 is 3.5:1.2:1.

[0023] Preferably, the mass of the complex enzyme in S4 can be 0.5-0.7% of the mass of the crude material in S4; more preferably, the mass of the complex enzyme in S54 can be 0.63% of the mass of the crude material in S4.

[0024] Preferably, the acid used to adjust the pH in S4 is hydrochloric acid and acetic acid.

[0025] Preferably, as described in S4, the pH is adjusted to 6.0, and ultrasonic extraction is performed at 60°C for 2 hours.

[0026] Preferably, the molar ratio of hydrochloric acid to acetic acid can be 1:2.2-3.5; more preferably, the molar ratio of hydrochloric acid to acetic acid can be 1:2.8.

[0027] Preferably, the density of extract 2 in S4 can be 1-1.2 g / mL; more preferably, the density of extract 2 in S4 can be 1.05 g / mL.

[0028] Preferably, the macroporous adsorption resin in S5 can be XAD1600N resin.

[0029] Preferably, the specific refining operation described in S5 is as follows:

[0030] (1) Soak the macroporous adsorption resin in 0.5-0.8 times the volume of the resin with ethanol for 20-24 hours; dissolve the extract in ethanol to a concentration of 0.2-0.4 g / mL to obtain solution A;

[0031] (2) Pack solution A and macroporous adsorption resin into a column at a mass ratio of 1:2-4.5, load the sample, and saturate for 20-40 min;

[0032] (3) Prepare elution buffer A by mixing sodium chloride solution of 2-3 g / mL, ethanol solution of 60%-80% by mass and acetic acid of 1%-2% by mass in a certain proportion;

[0033] (4) Elute with 20%-30% ethanol solution for 0-10 min; elute with eluent A for 10-40 min; elute with 3%-4% hydrochloric acid for 40-50 min; elute with 5%-7% sodium hydroxide solution for 50-60 min.

[0034] (5) Collect the eluent for 10-50 minutes, concentrate it, and obtain the refined extract.

[0035] More preferably, the specific operation of refining described in S5 is as follows:

[0036] (1) Soak the macroporous adsorption resin in ethanol at 0.6 times the volume of the resin for 20 hours; dissolve the extract in ethanol to a concentration of 0.25 g / mL to obtain solution A;

[0037] (2) Pack solution A and macroporous adsorption resin into a column at a mass ratio of 1:2.2, load the sample, and saturate for 30 min;

[0038] (3) Prepare elution buffer A by mixing 2.5 g / mL sodium chloride solution, 75% ethanol solution and 1% acetic acid in proportion;

[0039] (4) Elute with 30% ethanol solution for 0-10 min; elute with eluent A for 10-40 min; elute with 3%-4% hydrochloric acid solution for 40-50 min; elute with 5% sodium hydroxide solution for 50-60 min.

[0040] (5) Collect the eluent for 10-40 minutes, concentrate it, and obtain the refined extract.

[0041] Preferably, the mixing ratio in step (3) is a volume ratio of 1-2:5-7:1, and more preferably, the volume ratio is 1.6:5:1.

[0042] Preferably, the mass ratio of mannitol, isomaltitol, tert-butylhydroquinone, and magnesium stearate in S6 can be 15-25:1-8:0.5-1.5:5-12.

[0043] More preferably, the mass ratio of mannitol, isomaltitol, tert-butylhydroquinone, and magnesium stearate in S6 can be 20:5:1:10.

[0044] Preferably, the total mass of mannitol, isomaltitol, tert-butylhydroquinone, and magnesium stearate in S6 is 8%-10% of the mass of the crude material in S2; more preferably, the total mass of mannitol, isomaltitol, tert-butylhydroquinone, and magnesium stearate in S6 is 9%-9.5% of the mass of the crude material in S2.

[0045] Compared with the prior art, the present invention has the following beneficial effects:

[0046] 1. The three medicinal materials, Aconitum carmichaelii, Aconitum kusnezoffii, and Aconitum carmichaelii, contain highly toxic bisphenol alkaloids, which are easily hydrolyzed into less toxic monoester alkaloids. Further hydrolysis produces even smaller alkaloids without ester bonds, thus reducing toxicity. Therefore, decoction three times promotes hydrolysis, improves safety, and enhances efficacy.

[0047] 2. Panlong Qipian has a complex composition. This invention activates the pulverized coarse material with supercritical carbon dioxide. On the one hand, it can maximize the extraction of effective components from the Chinese medicinal materials, avoid the loss of components, and further improve the efficacy. On the other hand, it shortens the subsequent extraction time and improves efficiency.

[0048] 3. By using a compound enzyme extraction method, selecting appropriate enzymes and extraction conditions, the extraction time is shortened, and the loss and destruction of components caused by high temperatures are avoided, thereby further improving the efficacy.

[0049] 4. The obtained extract was purified by macroporous adsorption resin column chromatography. By optimizing the eluent, and through experiments, it was found that collecting the eluent at a specific time period can maximize the extraction of active ingredients and significantly improve the efficacy.

[0050] 5. By preparing tablets with mannitol, isomaltitol, tert-butylhydroquinone, and magnesium stearate in a specific ratio, the stability of the product is greatly improved.

[0051] 6. The Panlongqi tablets prepared by the production process provided by this invention have good effects of promoting blood circulation, removing blood stasis, dispelling wind and dampness, reducing swelling and relieving pain, and have extremely high stability, making them suitable for industrial promotion. Detailed Implementation

[0052] To make the technical means, creative features, achieved objectives, and effects of this invention readily understandable, the invention is further illustrated below with specific embodiments. However, these embodiments are merely preferred embodiments and not all embodiments. Other embodiments obtained by those skilled in the art based on the embodiments described herein without creative effort are all within the scope of protection of this invention. It is worth noting that the raw materials used in this invention are all common commercially available products, and their sources are not specifically limited. The technical and scientific terms used in the embodiments have the meanings commonly understood by those skilled in the art to which this invention pertains.

[0053] The dosage of each Chinese herbal raw material is shown in Table 1 below.

[0054] Table 1

[0055] Panlong Seven 12 copies Balima 8 copies Aconitum carmichaelii 2 copies Gentiana macrophylla 12 copies Overpass Dragon 8 copies Iron bar hammer 2 copies Achyranthes bidentata 8 copies Angelica sinensis 42 copies Ginseng 2 copies Salvia miltiorrhiza 25 copies Paris polyphylla 25 copies Trachelospermum jasminoides 8 copies Acanthopanax senticosus 12 copies Frog Seven 2 copies Ram's Horn Seven 8 copies Valerian 8 copies Aconitum carmichaelii 2 copies Woody Scent 8 copies mastic 8 copies Zusi Ma 2 copies White Hair Seven 3 copies Mouse Seven 3 copies Eucommia 12 copies safflower 8 copies Strengthening Muscle Pill 3 copies Myrrh 8 copies Stretching Grass 3 copies Pillar Polygonum 8 copies Bamboo Root Seven 8 copies total 260 copies

[0056] Example 1

[0057] S1: Take Aconitum carmichaelii, Aconitum kusnezoffii, and Aconitum carmichaelii according to the formula ratio, crush and sieve them, add 10 times the amount of water, soak for 30 minutes, decoct for 2 hours, add 8 times the amount of water a second time, decoct for 1 hour, add 4 times the amount of water a third time, decoct for 1 hour, filter, concentrate to obtain extract 1 with a density of 1.1 g / mL.

[0058] S2: Take the following ingredients according to the formula: Zhuangjin Dan, Du Zhong, Zhu Zi Shen, Hong Hua, Mo Yao, Ba Zhao Ma, Ru Xiang, Luo Shi Teng, Shen Jin Cao, Wu Jia Pi, Pan Long Qi, Dang Gui, Qing Hua Qi, Qin Jiao, Mu Xiang, Lao Shu Qi, Zhi Zhu Liao, Niu Xi, Dan Shen, Chong Lou, Zu Si Ma, Zhu Gen Qi, Bai Mao Qi, Guo Shan Long, Yang Jiao Qi, and Valerian. Grind them into powder and pass them through a 100-mesh sieve to obtain coarse material.

[0059] S3: The coarse material is activated and dried in a supercritical carbon dioxide environment; the activation temperature is 45℃, the pressure is 16Mpa, and the time is 20min.

[0060] S4: Add deionized water to the activated crude material, add 0.98 parts of cellulase, 0.34 parts of mannanase and 0.28 parts of penicillin oxalate β-glucosidase, add a mixture of hydrochloric acid and acetic acid (the molar ratio of hydrochloric acid and acetic acid can be 1:2.8) to adjust the pH to 6, extract with ultrasound at 60℃ for 2 hours, and concentrate under vacuum to obtain extract 2 with a density of 1.05 g / mL;

[0061] S5: Purification of extracts 1 and 2 by macroporous adsorption resin column chromatography (XAD1600N macroporous adsorption resin):

[0062] (1) Soak the macroporous adsorption resin in ethanol at 0.6 times the volume of the resin for 20 hours; dissolve the extract in ethanol to a concentration of 0.25 g / mL to obtain solution A;

[0063] (2) Pack solution A and macroporous adsorption resin into a column at a mass ratio of 1:2.2, load the sample, and saturate for 30 min;

[0064] (3) Prepare elution buffer A by mixing 2.5 g / mL sodium chloride solution, 75% ethanol solution and 1% acetic acid in a volume ratio of 1.6:5:1;

[0065] (4) Elute with 30% ethanol solution for 0-10 min; elute with eluent A for 10-40 min; elute with 3%-4% hydrochloric acid solution for 40-50 min; elute with 5% sodium hydroxide solution for 50-60 min.

[0066] (5) Collect the eluent for 10-40 minutes, concentrate it, and obtain the refined extract.

[0067] S6: Add 12.7 parts mannitol, 3.18 parts isomaltitol, 0.64 parts tert-butylhydroquinone, and 6.35 parts magnesium stearate to the refined extract, mix, spray dry, compress into tablets, and coat with sugar to obtain Panlongqi tablets.

[0068] Example 2

[0069] S1: Take Aconitum carmichaelii, Aconitum kusnezoffii, and Aconitum carmichaelii according to the formula ratio, crush and sieve them, add 12 times the amount of water, soak for 35 minutes, decoct for 3 hours, add 10 times the amount of water a second time, decoct for 2 hours, add 5 times the amount of water a third time, decoct for 2 hours, filter, concentrate to obtain extract 1 with a density of 1.05 g / mL.

[0070] S2: Take the following ingredients according to the formula ratio: Zhuangjin Dan, Du Zhong, Zhu Zi Shen, Hong Hua, Mo Yao, Ba Zhao Ma, Ru Xiang, Luo Shi Teng, Shen Jin Cao, Wu Jia Pi, Pan Long Qi, Dang Gui, Qing Hua Qi, Qin Jiao, Mu Xiang, Lao Shu Qi, Zhi Zhu Liao, Niu Xi, Dan Shen, Chong Lou, Zu Si Ma, Zhu Gen Qi, Bai Mao Qi, Guo Shan Long, Yang Jiao Qi, and Valerian. Grind them into powder and pass them through an 80-mesh sieve to obtain coarse material.

[0071] S3: The coarse material is activated and dried in a supercritical carbon dioxide environment; the activation temperature is 60℃, the pressure is 20Mpa, and the time is 30min.

[0072] S4: Add deionized water to the activated crude material, add 1.02 parts of cellulase, 0.51 parts of mannanase and 0.25 parts of penicillin oxalate β-glucosidase, add a mixture of hydrochloric acid and acetic acid (the molar ratio of hydrochloric acid and acetic acid can be 1:2.2) to adjust the pH to 6, extract with ultrasound at 55℃ for 2 hours, and concentrate under vacuum to obtain extract 2 with a density of 1.1 g / mL;

[0073] S5: Purification of extracts 1 and 2 by macroporous adsorption resin column chromatography (XAD1600N macroporous adsorption resin):

[0074] (1) Soak the macroporous adsorption resin in ethanol at 0.8 times the volume of the resin for 24 hours; dissolve the extract in ethanol to a concentration of 0.3 g / mL to obtain solution A;

[0075] (2) Pack solution A and macroporous adsorption resin into a column at a mass ratio of 1:3, load the sample, and saturate for 30 min.

[0076] (3) Prepare elution buffer A by mixing 2.5 g / mL sodium chloride solution, 75% ethanol solution and 1% acetic acid in a volume ratio of 1.8:6:1;

[0077] (4) Elute with 30% ethanol solution for 0-10 min; elute with eluent A for 10-40 min; elute with 3%-4% hydrochloric acid solution for 40-50 min; elute with 5% sodium hydroxide solution for 50-60 min.

[0078] (5) Collect the eluent for 10-40 minutes, concentrate it, and obtain the refined extract.

[0079] S6: Add 12.15 parts mannitol, 4.86 parts isomaltitol, 0.65 parts tert-butylhydroquinone, and 6.48 parts magnesium stearate to the refined extract, mix, spray dry, compress into tablets, and coat with sugar to obtain Panlongqi tablets.

[0080] Comparative Example 1

[0081] S1: Take Aconitum carmichaelii, Aconitum kusnezoffii, and Aconitum carmichaelii according to the formula ratio, crush and sieve them, add 10 times the amount of water, soak for 30 minutes, and decoct for 4 hours.

[0082] The remaining operations are the same as in Example 1.

[0083] Comparative Example 2

[0084] S3 is not performed, meaning the coarse material is directly enzymatically hydrolyzed without activation. The remaining operations are the same as in Example 1.

[0085] Comparative Example 3

[0086] S4: Add 1.19 parts of cellulase and 0.41 parts of mannanase. The remaining operations are the same as in Example 1.

[0087] Comparative Example 4

[0088] S4: Add 1.24 parts of cellulase and 0.36 parts of Penicillium oxalate β-glucosidase, and the rest of the operation is the same as in Example 1.

[0089] Comparative Example 5

[0090] S4: Add 0.87 parts of mannanase and 0.73 parts of penicillin oxalate β-glucosidase, and the rest of the operation is the same as in Example 1.

[0091] Comparative Example 6

[0092] S5: (3) Prepare elution buffer A by mixing 2.5 g / mL sodium chloride solution, 75% ethanol solution and 1% acetic acid in a volume ratio of 3:1:4; the remaining operations are the same as in Example 1.

[0093] Comparative Example 7

[0094] S5: (3) Prepare elution buffer A by mixing 2.5 g / mL sodium chloride solution and 75% ethanol solution in a volume ratio of 1.6:5; the remaining operations are the same as in Example 1.

[0095] Comparative Example 7

[0096] S5: (3) Prepare elution solution A by mixing 75% ethanol solution and 1% acetic acid in a volume ratio of 5:1; the remaining operations are the same as in Example 1.

[0097] Comparative Example 8

[0098] S5: (5) Collect the eluent from 0 to 60 min, concentrate it, and obtain the purified extract. The remaining operations are the same as in Example 1.

[0099] Comparative Example 9

[0100] S5: (5) Collect the eluent after 40-60 minutes, concentrate it, and obtain the purified extract. The remaining operations are the same as in Example 1.

[0101] Comparative Example 10

[0102] S6: Add 8.76 parts mannitol, 10.51 parts isomaltitol, 0.09 parts tert-butylhydrogen, and 3.5 parts magnesium stearate to the refined extract, mix, spray dry, compress into tablets, and coat with sugar to obtain Panlongqi tablets.

[0103] Test case

[0104] 1. Stability Test

[0105] The samples were subjected to related substance detection after being stored at 60℃ for 0 days and 30 days (detection method: high performance liquid chromatography, C8 column, wavelength: 205nm, methanol, acetonitrile, water (5:40:53)). The content of related substances in the samples stored at 60℃ for 30 days is shown in Table 2.

[0106] Table 2. Stability Results

[0107]

[0108]

[0109] As can be seen from the data in Table 2, the stability of Panlongqi tablets prepared in Examples 1-2 is significantly better than that in Comparative Examples 1-10, especially Comparative Example 10. This shows that the production process of the present invention provides stability for Panlongqi tablets, especially by preparing tablets with mannitol, isomaltitol, tert-butylhydroquinone, and magnesium stearate in a specific ratio, which greatly improves the stability of the product.

[0110] 2. Analgesia Experiment

[0111] The analgesic activity of Panlongqi tablets was determined using the writhing test. Seventy mice, weighing (21.2±4.3g), were randomly divided into 14 groups of 5 mice each. The mice were tested using Panlongqi tablets obtained in Examples 1-2 and Control Examples 1-10, a blank group (physiological saline), and ibuprofen tablets (positive control group), respectively. The dosage was 0.2g / 10g. Forty minutes after the last administration, 0.2mL of 0.6% glacial acetic acid was injected intraperitoneally per mouse. The writhing response (abdomen contracting into an "S" shape, body twisting, hind limb extension, and peristalsis, etc.) and the number of writhing movements were observed and recorded within 15 minutes.

[0112] Analgesia rate = (Number of writhing movements in the control group / Number of writhing movements in the medication group) / Number of writhing movements in the control group * 100%

[0113] Table 3. Effects of Panlongqi tablets prepared in the examples and comparative examples on acetic acid-induced pain in mice.

[0114]

[0115]

[0116] Note: Compared with the control group, **P<0.01; *P<0.05.

[0117] Measuring the change in pain induced by acetic acid in mice using the writhing test is a classic method for evaluating analgesic effects. This experiment used 70 mice, with no deaths, making the effective sample size 70. Table 3 shows that within 15 minutes, mice in Examples 1-2 had an average of fewer than 6 writhing movements, with an analgesic rate exceeding 80.54% and a writhing latency exceeding 7.7 minutes, comparable to the positive control group. Mice in Comparative Examples 1-9 had an average of 12-14 writhing movements, with an analgesic rate of 47.69%-50.37% and a writhing latency of 4-5 minutes. The analgesic effect of Comparative Example 10 was slightly higher than that of Comparative Examples 1-9. Therefore, the Panlongqi tablets prepared in this invention have better analgesic effects.

[0118] 3. Anti-inflammatory experiment

[0119] The anti-inflammatory activity of Panlongqi tablets was determined using the mouse ear swelling method. Seventy mice were selected, weighed (22.1±0.85g), numbered, and randomly divided into 14 groups of 5 mice each. The mice were treated with Panlongqi tablets obtained in Examples 1-2 and Comparative Examples 1-10, a blank group (physiological saline), and ibuprofen emulsion tablets (positive control), respectively. Treatment was administered for 5 consecutive days at a dose of 0.2g / 10g. Forty-five minutes after the last administration, 2.5μg of TPA (phorbol ester) was evenly applied to both sides of the right ear of each mouse. Four hours later, the mice were euthanized by cervical dislocation, and ear pieces were cut off. One ear piece was taken from the same location on each ear using a 0.8cm punch, and weighed. The weight difference between the two ear pieces was used as the degree of swelling, and the swelling inhibition rate was calculated.

[0120] Swelling inhibition rate = (weight of ear patch in blank group / weight of ear patch in drug group) / weight of ear patch in blank group * 100%

[0121] Table 4. Effects of Panlongqi tablets prepared in the examples and comparative examples on TPA (phorbol ester)-induced ear swelling in mice.

[0122]

[0123]

[0124] Note: Compared with the control group, **P<0.01; *P<0.05.

[0125] The mouse ear swelling method is inexpensive, easy to operate, easy to measure, and has a stable model, making it a commonly used method for studying the anti-inflammatory activity of drugs. This experiment used 70 mice, with no deaths, resulting in a valid sample size of 70. As shown in Table 4, the swelling inhibition rates of Examples 1-2 reached over 39%, comparable to the positive control group. However, the swelling inhibition rates of Comparative Examples 1-9 were between 27% and 29%, significantly lower than the Examples. Comparative Example 10 showed a slightly better swelling inhibition rate than the other comparative examples.

[0126] 4. Anti-arthritis experiment

[0127] Forty-two volunteers with knee osteoarthritis were randomly divided into 14 groups of three. Each group received one of the following medications: Panlongqi tablets (obtained in Examples 1-2 and Comparative Examples 1-10), a control group, or ibuprofen. The dosage was one tablet daily for all participants. The control group received no medication. The experiment was repeated for 30 days. During the treatment period, the time of redness and swelling disappearance and the time of pain disappearance were recorded. After 30 days of treatment, medication was discontinued, and any recurrence of symptoms within 30 days was recorded.

[0128] Table 5. Arthritis condition in the subjects.

[0129]

[0130]

[0131] As shown in Table 5, the efficacy of Panlongqi tablets prepared in Examples 1-2 is comparable to that of the positive control group, while the efficacy of Panlongqi tablets prepared in Comparative Examples 1-10 is significantly worse than that of the examples. The Panlongqi tablets prepared using the production process provided by this invention have good effects in promoting blood circulation, removing blood stasis, dispelling wind and dampness, reducing swelling and relieving pain, and exhibit extremely high stability.

[0132] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, and is not intended to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions made by those skilled in the art to the technical solution of the present invention do not depart from the essence and scope of the technical solution of the present invention.

Claims

1. A production process of Aspidistra elatior Blume leaf, characterized by, Comprise the following steps: S1: take the Radix Aconiti, Radix Aconiti, Radix Aconiti, iron hammer powder, add water 12-14 times, soak 25-35 min, decoct 2-3h, add water 8-10 times, decoct 1-2h, add water 4-5 times, decoct 1-2h, filter, concentrate to extract 1; S2: take the Dan, Eucommia ulmoides, Radix Anemarrhenae, safflower, myrrh, eight cover, frankincense, Luo Shiteng, Stachys affinis, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Angelica sinensis, Qinglongqi, Gentiana crassicaulis, Radix Aucklandiae, Radix Acanthopanacis Senticosi, Polygonum perfoliatum, Radix Hedysari, Radix Salviae Miltiorrhizae, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi, Radix Acanthopanacis Senticosi ​ ​ ​ ​ ​ ​ ​ ​ ​ 2. The production process according to claim 1, characterized in that, ​ 3. The production process according to claim 1, characterized in that, ​ 4. The production process according to claim 1, characterized in that, ​

Images